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400 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What were the findings when comparing conventional chest physiotherapy (CCPT) with other airway clearance techniques for individuals with cystic fibrosis in terms of respiratory function and individual preference? Please answer this question based on the information provided below:
Comparison of high frequency chest compression and conventional chest physiotherapy in hospitalized patients with cystic fibrosis.
Clearance of bronchial secretions is essential in the management of cystic fibrosis (CF) patients admitted for acute pulmonary exacerbation. Conventional physiotherapy (CPT) is labor-intensive, time-consuming, expensive, and may not be available as frequently as desired during hospitalization. High frequency chest compression (HFCC), which uses an inflatable vest linked to an air-pulse delivery system, may offer an attractive alternative. To study this, we prospectively studied 50 CF patients admitted for acute pulmonary exacerbation who were randomly allocated to receive either HFCC or CPT three times a day. On admission, clinical status and pulmonary function tests (PFT) in the HFCC group were not significantly different from those measured in the CPT group. Significant improvements in clinical status and PFT were observed after 7 and 14 d of treatment, and were similar in the two study groups, leading to patient discharge after similar periods of hospitalization. We conclude that HFCC and CPT are equally safe and effective when used during acute pulmonary exacerbations in CF patients. We speculate that HFCC may provide an adequate alternative in management of CF patients in a hospital setting.
Comparison of manual and mechanical chest percussion in hospitalized patients with cystic fibrosis.
We compared the efficacy of manual and mechanical chest percussion during hospitalization for acute exacerbations of cystic fibrosis by evaluating changes in spirometry values. Fifty-one participants were randomly assigned to receive manual or mechanical chest percussion three times a day. Twenty-two participated during one subsequent admission and were assigned to the opposite form of chest percussion. The two groups were equal in severity of illness (mean National Institutes of Health score (+/- SEM): manual = 66.7 +/- 2.2; mechanical = 35.8 +/- 2.2; p = not significant). Mean improvement in forced expiratory volume at 1 second, forced vital capacity, and forced expiratory flow between 25% and 75% of forced vital capacity (+/- SEM) for manual percussion was 32.6% +/- 7%, 27.2% +/- 5%, and 38.1% +/- 10%, and for mechanical percussion was 28.5% +/- 4%, 28.7% +/- 4%, and 25.1% +/- 8%, respectively; p = not significant. Our participants did not prefer mechanical chest percussion. Although equal efficacy of outpatient therapy remains to be proved, this study suggests that patients can be encouraged to use the form of chest percussion that they prefer.
Relative effects of bronchial drainage and exercise for in-hospital care of patients with cystic fibrosis.
Bronchial hygiene therapy is a standard part of the treatment of patients with cystic fibrosis (CF). Coughing alone promotes sputum expectoration and is probably the primary effective component of standard bronchial hygiene therapy. The purpose of this study was to determine whether substituting regular exercise, which also promotes coughing, for two of three daily bronchial hygiene treatments would affect the expected improvements in pulmonary function and exercise response in hospitalized patients with CF. Seventeen patients with CF hospitalized (means length of stay = 13.0 +/- 2.6 days) for an acute exacerbation of their pulmonary disease participated in the study. The patients were randomly assigned to either a group that participated in two cycle ergometer exercise sessions and one bronchial hygiene treatment session per day (EX Group [n = 9]) or a group that participated in three bronchial hygiene treatment sessions per day (PD Group [n = 8]). Pulmonary functions and responses to a progressive, incremental cycle ergometer exercise test were measured on admission and before discharge. Bronchial hygiene therapy consisted of postural drainage, in six positions, with chest percussion and vibration. Therapeutic exercise was of moderate intensity and was individually adjusted based on the patient's heart rate and arterial oxygen saturation response to the admission exercise test. Coughing was encouraged during and after all treatments. Pulmonary function and exercise response were significantly improved over the period of hospitalization in both groups; the improvements were the same in the two groups. These results indicate that, in some hospitalized patients with CF, exercise therapy may be substituted for at least part of the standard protocol of bronchial hygiene therapy.
Comparison of effects of an intrapulmonary percussive ventilator to standard aerosol and chest physiotherapy in treatment of cystic fibrosis.
Impaired mucociliary clearance due to defective ion and water transport and the effects of chronic airway infections lead to stasis of secretions and progressive pulmonary damage in patients with cystic fibrosis (CF). Methods to improve removal of tenacious lung secretions in CF patients contribute to slowing the decline in respiratory function. We have evaluated an intrapulmonary percussive ventilator (IPV), which is a device designed to enhance airway clearance and preserve lung function. A previous pilot study by us had determined that the device was acceptable to patients and is safe. We undertook a 6 month parallel comparative trial of the IPV versus standard, manual chest physiotherapy in 16 CF children and adults. No significant differences in spirometric measures, numbers of hospitalizations, use of oral or IV antibiotics, or anthropometric measurements were detected between the standard aerosol/chest physiotherapy group and the IPV group over the duration of the trial. Patient acceptance, as determined by participant survey, was good. The device appeared to be safe and durable. It was concluded that the IPV is as effective as standard aerosol and chest physiotherapy in preserving lung function and anthropometric measures, and there was no difference in the use of antibiotics and hospitalizations.
Comparison of the flutter device to standard chest physiotherapy in hospitalized patients with cystic fibrosis: a pilot study.
STUDY OBJECTIVE: A preliminary study comparing the efficacy and safety of the flutter device (Flutter) to standard, manual chest physiotherapy (CPT) in hospitalized cystic fibrosis (CF) patients undergoing an acute pulmonary exacerbation.
DESIGN: Open label, comparative trial with alternate assignment.
SETTING: Community and childrens' hospital acute-care wards.
PARTICIPANTS: Twenty-two CF patients (ages 8 to 44 years) undergoing a total of 33 hospitalizations for acute pulmonary exacerbation.
INTERVENTIONS: Complete pulmonary function tests (PFTs) were done at baseline (admission), weekly, and upon discharge from the hospital. Clinical score (CS) was determined at the time of hospital admission and at discharge. Participants were assigned to receive supervised Flutter therapy or standard, manual CPT four times per day during the hospitalization. Patients were monitored for complications, including hemoptysis, hypoxemia, and pneumothorax.
RESULTS: The groups (CPT and Flutter) did not differ at baseline in demographics or Shwachman score, nor was length of hospitalization different. Significant improvements were noted from admission to discharge in CS and PFT results within each group. Mean percent change in CS and PFT results between CPT and Flutter groups showed no significant difference from hospital admission to discharge. Subsequent power analysis using the observed difference in percent change from admission to discharge for FEV1 indicated that to attain 80% power at alpha = 0.05, a sample of 219 subjects in each group would be necessary.
SUMMARY: Comparative trials of airway clearance techniques with sufficient sample size are lacking. Although the Flutter appears to be a useful device for independent, cost-effective, and safe administration of CPT in this pilot study, a much larger clinical trial would be necessary to make definitive conclusions.
Comparison of the flutter device to standard chest physiotherapy in hospitalized patients with cystic fibrosis: a pilot study.
STUDY OBJECTIVE: A preliminary study comparing the efficacy and safety of the flutter device (Flutter) to standard, manual chest physiotherapy (CPT) in hospitalized cystic fibrosis (CF) patients undergoing an acute pulmonary exacerbation.
DESIGN: Open label, comparative trial with alternate assignment.
SETTING: Community and childrens' hospital acute-care wards.
PARTICIPANTS: Twenty-two CF patients (ages 8 to 44 years) undergoing a total of 33 hospitalizations for acute pulmonary exacerbation.
INTERVENTIONS: Complete pulmonary function tests (PFTs) were done at baseline (admission), weekly, and upon discharge from the hospital. Clinical score (CS) was determined at the time of hospital admission and at discharge. Participants were assigned to receive supervised Flutter therapy or standard, manual CPT four times per day during the hospitalization. Patients were monitored for complications, including hemoptysis, hypoxemia, and pneumothorax.
RESULTS: The groups (CPT and Flutter) did not differ at baseline in demographics or Shwachman score, nor was length of hospitalization different. Significant improvements were noted from admission to discharge in CS and PFT results within each group. Mean percent change in CS and PFT results between CPT and Flutter groups showed no significant difference from hospital admission to discharge. Subsequent power analysis using the observed difference in percent change from admission to discharge for FEV1 indicated that to attain 80% power at alpha = 0.05, a sample of 219 subjects in each group would be necessary.
SUMMARY: Comparative trials of airway clearance techniques with sufficient sample size are lacking. Although the Flutter appears to be a useful device for independent, cost-effective, and safe administration of CPT in this pilot study, a much larger clinical trial would be necessary to make definitive conclusions.
Long-term comparative trial of conventional postural drainage and percussion versus positive expiratory pressure physiotherapy in the treatment of cystic fibrosis.
We report the results of a long-term comparative trial of physiotherapy by the positive expiratory pressure (PEP) technique with a PEP mask (Astra Meditec) versus conventional postural drainage and percussion (PD&P). Forty patients, ages 6 to 17 years, with Shwachman scores between 52 and 93, attending the cystic fibrosis clinic were enrolled in the study and randomly assigned to one of two groups. Group A (control) continued to perform physiotherapy by using PD&P for a 1-year period, whereas patients assigned to group B performed physiotherapy with the PEP technique for the same period. Compliance with physiotherapy was closely monitored for both groups throughout the study. Clinical status and pulmonary function (forced vital capacity [FVC], FEV1, and FEF25-75) were measured at 3-month intervals. Group B (PEP) demonstrated improved pulmonary function in all parameters as measured by change in percent predicted value for age, gender, and height. The changes in pulmonary function over the study period were: FVC, +6.57; FEV1, +5.98; and FEF25-75, +3.32. This improvement was significantly different from that of group A (PD&P) whose pulmonary function declined in all parameters (FVC, -2.17; FEV1, -2.28; FEF25-75, -0.24). The differences between treatment groups were statistically significant for the changes in FVC (p = 0.02) and FEV(1) (p = 0.04). Our results indicate that for our patients with cystic fibrosis, pulmonary physiotherapy with the PEP technique was superior to conventional physiotherapy with the PD&P technique.
Long-term comparative trial of conventional postural drainage and percussion versus positive expiratory pressure physiotherapy in the treatment of cystic fibrosis.
We report the results of a long-term comparative trial of physiotherapy by the positive expiratory pressure (PEP) technique with a PEP mask (Astra Meditec) versus conventional postural drainage and percussion (PD&P). Forty patients, ages 6 to 17 years, with Shwachman scores between 52 and 93, attending the cystic fibrosis clinic were enrolled in the study and randomly assigned to one of two groups. Group A (control) continued to perform physiotherapy by using PD&P for a 1-year period, whereas patients assigned to group B performed physiotherapy with the PEP technique for the same period. Compliance with physiotherapy was closely monitored for both groups throughout the study. Clinical status and pulmonary function (forced vital capacity [FVC], FEV1, and FEF25-75) were measured at 3-month intervals. Group B (PEP) demonstrated improved pulmonary function in all parameters as measured by change in percent predicted value for age, gender, and height. The changes in pulmonary function over the study period were: FVC, +6.57; FEV1, +5.98; and FEF25-75, +3.32. This improvement was significantly different from that of group A (PD&P) whose pulmonary function declined in all parameters (FVC, -2.17; FEV1, -2.28; FEF25-75, -0.24). The differences between treatment groups were statistically significant for the changes in FVC (p = 0.02) and FEV(1) (p = 0.04). Our results indicate that for our patients with cystic fibrosis, pulmonary physiotherapy with the PEP technique was superior to conventional physiotherapy with the PD&P technique.
Long-term comparative trial of conventional postural drainage and percussion versus positive expiratory pressure physiotherapy in the treatment of cystic fibrosis.
We report the results of a long-term comparative trial of physiotherapy by the positive expiratory pressure (PEP) technique with a PEP mask (Astra Meditec) versus conventional postural drainage and percussion (PD&P). Forty patients, ages 6 to 17 years, with Shwachman scores between 52 and 93, attending the cystic fibrosis clinic were enrolled in the study and randomly assigned to one of two groups. Group A (control) continued to perform physiotherapy by using PD&P for a 1-year period, whereas patients assigned to group B performed physiotherapy with the PEP technique for the same period. Compliance with physiotherapy was closely monitored for both groups throughout the study. Clinical status and pulmonary function (forced vital capacity [FVC], FEV1, and FEF25-75) were measured at 3-month intervals. Group B (PEP) demonstrated improved pulmonary function in all parameters as measured by change in percent predicted value for age, gender, and height. The changes in pulmonary function over the study period were: FVC, +6.57; FEV1, +5.98; and FEF25-75, +3.32. This improvement was significantly different from that of group A (PD&P) whose pulmonary function declined in all parameters (FVC, -2.17; FEV1, -2.28; FEF25-75, -0.24). The differences between treatment groups were statistically significant for the changes in FVC (p = 0.02) and FEV(1) (p = 0.04). Our results indicate that for our patients with cystic fibrosis, pulmonary physiotherapy with the PEP technique was superior to conventional physiotherapy with the PD&P technique.
Role of conventional physiotherapy in cystic fibrosis.
Because of the time and the emotional cost involved in performing daily conventional chest physiotherapy in patients with cystic fibrosis, a 3-year prospective study was undertaken to compare the long-term effects of postural drainage accompanied by percussion and the forced expiratory technique with the effects of the forced expiratory technique alone. Patients who performed the forced expiratory technique alone had mean annual rates of decline that were significantly different from zero for forced expiratory volume in 1 second (p less than 0.001), forced expiratory flow between 25% and 75% of vital capacity (p less than 0.001), and Shwachman clinical score (p less than 0.004). In the group performing conventional physiotherapy with percussion and postural drainage, only the mean annual rate of decline for forced expiratory flow between 25% and 75% of vital capacity was significantly different from zero (p less than 0.03), and it was significantly different from the mean rate of decline associated with the forces expiratory technique alone (p less than 0.04). We conclude that conventional chest physiotherapy should remain a standard component of therapy in cystic fibrosis.
Face mask physiotherapy in cystic fibrosis.
The use of the 'PEP' mask with forced expiratory coughing was compared with conventional physiotherapy over a one month period. No difference was shown in symptom scores, sputum production, or simple lung function tests. The mask was well accepted and allowed independent treatment by older patients.
Comparison of a positive expiratory pressure (PEP) mask with postural drainage in patients with cystic fibrosis.
The use of a positive expiratory pressure (PEP) mask was compared with postural drainage in the treatment of 10 patients with cystic fibrosis. The patients were allocated randomly in a crossover fashion to the two regimens and evaluated initially by a physiotherapist and over a 4 week treatment period by use of a diary card. There was no significant difference in sputum production or change in lung function between each technique as assessed by the physiotherapist. Diary card evaluation also failed to demonstrate a difference in sputum production, symptom score or peak expiratory flow rate between the 4 week treatment periods. It was concluded that PEP mask therapy is an acceptable and effective alternative to postural drainage in interval therapy of patients with cystic fibrosis, although the patients have tended to revert to postural drainage during acute exacerbations.
Options:
A: CCPT showed significant improvement in respiratory function compared to other techniques, and participants preferred CCPT.
B: There was no difference in respiratory function between CCPT and other techniques, but participants tended to prefer self-administered techniques.
C: Other airway clearance techniques showed significant improvement in respiratory function compared to CCPT, and participants had no preference.
D: CCPT showed significant improvement in respiratory function compared to other techniques, but participants preferred self-administered techniques. | B |
401 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What are the findings regarding the efficacy and complications of medical versus surgical methods for first-trimester abortion? Please answer this question based on the information provided below:
A randomized comparison of medical abortion and surgical vacuum aspiration at 10-13 weeks gestation.
BACKGROUND: Since 1991, mifepristone in combination with a prostaglandin analogue has been licensed for termination of pregnancy in the UK at up to 9 weeks amenorrhoea, and since 1995, beyond 13 weeks. Surgical methods are used almost exclusively at 10-13 weeks amenorrhoea.
METHODS: A patient-centred, partially randomized, controlled trial was carried out. Those who expressed a strong preference for either medical (n = 15) or surgical (n = 62) abortion were allocated to that method. The remainder agreed to be randomized. The medical method (n = 188) was mifepristone 200 mg followed by misoprostol up to 3 doses, and surgery (n = 180) was by vacuum aspiration under general anaesthesia. Outcome measures included efficacy rates, medical complications within 8 weeks of the procedure, patient preferences and acceptability.
RESULTS: Among women who underwent medical abortion, 5.4% required a second procedure compared with 2.1% who had surgery, although this difference was not statistically significant. Side effects experienced were higher in women who underwent medical abortion compared with those who underwent surgery. There were no significant differences in the rates of major complications up to 8 weeks. Prior to termination, 80% of women had a preference for a method, with 72% preferring medical and 28% preferring surgical abortion. Following abortion, 70% of those who underwent medical termination and 79% who underwent surgery would opt for the same method in the future.
CONCLUSION: Medical abortion is safe and effective at 10-13 weeks gestation and should be considered an option for those women who wish to avoid surgery and anaesthesia.
Randomized comparison of efficacy, acceptability and cost of medical versus surgical abortion.
This randomized trial was performed to examine the clinical efficacy of, patient acceptance of, and provider resources needed for medical and surgical abortion in women with pregnancies up to 49 days' gestation. Women with no pre-treatment preference for method of abortion were randomized to medical abortion with methotrexate and misoprostol (group 1) or surgical abortion under local anesthesia using manual vacuum aspiration (group 2). Women in group 1 received methotrexate 50 mg orally followed 5 to 6 days later by misoprostol 800 microg vaginally; the misoprostol dose was repeated if the abortion did not occur. All subjects returned for a follow-up evaluation 7 and 14 days after the methotrexate or 14 days after the vacuum aspiration. The time spent by clinical staff for all interactions with participants was prospectively recorded. Enrollment of 50 subjects took 24 months; 25 women were randomized to each group. The complete abortion rates by study day 15 were 83% (95% CI 68, 98%) and 96% (95% CI 88, 100%) for groups 1 and 2, respectively. Of the women randomized to a surgical abortion, 92% (95% CI 81, 100%) stated they would choose a surgical for a next abortion, whereas only 63% (95% CI 43, 82%) of women randomized to a medical abortion would choose that option in the future. Overall, surgical abortion requires 0 to 10% more personnel cost than medical abortion using methotrexate and misoprostol. In women who did not have a strong preference between medical and surgical abortion, the side effect profile and patient acceptability was significantly better for surgical abortion compared to medical abortion.
A comparison of medical abortion (using mifepristone and gemeprost) with surgical vacuum aspiration: efficacy and early medical sequelae.
A total of 363 women undergoing legal abortion at < 63 days of amenorrhoea were allocated by a patient-centered, partially randomized study design to undergo medical abortion (using mifepristone 600 mg followed 48 h later by gemeprost 1 mg vaginal pessary) or vacuum aspiration (performed under general anaesthesia). The aim of the study was to compare the efficacy and complications of the two procedures. Main outcome measures included efficacy rates, medical complications within 21 days of abortion and unplanned family doctor consultation rates within 8 weeks following abortion. Sequelae such as pain, vaginal bleeding and recovery time were assessed by the change in haemoglobin level, the time taken to return to work or normal activity and the analgesic use. Results were gestation-related; at 50 days of amenorrhoea there was little to choose between the two procedures. At 50-63 days of amenorrhoea medical abortion becomes more painful and less effective, whereas vacuum aspiration retains high tolerance and efficacy. Women who are unsure which method to use are likely to find vacuum aspiration more acceptable at longer gestations.
Mifepristone or vacuum aspiration in termination of early pregnancy.
This trial compared the termination of early pregnancy (amenorrhoea less than 43 days) by 600 mg orally of the antiprogesteron Mifepristone to the traditional method of vacuum aspiration. Fifty women were randomly assigned to either of the treatments. All the patients treated with vacuum aspiration had a complete abortion. Three of these patients developed pelvic inflammatory diseasae (PID) after the aspiration. Another patient had the uterus perforated during the procedure, and an emergency laparotomy had to be performed. The patients in the evacuation group spent more days in bed and needed longer sick leave after the treatment than the patients in the Mifepristone group. In the Mifepristone group, six patients had incomplete abortions and all were treated by evacuation. Three of the patients developed PID after the evacuation. A decrease of 40% or more in beta hCG from the initial value to the value 1 week later were invariably associated with complete abortion. In both groups the changes in hemoglobin were insignificant and no patients needed blood transfusion or emergency evacuation. The Mifepristone treatment is a simple and safe alternative to vacuum aspiration for termination of early pregnancies.
Medical versus surgical abortion efficacy, complications and leave of absence compared in a partly randomized study.
To provide optimal information to women choosing between early medical and surgical abortion, rigorous comparisons of the two methods are warranted. We compared the outcome of 1135 consecutive women with gestational age (GA) < or = 63 days receiving either a medical (600 mg mifepristone and 1 mg gemeprost) or a surgical abortion (vacuum aspiration in general anesthesia). One hundred eleven of these women were randomized for abortion method. Surgical interventions and complications leading to readmission within the following 15 weeks were identified through a computer system. Information about antibiotic treatment, leave of absence and number of contacts to the health care system were obtained from mailed questionnaires. The number of complications was identical after the two methods, but surgical abortion was associated with a higher success rate [97.7% (708/725) vs. 94.1% (386/410), p < .01] and also with a higher risk of antibiotic treatment than medical abortion [7.8% (37/467) vs. 3.7% (13/356), p < .05]. The median leave of absence was shorter in women choosing a medical (1 day) than a surgical termination (2 days), p < .05. On average, one third of all the women requested at least one extra unscheduled consultation apart from a routine follow-up visit. We conclude that the chance of a primary successful termination at GA < or = 63 days is higher after a surgical abortion in general anesthesia compared to a medical abortion induced with 600 mg mifepristone and 1 mg gemeprost. A surgical abortion is associated with an increased risk of antibiotic treatment compared to medical abortion. The women's need for follow-up might be higher than we expect.
Randomized comparison of prostaglandin treatment in hospital or at home with vacuum aspiration for termination of early pregnancy.
In the present study the efficacy and the acceptability of vaginal administration of a prostaglandin E analogue (9-deoxo-16, 16-dimethyl-9-methylene-PGE2) in hospital or at home were randomly compared with vacuum aspiration for termination of very early pregnancy. Prerequisites for acceptance of the patients were a normal pregnancy, a duration of amenorrhea of 49 days or less, at least one previous full-term pregnancy, and a healthy status. Fifty-three patients fulfilled these criteria and adhered to the protocol. Seventeen patients were treated with prostaglandin at home, 18 with prostaglandin in the hospital (9-methylene-PGE2, 50 to 60 mg twice at 6-hour intervals), and 18 with vacuum aspiration. Each patient was interviewed twice by a trained female psychologist before the treatment and two weeks after. Both the surgical and the nonsurgical methods (at home and in the hospital) were found to be equally effective in terms of frequency of complete abortion. Prostaglandin therapy was associated with a higher frequency of gastrointestinal side effects, pain, and a longer duration of bleeding than was the surgical procedure. The acceptability study showed that prostaglandin treatment was positively received. The patients who were treated with prostaglandin remained very positive after the abortion; a majority of these patients intended to use the same procedure in case of a repeated abortion, and would also recommend the treatment to a relative or a friend. The results of the present study indicate that termination of early pregnancy by a medical method, even if self-administered, is an acceptable procedure at least in selected patients. Further efforts to improve the treatment seem therefore justified.
Menstrual regulation by intramuscular injections of 16-phenoxy-tetranor PGE2 methyl sulfonylamide or vacuum aspiration. A randomized multicentre study. World Health Organization Task Force on Post-ovulatory Methods for Fertility Regulation.
A multicentre trial was conducted to compare the efficacy and side-effects of an intramuscularly administered PGE2 analogue and vacuum aspiration in women with a delay of up to 21 days in the expected onset of menses. A total of 473 such women were randomly allocated to treatment with either 16-phenoxy-W-17, 18, 19, 20-tetranor PGE2 methyl sulfonylamide (three intramuscular injections of 0.5 mg at 3-h intervals) or vacuum aspiration, and the outcome of therapy assessed 1, 2 and 6-8 weeks later. Retrospective analysis of hCG levels indicated that 419 (88.6%) women had been pregnant at the time of treatment. With few exceptions, administration of the PGE2 analogue induced vaginal bleeding in both pregnant and non-pregnant women but the duration and subjectively perceived amount of bleeding were greater than after vacuum aspiration. Both treatments were equally effective. In pregnant women the overall frequency of complete abortion was 91% for prostaglandin treatment and 94% for vacuum aspirations. If non-pregnant women were included, the respective success rates (i.e. percentages of women not pregnant 2 weeks after treatment) were 92% and 95%. Gastrointestinal side-effects and lower abdominal pain requiring intramuscular analgesia were more common after prostaglandin therapy than following vacuum aspiration in both pregnant and non-pregnant women.
Options:
A: Medical methods, particularly prostaglandins alone, are less effective and associated with longer bleeding duration compared to surgical methods.
B: Surgical methods are less effective and associated with more complications compared to medical methods.
C: There is no difference in efficacy and complications between medical and surgical methods for first-trimester abortion.
D: Medical methods are more effective and associated with fewer complications compared to surgical methods. | A |
402 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What is the clinical effectiveness of combining surgical resection with whole brain radiation therapy (WBRT) compared to WBRT alone in the treatment of single brain metastasis? Please answer this question based on the information provided below:
A randomized trial to assess the efficacy of surgery in addition to radiotherapy in patients with a single cerebral metastasis.
BACKGROUND: Cerebral metastasis is a common oncologic problem that occurs in 15-30% of cancer patients; approximately half such metastases are single. Previous retrospective studies and two randomized trials reported that the addition of surgical extirpation prior to radiation therapy increased survival, neurologic function, and quality of life compared with radiation alone in patients with a single brain metastasis.
METHODS: A randomized controlled trial was conducted in which patients with a single brain metastasis were allocated to undergo radiation alone or surgery plus radiation. Radiation consisted of 3000 centigray to the whole brain in 10 fractions.
RESULTS: Forty-three patients received radiation alone and 41 patients surgery plus radiation. All but two of the study patients died. No difference in survival was detected between the groups; the median survival for the radiation group was 6.3 months (95% confidence interval, 3-11.4) compared with 5.6 months for the surgery plus radiation group (95% confidence interval, 3.9-7.2) (P = 0.24). Most patients died within the first year (69.8% in the radiation arm vs. 87.8% in the surgery plus radiation arm). There were no significant differences in the 30-day mortality, morbidity, or causes of death. Extracranial metastases was an important predictor of mortality (relative risk, 2.3). The mean proportion of days that the Karnofsky performance status was > or = 70% did not differ between the 2 groups.
CONCLUSIONS: This trial failed to demonstrate that the addition of surgery to radiation therapy improved outcome of patients with a single brain metastasis. Thus, the efficacy of surgery plus radiation compared with radiation alone needs to be addressed by further clinical trials and/or a meta-analysis.
A randomized trial of surgery in the treatment of single metastases to the brain.
To assess the efficacy of surgical resection of brain metastases from extracranial primary cancer, we randomly assigned patients with a single brain metastasis to either surgical removal of the brain tumor followed by radiotherapy (surgical group) or needle biopsy and radiotherapy (radiation group). Forty-eight patients (25 in the surgical group and 23 in the radiation group) formed the study group; 6 other patients (11 percent) were excluded from the study because on biopsy their lesions proved to be either second primary tumors or inflammatory or infectious processes. Recurrence at the site of the original metastasis was less frequent in the surgical group than in the radiation group (5 of 25 [20 percent] vs. 12 of 23 [52 percent]; P less than 0.02). The overall length of survival was significantly longer in the surgical group (median, 40 weeks vs. 15 weeks in the radiation group; P less than 0.01), and the patients treated with surgery remained functionally independent longer (median, 38 weeks vs. 8 weeks in the radiation group; P less than 0.005). We conclude that patients with cancer and a single metastasis to the brain who receive treatment with surgical resection plus radiotherapy live longer, have fewer recurrences of cancer in the brain, and have a better quality of life than similar patients treated with radiotherapy alone.
Treatment of single brain metastasis: radiotherapy alone or combined with neurosurgery?
Most patients treated for single or multiple brain metastases die from progression of extracranial tumor activity. This makes it uncertain whether the combination of neurosurgery and radiotherapy for treatment of single brain metastasis will lead to better results than less invasive treatment with radiotherapy alone. The effect of neurosurgical excision plus radiotherapy was compared with radiotherapy alone in a prospectively randomized trial with 63 evaluable patients with systemic cancer and a radiological diagnosis of single brain metastasis. Radiotherapy was given to the whole brain by a novel scheme of 2 fractions per day of each 2 Gy for a total of 40 Gy. Before randomization, patients were stratified by site (lung cancer vs nonlung cancer) and status of extracranial disease (progressive vs stable). Survival as such and functionally independent survival (FIS; defined as World Health Organization performance status < or = 1 and neurological function < or = 1) were compared between both treatment arms. The combined treatment compared with radiotherapy alone led to a longer survival (p = 0.04) and a longer FIS (p = 0.06). This was most pronounced in patients with stable extracranial disease (median survival, 12 vs 7 mo; median FIS, 9 vs 4 mo). Patients with progressive extracranial cancer had a median overall survival of 5 months and a FIS of 2.5 months irrespective of given treatment. Improvement in functional status occurred more rapidly and for longer periods of time after neurosurgical excision and radiotherapy than after radiotherapy alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Options:
A: Combining surgical resection with WBRT significantly improves overall survival compared to WBRT alone.
B: Combining surgical resection with WBRT significantly increases the duration of functionally independent survival (FIS) compared to WBRT alone.
C: Combining surgical resection with WBRT significantly increases adverse effects compared to WBRT alone.
D: Combining surgical resection with WBRT significantly reduces the number of deaths due to neurological causes compared to WBRT alone. | B |
403 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What were the findings regarding the efficacy and safety of traditional Chinese medicinal herbs in the treatment of acute pancreatitis? Please answer this question based on the information provided below:
[Clinical early intervention of Tongxia Huayu Decoction on pancreatic microcirculatory disturbance in severe acute pancreatitis].
OBJECTIVE: To study the mechanisms of Tongxia Huayu Decoction (a Chinese herbal decoction for purgation and removing blood stasis) in prognostic improvement for severe acute pancreatitis by early intervention on pancreatic microcirculatory disturbance.
METHODS: Fifty-three patients with severe acute pancreatitis were divided randomly into treatment group (n=28) and control group (n=25). Tongxia Huayu Decoction was given to the patients in treatment group in addition to the normal treatment in control group for one week. The clinical symptoms and signs, hemodiastase, urinary amylase, C-reactive protein (CRP) and endothelin (ET) of the patients in the two groups before and after treatment were observed and detected.
RESULTS: The total response rate of the treatment group was 98.4%, while that of the control group was 80%, with significant difference between them (P<0.05). There was no significant difference of the contents of hemodiastase, urinary amylase, CRP and ET between the two groups before treatment, while they were significantly decreased after treatment (P<0.01) with more obvious change in treatment group (P<0.01).
CONCLUSION: Tongxia Huayu Decoction brings satisfied therapeutic effect on severe acute pancreatitis. The mechanisms may associate with its reducing function on ET releasing so as to inhibit the pancreatic microcirculatory disturbance and acinar cell injury induced by ET.
[Effects of Salvia miltiorrhiza on serum levels of inflammatory cytokines in patients with severe acute pancreatitis].
OBJECTIVE: To study the effects of Salvia miltiorrhiza on serum levels of cytokines including interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) in patients with severe acute pancreatitis (SAP).
METHODS: Thirty-six SAP patients were randomly divided into Salvia miltiorrhiza-treated group and non-Salvia miltiorrhiza-treated group with eighteen patients in each group. Fourteen age-matched healthy volunteers were assigned to control group. Serum levels of IL-6, IL-8, and TNF-alpha were tested within 24 hours of admission and 7 days after admission.
RESULTS: Compared with those of the healthy volunteers, serum levels of the three cytokines of the SAP patients were significantly elevated (P<0.05). Serum levels of the three cytokines were significantly decreased in both Salvia miltiorrhiza-treated group and non-Salvia miltiorrhiza-treated group after 7-day treatment (P<0.05). The declining of the serum levels of the three cytokines in Salvia miltiorrhiza-treated group was more obvious than that in non-Salvia miltiorrhiza-treated group.
CONCLUSION: Salvia miltiorrhiza can treat SAP patients by reducing the serum levels of IL-6, IL-8, and TNF-alpha.
Options:
A: Chinese medicinal herbs showed a statistically significant benefit over routine treatment in reducing mortality rates, length of hospital stay, and the need for operative intervention.
B: Chinese medicinal herbs showed some potential benefit over routine treatment in reducing mortality rates, length of hospital stay, and the need for operative intervention, but the evidence was not statistically significant due to the low quality of the trials.
C: Chinese medicinal herbs were found to be ineffective and unsafe for the treatment of acute pancreatitis.
D: The trials showed no difference between Chinese medicinal herbs and routine treatment in terms of efficacy and safety. | B |
404 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What were the findings regarding the efficacy and safety of rofecoxib in the treatment of rheumatoid arthritis? Please answer this question based on the information provided below:
Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group.
BACKGROUND: Each year, clinical upper gastrointestinal events occur in 2 to 4 percent of patients who are taking nonselective nonsteroidal antiinflammatory drugs (NSAIDs). We assessed whether rofecoxib, a selective inhibitor of cyclooxygenase-2, would be associated with a lower incidence of clinically important upper gastrointestinal events than is the nonselective NSAID naproxen among patients with rheumatoid arthritis.
METHODS: We randomly assigned 8076 patients who were at least 50 years of age (or at least 40 years of age and receiving long-term glucocorticoid therapy) and who had rheumatoid arthritis to receive either 50 mg of rofecoxib daily or 500 mg of naproxen twice daily. The primary end point was confirmed clinical upper gastrointestinal events (gastroduodenal perforation or obstruction, upper gastrointestinal bleeding, and symptomatic gastroduodenal ulcers).
RESULTS: Rofecoxib and naproxen had similar efficacy against rheumatoid arthritis. During a median follow-up of 9.0 months, 2.1 confirmed gastrointestinal events per 100 patient-years occurred with rofecoxib, as compared with 4.5 per 100 patient-years with naproxen (relative risk, 0.5; 95 percent confidence interval, 0.3 to 0.6; P<0.001). The respective rates of complicated confirmed events (perforation, obstruction, and severe upper gastrointestinal bleeding) were 0.6 per 100 patient-years and 1.4 per 100 patient-years (relative risk, 0.4; 95 percent confidence interval, 0.2 to 0.8; P=0.005). The incidence of myocardial infarction was lower among patients in the naproxen group than among those in the rofecoxib group (0.1 percent vs. 0.4 percent; relative risk, 0.2; 95 percent confidence interval, 0.1 to 0.7); the overall mortality rate and the rate of death from cardiovascular causes were similar in the two groups.
CONCLUSIONS: In patients with rheumatoid arthritis, treatment with rofecoxib, a selective inhibitor of cyclooxygenase-2, is associated with significantly fewer clinically important upper gastrointestinal events than treatment with naproxen, a nonselective inhibitor.
The safety profile, tolerability, and effective dose range of rofecoxib in the treatment of rheumatoid arthritis. Phase II Rofecoxib Rheumatoid Arthritis Study Group.
Nonsteroidal anti-inflammatory drugs. (NSAIDs) inhibit both cyclooxygenase (COX)-1 and COX-2 isoenzymes and are effective in the treatment of inflammatory disorders. This 8-week, double-masked, placebo-controlled trial was undertaken to assess the safety profile, tolerability, and effective dose range of once-daily rofecoxib, a COX-2-specific inhibitor, in the treatment of rheumatoid arthritis (RA). After a 3- to 15-day washout of prior NSAID therapy, 658 patients were randomly allocated to receive placebo or rofecoxib 5 mg, 25 mg, or 50 mg once daily. Safety profile, tolerability, and efficacy were evaluated after 2, 4, and 8 weeks of therapy. Six hundred fifty-eight patients (168, 158, 171, and 161 in the placebo and 5-mg, 25-mg, and 50-mg rofecoxib groups, respectively) were enrolled at 79 clinical centers in the United States. Mean age was 55 years, mean duration of RA was 10 years, and 506 (77%) of the 658 patients were female. All groups had similar baseline demographic characteristics. Patients taking rofecoxib 25 and 50 mg showed significant clinical improvement compared with those taking placebo; 43.9% in the rofecoxib 25-mg group and 49.7% in the rofecoxib 50-mg group completed the treatment period and achieved an American College of Rheumatology 20 response (P = 0.025 and 0.001 vs. placebo, respectively). The 5-mg dose of rofecoxib did not differ significantly from placebo. Patients in the rofecoxib 25- and 50-mg groups showed significant improvement in key individual efficacy measurements, including patient global assessment of pain, patient and investigator global assessment of disease activity, and Stanford Health Assessment Questionnaire Disability Index (P<0.05 vs placebo). Compared with placebo, significantly fewer patients in the 25-mg and 50-mg rofecoxib groups discontinued therapy because of lack of efficacy (P = 0.02 and P = 0.032, respectively). Our results show that rofecoxib 25 and 50 mg once daily was effective and generally well-tolerated in patients with RA.
Options:
A: Rofecoxib showed greater efficacy than placebo and had a similar safety profile, but it was associated with a higher risk of myocardial infarction compared to naproxen.
B: Rofecoxib showed no significant difference in efficacy compared to placebo and had a higher rate of gastrointestinal events compared to naproxen.
C: Rofecoxib demonstrated lower efficacy than naproxen and had a similar risk of cardiovascular events as placebo.
D: Rofecoxib showed greater efficacy than naproxen and had a lower risk of gastrointestinal events compared to placebo. | A |
405 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What are the effects of supportive devices such as slings, wheelchair attachments, and orthoses on shoulder subluxation, pain, function, and contracture in stroke patients? Please answer this question based on the information provided below:
Strapping the shoulder in patients following a cerebrovascular accident (CVA): A pilot study.
This pilot study was undertaken to determine the effectiveness of a strapping technique to prevent the onset of shoulder pain in the hemiplegic upper limb of patients following a Cerebrovascular Accident (CVA). Eight patients with no voluntary movement in their hemiplegic upper limb were selected for inclusion within 48 hours of their admission to hospital. Four subjects were assigned to a strapping group and four were assigned to a non-strapping group. Each subject was assessed daily for the presence of shoulder pain utilising the Ritchie Articular Index, adapted for use with hemiplegic patients by Bohannon and LeFort (1986). The number of pain free days for each patient was recorded and a comparison made between the two groups. Results indicated that subjects in the strapping group experienced a significantly longer pain free period (mean=21 days) compared with the non-strapping group (mean=5.5 days). This pilot study demonstrated that strapping the affected shoulder following CVA did delay the onset of shoulder pain. However, further investigation with a larger study population is required to evaluate the effectiveness of the strapping technique against other factors.
A randomized controlled trial of strapping to prevent post-stroke shoulder pain.
OBJECTIVE: To determine whether strapping the shoulder in hemiplegic stroke patients: (1) prevents the development, or reduces the severity, of shoulder pain, (2) preserves range of movement in the shoulder, and (3) improves the functional outcomes for the arm and patient overall.
DESIGN: A prospective, randomized, single-blind controlled trial of shoulder strapping versus no strapping.
SETTING: Care of the elderly wards in a teaching hospital, Christchurch, New Zealand.
SUBJECTS: All patients admitted with an acute hemiplegic stroke, who had persisting weakness of shoulder abduction.
INTERVENTION: The treatment group had their affected shoulder strapped for six weeks from randomization in addition to standard physiotherapy.
MAIN OUTCOME MEASURES: All subjects were assessed at entry (week 0), at end of the treatment phase (week 6) and two months later (week 14). A visual analogue scale (VAS) was used to assess shoulder pain severity whereas shoulder range of movement to the point of pain (SROMP) assessed passive range of movement and pain. Functional Independence Measure (FIM), Motor Assessment Scale (MAS) and Rankin Disability Index measured functional outcomes.
RESULTS: Ninety-eight subjects participated (49 strapped, 49 controls). Intention to treat analysis showed no significant difference in pain, range of movement or functional outcomes after the intervention phase or at the final assessment. However there were trends for less pain at six weeks (VAS, p = 0.11) and better final upper limb function (MAS, p = 0.16) in strapped patients. Skin reactions were uncommon (6.1%). The presence of neglect or sensory loss, but not subluxation, at baseline was independently associated with poor outcome. Range of movement was lost early (mean difference SROMP between hemiplegic and contralateral shoulders at baseline = 15.2 degrees (95% CI 10.9-19.5)) and continued throughout the study. Shoulder strapping did not alter the rate at which range of movement was lost.
CONCLUSIONS: No significant benefit with shoulder strapping was demonstrated and reasons for this are discussed. Range of movement in the hemiplegic shoulder is lost very early and any preventive treatments need to begin within the first 1-2 days after a stroke.
Shoulder sling for hemiplegia: friend or foe?
Options:
A: Supportive devices prevent subluxation, decrease pain, increase function, and do not increase contracture.
B: Supportive devices prevent subluxation and decrease pain, but do not increase function and may increase contracture.
C: Supportive devices have insufficient evidence to conclude their effectiveness in preventing subluxation, decreasing pain, increasing function, or affecting contracture.
D: Supportive devices increase subluxation, increase pain, decrease function, and increase contracture. | C |
406 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What are the potential benefits of exercise therapy for patients with Multiple Sclerosis (MS) who are not currently experiencing an exacerbation? Please answer this question based on the information provided below:
The effects of home-based resistance exercise on balance, power, and mobility in adults with multiple sclerosis.
OBJECTIVE: To examine the effects of an 8-week home-based resistance exercise program on balance, power, and mobility in adults with multiple sclerosis.
DESIGN: Experimental group design.
SETTING: General community.
PARTICIPANTS: Twenty-nine women (age, 50.3+/-8.5 y) and 8 men (age, 51.1+/-7.1 y) were stratified by disability level and age and were randomized into exercise (n=19) and control (n=17) groups.
INTERVENTION: The exercise group had lower-extremity resistance training 3 times a week. The control group maintained current level of physical activity.Main outcome measures Primary outcome measures included balance, as measured by anteroposterior sway, mediolateral sway, and sway velocity using the AccuSway(PLUS) force platform; mobility as assessed with the Up and Go test; and leg power as assessed with the Leg Extensor Power Rig.
RESULTS: Leg extensor power improved significantly in the exercise group (pretest, 3.19+/-1.36 W/kg; posttest, 3.95+/-1.23 W/kg; P=.004), although measures of balance and mobility did not change.
CONCLUSIONS: The home-based resistance program was well tolerated by participants and offered a practical means to improve leg extensor power in a short period of time.
A comparison of two physiotherapy treatment approaches to improve walking in multiple sclerosis: a pilot randomized controlled study.
OBJECTIVE: To use a pilot study to compare two physiotherapy approaches to improve walking in patients with gait disturbance due to multiple sclerosis (MS).
DESIGN: Patients were assessed and then randomly assigned to one of two groups using a block randomization technique. They were treated by the research physiotherapist for a minimum of 15 treatments over a 5-7-week period and then reassessed by an independent therapist one week after treatment.
SETTING: Both assessment and treatment were undertaken at a specialist rehabilitation centre.
SUBJECTS: Outpatients with clinically stable MS (chronic progressive or relapsing-remitting types) who were referred for physiotherapy to improve their mobility.
INTERVENTION: Comparison was between a facilitation (impairment-based) approach and a task-oriented (disability-focused) approach.
OUTCOME: Mobility was assessed using four measures: the 10-metre timed walk, the Rivermead Mobility Index, stride length and the Rivermead Visual Gait Assessment. Balance was assessed using the Berg Balance Test.
RESULTS: Twenty-three patients were entered, and 10 in each group completed the study. The groups were similar on all measured items both before and after treatment. There was no significant difference in improvement between the two approaches. Following treatment, patients in both groups showed a significant overall improvement (p < 0.05) in both impairment and disability measures.
CONCLUSIONS: No significant differences in effectiveness between the two methods were demonstrated. Both a task-oriented approach and a facilitation approach to the treatment of MS outpatients were associated with improved mobility.
Effects of a short-term exercise training program on aerobic fitness, fatigue, health perception and activity level of subjects with multiple sclerosis.
Multiple sclerosis (MS) patients of an inpatient rehabilitation program have been randomly assigned to an exercise training (MS-ET) or nontraining group (MS-NI). Before and after 4 weeks of aerobic exercise training, a graded maximal exercise test with measurement of gas exchange and a lung function test was administered to all 26 patients fulfilling the inclusion criteria. Activity level, fatigue and health perception were measured by means of questionnaires. Twenty-six healthy persons served as control group and were matched in respect of age, gender and activity level. Training intervention consisted of 5x30 min sessions per week of bicycle exercise with individualised intensity. Compared with baseline, the MS training group demonstrated a significant rightward placement of the aerobic threshold (AT) (VO2+13%; work rate [WR])+11%), an improvement of health perception (vitality+46%; social interaction+36%), an increase of activity level (+17%) and a tendency to less fatigue. No changes were observed for the MS-NI group and the control groups. Maximal aerobic capacity and lung function were not changed by either training or nontraining in all four groups. Overall compliance to the training program was quite low (65%), whereas incidence of symptom exacerbation by physical activity has been lower than expected (6%).
Impact of aerobic training on fitness and quality of life in multiple sclerosis.
Fifty-four multiple sclerosis (MS) patients were randomly assigned to exercise (EX) or nonexercise (NEX) groups. Before and after 15 weeks of aerobic training, aspects of fitness including maximal aerobic capacity (VO2max), isometric strength, body composition, and blood lipids were measured. Daily activities, mood, fatigue, and disease status were measured by the Profile of Mood States (POMS), Sickness Impact Profile (SIP), Fatigue Severity Scale (FSS), and neurological examination. Training consisted of 3 x 40-minute sessions per week of combined arm and leg ergometry. Expanded Disability Status Scale (EDSS) scores were unchanged, except for improved bowel and bladder function in the EX group. Compared with baseline, the EX group demonstrated significant increases in VO2max, upper and lower extremity strength, and significant decreases in skinfolds, triglyceride, and very-low-density lipoprotein (VLDL). For the EX group, POMS depression and anger scores were significantly reduced at weeks 5 and 10, and fatigue was reduced at week 10. The EX group improved significantly on all components of the physical dimension of the SIP and showed significant improvements for social interaction, emotional behavior, home management, total SIP score, and recreation and past times. No changes were observed for EX or NEX groups on the FSS. Exercise training resulted in improved fitness and had a positive impact on factors related to quality of life.
Physical rehabilitation has a positive effect on disability in multiple sclerosis patients.
BACKGROUND: Although physical rehabilitation is commonly administered to MS patients, its efficacy has not been established.
OBJECTIVE: We assessed the efficacy of an inpatient physical rehabilitation program on impairment, disability, and quality of life of MS patients with a randomized, single-blind, controlled trial.
METHODS: Fifty ambulatory MS patients were assigned to 3 weeks of inpatient physical rehabilitation (study treatment) or exercises performed at home (control treatment). Patients were evaluated at baseline and at 3, 9, and 15 weeks by a blinded examining physician.
RESULTS: No changes in impairment occurred in either group, as measured by the Expanded Disability Status Scale. At the end of the intervention the study group improved significantly in disability, as assessed by the Functional Independence Measure (FIM) motor domain, compared with controls (p = 0.004), and the improvement persisted at 9 weeks (p = 0.001). The effect size statistic was usually large or moderate in all scale scores of the FIM motor domain at 3 weeks and moderate to fair thereafter. The study group also improved in overall health-related quality of life profile compared with controls; however, the difference was significant only for the mental composite score at 3 (p = 0.008) and 9 weeks (p = 0.001).
CONCLUSIONS: Despite unchanging impairment, physical rehabilitation resulted in an improvement in disability and had a positive impact on mental components of health-related quality of life perception at 3 and 9 weeks.
Controlled randomised crossover trial of the effects of physiotherapy on mobility in chronic multiple sclerosis.
OBJECTIVES: To determine whether physiotherapy can improve mobility in chronic multiple sclerosis and whether there is a difference between treatment at home and as a hospital outpatient?
METHODS: A randomised controlled crossover trial was undertaken in patients with chronic multiple sclerosis who had difficulty walking and were referred from neurology clinics: allocation was to one of six permutations of three 8 week treatment periods separated by 8 week intervals: treatments consisted of physiotherapy at home, as an outpatient, or "no therapy". The main outcome measures were based on independent assessments at home and included mobility related disability (primary outcome: the Rivermead mobility index), gait impairments, arm function, mood, and subjective patient and carer ratings. Therapy was assessed by recording delivery, achievement of set targets, patient and carer preference, and cost.
RESULTS: On the Rivermead mobility index (scale 0-15) (primary outcome) there was a highly significant (p<0.001) treatment effect of 1.4-1.5 units favouring hospital or home based therapy over no therapy: this was supported by other measures of mobility, gait, balance, and the assessor's global "mobility change" score: there was no major difference between home and hospital. Carers preferred home treatment but neither they nor patients discerned greater benefit there. Estimated costs of home physiotherapy were 25 pounds/session and those at hospital were 18 pounds (including 7 pounds patient travel costs).
CONCLUSION: A course of physiotherapy is associated with improved mobility, subjective wellbeing, and improved mood in chronic multiple sclerosis compared with no treatment but benefit may only last a few weeks: there is little to choose between home and hospital based therapy but the first is more costly, mainly due to skilled staff travelling time.
Options:
A: Improvement in muscle power function, exercise tolerance, and mobility-related activities.
B: Significant reduction in fatigue and perception of handicap.
C: No improvement in mood or any physical functions.
D: Deleterious effects on health-related quality of life. | A |
407 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What are the comparative benefits of home-based versus center-based physical activity programs for older adults with cardiovascular disease, chronic obstructive pulmonary disease (COPD), or peripheral vascular disease (PVD)? Please answer this question based on the information provided below:
Group- vs home-based exercise training in healthy older men and women. A community-based clinical trial.
OBJECTIVE: --To determine the effectiveness of group- vs home-based exercise training of higher and lower intensities among healthy, sedentary older adults.
DESIGN: --Year-long randomized, controlled trial comparing (1) higher-intensity group-based exercise training; (2) higher-intensity home-based exercise training; (3) lower-intensity home-based exercise training; or (4) assessment-only control.
SETTING: --General community located in northern California.
PARTICIPANTS: --One hundred sixty women and 197 men 50 to 65 years of age who were sedentary and free of cardiovascular disease. One out of nine persons contacted through a community random-digit-dial telephone survey and citywide promotion were randomized.
INTERVENTIONS: --For higher-intensity exercise training, three 40-minute endurance training sessions per week were prescribed at 73% to 88% of peak treadmill heart rate. For lower-intensity exercise training, five 30-minute endurance training sessions per week were prescribed at 60% to 73% of peak treadmill heart rate.
MAIN OUTCOME MEASURES: --Treadmill exercise test performance, exercise participation rates, and heart disease risk factors.
RESULTS: --Compared with controls, subjects in all three exercise training conditions showed significant improvements in treadmill exercise test performance at 6 and 12 months (P less than .03). Lower-intensity exercise training achieved changes comparable with those of higher-intensity exercise training. Twelve-month exercise adherence rates were better for the two home-based exercise training conditions relative to the group-based exercise training condition (P less than .0005). There were no significant training-induced changes in lipid levels, weight, or blood pressure.
CONCLUSIONS: --We conclude that (1) this community-based exercise training program improved fitness but not heart disease risk factors among sedentary, healthy older adults; (2) home-based exercise was as effective as group exercise in producing these changes; (3) lower-intensity exercise training was as effective as higher-intensity exercise training in the home setting; and (4) the exercise programs were relatively safe.
Long-term effects of varying intensities and formats of physical activity on participation rates, fitness, and lipoproteins in men and women aged 50 to 65 years.
BACKGROUND: Although exercise parameters such as intensity and format have been shown to influence exercise participation rates and physiological outcomes in the short term, few data are available evaluating their longer-term effects. The study objective was to determine the 2-year effects of differing intensities and formats of endurance exercise on exercise participation rates, fitness, and plasma HDL cholesterol levels among healthy older adults.
METHODS AND RESULTS: Higher-intensity, group-based exercise training; higher-intensity, home-based exercise; and lower-intensity, home-based exercise were compared in a 2-year randomized trial. Participants were 149 men and 120 postmenopausal women 50 to 65 years of age who were sedentary and free of cardiovascular disease. Recruitment was achieved through a random digit-dial community telephone survey and media promotion. All exercise occurred in community settings. For higher-intensity exercise training, three 40-minute endurance training sessions per week were prescribed at 73% to 88% of peak treadmill heart rate. For lower-intensity exercise, five 30-minute endurance training sessions per week were prescribed at 60% to 73% of peak treadmill heart rate. Treadmill exercise performance, lipoprotein levels and other heart disease risk factors, and exercise adherence were evaluated at baseline and across the 2-year period. Treadmill exercise test performance improved for all three training conditions during year 1 and was successfully maintained during year 2, particularly for subjects in the higher-intensity, home-based condition. Subjects in that condition also showed the greatest year 2 exercise adherence rates (P < .003). Although no significant increases in HDL cholesterol were observed during year 1, by the end of year 2 subjects in the two home-based training conditions showed small but significant HDL cholesterol increases over baseline (P < .01). The increases were particularly pronounced for subjects in the lower-intensity condition, whose exercise prescription required more frequent exercise sessions per week. For all exercise conditions, increases in HDL cholesterol were associated with decreases in waist-to-hip ratio in both men and women (P < .04).
CONCLUSIONS: While older adults can benefit from initiating a regular regimen of moderate-intensity exercise in terms of improved fitness levels and small improvements in HDL cholesterol levels, the time frame needed to achieve HDL cholesterol change (2 years) may be longer than that reported previously for younger populations. Frequency of participation may be particularly important for achieving such changes. Supervised home-based exercise regimens represent a safe, attractive alternative for achieving sustained participation.
Group- vs home-based exercise training in healthy older men and women. A community-based clinical trial.
OBJECTIVE: --To determine the effectiveness of group- vs home-based exercise training of higher and lower intensities among healthy, sedentary older adults.
DESIGN: --Year-long randomized, controlled trial comparing (1) higher-intensity group-based exercise training; (2) higher-intensity home-based exercise training; (3) lower-intensity home-based exercise training; or (4) assessment-only control.
SETTING: --General community located in northern California.
PARTICIPANTS: --One hundred sixty women and 197 men 50 to 65 years of age who were sedentary and free of cardiovascular disease. One out of nine persons contacted through a community random-digit-dial telephone survey and citywide promotion were randomized.
INTERVENTIONS: --For higher-intensity exercise training, three 40-minute endurance training sessions per week were prescribed at 73% to 88% of peak treadmill heart rate. For lower-intensity exercise training, five 30-minute endurance training sessions per week were prescribed at 60% to 73% of peak treadmill heart rate.
MAIN OUTCOME MEASURES: --Treadmill exercise test performance, exercise participation rates, and heart disease risk factors.
RESULTS: --Compared with controls, subjects in all three exercise training conditions showed significant improvements in treadmill exercise test performance at 6 and 12 months (P less than .03). Lower-intensity exercise training achieved changes comparable with those of higher-intensity exercise training. Twelve-month exercise adherence rates were better for the two home-based exercise training conditions relative to the group-based exercise training condition (P less than .0005). There were no significant training-induced changes in lipid levels, weight, or blood pressure.
CONCLUSIONS: --We conclude that (1) this community-based exercise training program improved fitness but not heart disease risk factors among sedentary, healthy older adults; (2) home-based exercise was as effective as group exercise in producing these changes; (3) lower-intensity exercise training was as effective as higher-intensity exercise training in the home setting; and (4) the exercise programs were relatively safe.
Comparison of effects of supervised versus self-monitored training programmes in patients with chronic obstructive pulmonary disease.
The effects of two 8 week programmes of reconditioning in chronic obstructive pulmonary disease (COPD) patients were studied. Forty one subjects (mean+/-SD) 644.5) yrs; forced expiratory volume in one second (FEV1) 1.09+/-0.16 L; 40.6+/-6.2% predicted were randomly assigned either to supervised training on a treadmill, 4 days x week(-1) (group S; n=21) or walking 3 or 4 km in 1 h 4 days x week(-1), self-monitored with a pedometer, with weekly visits to encourage adherence (group SM; n=20). Patients were evaluated with the chronic respiratory diseases questionnaire (CRQ) and two exercise tests on a treadmill: incremental (IT) and constant (CT), above lactic threshold or 70% of maximal oxygen uptake (VO2, max) with arterial blood lactate determinations. Estimated mean work rate of training was 69+/-27 W and 25+/-5 W respectively for groups S and SM. Both types of training produced similar changes in the four dimensions of the CRQ. In group S reconditioning yielded significant (p<0.05) increases in VO2, max and increases in duration, with decreased lactate accumulation, ventilation, CO2 output (VCO2), heart rate (HR) and diastolic blood pressure (DBP) at the end of CT. They also adopted a deeper slower pattern of breathing during exercise. The SM group showed significant (p<0.05) increases in duration, lower HR and DBP at the end of CT. Significantly (p<0.05) different effects between S and SM programmes were changes in VO2, max 100+/-101 mL x min(-1) versus 5+/-101 mL x min(-1)), duration of the CT (8.1+/-4.4 min versus 3.9+/-4.7 min), VCO2 (-94+/-153 mL x min(-1) versus 48+/-252 mL x min(-1)), lactate accumulation (-1.3+/-2.2 mmol x L(-1) versus 0+/-1.2 mmol x L(-1) and respiratory rate at the end of CT (4.3+/-3.4 min(-1) versus -1+/-4.2 min(-1)). Supervised, intense training yields physiological improvements in severe chronic obstructive pulmonary disease patients not induced by self-monitored training. The self-monitored, less intense training, increases submaximal exercise endurance, although to a lesser degree.
Long-term effects of a maintenance program after supervised or self-monitored training programs in patients with COPD.
The evaluation of a 13-month maintenance program (MP) for 39 severe COPD patients with FEV(1)%pred 44(7)% who, as result of two different 8-week leg exercise training (LET) programs, one supervised at the hospital (group S; n = 20) and the other self-monitored (SM; n = 19), had achieved different levels of exercise tolerance. After LET, patients in group S had a higher maximal oxygen uptake and endurance time than patients in the SM group [ O(2)max 1.43(0.30) l. min(-1)] vs l.25(0.27) l. min(-1) and endurance-time 16(4) min vs 12 (5) min, respectively). During the MP patients were advised to walk vigorously at least 4 km/day, 4 times/wk. After the MP, while endurance time remained higher than at baseline, it had decreased ( p < 0.01) immediately after LET in both groups and no differences were evident between groups (11(4) min and 10(4), respectively). In contrast, Chronic Respiratory Diseases Questionnaire scores, which had improved significantly after LET in both groups, remained high. Long-term effects of MP were independent of the training strategy or whether physiological improvements had been obtained with the initial LET. SM exercise programs do not seem capable of maintaining physiological improvements in exercise tolerance, though "quality of life" can be maintained.
Value of a supervised exercise program for the therapy of arterial claudication.
PURPOSE: This study was performed to test the effectiveness of a formal supervised exercise program against a home-based exercise program for both walking ability and quality of life endpoints.
METHODS: Patients with arterial claudication were randomized to either a 12-week supervised exercise program (SUPEX) with weekly lectures relating to peripheral vascular disease or to a home exercise group (HOMEX) who attended an identical lecture program and received weekly exercise instruction. The study population included 29 men and 26 women, with a mean age of 69.1 +/- 8.1 years. Forty-seven patients completed the 12-week program, 46 were available for testing at completion, and 38 for 6-month testing. Claudication pain time (CPT) and maximum walking time (MWT) on a progressive treadmill exercise test were assessed at baseline, program completion, and 6 months. The Medical Outcomes Study Short Form-36 (SF-36) was administered at these intervals to assess effects on quality of life.
RESULTS: Each group improved (p < 0.001) in both CPT and MWT at the completion of the 12-week program, which was sustained at the 6-month follow-up. Increase in HOMEX CPT from baseline (3.6 +/- 2.73 minutes) to 6-month follow-up (6.6 +/- 3.17 minutes) was less than for the SUPEX group (3.8 +/- 2.74 to 11.2 +/- 4.02 minutes, respectively); similar results were obtained for MWT. At both completion and 6 months, there was a significant intergroup difference for CPT and MWT (p < 0.004) favoring SUPEX. For both groups, measures of health perception based on the SF-36 demonstrated improvement (p < 0.002) in Physical Function Subscale, Bodily Pain Subscale, and Physical Composite Score. There were no between-group differences on the subsets of the SF-36 at the three assessment intervals.
CONCLUSIONS: Supervised exercise programs provide superior increased walking ability in the noninterventional therapy of arterial claudication, and both supervised and home based exercise therapy result in improved SF-36 functional measures. The lack of intergroup differences in these measures may be a result of the high degree of interaction with healthcare providers in the HOMEX group. Although a supervised program results in optimal walking benefits, a highly structured home-based program provides similar functional improvement and may be a satisfactory alternative for patients with lesser walking requirements.
Hospital vs home-based exercise rehabilitation for patients with peripheral arterial occlusive disease.
Supervised, hospital-based exercise rehabilitation programs are effective for improving functional status for patients with claudication due to peripheral arterial occlusive disease. However, it has been suggested that unsupervised, home-based exercise programs, which have been relatively little evaluated, would be equally efficacious as compared with hospital-based programs. The authors tested the hypothesis that a hospital-based exercise rehabilitation program would improve treadmill exercise performance more than a home-based program. Of 20 consecutively enrolled patients with claudication, 10 were randomly placed into a supervised, hospital-based program and 10 into an unsupervised, home-based program for a three-month period. Exercise performance was evaluated by treadmill testing using a graded protocol. In addition, functional status was evaluated by the Walking Impairment Questionnaire (WIQ) and the Medical Outcomes Study SF-20 questionnaire (MOS). Patients in the hospital-based program were treated with treadmill walking three times a week for one hour/visit. Patients in the home-based program were instructed to walk at least three times a week and were contacted weekly to provide encouragement and to record compliance with the program. Patients in the hospital-based group improved peak walking time by 137%, pain-free walking time by 150%, and peak oxygen consumption by 19% (all P < 0.05). Patients reported an improved walking distance and speed according to WIQ data (both P < 0.05). In addition, the MOS physical functioning score in the hospital-based group improved by 20 percentage points (P < 0.05). In contrast, patients in the home-based program did not improve exercise performance measured on the treadmill. Improvement in the ability to walk on the treadmill was greater in the hospital-based than the home-based program (P < 0.05). The ability to walk distances was the only questionnaire measure that improved in persons who received the home-based program (P < 0.05). Preliminary results suggest that a supervised, hospital-based program is more effective for improving treadmill exercise performance than an unsupervised, home-based program.
Effects of home versus supervised exercise for patients with intermittent claudication.
PURPOSE: This study was performed to test the efficacy of a supervised, hospital-based exercise program compared with a home-based exercise program involving minimal supervision, for both walking ability and quality of life measures in patients with exercise-limiting intermittent leg claudication.
METHODS: Twenty-one patients were assigned randomly to 12 weeks of supervised exercise or to a home-based exercise group. After 12 weeks the participants in the supervised group transitioned to a home-based program. Both groups were then reevaluated at the end of 24 weeks. The initial claudication distance (ICD) and absolute claudication distance (ACD) on progressive treadmill exercise was measured at baseline, 12 weeks, and 24 weeks. Additionally, self-reported quality of life status was evaluated using the MOS SF-36 questionnaire.
RESULTS: Each group improved (P < 0.01) ACD from baseline to 12 weeks, which was sustained at the 24-week follow-up. Both groups experienced similar long-term improvements (P < 0.05) in ACD (521.5 +/- 253.4 meters to 741.9 +/- 365.6 meters for the supervised group, 532.2 +/- 263.5 meters to 715.0 +/- 394.4 meters in the home group, P not significant, between groups). The supervised group experienced a greater improvement (P < 0.01) in the ICD after 12 weeks than the home group but not at 24 weeks. The on-site group also experienced significant improvements in ICD after 24 weeks (P < 0.05). Neither group manifested an improvement in self-reported physical function or mental health as assessed by the MOS SF-36.
CONCLUSION: A structured exercise program was more effective in improving the ICD over a 24-week period than a less formal, home-based program. However, if patients are screened properly and receive adequate instruction, a home-based program can be a safe, low-cost alternative providing similar long-term (24 weeks) exercise benefits in ACD.
A comparison between an outpatient hospital-based pulmonary rehabilitation program and a home-care pulmonary rehabilitation program in patients with COPD. A follow-up of 18 months.
AIM: In this study, the effects of a 12-week hospital-based outpatient pulmonary rehabilitation program (HRP) are compared with those of a 12-week home-care rehabilitation program (HCRP) in COPD patients. A control group received no rehabilitation therapy.
METHODS: After randomization and stratification, effects on lung function, exercise performance (4-min walking test and cycle ergometer test), dyspnea, and leg effort during exercise, and well-being were assessed in 45 COPD patients with moderate to severe airflow limitation (mean [SD] FEV1 percent predicted, 42.8 [8.4]).
RESULTS: After HRP and HCRP, at 3 to 6 months after the start of the study, equal improvements were detected in exercise capacity and in Borg dyspnea and leg effort scores at similar work levels during the cycle test. However, whereas after HRP at longer term values tended to return to baseline outcome, after HCRP a further ongoing significant improvement in exercise capacity was observed, while Borg dyspnea scores remained significantly improved over 18 months. Improvements in cycle workload and dyspnea score were significantly better maintained after HCRP as compared with HRP. Lung function, arterial oxygen saturation, and heart frequency during exercise did not change. A significant improvement in well-being was maintained over 18 months in both rehabilitation groups.
CONCLUSION: Beneficial effects are achieved both after a HRP and a HCRP in COPD patients with moderate to severe airflow limitation. Yet we recommend to initiate HCRPs as improvements are maintained longer and are even further strengthened in this setting.
Options:
A: Center-based programs are superior for improving adherence rates in older adults with cardiovascular disease.
B: Home-based programs are superior for improving treadmill performance in older adults with PVD.
C: Center-based programs are superior for short-term improvements in older adults with PVD, but home-based programs have higher long-term adherence rates.
D: Home-based programs are consistently superior across all measures for older adults with COPD. | C |
408 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What does the evidence suggest about the clinical efficacy and safety of Botulinum toxin Type A (BtA) compared to anticholinergic drugs in the treatment of cervical dystonia? Please answer this question based on the information provided below:
Botulinum toxin versus trihexyphenidyl in cervical dystonia: a prospective, randomized, double-blind controlled trial.
BACKGROUND: Botulinum toxin type A (BTA) is replacing trihexyphenidyl as the treatment of choice for idiopathic cervical dystonia (ICD), but there has never been a direct comparative study.
METHODS: This trial compares the effectiveness of BTA with that of trihexyphenidyl in a prospective, randomized, double-blind design. Sixty-six consecutive patients with ICD were randomized to treatment with trihexyphenidyl tablets plus placebo injection or placebo tablets plus BTA injections. Tablets were administered daily according to a fixed schedule. Dysport or saline was injected under EMG guidance at study entry and again after 8 weeks. Patients were assessed for efficacy at baseline and after 12 weeks by different clinical rating scales.
RESULTS: Sixty-four patients completed the study, 32 in each group. Mean dose of BTA was 292 mouse units (first session) and 262 mouse units (second session). Mean dose of trihexyphenidyl was 16.25 mg. The changes on the Disability section of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS-Disability) (primary outcome), Tsui Scale, and the General Health Perception Subscale were significantly in favor of BTA. More patients treated with BTA had an improvement of at least three points on the TWSTRS-Disability (14 versus 6) and on the Tsui Scale (23 versus 12). Adverse effects were significantly less frequent in the BTA group.
CONCLUSION: BTA is significantly more effective in the treatment of ICD, with less adverse effects.
Options:
A: BtA provides more objective and subjective benefit than trihexyphenidyl and is better tolerated.
B: Anticholinergic drugs provide more objective and subjective benefit than BtA and are better tolerated.
C: BtA and anticholinergic drugs provide similar benefits and have similar tolerability.
D: There is no evidence to suggest any difference in efficacy and safety between BtA and anticholinergic drugs. | A |
409 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What was the conclusion regarding the effectiveness of population-based interventions for reducing fall-related injuries among older people? Please answer this question based on the information provided below:
Community-based tai chi and its effect on injurious falls, balance, gait, and fear of falling in older people.
BACKGROUND AND PURPOSE: It is important to determine the effect of adherence to a tai chi program on falls and related functional outcomes in older people. This study examined the effect of a community-based tai chi program on injurious falls, balance, gait, and fear of falling among people aged 65 years and older in Taiwan.
SUBJECTS AND METHODS: In 6 rural villages in Taichung County, 1,200 subjects participated in the initial assessment. During a 1-year intervention period, all study villages were provided with education on fall prevention. Two villages had been provided tai chi exercise (n=472 participants or "tai chi villagers"), and 4 villages served as control villages (n=728 participants or "control villagers"). Injurious falls were ascertained by telephone interviews every 3 months over a 2-year study period; additionally, balance, gait, and fear of falling were assessed in 2 follow-up assessments.
RESULTS: Eighty-eight subjects, 83 from the tai chi villages and 5 from the control villages, participated and practiced in the tai chi program (the group labeled "tai chi practitioners"). After the tai chi program, injurious falls among the control villagers significantly declined by 44% (adjusted rate ratio [RR]=0.56; 95% confidence interval [CI]=0.36-0.92). Compared with the results for the control villagers, the decline was 31% greater (RR=0.69; 95% CI=0.30-1.56) among the tai chi villagers and 50% greater (RR=0.5; 95% CI=0.11-2.17) among the tai chi practitioners; the results did not reach statistical significance. Furthermore, compared with the scores for the control villagers, the scores for the tai chi practitioners increased by 1.8 points (95% CI=0.2-3.4) on the Tinetti Balance Scale and increased by 0.9 point (95% CI=0.1-1.8) on the Tinetti Gait Scale. No significant changes in the fear of falling were detected among the tai chi practitioners, tai chi villagers, and control villagers.
DISCUSSION AND CONCLUSION: Tai chi can prevent a decline in functional balance and gait among older people. However, the reduction in injurious falls attained with tai chi did not reach statistical significance; the statistical inefficiency may have resulted partly from the large decline in injurious falls in control villagers. Finally, the unexpected effect of educational intervention on reducing injurious falls in different settings needs to be further examined.
Evaluation of an inter-organizational prevention program against injuries among the elderly in a WHO Safe Community.
The aim of the study was to evaluate the outcome of a participatory community-based prevention program against injuries among the elderly. A population-based quasi-experimental design was used with pre- and post-implementation measurements in an intervention and a control area. The program was based on cross-sectoral participation in detecting and taking action against injuries among the elderly. Change in the relative risk of injury was estimated by the odds ratio. Morbidity in moderately (AIS 2) severe injury in the study area was reduced from 46 per 1000 population years to 25 per 1000 population years (odds ratio 0.55; 95% confidence interval 0.46-0.65), while the minor (AIS 1) injuries increased (odds ratio 1.55; 95% confidence interval 1.21-1.91). The risk of severe or fatal (AIS 3-6) injuries remained constant. In the study area, only a slight decrease in the total morbidity rate was observed (odds ratio 0.87; 95% confidence interval 0.77-0.99). In the control area, there was no evident change in the total morbidity rates. Falls decreased or showed a tendency to decrease in the age groups 65 to 79-y-old in the study area, while they increased in the older age group. The results indicate that no sharp boundaries should be drawn between safety education, physical conditioning, environmental adjustments and secondary prevention measures when planning safety promotion among the elderly. Future studies should address these issues along with the methodological complexity associated with assessment of participatory community-based safety promotion programs.
The Harstad injury prevention study: community based prevention of fall-fractures in the elderly evaluated by means of a hospital based injury recording system in Norway.
STUDY OBJECTIVE: To describe a community based programme to prevent fractures resulting from falls and evaluate the outcome in terms of changes in fracture rates and short term hospital care costs.
DESIGN: Prospective intervention study.
SETTING: The Norwegian municipalities of Harstad (intervention) and Trondheim (reference) from 1 July 1985 to 30 June 1993.
PARTICIPANTS: The person-years of the study were estimated from yearly census data on people aged 65 years and over. There were 22970 person years in Harstad and 158911 in Trondheim.
MEASUREMENTS AND MAIN RESULTS: The variables were selected and coded according to the Nordic system and the data were collected as part of a national injury surveillance system. The first three years of the study provided baseline data, while the last five years involved community based interventions-eg, the removal of environmental hazards in homes and promotion of the use of safe footwear outdoors in winter. Rates of fracture from falls did not decline in nursing homes but decreased 26.3% in private homes (p < 0.01). In 65-79 year olds, there was a 48.7% reduction in fall-fracture rates for men in traffic areas in winter (p < 0.05). The data from the reference city, Trondheim, suggested a significant rise in fractures caused by falls. There was a 16.7% reduction in hospital admission rates of fall-fracture patients from private homes, indicating a substantial saving in short term hospital costs. The observed fall-fracture rate reductions in private homes and traffic areas suggest that major parts of the interventions were effective.
CONCLUSION: Fall-fracture prophylaxis in the aged is possible in a community based setting that utilises high quality, local injury data.
Options:
A: Population-based interventions showed no significant impact on reducing fall-related injuries among older people.
B: Population-based interventions resulted in a significant increase in fall-related injuries among older people.
C: Population-based interventions showed consistent reductions in fall-related injuries among older people, supporting their effectiveness.
D: The effectiveness of population-based interventions for reducing fall-related injuries among older people remains inconclusive due to lack of evidence. | C |
410 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What was the effect of adding Chinese herbal medicines, specifically Huangqi compounds, to chemotherapy in patients with colorectal cancer? Please answer this question based on the information provided below:
[Clinical observation on treatment of 38 cases of postoperational large intestinal cancer by fuzheng yiai decoction combined with chemotherapy].
OBJECTIVE: To investigate the clinical value of Fuzheng Yiai Decoction (FZYAD) in postoperational large intestinal Cancer after treatment.
METHODS: Thirty-eight cases treated by FZYAD combined with chemotherapy in the treated group were observed and compared with 30 patients in the control group treated with chemotherapy alone.
RESULTS: After treatment, patients' physical strength of the treated group was better than that of the control group (P < 0.01), meanwhile, the median survival time was longer (31.4 months vs 18 months, P < 0.01), the survival rate higher (P < 0.05), and the recurrence rate lower (21.05% vs 48.34%, P < 0.05) in comparison of the treated group and the control group. Moreover, the cellular immune function of the treated group was improved after treatment.
CONCLUSIONS: In treatment of postoperational large intestinal cancer, the effect of FZYAD combined chemotherapy is better than that of chemotherapy alone in immune function regulation, cancer inhibition, relapse prevention and survival time prolongation.
[Effect of chang'ai kangfu decoction on immunity in postoperational patients with large intestine cancer].
OBJECTIVE: To explore the effect of Chinese drug Chang'ai Kangfu decoction (CAKF) on immunity in post-operational patients with large intestine cancer (LIC).
METHODS: Forty-eight patients with LIC in Dukes' B, C stage after operation were randomly assigned to 3 groups, the CAKF group (16 cases), chemotherapy group (17 cases) and combination therapy (CAKF plus chemotherapy) group (15 cases). 5-FU and mitomycin C were given to the chemotherapy group. The dynamic changes of T-lymphocyte subsets, NK cells and immunoglobulins were investigated.
RESULTS: Before operation, the CD3+, CD4+, CD4+/CD8+ and the activity of NK cells in LIC patients were lower, but CD8+ was higher than that of normal level (P < 0.01), which indicated that cellular immunity in LIC was in immunosuppressive state, they all further reduced 1 week after operation, particularly CD3+ cell counts, but CD3+, CD4+ and the activity of NK cells normalized 1 month after operation in CAKF group, and 2 months were needed to normalize in combination therapy group. Both groups recovered to a certain extent in comparing with before treatment, but the chemotherapy group recovered slower. The similar results appeared in humoral immunity.
CONCLUSION: CAKF could obviously increase the immunity in LIC patients after operation.
Options:
A: There was no significant change in the side effects or immune response.
B: There was a significant reduction in nausea and vomiting, and an increase in certain T-lymphocyte subsets.
C: There was an increase in hepatotoxicity and myelosuppression.
D: There was a significant improvement in overall survival rates. | B |
411 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What is the impact of surgical resection combined with complete mediastinal lymph node dissection on survival in patients with resectable stage I to IIIA non-small cell lung cancer (NSCLC) compared to other surgical approaches or non-surgical therapies? Please answer this question based on the information provided below:
Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer: a phase III randomised controlled trial.
BACKGROUND: Results from phase II studies in patients with stage IIIA non-small-cell lung cancer with ipsilateral mediastinal nodal metastases (N2) have shown the feasibility of resection after concurrent chemotherapy and radiotherapy with promising rates of survival. We therefore did this phase III trial to compare concurrent chemotherapy and radiotherapy followed by resection with standard concurrent chemotherapy and definitive radiotherapy without resection.
METHODS: Patients with stage T1-3pN2M0 non-small-cell lung cancer were randomly assigned in a 1:1 ratio to concurrent induction chemotherapy (two cycles of cisplatin [50 mg/m(2) on days 1, 8, 29, and 36] and etoposide [50 mg/m(2) on days 1-5 and 29-33]) plus radiotherapy (45 Gy) in multiple academic and community hospitals. If no progression, patients in group 1 underwent resection and those in group 2 continued radiotherapy uninterrupted up to 61 Gy. Two additional cycles of cisplatin and etoposide were given in both groups. The primary endpoint was overall survival (OS). Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00002550.
FINDINGS: 202 patients (median age 59 years, range 31-77) were assigned to group 1 and 194 (61 years, 32-78) to group 2. Median OS was 23.6 months (IQR 9.0-not reached) in group 1 versus 22.2 months (9.4-52.7) in group 2 (hazard ratio [HR] 0.87 [0.70-1.10]; p=0.24). Number of patients alive at 5 years was 37 (point estimate 27%) in group 1 and 24 (point estimate 20%) in group 2 (odds ratio 0.63 [0.36-1.10]; p=0.10). With N0 status at thoracotomy, the median OS was 34.4 months (IQR 15.7-not reached; 19 [point estimate 41%] patients alive at 5 years). Progression-free survival (PFS) was better in group 1 than in group 2, median 12.8 months (5.3-42.2) vs 10.5 months (4.8-20.6), HR 0.77 [0.62-0.96]; p=0.017); the number of patients without disease progression at 5 years was 32 (point estimate 22%) versus 13 (point estimate 11%), respectively. Neutropenia and oesophagitis were the main grade 3 or 4 toxicities associated with chemotherapy plus radiotherapy in group 1 (77 [38%] and 20 [10%], respectively) and group 2 (80 [41%] and 44 [23%], respectively). In group 1, 16 (8%) deaths were treatment related versus four (2%) in group 2. In an exploratory analysis, OS was improved for patients who underwent lobectomy, but not pneumonectomy, versus chemotherapy plus radiotherapy.
INTERPRETATION: Chemotherapy plus radiotherapy with or without resection (preferably lobectomy) are options for patients with stage IIIA(N2) non-small-cell lung cancer.
FUNDING: National Cancer Institute, Canadian Cancer Society, and National Cancer Institute of Canada.
Randomized trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer. Lung Cancer Study Group.
BACKGROUND: It has been reported that limited resection (segment or wedge) is equivalent to lobectomy in the management of early stage (T1-2 N0) non-small cell lung cancer.
METHODS: A prospective, multiinstitutional randomized trial was instituted comparing limited resection with lobectomy for patients with peripheral T1 N0 non-small cell lung cancer documented at operation. Analysis included locoregional and distant recurrence rates, 5-year survival rates, perioperative morbidity and mortality, and late pulmonary function assessment.
RESULTS: There were 276 patients randomized, with 247 patients eligible for analysis. There were no significant differences for all stratification variables, selected prognostic factors, perioperative morbidity, mortality, or late pulmonary function. In patients undergoing limited resection, there was an observed 75% increase in recurrence rates (p = 0.02, one-sided) attributable to an observed tripling of the local recurrence rate (p = 0.008 two-sided), an observed 30% increase in overall death rate (p = 0.08, one-sided), and an observed 50% increase in death with cancer rate (p = 0.09, one-sided) compared to patients undergoing lobectomy (p = 0.10, one-sided was the predefined threshold for statistical significance for this equivalency study).
CONCLUSIONS: Compared with lobectomy, limited pulmonary resection does not confer improved perioperative morbidity, mortality, or late postoperative pulmonary function. Because of the higher death rate and locoregional recurrence rate associated with limited resection, lobectomy still must be considered the surgical procedure of choice for patients with peripheral T1 N0 non-small cell lung cancer.
Lobectomy versus limited resection in T1 N0 lung cancer.
Effectiveness of radical systematic mediastinal lymphadenectomy in patients with resectable non-small cell lung cancer: results of a prospective randomized trial.
OBJECTIVE: To evaluate the effectiveness of lymphadenectomy in the treatment of non-small cell lung cancer (NSCLC).
SUMMARY BACKGROUND DATA: The extent of lymphadenectomy in the treatment of NSCLC is still a matter of controversy. Although some centers perform mediastinal lymph node sampling (LS) with resection of only suspicious lymph nodes, others recommend a radical, systematic mediastinal lymphadenectomy (LA) to improve survival and to achieve a better staging.
METHODS: In a controlled, prospective, randomized clinical trial, the effects of LA on recurrence rates and survival were analyzed, comparing LS and LA in 169 patients with operable NSCLC.
RESULTS: After a median follow-up of 47 months, LA did not improve survival in the overall group of patients (hazard ratio: 0.78; 95% confidence interval: 0.47-1.24). Although recurrences rates tended to be reduced among patients who underwent LA, these decreases were not statistically significant (hazard ratio: 0.82; 95% confidence interval: 0.54-1.27). However, analysis of subgroups of patients according to histopathologic lymph node staging revealed that LA appears to prolong relapse-free survival (p = 0.037) with a borderline effect on overall survival (p = 0.058) in patients with limited lymph node involvement (pN1 disease or pN2 disease with involvement of only one lymph node level); in patients with pN0 disease, no survival benefit was observed.
CONCLUSIONS: Radical systematic mediastinal lymphadenectomy does not influence disease-free or overall survival in patients with NSCLC and without overt lymph node involvement. However, a small subgroup of patients with limited mediastinal lymph node metastases might benefit from a systematic lymphadenectomy.
Radical systematic mediastinal lymphadenectomy in non-small cell lung cancer: a randomized controlled trial.
The value of radical systematic lymphadenectomy in the treatment of bronchial carcinoma is controversial. In a randomized controlled clinical trial, radical lymphadenectomy was compared with conventional node dissection in 182 patients with non-small cell lung cancer. Comparison of short-term results revealed a significantly longer operating time in those undergoing systematic lymphadenectomy, but overall morbidity and mortality rates were comparable between groups. However, there were complications associated with radical lymphadenectomy such as prolonged air leakage and haemorrhage. Interim analysis of results at a median follow-up of 26.8 months showed no significant influence of radical lymphadenectomy on local recurrence-free interval, metastasis-free interval or cancer-related survival. In conclusion, radical systematic lymphadenectomy is a safe operation that leads to a better staging of non-small cell lung cancer, but its prognostic benefit is questionable.
Phase III study comparing chemotherapy and radiotherapy with preoperative chemotherapy and surgical resection in patients with non-small-cell lung cancer with spread to mediastinal lymph nodes (N2); final report of RTOG 89-01. Radiation Therapy Oncology Group.
PURPOSE: To compare the outcome of treatment of mediastinoscopy-verified N2 non-small-cell lung cancer treated with induction chemotherapy followed by either surgery or radiotherapy (RT), with both options followed by consolidation chemotherapy.
METHODS AND MATERIALS: A randomized Phase III trial for Stage IIIA (T1-T3N2M0) non-small cell lung cancer was conducted by the Radiation Therapy Oncology Group (RTOG) and Eastern Cooperative Oncology Group between April 1990 and April 1994. After documentation of N2 disease by mediastinoscopy or anterior mediastinotomy, patients received induction chemotherapy with cisplatin, vinblastine, and mitomycin-C. Mitomycin-C was later dropped from the induction regimen. Patients were then randomized to surgery or RT (64 Gy in 7 weeks) followed by cisplatin and vinblastine.
RESULTS: RTOG 89-01 accrued 75 patients, of whom 73 were eligible and analyzable. Twelve patients received induction chemotherapy but were not randomized to RT or surgery thereafter. Forty-five patients were randomized to postinduction RT or surgery. Of the analyzable patients, 90% had a Karnofsky performance score of 90-100, 18% had weight loss >5%, 37% had squamous cell histologic features, and 54% had bulky N2 disease. The distribution of bulky N2 disease was uniform among the treatment arms. The incidence of Grade 4 toxicity was 56% in patients receiving mitomycin-C and 29% in those who did not. Only 1 patient in each group had acute nonhematologic toxicity greater than Grade 3 (nausea and vomiting). No acute Grade 4 radiation toxicity developed. The incidences of long-term toxicity were equivalent across the arms. Three treatment-related deaths occurred: 2 patients in the surgical arms (one late pulmonary toxicity and one pulmonary embolus), and 1 patient in the radiation arm (radiation pneumonitis). Induction chemotherapy was completed in 78% of the patients. Complete resection was performed in 73% of 26 patients undergoing thoracotomy. Consolidation chemotherapy was completed in 75% of the patients. No statistically significant difference was found among the treatment arms. The overall progression-free survival rate was 53% at 1 year and 17% at 3 years. The median progression-free survival was 14 months. No difference in the 1-year survival rate (70% vs. 66%) or median survival time (19.4 vs. 17.4 months) between the surgery and RT arms. The median survival in the patients receiving induction chemotherapy only was 8.9 months. Mitomycin-C had no impact on survival (p = 0.75). No statistically significant difference was noted in the time to local failure between the surgical and RT arms.
CONCLUSION: The patient accrual to this trial made its results inconclusive, but several observations are notable. In this trial, histologic confirmation of N2 disease in the surgical and nonsurgical arms eliminated the usual biases from clinical staging. In this setting, local control and survival were essentially equal between the surgical and RT arms. The 3- and 5-year survival rates of nonsurgical therapy were comparable to published surgical trials of N2 disease.
Preoperative irradiation of cancer of the lung. Preliminary report of a therapeutic trial. A collaborative study.
Preoperative irradiation of cancer of the lung: final report of a therapeutic trial. A collaborative study.
Between May, 1963 and December, 1966, 17 medical centers cooperated in two separate but integrated therapeutic trials of primary lung cancer. One study was of patients with lesions considered operable at the time of diagnosis, and the other of patients with initially inoperable cancer but who were considered potentially operable after radiotherapy. Patients operable at the time of diagnosis were randomly assigned to receive either immediate surgery (278 patients) or preoperative radiotherapy followed by surgery (290 patients). All but one were followed until death or 5 years survival. Survival to each anniversary after randomization was almost identical for the two groups. At 5 years the survival rate was 14% after preoperative radiotherapy and 16% after immediate surgery. On the basis of the small standard error of the difference between these survival rates, a large advantage or a large disadvantage for preoperative radiotherapy is unlikely. Recurrence of cancer either locally or as distant metastasis was also similar in the two groups. Postoperative mortality was estimated to be 11% in the immediate surgery group, but cannot be estimated in a comparable fashion for the irradiated group. Certain postoperative complications were more frequent in the irradiated group, but survival during the first was not affected. Out of 425 patients initially considered to be inoperable, 152 were considered resectable after radiotherapy. These patients were randomly assigned to have either a thoracotomy and resection of their cancer if possible (78 patients) or no surgery (74 patients). Survival to each anniversary after randomization was very similar. After 5 years the survival rate was 8% for the group assigned to surgery and 6% for the group assigned to no surgery. The difference has a standard error of 4%.
Randomized study of chemotherapy and surgery versus radiotherapy for stage IIIA non-small-cell lung cancer: a National Cancer Institute of Canada Clinical Trials Group Study.
Thirty-one patients with stage IIIA (N2) non-small-cell lung cancer were randomized to receive radiotherapy alone or chemotherapy with cisplatin and vinblastine followed by surgery. Response rates to induction chemotherapy and radiotherapy were 50% and 53.3% respectively. Complete surgical resection was possible for 62.5% of patients. Median survival times were 16.2 and 18.7 months for radiotherapy alone and chemotherapy-surgery respectively (P = Ns), with no long-term improvement in survival seen with combined-modality treatment.
Chemo-radiotherapy versus chemo-surgery in stage IIIA non-small cell lung cancer.
Forty patients with non-small cell lung cancer stage IIIA, aged 33-72 years were allocated to two groups in order to get therapy of two different combined modalities. All the patients were staged and considered inoperable. Staging was done by bronchoscopy, CT scan, bone scan and in patients with mediastinal lymph nodes less than 2 cm in size by thoracotomy. Group A patients were programmed to have induction chemotherapy and then radiotherapy while patients of group B to have induction chemotherapy, of the same kind as Group A and then surgery. Chemotherapy included cis-platinum 90 mg/m(2) given once every 3 weeks for 4-6 courses. Radiotherapy of Group A patients was 5000 cGy in the primary tumor site and mediastinum. Toxicity was tolerable. The following results were obtained: a) high response rate (over 70%) after chemotherapy, b) 66% of Group B patients were redered operable and c) the survival rate was significantly higher in patients with chemo-surgery versus those with chemo-radiotherapy.
A randomised controlled trial of pre-operative chemotherapy followed, if feasible, by resection versus radiotherapy in patients with inoperable stage T3, N1, M0 or T1-3, N2, M0 non-small cell lung cancer.
The majority of patients with stage T3, N1, M0 or T1-3, N2, M0 non-small cell lung cancer are considered inoperable, and receive radical radiotherapy. This randomised trial aimed to assess whether, in this group of inoperable patients, a policy of neo-adjuvant chemotherapy (with mitomycin, ifosfamide and cisplatin (MIC) or mitomycin, vinblastine and cisplatin (MVP)) followed, if feasible, by surgery (CT-S), would result in better outcomes than radical radiotherapy (RT). The trial closed due to poor accrual, with only 48 patients randomised in 3 years. Only 4 of the 24 patients in the CT-S group had a complete resection, and of these, the 2 patients who had a pneumonectomy both died 12 days after surgery. There was no evidence of an improved survival in the CT-S group (median survival 13.8 months, compared with 11.3 months for the RT group), but because the trial failed to recruit we were unable to reach any reliable conclusions about these two treatment options.
Systematic lymph node dissection for clinically diagnosed peripheral non-small-cell lung cancer less than 2 cm in diameter.
The value of radical systematic lymphadenectomy for treatment of early-stage bronchial carcinoma is controversial. We performed a prospective randomized study to address this question. Altogether 115 patients with peripheral non-small-cell lung cancers smaller than 2 cm in diameter were enrolled in this study. They were randomly assigned into a lobectomy with lymph node sampling group (sampling group, n = 56) or a lobectomy with radical systematic lymph node dissection group (dissection group, n = 59). Inclusion criteria were based only on preoperative clinical studies. Four tumors were larger than 2 cm postoperatively. One patient had disseminated disease, and two had intrapulmonary metastases discovered at surgery. Two patients had small-cell carcinoma. There were four with pathologic N1 disease and seven with N2 disease in the dissection group and three with N1 and eight with N2 disease in the sampling group. The numbers of local and distant recurrences were two and six, respectively, in the dissection group and two and five in the sampling group. The overall 5-year survival was 81% in the dissection group and 84% in the sampling group. No significant differences in the recurrence rate or survival was seen between the groups. Our results demonstrate that clinically evaluated peripheral non-small-cell carcinomas smaller than 2 cm in diameter do not require radical systematic mediastinal and hilar lymph node dissection.
Video-assisted thoracoscopic lobectomy achieves a satisfactory long-term prognosis in patients with clinical stage IA lung cancer.
We designed a prospective trial to determine the long-term prognosis of video-assisted thoracoscopic (VATS) lobectomy versus conventional lobectomy for patients with clinical stage IA (T1N0M0) lung cancer. Between January 1993 and June 1994, 100 consecutive patients with clinical stage IA non-small cell lung carcinoma underwent either conventional lobectomy through an open thoracotomy (open group; n = 52) or VATS lobectomy (VATS group; n = 48). Lymph node dissections were performed in a similar manner in both groups. No significant differences were observed in the number of dissected lymph nodes between the 2 groups. Pathologic N1 and N2 disease was found in 3 and 1 patients, respectively, from the open group, and in 2 and 1 patients, respectively, from the VATS group. During the follow-up period, distant metastases and local or regional recurrences developed in 7 and 3 of the open group patients, respectively, and in 2 and 3 of the VATS group patients, respectively. Two and one of the open and VATS group patients developed second primary cancers, respectively. The overall survival rates 5 years after surgery were 85% and 90% in the open and VATS groups, respectively (log-rank test, p = 0.74; generalized Wilcoxon test, p = 0.91). VATS lobectomy with lymph node dissection achieved an excellent 5-year survival, similar to that achieved by the conventional approach.
Randomized trial of surgery versus radiotherapy in patients with stage IIIA (N2) non small-cell lung cancer after a response to induction chemotherapy. EORTC 08941.
Combined modality treatment of patients with stage III non small-cell lung cancer (NSCLC) has recently become widely accepted. Standard combinations are neoadjuvant chemotherapy followed by radiotherapy or concurrent chemotherapy and radiotherapy. The effect of combined modality treatment on survival is dependent on both the efficacy of chemotherapy to eradicate micrometastases and optimal local control. The European Organization for Research and Treatment of Cancer (EORTC) Lung Cancer Cooperative Group has chosen to investigate in a comparative way the side effects and the effect on survival of radiotherapy versus surgery in stage IIIA (N2) NSCLC.
Randomized controlled trial of resection versus radiotherapy after induction chemotherapy in stage IIIA-N2 non-small-cell lung cancer.
BACKGROUND: Induction chemotherapy before surgical resection increases survival compared with surgical resection alone in patients with stage IIIA-N2 non-small-cell lung cancer (NSCLC). We hypothesized that, following a response to induction chemotherapy, surgical resection would be superior to thoracic radiotherapy as locoregional therapy.
METHODS: Selected patients with histologic or cytologic proven stage IIIA-N2 NSCLC were given three cycles of platinum-based induction chemotherapy. Responding patients were subsequently randomly assigned to surgical resection or radiotherapy. Survival curves were estimated using Kaplan-Meier analyses from time of randomization.
RESULTS: Induction chemotherapy resulted in a response rate of 61% (95% confidence interval [CI] = 57% to 65%) among the 579 eligible patients. A total of 167 patients were allocated to resection and 165 to radiotherapy. Of the 154 (92%) patients who underwent surgery, 14% had an exploratory thoracotomy, 50% a radical resection, 42% a pathologic downstaging, and 5% a pathologic complete response; 4% died after surgery. Postoperative radiotherapy was administered to 62 (40%) of patients in the surgery arm. Among the 154 (93%) irradiated patients, overall compliance to the radiotherapy prescription was 55%, and grade 3/4 acute and late esophageal and pulmonary toxic effects occurred in 4% and 7%; one patient died of radiation pneumonitis. Median and 5-year overall survival for patients randomly assigned to resection versus radiotherapy were 16.4 versus 17.5 months and 15.7% versus 14%, respectively (hazard ratio = 1.06, 95% CI = 0.84 to 1.35). Rates of progression-free survival were also similar in both groups.
CONCLUSION: In selected patients with pathologically proven stage IIIA-N2 NSCLC and a response to induction chemotherapy, surgical resection did not improve overall or progression-free survival compared with radiotherapy. In view of its low morbidity and mortality, radiotherapy should be considered the preferred locoregional treatment for these patients.
A randomized trial of systematic nodal dissection in resectable non-small cell lung cancer.
PURPOSE: We conducted a randomized trial to investigate whether systematic nodal dissection (SND) is superior to mediastinal lymph nodal sampling (MLS) in surgical treatment of non-small cell lung cancer (NSCLC).
METHODS: The patients resectable clinical Stage I-IIIA NSCLC were randomly assigned to lung resection combined with SND or lung resection combined with MLS. After postoperative pathological re-staging, eligible cases were followed up until 30 November 2000. The Kaplan-Meier method was used for survival analysis. COX proportional hazards model was used for prognostic analysis.
RESULTS: Of the 532 patients who were enrolled in the study, 268 patients were assigned to lung resection combined with SND and 264 were assigned to lung resection combined with MLS. After surgical restaging only 471 cases were eligible for follow-up. The median survival was 59 months in the group given SND and 34 months in the group given MLS (P=0.0000 by the log rank test). There was significant difference in survival in Stage I (5-year survival 82.16 vs. 57.49%) and Stage IIIA (26.98 vs. 6.18%) by the log rank test and Breslow test. There was no significant yet marginal difference in survival by log rank test (10-year survival 32.04 vs. 26.92%, P=0.0523) but significant difference in survival by Breslow test (5-year survival 50.42 vs. 34.05%, P=0.0284) in Stage II. Types of mediastinal lymph node dissection, pTNM stage, tumor size and number of lymph node metastasis were four factors that influenced long-term survival rate by multivariate analysis.
CONCLUSIONS: As compared with MLS, lobectomy (pneumonectomy) combined with SND can improve survival in resectable NSCLC.
[Extent of lymphadenectomy in stage I-IIIA non-small cell lung cancer: a randomized clinical trial].
OBJECTIVE: To study the role of radical systematic mediastinal lymphadenectomy for non-small cell lung cancer (NSCLC).
METHODS: All 504 operable eligible cases with NSCLC were randomly divided to a radical lymphadenectomy (RL) group and a conventional lymph node dissection group (control) treated between Aug. 1989 and Dec. 1995. For patients postoperatively eligible, thirteen parameters (operation type, pathological type and grade, tumor size, total number of dissected lymph nodes, number of metastatic lymph nodes, metastasis ratio of lymph nodes, postoperative TNM staging, adjuvant therapy, recurrence or metastasis, morbidity, survival and life quality) were evaluated. The end point of follow-up was Dec. 31, 1998. Lost follow-up rate was 1.9%. The results were analyzed with soft were SPSS7.5. The cumulative survival was calculated by the Kaplan-Meier method and compared by the log rank test. The prognostic factors were analyzed by the Cox model.
RESULTS: There were 320 cases, 160 cases in each group, who entered the study. The mean numbers of dissected lymph nodes was 9.49 in the RL group and 3.63 in the control group. For stage I NSCLC patients, the 1,3,5,9-year survival rate was 91.8%, 86.9%, 81.4%, 74.2% respectively in the RL group and 88.7%, 72.5%, 58.5%, 52.1% respectively in the control group (P < 0.014). However, no statistically significant difference in survival rates between RL and control groups of patients with stage II and IIIA NSCLC. The postoperative TNM staging, metastasis ratio of lymph nodes, extent of lymphadenectomy were the factors influencing long term survival upon multivariable analysis.
CONCLUSION: Classical lobectomy or pneumonectomy with radical systematic mediastinal lymphadenectomy is the surgical treatment of choice for NSCLC.
Options:
A: Surgical resection combined with complete mediastinal lymph node dissection significantly improves survival compared to resection with lymph node sampling.
B: Surgical resection combined with complete mediastinal lymph node dissection does not show any significant improvement in survival compared to resection with lymph node sampling.
C: Surgical resection combined with complete mediastinal lymph node dissection significantly worsens survival compared to resection with lymph node sampling.
D: Surgical resection combined with complete mediastinal lymph node dissection shows no difference in survival compared to non-surgical therapies. | A |
412 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What is the impact of the timing of chest radiotherapy on the long-term survival of patients with limited-stage small cell lung cancer when combined with chemotherapy? Please answer this question based on the information provided below:
Initial versus delayed accelerated hyperfractionated radiation therapy and concurrent chemotherapy in limited small-cell lung cancer: a randomized study.
PURPOSE: To perform a randomized study of the optimal timing of thoracic radiation (RT) as accelerated hyperfractionated radiation therapy (ACC HFX RT) in combination with concurrent chemotherapy (CHT) in limited-stage small-cell lung cancer (SCLC).
PATIENTS AND METHODS: Between 1988 and 1992, 107 patients were enrolled and 103 were assessable. All patients received ACC HFX RT with 1.5 Gy twice daily to 54 Gy plus concurrent daily carboplatin/etoposide (C/E) (30 mg each) and four sequential cycles of cisplatin/etoposide (PE) (30 mg/m2 and 120 mg/m2, respectively, on days 1 to 3). Group I patients (n = 52) received concurrent chemoradiation at weeks 1 to 4, and group II (n = 51) at weeks 6 to 9. Patients who showed a complete response (CR) or partial response (PR) underwent prophylactic cranial irradiation (PCI) at weeks 16 to 17.
RESULTS: The median survival time was 34 months in group I and 26 months in group II, and the Kaplan-Meier 5-year survival rates were 30% and 15%, respectively. The difference was almost significant on univariate analysis (P = .052) and was significant on multivariate analysis (P = .027). Group I patients had a significantly higher local control rate than group II patients, but there was no difference between the two groups in distant metastasis rate. There was no difference in the incidence of acute or late grade 3 to 4 toxicity.
CONCLUSION: Initial administration of thoracic ACC HFX RT with concurrent C/E seems to produce better local control and survival rates than delayed administration.
Importance of timing for thoracic irradiation in the combined modality treatment of limited-stage small-cell lung cancer. The National Cancer Institute of Canada Clinical Trials Group.
PURPOSE: The importance of the timing of thoracic irradiation (TI) in the combined modality therapy of limited-stage small-cell lung cancer (SCLC) was assessed in a randomized trial.
METHODS: All 308 eligible patients received cyclophosphamide, doxorubicin, and vincristine (CAV) alternating with etoposide and cisplatin (EP) every 3 weeks for three cycles of each chemotherapy regimen. Patients randomized to early TI received 40 Gy in 15 fractions over 3 weeks to the primary site concurrent with the first cycle of EP (week 3), and late TI patients received the same radiation concurrent with the last cycle of EP (week 15). After completion of all chemotherapy and TI, patients without progressive disease received prophylactic cranial irradiation (25 Gy in 10 fractions over 2 weeks).
RESULTS: Although complete remission rates were not significantly different between the two arms, progression-free survival (P = .036) and overall survival (P = .008) were superior in the early TI arm. Patients in the late TI arm had a higher risk of brain metastases (P = .006).
CONCLUSION: The early administration of TI in the combined modality therapy of limited-stage SCLC is superior to late or consolidative TI.
Thoracic radiation therapy added to chemotherapy for small-cell lung cancer: an update of Cancer and Leukemia Group B Study 8083.
PURPOSE: To provide a 10-year update of the experience of the Cancer and Leukemia Group B (CALGB) in the addition of thoracic radiation therapy to chemotherapy in limited-stage small-cell lung cancer.
PATIENTS AND METHODS: Three hundred ninety-nine patients with limited-stage small-cell lung cancer were randomized to receive thoracic radiation therapy that started on day 1 (arm I) or day 64 of chemotherapy treatment (arm II), or chemotherapy alone with cyclophosphamide, vincristine, and etoposide (later, doxorubicin). Thoracic radiation therapy consisted of 4,000 rad to the tumor and mediastinum with a 1,000-rad boost. All patients received prophylactic cranial radiation to a dose of 3,000 rad.
RESULTS: Arm I patients had a median survival of 13.04 months, arm II patients 14.54 months, and arm III patients 13.58 months (log-rank test, P = .0072). Median time to clinical failure was 11 months in arm I, 11.21 months in arm II, and 8.7 months in arm III (log-rank test, P = .0004).
CONCLUSION: With 10 years of follow-up, the two arms that included thoracic radiation therapy remain superior to chemotherapy alone. The addition of thoracic radiation therapy to combination chemotherapy improved both complete response rates and survival, with increased but acceptable toxicity.
Randomized comparison of early versus late hyperfractionated thoracic irradiation concurrently with chemotherapy in limited disease small-cell lung cancer: a randomized phase II study of the Hellenic Cooperative Oncology Group (HeCOG).
BACKGROUND: Concurrent platinum etoposide chemotherapy given in combination with hyperfractionated thoracic radiation therapy (HTRT) in limited disease (LD) small cell lung cancer (SCLC) is associated with a high response rate and significant prolongation of survival. Given these results, the Hellenic Cooperative Oncology Group (HeCOG) performed a multicenter randomized phase II study in patients with LD SCLC to evaluate the timing of HTRT (early vs. late) when given concurrently with chemotherapy.
PATIENTS AND METHODS: To be eligible for the study, patients were required to have histologically or cytologically proven LD SCLC, confined to one hemithorax and/or ipsilateral mediastinal or supraclavicular lymphnodes and absence of pleural effusion or controlateral supraclavicular lymphnode involvement. Moreover, patients had to have a good performance status and adequate haematological, liver and renal function. Patients with LD SCLC were randomized to receive HTRT either concurrently with the first (Group A) or with the fourth (Group B) cycle of chemotherapy. Chemotherapy consisted of carboplatin administered at an AUC of six given as an i.v. 1-hour-infusion immediately followed by etoposide at a dose of 100 mg/m2 i.v. as a two-hour infusion for three consecutive days every three weeks up to a total of six cycles. Prophylactic cranial irradiation was also given to patients achieving a complete response.
RESULTS: 42 and 39 patients, were eligible for efficacy evaluation in group A and B respectively. The overall response rate was 76% in group A and 92.5% in group B (P = 0.07) with a complete response rate of 40.5% and 56.5%, respectively. After a median follow-up of 35 months, time to progression was 9.5 months in group A and 10.5 in group B (NS) while overall median survival was 17.5 and 17 months respectively (NS). The 2-year survival was 36% in group A and 29% in group B (NS) and the 3-year survival 22% and 13%, respectively (NS). The distant relapse rate was 38% in group A and 61% in group B (P = 0.046). Severe grade 3 4 anemia was recorded in 19% of group A and 12.5% of group B (NS), while severe leucopenia was recorded in 35.5% and 20.5% (P = 0.09) and neutropenic fever in 5% and 2.5% (NS), respectively. Severe thrombocytopenia did not differ significantly between the two treatment groups being 21.5% and 23%, respectively. Severe grade 2-3 esophageal toxicity was 19% in group A and 23% in group B (NS), while grade 3 lung toxicity was 5% and 7.5% (NS), respectively. No toxicity-related deaths were recorded.
CONCLUSION: Concurrent administration of HTRT with carboplatin etoposide is associated with a high response and survival rate. Although a trend for higher response rate was recorded in the group of patients who received late HTRT, the overall median, 2-year and 3-year survival rates did not differ significantly between the two treatment groups. The toxicity of this promising therapeutic approach was acceptable. Comparative phase III studies with an adequate number of patients are recommended in order to answer this question.
Early compared with late radiotherapy in combined modality treatment for limited disease small-cell lung cancer: a London Lung Cancer Group multicenter randomized clinical trial and meta-analysis.
PURPOSE: To replicate an earlier National Cancer Institute of Canada (NCIC) trial that examined the effect on survival of the timing of thoracic radiotherapy (TRT) in patients with limited disease small-cell lung cancer (SCLC).
PATIENTS AND METHODS: Patients received three cycles of cyclophosphamide, doxorubicin, and vincristine alternating with three cycles of etoposide and cisplatin. Three hundred twenty five chemotherapy- and radiotherapy-naïve patients were randomly assigned to either early TRT administered concurrently in the second cycle or late TRT administered concurrently with the sixth cycle; the dose was 40 Gy in 15 fractions over 3 weeks.
RESULTS: TRT was received by 92% and 82% of patients in the early and late arms, respectively (P = .01). Sixty-nine percent of patients in the early arm received all six courses of chemotherapy compared with 80% in the late arm (P = .003). There was no evidence of a survival difference; median overall survival time was 13.7 and 15.1 months in the early and late arms, respectively (P = .23). In a meta-analysis of all eight trials that compared early and late TRT, there were three in which the proportion of patients who completed their planned chemotherapy was similar between the TRT arms (hazard ratio [HR] = 0.73; 95% CI, 0.62 to 0.86) and five in which proportionally fewer patients in the early TRT arm completed their chemotherapy (HR = 1.06; 95% CI, 0.97 to 1.17).
CONCLUSION: This study failed to show a survival advantage for early TRT with chemotherapy in limited-stage SCLC, unlike the NCIC trial. However, the results of a meta-analysis suggest that it is essential to ensure that the delivery of chemotherapy is optimal when administered with early TRT.
Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results of the Japan Clinical Oncology Group Study 9104.
PURPOSE: To evaluate the optimal timing for thoracic radiotherapy (TRT) in limited-stage small-cell lung cancer (LS-SCLC), the Lung Cancer Study Group of the Japan Clinical Oncology Group conducted a phase III study in which patients were randomized to sequential TRT or concurrent TRT.
PATIENTS AND METHODS: We treated 231 patients with LS-SCLC. TRT consisted of 45 Gy over 3 weeks (1.5 Gy twice daily), and the patients were randomly assigned to receive either sequential or concurrent TRT. All patients received four cycles of cisplatin plus etoposide every 3 weeks (sequential arm) or 4 weeks (concurrent arm). TRT was begun on day 2 of the first cycle of chemotherapy in the concurrent arm and after the fourth cycle in the sequential arm.
RESULTS: Concurrent radiotherapy yielded better survival than sequential radiotherapy (P =.097 by log-rank test). The median survival time was 19.7 months in the sequential arm versus 27.2 months in the concurrent arm. The 2-, 3-, and 5-year survival rates for patients who received sequential radiotherapy were 35.1%, 20.2%, and 18.3%, respectively, as opposed to 54.4%, 29.8% and 23.7%, respectively, for the patients who received concurrent radiotherapy. Hematologic toxicity was more severe in the concurrent arm. However, severe esophagitis was infrequent in both arms, occurring in 9% of the patients in the concurrent arm and 4% in the sequential arm.
CONCLUSION: This study strongly suggests that cisplatin plus etoposide and concurrent radiotherapy is more effective for the treatment of LS-SCLC than cisplatin plus etoposide and sequential radiotherapy.
Randomized study of initial versus late chest irradiation combined with chemotherapy in limited-stage small-cell lung cancer. Aarhus Lung Cancer Group.
PURPOSE: To evaluate if the timing of chest irradiation with respect to chemotherapy would influence survival and local and distant control in patients with limited-stage small-cell lung cancer (LSCLC).
PATIENTS AND METHODS: From 1981 to 1989, 199 consecutive patients with LSCLC were randomly allocated to receive initial chest irradiation (ICI; n = 99) or late chest irradiation (LCI; n = 100) given 18 weeks delayed. Both groups received the same nine cycles of combination chemotherapy: three cycles of cisplatin and etoposide and six cycles of cyclophosphamide, doxorubicin, and vincristine. In the first part of the study, prophylactic cranial irradiation (PCI) was only given to patients randomized to ICI, but after inclusion of 42 patients in the LCI arm, the protocol was changed, so that all patients received PCI independent of the timing of the chest irradiation (CI). A total of 157 patients received PCI with a radiation dose of 25 Gy in 11 fractions.
RESULTS: The timing of radiotherapy had no significant effect on the 2-year overall survival rate (20% after ICI v 19% after LCI, P = .4) or the 2-year in-field recurrence rate (72% after ICI v 68% after LCI, P = .2). Median survival durations were 10.5 (ICI) and 12.0 (LCI) months. Similarly, no difference in the 2-year incidence of CNS recurrences was found between the 2 arms in patients who received PCI (19% after ICI v 13% after LCI, P = .24). Bone marrow toxicity was acceptable, as 15% developed World Health Organization (WHO) grade 4 leukocytopenia and 4% grade 4 thrombocytopenia. Grade 4 leukocytopenia was more pronounced in the ICI group. There was no difference in the frequency and severity of other toxicities between the 2 groups.
CONCLUSION: Timing of CI did not significantly influence the incidence of in-field recurrences, CNS recurrences, or overall survival.
Options:
A: Early chest radiotherapy significantly improves both 2-year and 5-year survival rates.
B: Late chest radiotherapy significantly improves both 2-year and 5-year survival rates.
C: There is no significant difference in 2-year and 5-year survival rates between early and late chest radiotherapy.
D: Early chest radiotherapy significantly improves 2-year survival rates but not 5-year survival rates. | C |
413 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What were the findings regarding the comparison between laparoscopic transabdominal preperitoneal (TAPP) and laparoscopic totally extraperitoneal (TEP) techniques for inguinal hernia repair in terms of clinical effectiveness and complications? Please answer this question based on the information provided below:
Transabdominal or totally extraperitoneal laparoscopic hernia repair?
Laparoscopic repair of inguinal hernias follows some principles that have already proven its efficiency, as a posterior approach and the prosthetic repair that allows a "tension-free" repair with consequent early return to work and low recurrence rate. To determine the most appropriate laparoscopic repair, we compared the transabdominal preperitoneal (TAPP) and the totally extraperitoneal (TEP) approach. Patients undergoing TAPP and TEP were compared regarding technical feasibility and difficulties, time until return to work and follow-up, including intraoperative and postoperative complications. Seventy-eight patients (108 hernias) were submitted to TAPP and 67 (100 hernias) were repaired through TEP. All data were analyzed by Yates-corrected chi-square test to qualitative analysis of each group and p < or = 0.05 was considered significant. Both procedures were indicated mainly for bilateral and/or recurrent hernias (68%). The operative time was shorter in TAPP (not statistically significant). Surgeons complained of more technical difficulties while performing the TEP approach (70% complaints of difficulty in TEP--four conversions to TAPP). There was no difference in hospital stay (mean of 30 h) and return to work (TAPP 7 days and TEP 5.5 days). Regarding the complication rate (TAPP = 20.5% and TEP = 13.5%; not significant), none were related to the pneumoperitoneum technique or its systemic effects. In the TAPP approach, two trocar site hernias occurred, and in the TEP approach, one severe cellulitis occurred, which was managed without surgical intervention. The mean follow-up period for each procedure was not the same, so the recurrence rates are not comparable statistically (rate of 1.85% in TAPP and 0 in TEP). Both techniques are safe and have the same advantages, but TAPP is easier: a better view of the anatomy is achieved, shortening the learning curve. We suggest that TAPP can be an adequate laparoscopic approach to groin hernias. A longer follow-up period and more cases are needed to determine recurrence rates.
Laparoscopic hernioplasty. TAPP vs TEP.
This study compares the results of two laparoscopic hernioplasties: the transabdominal preperitoneal (TAPP) and the totally extraperitoneal (TEP). Over a 43-month period 1,115 laparoscopic hernioplasties, 733 TAPP and 382 TEP, were performed in 866 patients. There were 11 major complications in the TAPP group (2 recurrences, 6 trocar hernias, 1 small-bowel obstruction, 1 trocar, and 1 dissection injury of the small bowel) compared to 1 recurrence and no intraperitoneal complications in the TEP group. Five TEP procedures required conversion to the TAPP approach, resulting in one umbilical hernia. The median time to return to work did not vary with the approach, but was prolonged in patients compensated for time off, 16 vs 8 days for noncompensated patients. Results suggested that both techniques shortened recovery and eliminated most early failures, but the totally extraperitoneal approach reduced the potential for intraperitoneal complications and may be the procedure of choice in most situations.
A comparative study of laparoscopic extraperitoneal and transabdominal preperitoneal herniorrhaphy.
Laparoscopic minimally invasive surgical procedures are gaining popularity. Laparoscopic hernia repair is now less controversial and more readily acceptable, with at present numerous technical modifications described in an attempt to define the best procedure. Between November 1992 and February 1995, a nonrandomized trial of laparoscopic inguinal herniorrhaphy was performed on 115 patients with a total of 120 hernias. Of these 58 patients with 60 hernias underwent the transabdominal preperitoneal patch repair (TAPP) without plug and 57 patients with a total of 60 hernias were offered the extraperitoneal (EXTRA) approach using a distension balloon. The average operative time was 55 min for the TAPP and 50 min for the EXTRA procedure. The overall recurrence rate was 1.7% with a follow up of 1-27 months. The recurrence rate was 3.4% for the TAPP and none for the EXTRA approach. All patients returned to their normal activity within 1 week of discharge. Patients undergoing the EXTRA repair consumed less amount of narcotic analgesic than did the group undergoing the TAPP repair. Of the EXTRA group 58% did not require any analgesic, compared to 22% of the TAPP group (p < 05). There were no intraoperative complications. A total of 8 (6.9%) postoperative complications occurred in 115 patients. Four complications (6.9%) occurred in the TAPP procedure: 2 transient urinary retentions, 1 pulmonary edema, and 1 Richter's type hernia. Four (6.9%) complications occurred in the EXTRA procedure: 1 urinary retention, 2 abdominal wall ecchymoses, and 1 thoracic pain. Hospital stay was shorter for the EXTRA group: 57% were discharged the same day and 98% were discharged within 24 h of their operations for the EXTRA group compared to 10 and 84%, respectively, for the TAPP (p < 0.05). Laparoscopic extraperitoneal hernia repair can be accomplished with shorter hospitalization and less analgesic requirement than the TAPP repair. The overall incidence of complications, the recurrence rate, and the return to normal activity were not different between the two types of repair.
A multicentric comparison of transabdominal versus totally extraperitoneal laparoscopic hernia repair using PARIETEX meshes.
The authors report a series of 1972 inguinal hernias treated between 1993 and 1997 by the insertion of a PARIETEX mesh via either a transabdominal-preperitoneal (TAPP) (1,290 procedures) or a totally extraperitoneal TEP approach (682 procedures). Pain scores were equivalent in both groups, while the hospital stay and time to return to normal activity was lower in the TEP group than in the TAPP group (p<0.001). In both groups, the average incidence of the total reported events (complications) was around 10% with no statistical difference. This ratio seemed to compare favorably to previously published reports. Chronic pain was extremely rare (0.6% and 0.7% in the TAPP and TEP groups, respectively). Whatever the approach was, sepsis was also very rare (1/1,526 laparoscopic procedures). These findings illustrate the local tolerance of the mesh. Recurrence rates were below 1% with no statistical difference between groups. This retrospective study demonstrates the clinically apparent local tolerance of this type of mesh. Prospective and long-term clinical results will be necessary to demonstrate that the optimized short-term tolerance of PARIETEX mesh will influence the long term functional results.
Metabolic responses after laparoscopic or open hernia repair.
BACKGROUND: The purpose of a prospective randomized study was to compare the surgical trauma in patients undergoing laparoscopic or open hernia repair.
METHODS: Postoperative pain, analgesic consumption, and metabolic response to surgery were assessed in 30 patients undergoing laparoscopic (group 1; n = 15) or open (group II; n = 15; Shouldice repair) unilateral inguinal hernia repair. Both groups were comparable with respect to age, sex, and type and size of inguinal hernia.
RESULTS: Postoperative visual analogue scales (VAS) for pain were reduced on mobilization for patients of group I with a significant difference (P = 0.02) on the operative day, whereas pain scores at rest and analgesic requirements were similar for both groups. No differences between groups I and II were found in postoperative levels of interleukin-1, interleukin-6, tumor necrosis factor alpha, C-reactive protein, fibrinogen, transferrin, alpha-1-antitrypsin, and white blood cells. Postoperative polymorphonuclear (PMN) elastase concentrations remained within normal range in group II but showed a significant increase in patients operated laparoscopically for postoperative days 1 and 2.
CONCLUSIONS: No major surgical trauma was found after herniorraphy compared to open hernia repair.
Prospective randomized trial comparing postoperative pain and return to physical activity after transabdominal preperitoneal, total preperitoneal or Shouldice technique for inguinal hernia repair.
In a prospective randomized study postoperative pain, analgesic consumption, return to physical activity and work, cosmetic result and experience with the type of operation were assessed in 86 patients undergoing inguinal hernia repair by means of either the Shouldice technique (n = 34), the laparoscopic transabdominal preperitoneal (TAPP) (n = 28) or total preperitoneal (TPP) (n = 24) repair. Patients having TAPP repair had decreased visual analogue scale scores for pain on the day of operation compared with those undergoing TPP and Shouldice repair (4.8 versus 6.5 and 6.2 respectively, P = 0.02) and on the first postoperative day compared with TPP (4.0 versus 6.0, P = 0.01). There was no difference between the three groups for days 2, 3, 4, 5 and 30 after operation. Patient satisfaction with the operation, analgesic consumption, return to physical activity such as walking, driving, climbing stairs, running, bicycling and sexual intercourse, as well as return to work, was comparable in the three groups. There was a better cosmetic result after TAPP and TPP repair. This study failed to demonstrate significant benefits from laparoscopic hernia repair over the Shouldice technique.
Totally extraperitoneal endoscopic inguinal hernia repair (TEP).
BACKGROUND: This report reviews our experience with 5,203 totally extraperitoneal (TEP) endoscopic hernia repairs performed in 3,868 patients over the 7.5-year period between May 1994 and December 2001, 34.5% of whom had bilateral hernias and 13% recurrent hernias.
METHODS: We performed TEP as the method of choice in more than 92% of all the patients presenting with inguinal hernia, including those with incarcerated, strangulated, or inguinoscrotal hernias. After reduction of the hernial sac and appropriate dissection of the preperitoneal space, we placed a slit-free 10 x 15-cm polypropylene mesh without the use of staple fixation.
RESULTS: Altogether, 29 recurrent hernias (0.6%) were observed, more than 50% of which occurred during the first 2 years after the technique was introduced (1.8%). During subsequent years, the recurrence rate settled to approximately 0.3%. Regarding intraoperative complications, we observed eight injuries to the bladder. At this writing, no bowel injuries or damage to iliac vessels has been seen. Postoperatively, we noted only a single case of mesh infection. In 14 cases (0.4%), postoperative hemorrhage necessitated either inguinal or endoscopic reoperation. As a further major complication, a small bowel obstruction caused by inadequate closure of a peritoneal lesion occurred in two patients (0.05%). The overall reoperation rate for the 3,868 patients was 0.6%.
CONCLUSIONS: We consider TEP to be a procedure that carries an acceptably low complication rate, combining the advantages of minor access surgery and mesh reinforcement of the groin. This approach is associated with early postoperative return to usual activities and a very low recurrence rate.
Laparoscopic transperitoneal versus extraperitoneal inguinal hernia repair: a prospective clinical trial.
A prospective series of 106 inguinal hernias in 91 patients is studied, comparing two methods of laparoscopic hernia repair: a transperitoneal technique with preperitoneal stapled mesh fixation (TransAbdominal PrePeritoneal or TAPP-technique) performed in 33 patients, and a totally extraperitoneal placement of non stapled mesh (Totally ExtraPeritoneal Approach or TEPA-technique) performed in 58 patients. Conversions to open repair were equally frequent (5% vs. 7% respectively) and were due to adhesions, haemorrhage, irreducible intestinal loop in the hernial sac or important subcutaneous emphysema. Minor postoperative complications included regional seroma or haematoma, testicular pain and meralgia paraesthetica. There was no mortality nor long lasting complication. Recurrence rates in both groups amounted 2.7% (TAPP) and 2.8% (TEPA) respectively after a mean follow-up of 15.8 months (TAPP) and 17.6 months (TEPA). In both groups early recovery of normal activities was noted, after a mean of respectively 13.6 days (TAPP) and 12.9 days (TEPA). It is concluded that the transabdominal route and the totally extraperitoneal approach for laparoscopic herniorrhaphy are both adequate techniques for inguinal hernia repair with similar complication and short-term recurrence rates.
Options:
A: TAPP was found to be significantly more effective than TEP in terms of shorter operation duration and fewer complications.
B: TEP was found to be significantly more effective than TAPP in terms of shorter operation duration and fewer complications.
C: There was no statistical difference between TAPP and TEP in terms of operation duration, haematoma, length of stay, time to return to usual activity, and recurrence, but TAPP had higher rates of port-site hernias and visceral injuries, while TEP had more conversions.
D: Both TAPP and TEP were found to have high rates of vascular injuries and deep/mesh infections, with no clear advantage of one technique over the other. | C |
414 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What were the findings regarding the effectiveness of distraction techniques as an adjunctive treatment for people with schizophrenia? Please answer this question based on the information provided below:
Long-term effects of teaching behavioral strategies for managing persistent auditory hallucinations in schizophrenia.
1. Attendance at a 10-week class designed to teach behavioral management strategies to people with schizophrenia was effective in reducing some of the negative characteristics of auditory hallucinations for 12 months and in reducing anxiety for 9 months after completion of the class. 2. The sustained improvement experienced by class participants was characterized by their voices being less frequent and more mumbled and the participants feeling more in control, less distractible, and less anxious. 3. Participants recommended that other mental health consumers take similar classes to learn how to better manage their voices. 4. Monthly support groups may help participants maintain gains lost during the follow-up period.
Symptom management of auditory hallucinations in schizophrenia. Results of 1-year follow up.
1. The majority of participants reported that they were still using behavioral strategies to manage their auditory hallucinations throughout the 12-month follow-up period and that they had experienced a decrease in symptom severity. 2. The answers to managing the symptom of auditory hallucinations are as individual as the symptom itself. All of the behavioral management strategies worked for at least one participant, but no strategy worked for everyone. 3. Practicing strategies in a group and at home seemed to promote long-term use of the behavioral strategies.
Auditory hallucinations in schizophrenia. Group experience in examining symptom management and behavioral strategies.
Treating problem-solving deficits on an acute care psychiatric inpatient unit.
Neuropsychological deficits in problem-solving are commonly found in patients with schizophrenia and severe affective disorders. However, in an acute care setting, treatment efforts do not typically target these deficits, even though they can impede recovery. This study aimed to evaluate the effectiveness of short-term problem-solving remediation in acutely ill psychiatric inpatients. Twenty-eight psychiatric inpatients identified as having a verbal problem-solving deficit received 6 h of either verbal problem-solving remediation or placebo instruction. Before and after treatment a nurse rated the patient's psychiatric status and the patient completed verbal and nonverbal problem-solving tests, and a self-report rating of symptoms and ability to cope with symptoms. Both groups of patients improved on the measure of verbal problem solving, but those receiving problem-solving remediation improved significantly more. Both groups made symptomatic improvement, but the patients receiving problem-solving remediation made significantly more improvement on the measure of coping ability and the nurses rated them as more improved, both psychiatrically and with regard to coping skills. Verbal problem-solving deficits are responsive to short-term remediation in an acute care setting, and treatment effects may generalize to improve ability to cope with psychiatric symptoms.
A trial of two cognitive-behavioural methods of treating drug-resistant residual psychotic symptoms in schizophrenic patients: I. Outcome.
Despite neuroleptic medication, many schizophrenic patients continue to experience residual positive psychotic symptoms. These residual symptoms cause distress and disability. We report a controlled trial of two cognitive-behavioural treatments to alleviate residual hallucinations and delusions. Forty-nine patients were recruited into the trial, of whom 27 entered the trial and completed post-treatment assessment, and 23 were reassessed at six-month follow-up. Patients were randomly allocated to either coping strategy enhancement (CSE) or problem solving (PS). Half the patients were allocated to a high-expectancy positive demand condition and half to a counter-demand condition to evaluate expectation of improvement. Patients receiving either cognitive-behavioural treatment showed significant reductions in psychotic symptoms compared with those in the waiting period, who showed no improvement. There was some evidence, although equivocal, that patients receiving CSE improved more than those receiving PS. There was no evidence that improvements generalised to negative symptoms or social functioning, nor was there evidence that expectancy of treatment benefit contributed to the treatment effect.
A trial of two cognitive behavioural methods of treating drug-resistant residual psychotic symptoms in schizophrenic patients. II. Treatment-specific changes in coping and problem-solving skills.
Changes in coping skills and problem-solving skills were examined in two groups of schizophrenic patients. The groups received either coping skills enhancement or problem-solving treatments to reduce their drug-resistant residual psychotic symptoms. The coping skills group showed significant increases both in the number of positive coping strategies used and in their efficacy, whereas the problem-solving group showed a decrease in these measures during treatment. Both groups showed significant improvements in problem-solving skills. Changes in coping but not problem solving were significantly related to decreases in psychotic symptoms during treatment. It was concluded that treatment involving the teaching of coping skills had a specific treatment effect.
Options:
A: Distraction techniques significantly improved mental state and engagement in the studies.
B: Distraction techniques had a clear effect on mental state but did not significantly engage people in the studies.
C: Distraction techniques did not have a clear effect on mental state and did not significantly engage people in the studies.
D: Distraction techniques worsened the mental state of participants and led to higher dropout rates. | C |
415 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What is the efficacy of plasma alkalinisation with sodium bicarbonate (NaHCO3) for the treatment of acute organophosphorus pesticide (OP) poisoning? Please answer this question based on the information provided below:
Effect of high doses of sodium bicarbonate in acute organophosphorous pesticide poisoning.
The sodium bicarbonate (NaHCO3) dosage used in treating the patients with organophosphorous pesticide (OP) poisoning did not result in sufficient alkalinization of the blood. We thus investigated the effects of higher doses by infusion (5 mEq/kg over 1 hour, followed by 5-6 mEq/kg daily until recovery or death) to maintain the arterial pH between 7.45 and 7.55. There were 26 (14 M and 12 F) patients aged 24.1 +/- 9.7 years and 27 (16 M and 11 F) aged 25.7 +/- 9.1 years in the test and contro groups, respectively. Arterial blood pH of the test group (7.48 +/- 0.02) was much higher (p < 0.0001) than the controls (7.36 +/- 0.02). The total atropine doses used for the control patients (129.45 +/- 61 mg) was significantly (p = 0.048) higher than the controls (93.4 +/- 59.1 mg). Hospitalization days were statistically higher (p = 0.037) in the controls (5.59 +/- 1.97 days) than in the bicarbonate group (4.33 +/- 1.99 days). Infusion of high doses of NaHCO3 appears to be beneficial in treatment of patients with OP poisoning.
Options:
A: Plasma alkalinisation with NaHCO3 significantly improves outcomes in acute OP poisoning.
B: Plasma alkalinisation with NaHCO3 shows a trend towards improved outcomes but lacks statistically significant evidence.
C: Plasma alkalinisation with NaHCO3 has no effect on the outcomes of acute OP poisoning.
D: Plasma alkalinisation with NaHCO3 worsens the outcomes of acute OP poisoning. | B |
416 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What is the effectiveness and safety of Botulinum Toxin type A (BtA) in the treatment of hemifacial spasm? Please answer this question based on the information provided below:
Treatment of hemifacial spasm with botulinum toxin.
The effectiveness of botulinum toxin injections in 11 patients with hemifacial spasm was investigated in a prospective placebo-controlled blinded study. The patients were treated with four sets of injections to various facial muscles, selected by clinical evaluation. Three injections were with graded doses of toxin and one was with placebo. The order of injections was random and unknown to the patients. Results were scored both subjectively by patient assessment of symptoms and objectively by blinded review of videotapes made one month after each injection. Subjective improvement occurred after 79% of injections with botulinum toxin, regardless of dose of toxin. Only 1 patient improved after placebo. Objective improvement was seen after 84% of injections with botulinum toxin. No patient showed objective improvement after placebo injection. The most frequent side effect was facial weakness, seen after 97% of injections of botulinum toxin. Facial bruising (20%), diplopia (13%), ptosis (7%), and various other mild side effects were seen less frequently. Botulinum toxin appears to be an effective and safe method of therapy for hemifacial spasm.
Options:
A: BtA is not effective and has significant safety concerns.
B: BtA is effective but has significant safety concerns.
C: BtA is effective and safe.
D: BtA is neither effective nor safe. | C |
417 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What are the potential benefits of incorporating family therapy as an adjunct to medication for treating asthma in children? Please answer this question based on the information provided below:
Family therapy in the treatment of severe childhood asthma.
Eighteen children with severe, chronic bronchial asthma were randomly divided into two groups. The families in one group received family therapy while the others served as a control group in a controlled family therapy study. Later the control families were also offered therapy in a before-after therapy design. All children were followed for 3 1/2 yr. Asthma symptoms, functional impairment and the use of drug (from diaries) were rated in ten different ways during eight months before and eight months after the family therapy. Improvement in the clinically most important variable, i.e. general pediatric assessment, was greater in the children in the family therapy group compared to the control group (p less than 0.05) Twelve children who received family therapy showed significant improvement after treatment concerning general pediatric assessment (p less than 0.01), clinical grading (p less than 0.05), peak expiratory flow (p less than 0.05), days with functional impairment/yr (p less than 0.05), no. of doses of inhaled Beta-2-agonists/month (p less than 0.01) and nights when Beta-2-agonists were inhaled (p less than 0.05). The children who only received conventional medical treatment showed no significant change in asthma symptoms. We draw the conclusion that family therapy may represent a valuable therapeutic tool in the management of severe asthma.
Childhood asthma. A controlled trial of family psychotherapy.
In an attempt to evaluate the effectiveness of family psychotherapy as an adjunct conventional treatment in childhood asthma, children with moderate to severe asthma were randomly allocated to a control group or to an experimental group; the latter group received 6 hours of family treatment during a 4-month period, and both groups had standard medical treatment. While there was no significant difference between the two groups on three parameters, the experimental group were significantly better in day-wheeze score and thoracic gas volume. These results suggest that family treatment in selected cases may have a place in the overall management of childhood asthma, and that more research with larger numbers of children is necessary.
Options:
A: Improvement in gas volume, peak expiratory flow rate, daytime wheeze, overall clinical assessment, and reduction in functionally impaired days.
B: Significant reduction in medication use and forced expiratory volume.
C: No observable benefits in any clinical or functional outcomes.
D: Complete cure of asthma symptoms without the need for medication. | A |
418 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What interventions have been found to potentially reduce the incidence of stress fractures in military personnel, and what considerations should be taken into account regarding these interventions? Please answer this question based on the information provided below:
The use of a pneumatic leg brace in soldiers with tibial stress fractures--a randomized clinical trial.
STUDY DESIGN: Single blind randomized controlled replication study.
OBJECTIVES: Evaluate the effect of a pneumatic leg brace on return-to-activity and pain in soldiers with tibial stress fractures.
METHODS AND MEASURES: Thirty-one subjects diagnosed with tibial stress fractures were randomly assigned to either a brace or control group. Dependent variables included time to pain-free single-leg hopping, visual analog pain scale, and time to a pain-free 1-mile run. Twenty subjects (10 brace, 10 control) completed a detailed functional progression culminating in a 1-mile run.
RESULTS: There was no difference between groups for time to pain-free hop (p > 0.86; power = 0.43) and time to pain-free 1-mile run (p > 0.24; power = 0.92). Subjects in both groups experienced statistically significant improvements in pain measurements (p < 0.002), but no difference was found between groups (p > 0.93).
CONCLUSION: The current study demonstrated no added benefit of Aircast leg braces in the treatment of tibial stress fractures in the military training environment.
A prospective study on the management of shin splints.
Prevention of stress fractures using custom biomechanical shoe orthoses.
In a prospective study of stress fractures the hypothesis that training with custom made biomechanical shoe orthoses could lessen the incidence of stress fractures in infantry recruits was tested. Recruits were assigned randomly to groups and given soft biomechanical orthoses or semirigid biomechanical orthoses and compared with a control group that did not train in biomechanical orthoses. All recruits wore infantry boots with soles designed like those of basketball shoes. Recruits were examined biweekly during 14 weeks of basic training. The incidence of stress fractures was 15.7% for the recruits with the semirigid biomechanical orthoses, 10.7% for the recruits with the soft biomechanical orthoses, and 27% for the control group. The soft biomechanical orthoses were tolerated better by the recruits than were the semirigid devices. Among trainees at high risk for stress fractures, prophylactic use of custom made biomechanical orthoses may be warranted.
A prospective study of the effect of foot orthoses composition and fabrication on comfort and the incidence of overuse injuries.
BACKGROUND: Foot orthoses are widely prescribed both to treat existing pathological conditions and to prevent overuse injuries, but little is known about the effect of their material composition and fabrication technique on patient comfort and the incidence of overuse injuries.
MATERIALS AND METHODS: The acceptance rates and comfort scores of soft custom, soft prefabricated, semirigid biomechanical, and semirigid prefabricated orthoses and their effect on the incidence of stress fractures, ankle sprains, and foot problems were studied in a prospective, randomized, single-blinded clinical trial among 874 infantry recruits during basic training.
RESULTS: A statistically significantly lower number of recruits given soft prefabricated orthoses (53%) finished basic training in their assigned devices than in the soft custom group (72%), in the semirigid biomechanical group (75%), and in the semirigid prefabricated group (82%) (p = .003). For recruits who finished training in their assigned orthoses, the soft custom (3.54) and soft prefabricated (3.43) orthoses had significantly higher comfort scores than the semirigid biomechanical (3.23) and prefabricated (3.17) orthoses, (p = .0001). There was no statistically significant difference in the incidence of stress fractures, ankle sprains, or foot problems between recruits using the different types of orthoses.
CONCLUSIONS: These findings suggest that if a foot orthosis is being dispensed as prophylaxis for overuse injuries in an active, healthy population, there is little justification for prescribing semirigid biomechanical orthoses. Their cost is high compared to other types of orthoses, without an advantage in comfort or a reduction in stress fractures, ankle sprains, and foot problems.
A prospective study of the effect of foot orthoses composition and fabrication on comfort and the incidence of overuse injuries.
BACKGROUND: Foot orthoses are widely prescribed both to treat existing pathological conditions and to prevent overuse injuries, but little is known about the effect of their material composition and fabrication technique on patient comfort and the incidence of overuse injuries.
MATERIALS AND METHODS: The acceptance rates and comfort scores of soft custom, soft prefabricated, semirigid biomechanical, and semirigid prefabricated orthoses and their effect on the incidence of stress fractures, ankle sprains, and foot problems were studied in a prospective, randomized, single-blinded clinical trial among 874 infantry recruits during basic training.
RESULTS: A statistically significantly lower number of recruits given soft prefabricated orthoses (53%) finished basic training in their assigned devices than in the soft custom group (72%), in the semirigid biomechanical group (75%), and in the semirigid prefabricated group (82%) (p = .003). For recruits who finished training in their assigned orthoses, the soft custom (3.54) and soft prefabricated (3.43) orthoses had significantly higher comfort scores than the semirigid biomechanical (3.23) and prefabricated (3.17) orthoses, (p = .0001). There was no statistically significant difference in the incidence of stress fractures, ankle sprains, or foot problems between recruits using the different types of orthoses.
CONCLUSIONS: These findings suggest that if a foot orthosis is being dispensed as prophylaxis for overuse injuries in an active, healthy population, there is little justification for prescribing semirigid biomechanical orthoses. Their cost is high compared to other types of orthoses, without an advantage in comfort or a reduction in stress fractures, ankle sprains, and foot problems.
Prevention of lower extremity stress fractures: a controlled trial of a shock absorbent insole.
A prospective controlled trial was carried out to determine the usefulness of a viscoelastic polymer insole in prevention of stress fractures and stress reactions of the lower extremities. The subjects were 3,025 US Marine recruits who were followed for 12 weeks of training at Parris Island, South Carolina. Polymer and standard mesh insoles were systematically distributed in boots that were issued to members of odd and even numbered platoons. The most important finding was that an elastic polymer insole with good shock absorbency properties did not prevent stress reactions of bone during a 12-week period of vigorous physical training. To control for the confounding effects of running in running shoes, which occurred for about one and one-half hours per week for the first five weeks, we also examined the association of age of shoes and cost of shoes with injury incidence. A slight trend of increasing stress injuries by increasing age of shoes was observed. However, this trend did not account for the similarity of rates in the two insole groups. In addition, we observed a strong trend of decreasing stress injury rate by history of increasing physical activity, as well as a higher stress injury rate in White compared to Black recruits. The results of the trial were not altered after controlling for these factors. This prospective study confirms previous clinical reports of the association of stress fractures with physical activity history. The clinical application of a shock absorbing insole as a preventive for lower extremity stress reactions is not supported in these uniformly trained recruits. The findings are relevant to civilian populations.
On shock absorbent insoles to prevent bone fractures.
A prospective study of the effect of a shock-absorbing orthotic device on the incidence of stress fractures in military recruits.
In a prospective study of stress fractures the hypothesis that a shock-absorbing orthotic device worn within military boots could lessen the incidence of stress fractures was tested. The incidence of metatarsal, tibial, and femoral stress fractures was lower in the orthotic group, but only the latter difference was statistically significant. The time of onset and the location of stress fractures between orthotic and nonorthotic users did not differ. These findings suggest that the incidence of femoral stress fractures, which are the most dangerous type of stress fracture because of their high risk of developing into displaced fractures, can be reduced by an orthotic device.
Combined effect of foot arch structure and an orthotic device on stress fractures.
In a prospective study, quantitative measures of the structure of the longitudinal arch of the foot were established and related to the incidence of stress fractures in the bones of the lower limbs of military recruits. In addition, the role of a semirigid orthotic device (Langer military stress orthotic) in preventing stress fractures was evaluated as a function of the structure of the longitudinal arch. Femoral and tibial stress fractures were found to be more prevalent in the presence of feet with high arches, whereas the incidence of metatarsal fractures was higher in feet with low arches. The use of an orthotic device reduced the incidence of femoral stress fractures only in the presence of feet with high arches and the incidence of metatarsal fractures only among feet with low arches. The findings suggest that the normal foot with a low arch acts as a better shock absorber than the normal foot with a high arch, and that an orthotic device may improve the shock absorbing capacity of the arch.
Prevention of overuse injuries of the foot by improved shoe shock attenuation. A randomized prospective study.
In a randomized prospective study among 390 recruits, the hypothesis that improved shoe shock attenuation could lessen the incidence of overuse injuries was tested. During the 14 weeks of training, 90% of the recruits sustained overuse injuries. Recruits training in a modified basketball shoe had a statistically significant lower incidence of metatarsal stress fractures and foot overuse injuries, compared with standard infantry boots, but their overall incidence of overuse injuries was not reduced. The effect of improved shoe shock attenuation was limited to those overuse injuries resulting from vertical impact loads.
Relationship between footwear comfort of shoe inserts and anthropometric and sensory factors.
PURPOSE: The purposes of this study were (a) to determine lower extremity anthropometric and sensory factors that are related to differences in comfort perception of shoe inserts with varying shape and material and (b) to investigate whether shoe inserts that improve comfort decrease injury frequency in a military population.
METHODS: 206 military personnel volunteered for this study. The shoe inserts varied in arch and heel cup shape, hardness, and elasticity in the heel and forefoot regions. A no insert condition was included as the control condition. Measured subject characteristics included foot shape, foot and leg alignment, and tactile and vibration sensitivity of the plantar surface of the foot. Footwear comfort was assessed using a visual analog scale. Injury frequency was evaluated with a questionnaire. The statistical analyses included Student's t-tests for repeated measures, ANOVA (within subjects), MANOVA (within insert combinations), and chi-square tests.
RESULTS: The average comfort ratings for all shoe inserts were significantly higher than the average comfort rating for the control condition. The incidence of stress fractures and pain at different locations was reduced by 1.5-13.4% for the insert compared with the control group. Foot arch height, foot and leg alignment, and foot sensitivity were significantly related to differences in comfort ratings for the hard/soft, the viscous/elastic, and the high arch/low arch insert combinations.
CONCLUSIONS: Shoe inserts of different shape and material that are comfortable are able to decrease injury frequency. The results of this study showed that subject specific characteristics influence comfort perception of shoe inserts.
Effects of ankle dorsiflexion range and pre-exercise calf muscle stretching on injury risk in Army recruits.
This study investigated effects of ankle dorsiflexion range and pre-exercise calf muscle stretching on relative risk of selected injuries in 1093 male Army recruits undertaking 12 weeks of intensive training. Prior to training, ankle dorsiflexion range was measured and recruits were allocated to stretch and control groups using a quasi-random procedure. The stretch group stretched calf muscles under supervision prior to all intense exercise. The control group stretched upper limb muscles instead. Forty-eight injuries were recorded. Survival analysis indicated that ankle dorsiflexion range was a strong predictor of injury (p = 0.03). Definitive evidence of an effect of stretching on injury risk was not found (p = 0.76), but the sample size may have been insufficient to detect such an effect.
A randomized trial of preexercise stretching for prevention of lower-limb injury.
PURPOSE: This study investigated the effect of muscle stretching during warm-up on the risk of exercise-related injury.
METHODS: 1538 male army recruits were randomly allocated to stretch or control groups. During the ensuing 12 wk of training, both groups performed active warm-up exercises before physical training sessions. In addition, the stretch group performed one 20-s static stretch under supervision for each of six major leg muscle groups during every warm-up. The control group did not stretch.
RESULTS: 333 lower-limb injuries were recorded during the training period, including 214 soft-tissue injuries. There were 158 injuries in the stretch group and 175 in the control group. There was no significant effect of preexercise stretching on all-injuries risk (hazard ratio [HR] = 0.95, 95% CI 0.77-1.18), soft-tissue injury risk (HR = 0.83, 95% CI 0.63-1.09), or bone injury risk (HR = 1.22, 95% CI 0.86-1.76). Fitness (20-m progressive shuttle run test score), age, and enlistment date all significantly predicted injury risk (P < 0.01 for each), but height, weight, and body mass index did not.
CONCLUSION: A typical muscle stretching protocol performed during preexercise warm-ups does not produce clinically meaningful reductions in risk of exercise-related injury in army recruits. Fitness may be an important, modifiable risk factor.
Prevention of common overuse injuries by the use of shock absorbing insoles. A prospective study.
Sedentary individuals, particularly new military recruits, who start a physical training program have a substantial risk of developing an overuse injury of the lower limb. In this study we investigated the effect of neoprene insoles on the incidence of overuse injuries during 9 weeks of basic military training. The experimental group consisted of 237 randomly selected new recruits, while 1151 recruits were the control group. Insoles were given to the experimental group and compliance was monitored. A panel of doctors documented and classified all injuries occurring during the 9 week period. A total of 54 (22.8%) and 237 (31.9%) injuries were reported in the experimental and control groups, respectively. In both groups, the majority of injuries were overuse (experimental group, 90.7%; control group, 86.4%). The mean weekly incidence of total overuse injuries and tibial stress syndrome was significantly lower (P less than 0.05) in the experimental group. The mean incidence of stress fractures was lower in the experimental group but not significantly so (0.05 less than P less than 0.1). This study shows that the incidence of total overuse injuries and tibial stress syndrome during 9 weeks of basic military training can be reduced by wearing insoles.
Does calcium supplementation prevent bone stress injuries? A clinical trial.
This study investigated the effect of calcium supplementation in preventing bone stress injuries. Healthy male military recruits (N = 1,398) served as subjects, of which 247 were randomly allocated to an experimental group (E) while 1,151 served as a control group (C). For 9 weeks both groups wore the same footwear and had the same physical training program. The baseline dietary intake of calcium in 50 randomly selected subjects of each group was assessed using a 24-hr dietary record. The E group received a daily calcium supplement while the C group did not. Injuries were monitored in all subjects by a panel of doctors who followed specific diagnostic criteria. The mean weekly injury incidence for all overuse injuries, but specifically tibial stress syndrome and stress fractures, was similar in both groups. Mean baseline daily dietary calcium intake was above 800 mg in both subgroups. This study demonstrated that large-scale calcium supplementation (500 mg/day) beyond usual dietary intake did not influence the risk of developing bone stress injuries during a 9-wk physical training program in these young military recruits.
The effect of a pneumatic leg brace on return to play in athletes with tibial stress fractures.
A total of 18 competitive and recreational athletes were enrolled in a randomized, prospective study looking at the effect of pneumatic leg braces on the time to return to full activity after a tibial stress fracture. All patients had positive bone scans and 15 had positive radiographic findings by Week 12. There were two treatment groups. The traditional treatment group was treated with rest and, after 3 pain-free days, a gradual return to activity. The pneumatic leg brace (Aircast) group had the brace applied to the affected leg and then followed the same return to activity guidelines. The guidelines consisted of a detailed functional progression that allowed pain-free return to play. The brace group was able to resume light activity in 7 days (median) and the traditional group began light activity in 21 days (median). The brace group returned to full, unrestricted activity in 21 +/- 2 days, and the traditional group required 77 +/- 7 days to resume full activity. The Aircast pneumatic brace is effective in allowing athletes with tibial stress fractures to return to full, unrestricted, pain-free activity significantly sooner than traditional treatment.
Options:
A: Leg muscle stretching during warm-up before exercise, with a focus on flexibility and injury prevention.
B: Shock-absorbing inserts in footwear, with attention to comfort and tolerability.
C: Pneumatic braces for rehabilitation, with emphasis on reducing time to full activity.
D: Nutritional supplements to strengthen bone density, with a focus on overall health. | B |
419 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What was the conclusion regarding the safety and efficacy of percutaneous transluminal angioplasty with or without stenting for vertebral artery stenosis when compared to medical care alone? Please answer this question based on the information provided below:
Endovascular versus surgical treatment in patients with carotid stenosis in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS): a randomised trial.
BACKGROUND: Percutaneous transluminal angioplasty and stenting (endovascular treatment) can be used to treat carotid stenosis, but risks and benefits are uncertain. We therefore compared endovascular treatment with conventional carotid surgery.
METHODS: In a multicentre clinical trial, we randomly assigned 504 patients with carotid stenosis to endovascular treatment (n=251) or carotid endarterectomy (n=253). For endovascular patients treated successfully, we used stents in 55 (26%) and balloon angioplasty alone in 158 (74%). An independent neurologist followed up patients. Analysis was by intention to treat.
FINDINGS: The rates of major outcome events within 30 days of first treatment did not differ significantly between endovascular treatment and surgery (6.4% vs 5.9%, respectively, for disabling stroke or death; 10.0% vs 9.9% for any stroke lasting more than 7 days, or death). Cranial neuropathy was reported in 22 (8.7%) surgery patients, but not after endovascular treatment (p<0.0001). Major groin or neck haematoma occurred less often after endovascular treatment than after surgery (three [1.2%] vs 17 [6.7%], p<0.0015). At 1 year after treatment, severe (70-99%) ipsilateral carotid stenosis was more usual after endovascular treatment (25 [14%] vs seven [4%], p<0.001). However, no substantial difference in the rate of ipsilateral stroke was noted with survival analysis up to 3 years after randomisation (adjusted hazard ratio=1.04, 95% CI 0.63-1.70, p=0.9).
INTERPRETATION: Endovascular treatment had similar major risks and effectiveness at prevention of stroke during 3 years compared with carotid surgery, but with wide CIs. Endovascular treatment had the advantage of avoiding minor complications.
Options:
A: Percutaneous transluminal angioplasty with or without stenting is clearly more effective and safer than medical care alone.
B: There is currently insufficient evidence to assess the effects of percutaneous transluminal angioplasty with or without stenting for vertebral artery stenosis.
C: Medical care alone is more effective and safer than percutaneous transluminal angioplasty with or without stenting.
D: Percutaneous transluminal angioplasty with or without stenting is associated with a high risk of strokes and deaths within 30 days of treatment. | B |
420 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What is the evidence for the benefit of corticosteroids in the treatment of pulmonary sarcoidosis based on randomised controlled trials? Please answer this question based on the information provided below:
Inhaled budesonide in pulmonary sarcoidosis: a double-blind, placebo-controlled study. Dutch Study Group on Pulmonary Sarcoidosis.
In a double-blind, placebo-controlled study, we assessed the efficacy of inhaled budesonide on the course of newly diagnosed pulmonary sarcoidosis and whether budesonide treatment could postpone oral corticosteroid treatment. We evaluated: 1) symptoms; 2) chest radiography; 3) angiotensin-converting enzyme (ACE) in serum; and 4) lung function. Patients with histologically confirmed pulmonary sarcoidosis with chest radiographic stages I, II or III, and with an abnormal lung function (inspiratory vital capacity (IVC) < 79% of predicted or transfer factor of the lungs for carbon monoxide (TL,CO) < 77% pred) were included. Patients with radiographic stage II or III but with normal lung function were included when more than 20% of the total cell population in bronchoalveolar lavage fluid (BALF) was lymphocytes. Forty seven patients received placebo or budesonide (1.2 mg) once daily via a Nebuhaler for 6 months, followed by 6 months without treatment. Based on predetermined criteria, 11 patients were excluded during the blind treatment period as they needed oral prednisone: seven (28%) patients in the placebo group (n = 25) and four (18%) patients in the budesonide group (n = 22). Patient's Global Clinical Impression (GCI) score showed a significant difference in favour of budesonide. IVC showed a significant difference of 7.9% predicted between the two groups during the active treatment period. This difference persisted during follow-up, when the difference was 9.4% pred. TL,CO remained nearly unchanged over time, with no difference between the groups. Improvements in chest radiographic appearance and changes in serum ACE were similar for the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Use of fluticasone in acute symptomatic pulmonary sarcoidosis.
BACKGROUND: Inhaled corticosteroids have been used with variable success in sarcoidosis. The role of the inhaled corticosteroid fluticasone in symptomatic pulmonary patients was studied.
METHODS: Twenty-two patients at five institutions who had been given an initial dose of oral corticosteroids within the prior four weeks were enrolled in a randomized double blind trial of inhaled fluticasone. An algorithm for the dosage of prednisone including rules for reducing dose was developed and applied at all centers.
RESULTS: Of the 21 patients seen for more than one visit, 10 received fluticasone and 11 placebo. There was no significant difference in the improvement of vital capacity or average daily dose of prednisone for the fluticasone versus placebo. Eight of ten patients taking fluticasone had improvement in cough, while only 6 of 11 patients on placebo had improved cough despite taking oral corticosteroids (p = 0.36, N.S.). The algorithm for decreasing corticosteroid dosage was exactly applied in over 80% of patient visits and oral corticosteroids were used throughout most of the year of treatment. Patients registered higher complaints regarding increased appetite and polyuria when on ten mg or more prednisone a day. There was no clinical difference in the rate of toxicity for the fluticasone versus placebo group.
CONCLUSION: A standard approach to tapering oral corticosteroids was followed in over 80% of patient visits. Oral corticosteroids were associated with significant complaints, while inhaled corticosteroids were well tolerated.
Randomized trial of inhaled fluticasone propionate in chronic stable pulmonary sarcoidosis: a pilot study.
Pulmonary sarcoidosis is a disease in which the pathological processes are distributed along lymphatic pathways, particularly those around the bronchovascular bundles. Delivery of disease-modulating drugs by the inhaled route is therefore an attractive option. The aim of this study was to determine the efficacy of inhaled fluticasone propionate 2 mg x day(-1) in adults with stable pulmonary sarcoidosis. Forty-four adult patients (22 from each centre) were enrolled from outpatient clinics in two London teaching hospitals in a two centre, double-blind, randomized, placebo-controlled trial. Primary end points were home recordings of peak expiratory flow rate (PEFR), forced expiratory volume in one second (FEV1), and forced vital capacity (FVC). Secondary end points were symptom scores, use of rescue bronchodilator medication, and clinic values for PEFR, FEV1, FVC, forced mid-expiratory flow (FEF25-75%), diffusion capacity of the lung for carbon monoxide (DL,CO), and total lung capacity (TLC). Symptom scores of cough, breathlessness and wheeze were lower in the active treatment group, but this did not reach statistical significance, and a general health perception assessment (Short Form (SF)-36) showed a difference between active and placebo treatment. No significant differences were found between the two groups in any physiological outcome measure. No new adverse reactions were detected. The results of this pilot study do not show an objective benefit of inhaled fluticasone propionate in pulmonary sarcoidosis where the disease is stable and is controlled without the use of inhaled corticosteroids.
Inhaled budesonide influences cellular and biochemical abnormalities in pulmonary sarcoidosis.
In a randomized, double-blind study 19 patients with newly-detected pulmonary sarcoidosis were treated with either inhaled budesonide, 800 micrograms twice daily (n = 9), or placebo (n = 10) for 8-10 weeks. Before and after treatment, chest roentgenograms, lung function tests, bronchoalveolar lavage (BAL) and biochemical tests were performed. Angiotensin converting enzyme (ACE) activity and beta2-microglobulin (beta 2M) concentrations were measured in serum. The same tests, as well as albumin and hyaluronan were measured in the BAL-fluid. The total cell number in BAL-fluid, differential counts and lymphocyte subpopulations were determined (total T- and B-lymphocytes, T-helper/inducer (OKT-4) and T-suppressor/cytotoxic (OKT-8) lymphocytes). No significant changes in chest roentgenograms or lung function tests were observed during the short study time. However, a decrease in serum ACE (p less than 0.1) and beta 2 M (p less than 0.05) as well as in BAL-hyaluronan (p less than 0.01) was found in the budesonide-treated patients as well as a decrease in the percentage of BAL T-lymphocytes (p less than 0.05) and the T4/T8 ratio (p less than 0.1). No significant changes were seen in the placebo group. The findings suggest that treatment with inhaled budesonide influences biochemical and cellular findings in patients with early sarcoidosis in the same way as treatment with systemic corticosteroids. The results may also explain clinical effects seen in sarcoidosis patients treated with inhaled corticosteroids. However, further studies are required to determine the long-term clinical benefits of inhaled steroids in pulmonary sarcoidosis.
A controlled trial of prednisone treatment of sarcoidosis.
Treatment of sarcoidosis. Report of a controlled therapeutic trial.
Effect of beclomethasone dipropionate (BDP) as extrafine aerosol on bronchoalveolar lavage (BAL) lymphocytes in chronic sarcoidosis.
BACKGROUND AND AIM OF THE STUDY: Patients with pulmonary sarcoidosis can benefit from inhaled corticosteroids. In this study we assessed the effect of beclomethasone dipropionate (BDP), administered as extrafine, HFA(hydrofluoroalkane)-driven aerosol with high peripheral deposition, on bronchoalveolar lavage (BAL) lymphocyte numbers, as a marker of the disease.
METHODS: Fifteen patients with newly-diagnosed pulmonary sarcoidosis (Stages I-III) received either BDP 800 microg daily (n = 6) or placebo (n = 9) for 6 months in a parallel-group design. Before and after treatment, clinical and radiological states were assessed, bronchoalveolar lavage (BAL) performed, and the cellular composition of BAL fluid as well as cytokine production by BAL lymphocytes determined.
RESULTS: BDP caused a decrease in the percentage of BAL lymphocytes in the BDP (p < 0.05) but not the placebo group. HLA-DR expression on lymphocytes was diminished after BDP (p < 0.05), while intracellular cytokine production by lymphocytes was not altered. Chest radiography suggested an improvement in the BDP group. There was also a rise (p < 0.05) in the diffusing capacity for carbon monoxide.
CONCLUSIONS: Though based on a small group of patients, the present findings suggest that in patients with pulmonary sarcoidosis of stage II and minor functional impairment, inhalation of high doses of BDP as extrafine, peripherally deposited aerosol is associated with a reduction in the number of BAL lymphocytes, in parallel with improvements in other markers of the disease.
Effect of beclomethasone dipropionate (BDP) as extrafine aerosol on bronchoalveolar lavage (BAL) lymphocytes in chronic sarcoidosis.
BACKGROUND AND AIM OF THE STUDY: Patients with pulmonary sarcoidosis can benefit from inhaled corticosteroids. In this study we assessed the effect of beclomethasone dipropionate (BDP), administered as extrafine, HFA(hydrofluoroalkane)-driven aerosol with high peripheral deposition, on bronchoalveolar lavage (BAL) lymphocyte numbers, as a marker of the disease.
METHODS: Fifteen patients with newly-diagnosed pulmonary sarcoidosis (Stages I-III) received either BDP 800 microg daily (n = 6) or placebo (n = 9) for 6 months in a parallel-group design. Before and after treatment, clinical and radiological states were assessed, bronchoalveolar lavage (BAL) performed, and the cellular composition of BAL fluid as well as cytokine production by BAL lymphocytes determined.
RESULTS: BDP caused a decrease in the percentage of BAL lymphocytes in the BDP (p < 0.05) but not the placebo group. HLA-DR expression on lymphocytes was diminished after BDP (p < 0.05), while intracellular cytokine production by lymphocytes was not altered. Chest radiography suggested an improvement in the BDP group. There was also a rise (p < 0.05) in the diffusing capacity for carbon monoxide.
CONCLUSIONS: Though based on a small group of patients, the present findings suggest that in patients with pulmonary sarcoidosis of stage II and minor functional impairment, inhalation of high doses of BDP as extrafine, peripherally deposited aerosol is associated with a reduction in the number of BAL lymphocytes, in parallel with improvements in other markers of the disease.
No effect of high-dose inhaled steroids in pulmonary sarcoidosis: a double-blind, placebo-controlled study.
OBJECTIVE: To evaluate whether inhaled steroids in high doses might be of therapeutic value in pulmonary sarcoidosis.
DESIGN: Randomized, double blind and placebo controlled parallel study.
SETTING: The out-patient clinic of the Department of Pulmonary Medicine, Gentofte Hospital, Copenhagen, Denmark.
SUBJECTS: Twenty-one untreated patients (17 males, 4 females, median age 33 years, range 21-65) and eight patients treated with systemic prednisolone. All patients had biopsy proven pulmonary sarcoidosis radiological stage I-III.
INTERVENTIONS: Treatment with either inhaled budesonide 1.2 mg day-1-2.0 mg day-1 (n = 9) or placebo (n = 12) for 12 months.
MAIN OUTCOME MEASURES: Clinical (cough, chest pain, dyspnoea) and paraclinical variables (chest X-ray, gallium scintigraphy, pulmonary function tests, and biochemical markers of disease activity: blood leukocytes, lymphocytes, serum (S-) angiotensin converting enzyme (ACE), S-1,25-OH-cholecalciferol, plasma (P-) calcium, P-immunoglobulins) were recorded before treatment, every three months during treatment, and 6 months after treatment had been discontinued.
RESULTS: There were no significant differences between the recorded variables in the budesonide and placebo groups. In general, a regression of disease activity was observed in both groups. Two patients in the treatment group, treated with 2.0 mg budesonide/day, and two in the placebo group had progression in disease and were put on systemic steroids.
CONCLUSION: Inhaled budesonide in doses of 1.2-2.0 mg day-1 had no recognizable therapeutic effect on pulmonary sarcoidosis.
Early treatment of stage II sarcoidosis improves 5-year pulmonary function.
STUDY OBJECTIVE: To evaluate the 5-year prognosis of patients with stage I and stage II newly detected (< 3 months) pulmonary sarcoidosis treated immediately after diagnosis with prednisolone for 3 months followed by inhaled budesonide for 15 months.
DESIGN: Randomized, double-blind, placebo-controlled, parallel-group study for 18 months. Thereafter, open follow-up without treatment.
SETTING: Twenty pulmonary medicine departments in Finland.
PATIENTS: One hundred eighty-nine adult patients, most of them with normal lung function, were randomized to treatment. One hundred forty-nine patients were followed up for 5 years: 79 patients with initial stage I disease and 70 patients with stage II disease.
TREATMENT: Oral prednisolone for 3 months followed by inhaled budesonide for 15 months (800 microg bid), or placebo tablets followed by placebo inhaler therapy. Thereafter, treatment only on an individual basis in the case of clinical deterioration.
MEASUREMENTS: Yearly follow-up visits with chest radiographs, lung function tests (FEV(1), FVC), diffusion capacity of the lung for carbon monoxide (DLCO), serum angiotensin-converting enzyme (SACE), and serum and urinary calcium measurements.
RESULTS: No initial differences were observed in chest radiographic findings between the active-treatment and placebo-treatment groups, either in patients with initial stage I or stage II(-III) disease. However, after the 5-year follow-up, 18 steroid-treated patients (26%) and 30 placebo-treated patients (38%) still had remaining chest radiographic changes. Placebo-treated patients more frequently required treatment with corticosteroids during the 5-year follow-up (p < 0.05). Steroid-treated patients with initial stage II(-III) disease improved more in FVC and DLCO (p < 0.05). No differences in reported adverse events or in SACE, serum calcium, or urinary calcium values were seen.
CONCLUSION: Immediate treatment of pulmonary stage II(-III) sarcoidosis-but not stage I disease-improved the 5-year prognosis with regard to lung function variables.
Oral prednisolone followed by inhaled budesonide in newly diagnosed pulmonary sarcoidosis: a double-blind, placebo-controlled multicenter study. Finnish Pulmonary Sarcoidosis Study Group.
STUDY OBJECTIVE: To evaluate the efficacy of oral prednisolone, followed by inhaled budesonide, in patients with newly diagnosed (<3 months) stage I and stage II pulmonary sarcoidosis.
DESIGN: Double-blind, placebo-controlled, parallel-group, multicenter study.
SETTING: Twenty pulmonary medicine departments in Finland.
PATIENTS: One hundred eighty-nine adult patients were randomized to treatment. Patients with erythema nodosum or stage IV sarcoidosis (pulmonary fibrosis), and patients requiring immediate treatment with oral corticosteroids for extrapulmonary lesions or chronic illnesses were excluded.
TREATMENT: The patients received either oral prednisolone for 3 months (20 mg/d for 8 weeks, 15 mg/d for 2 weeks, and 10 mg/d for 2 weeks) followed by inhaled budesonide (Pulmicort Turbuhaler; Astra Draco; Lund, Sweden) for 15 months at 800 microg bid, or placebo tablets followed by placebo inhaler therapy.
MEASUREMENTS: Chest radiographs, lung volumes (FVC), diffusing capacity of the lung for carbon monoxide (D(LCO)), serum angiotensin-converting enzyme (SACE), and beta2-microglobulin at 3-month intervals.
RESULTS: After 3 months of treatment, radiographic improvements were seen in the active-treatment group when compared to the placebo-treatment group. At 6 months, the difference was still statistically significant. Later, no differences were found. In patients with initial stage I lesions, neither the FVC nor the D(LCO) (the percent predicted mean values) changed during the study, as they were normal from the beginning. In patients with initial stage II disease, the difference in the FVC mean values between the groups also remained unchanged throughout the study. In stage II patients treated for 18 months, but not earlier, the difference in D(LCO) became statistically significant; the largest differences were seen in patients with initial FVC values <80% of predicted and D(LCO) values <75% of predicted. The decrease in SACE in the active-treated stage II patients was significantly larger than in the placebo-treated patients. No difference was observed in adverse events between the active-treated patients and the placebo-treated patients.
CONCLUSION: Treatment is not required for patients with stage I disease. An initial treatment with prednisolone followed by long-term inhalation of budesonide is more effective than placebo in patients with stage II disease. Sequential oral and inhaled corticosteroid therapy may be an alternative treatment regimen for stage II sarcoidosis patients, rather than long-term oral corticosteroid therapy alone.
Inhaled corticosteroid therapy in pulmonary sarcoidosis.
Corticosteroid therapy of intrathoracic sarcoidosis stages I and II--results of a controlled clinical trial.
It is difficult to evaluate the efficacy of sarcoidosis therapy. There are high rates of spontaneous remission, frequently pushing course and tendency to relapses after treatment. 280 patients with histologically confirmed mediastino-pulmonary sarcoidosis in stage I and II without extrapulmonary manifestations have been admitted until now in a controlled clinical trial. More than 150 of them have been analysed after a follow-up of 3 to 5 years, in 40 cases already to 7 years. The patients have been treated by prednisolone and isoniazide for six and 12 months respectively and compared with a non-treated control group. 6 and 12 months after the start of observation X-ray regression has been more often observed in the treated than in the non-treated patients. However, the results after 3 and 5 years were nearly similar in all groups: improvement in 75% and complete resolution in 60% respectively. It seems to us therefore that prednisolone shows only an effect on the early stage of sarcoidosis but is without any influence on the late X-ray results. In consequence corticosteroid therapy is clearly indicated only in patients with progressive course of the disease.
[Prognosis and indications of corticosteroid treatment of intrathoracic sarcoidosis--conclusions from a prospective study].
Preliminary results of a prospective clinical trial to evaluate the value of corticosteroid therapy of intrathoracic sarcoidosis had demonstrated that there were no differences between treated and untreated patients with regard to the clinical, radiological and functional outcome after several years. In one hundred and seventy two patients we could check the former results by identical tests after a longer follow-up period (mean 8,9 years) and by additional physiological assessments, i.e. Cstat, DLCO, DM, VC, which seem to be more significant for early detection of functional disorders in sarcoidosis. Again the findings showed no significant differences neither between patients treated with prednisolone for 12 or 6 months respectively nor when compared to the untreated group. In conclusion we do not treat patients with asymptomatic intrathoracic sarcoidosis and without extrapulmonary manifestations before the disease shows no regressive course within one year or when a progressive course is observed.
The possible influence of corticosteroid therapy on the natural course of pulmonary sarcoidosis. Late results of a continuing clinical study.
[Erster Bericht über eine kontrollierte klinische Untersuchung zur Prednisolon-Behandlung der thorakalen Sarkoidose].
117 patients with histologically confirmed mediastino-pulmonary sarcoidosis stage I and II without extrapulmonary manifestations were included in a controlled therapeutic trial. 92 patients remained for analysis. Among these 54 were treated for 6 or 12 months with prednisolone and isoniacid; 38 were not treated. 6 and 12 months after beginning the observation, improvement was more frequent in the treated group. After 3 years and 5 years (45 patients only) however differences were no more evident: improvement was observed in about 80 per cent, complete remission in about 65 per cent in treated and untreated patients. In both groups, patients presenting dissemination in the lungs had worse results than those with hilo-mediastinal adenopathy associated or not with pulmonary dissemination. Prednisolone seems to have effects in the early phase of sarcoidosis but is apparently not so effective in respect to the general development of the illness and in preventing pulmonary fibrosis. Therefore strict indication for therapy with corticosteroids of sarcoidosis exist when progressive pulmonary dissemination and/or reduction of pulmonary function is evident.
Corticosteroid therapy of pulmonary sarcoidosis. A prospective evaluation of alternate day and daily dosage in stage II disease.
Thirty-nine sarcoidosis patients with pulmonary infiltrations (stage II) of less than 5 years duration and not treated earlier with corticosteroids were randomly allocated for treatment with methylprednisolone for 7 months or for observation without therapy. Every other treated patient was given the drugs daily and every other followed an alternate-day regimen. After 7 months the chest radiographic finding, the forced vital capacity and the diffusion capacity for carbon monoxide were superior in the treated group. There was no difference between the two drug regimens. After 24 and 48 months no statistically significant differences between the untreated and the treated groups were found.
Corticosteroid therapy in sarcoidosis. A five-year, controlled follow-up study.
Options:
A: Oral steroids improved chest X-ray results and symptoms over 3-24 months, but there is little evidence of improvement in lung function.
B: Inhaled steroids showed significant improvement in lung function and chest X-ray results over 3-24 months.
C: Both oral and inhaled steroids showed significant improvement in lung function and chest X-ray results over 3-24 months.
D: Neither oral nor inhaled steroids showed any significant improvement in chest X-ray results, symptoms, or lung function. | A |
421 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What is the effect of adding intravenous aminophylline to conventional therapy in children with acute severe asthma? Please answer this question based on the information provided below:
Intravenous theophylline in pediatric status asthmaticus. A prospective, randomized, double-blind, placebo-controlled trial.
This study was conducted to determine whether intravenous theophylline, added to inhaled albuterol and intravenous methylprednisolone, provides a clinically significant benefit in the treatment of pediatric status asthmaticus. Patients aged 2 to 10 years were randomized to receive either intravenous theophylline or placebo. All patients received aerosolized albuterol and intravenous methylprednisolone. There was no difference between groups in the improvement of a clinical asthma score over time, in oxygen requirement, or in the number of albuterol treatments required. Theophylline group patients experienced more nausea, emesis, and insomnia. We conclude that there is no benefit in adding theophylline to treatment with methylprednisolone and albuterol for pediatric status asthmaticus. Furthermore, there are significantly more adverse effects associated with the use of theophylline.
Efficacy of intravenously administered theophylline in children hospitalized with severe asthma.
PURPOSE: To determine whether intravenously administered theophylline, when added to frequently nebulized albuterol and intravenously administered methylprednisolone, benefits children hospitalized with severe asthma.
DESIGN: Prospective, randomized, placebo-controlled, parallel-group, double-blind study.
SETTING: Inpatient pediatric service at a tertiary-care teaching hospital.
PATIENTS: Twenty-one children 5 to 18 years of age.
INTERVENTIONS: All patients received 2.5 to 5.0 mg of nebulized albuterol every 20 minutes to every 6 hours, intravenously administered methylprednisolone (1 mg/kg every 6 hours), and either intravenously administered theophylline (as aminophylline) or placebo for 36 hours. Serum theophylline concentrations were maintained between 55 and 110 mumol/L (between 10 and 20 micrograms/ml) by adjusting loading doses and continuous infusion rates.
MEASUREMENTS AND MAIN RESULTS: Forced expired volume in 1 second (FEV1) and clinical score were measured at 0, 1, 3, 6, 12, 24, and 36 hours after the start of each individual study. The total number of nebulizations, total albuterol dosage, adverse effects, and duration of hospital stay were recorded. Twelve children received theophylline and nine received placebo. The two groups did not differ significantly in age, sex, or baseline FEV1. In both groups, clinical score significantly improved from baseline by 12 hours, and FEV1 by 24 hours (p < 0.05). There were no significant differences between the groups in FEV1 or clinical score at any of the measured time points. There were no significant differences in rate of improvement in FEV1, total number of nebulizations, total albuterol dosage, or duration of hospital stay. Adverse effects were mild and infrequent and did not differ significantly between the two groups.
CONCLUSIONS: Theophylline, at therapeutic concentrations, did not additionally benefit children hospitalized with severe asthma who were being treated frequently with nebulized albuterol and with methylprednisolone intravenously.
Hospital treatment of asthma: lack of benefit from theophylline given in addition to nebulized albuterol and intravenously administered corticosteroid.
STUDY OBJECTIVE: To determine the efficacy of theophylline when given in addition to nebulized albuterol and intravenously administered corticosteroid to children hospitalized with mild to moderate asthma.
DESIGN: Randomized, prospective, placebo-controlled, double-blind trial.
SETTING: Tertiary-care children's hospital.
PATIENTS: Twenty-nine patients with asthma between the ages of 2 and 16 years completed the study. The treatment and placebo groups were similar in age, gender, race, illness severity, and emergency department treatment.
INTERVENTIONS: All patients received intravenously administered methylprednisolone and nebulized albuterol. The treatment group received intravenous theophylline therapy and the placebo group dextrose in water. When intravenously administered medications were discontinued, therapy continued with oral administration of theophylline (or placebo) and of prednisone.
MEASUREMENTS AND MAIN RESULTS: Twice-daily assessments of clinical asthma symptoms were made by using a scoring system consisting of respiratory rate, inspiratory/expiratory ratio, wheeze, and accessory muscle use. Time required to reach study discharge criteria (asthma score < or = 2) (30.4 +/- 16.8 vs 27.0 +/- 10.3 hours; p = 0.51) and the rate of improvement of the clinical asthma score (-0.10 +/- 0.05 unit/hr vs -0.11 +/- 0.09 unit/hr; p = 0.88) were not significantly different between the theophylline and placebo groups. The number of albuterol aerosol treatments required and the adverse effects experienced were not significantly different between groups.
CONCLUSION: When the combination of systemically administered corticosteroid and inhaled albuterol is used in the treatment of children hospitalized with mild to moderate asthma, addition of theophylline may not be justified.
Theophylline does not shorten hospital stay for children admitted for asthma.
OBJECTIVE: To determine if the use of intravenous theophylline, in the form of aminophylline, when added to systemic corticosteroids and aerosolized beta 2-agonists, enhances the improvement of children with acute asthma exacerbations.
DESIGN: A double-blind, placebo-controlled, randomized, clinical trial.
SETTING: The University of Maryland Medical Center, Baltimore, an urban primary- and tertiary-care pediatric medical center.
PATIENTS: Forty-two children, aged 2 to 18 years, admitted to the hospital for acute exacerbations of asthma.
METHODS: Patients were randomized to receive either intravenous theophylline to maintain a serum level greater than 55 mumol/L or a placebo infusion. All patients received methylprednisolone and nebulized albuterol. A clinical severity score was assessed twice daily.
RESULTS: The mean length of stay for the treatment and control groups was 52.3 +/- 32.3 hours and 48.2 +/- 26.6 hours, respectively (t = 0.45, P = .65). The rate of improvement of clinical scores was similar.
CONCLUSION: These data suggest that the addition of theophylline to albuterol and corticosteroids does not enhance improvement of children admitted to the hospital with asthma.
Efficacy of aminophylline in the treatment of acute asthma exacerbation in children.
BACKGROUND: The role of aminophylline (ethylene diamine salt of theophylline) in the treatment of acute exacerbation of asthma has not been well established in children.
OBJECTIVE: The aim of the study was to determine the additional therapeutic benefit of intravenous aminophylline in the treatment of children hospitalized for acute asthmatic exacerbation and treated with inhaled bronchodilators and glucocorticoid therapy.
METHODS: Thirty-eight children aged from 2 to 16 years (mean age 5.64 +/- 3.31), admitted for acute exacerbation of asthma, participated in a prospective, randomized, double-blind, placebo-controlled study. All the subjects received methylprednisolone, administered intravenously, and nebulized salbutamol. The treatment group received intravenous aminophylline therapy and the placebo group received 0.9% saline solution for 24 hours.
RESULTS: The number of salbutamol nebulizations needed and the clinical asthma scoring were recorded both at onset and at the end of 24 hours. There was no significant difference in either the mean number of nebulizations or the clinical asthma scores between the two groups (P = .7843, P = .8452).
CONCLUSION: Intravenous aminophylline (ethylene diamine salt of theophylline) demonstrated no additional beneficial effect to the combination of beta adrenergic agonists and glucocorticoid treatment in acute asthma attack in children.
Aminophylline therapy does not improve outcome and increases adverse effects in children hospitalized with acute asthmatic exacerbations.
OBJECTIVE: To evaluate the effects of aminophylline (Am) in children hospitalized with asthma.
METHODS: Prospective, randomized, double-blind, placebo-controlled trial. Subjects were children between the ages of 5 and 18 years admitted for asthma exacerbation to either a tertiary care children's hospital or an inner-city general hospital in New York. Exclusion criteria were admission to the intensive care unit, initial theophylline level > 5 micrograms/dL, or the presence of other systemic disorders. All patients received nebulized albuterol therapy and intravenous glucocorticosteroids in standardized doses. Thirty-one patients were randomized to receive either an Am bolus followed by continuous Am infusion or placebo (P) bolus and infusion. The outcome variables were: duration of hospitalization, percent of predicted peak expiratory flow rates recorded at 12-hour intervals, number of albuterol treatments required, and adverse effects.
RESULTS: There were no significant differences at study entry in age, sex, race, number of previous hospital admissions, prior medications used, clinical symptom scores, or initial peak flow rates for the two groups. For 26 patients who completed this study, 15 patients in the P group were hospitalized for a mean duration of 2.33 +/- 1.3 days, whereas 11 patients in the Am group required 2.58 +/- 1.5 days. There were no significant differences between the two groups for hospital days, peak flow rates at any time interval, or amount of albuterol therapy required (P > .2). In the Am group, 6 of the 14 patients who entered the study experienced significant adverse effects consisting of nausea, emesis, headache, abdominal pain, and palpitations. Only 1 of 17 patients in the P group had an adverse effect (P < .05).
CONCLUSIONS: There is no benefit and considerable risk of adverse effects associated with the use of Am in hospitalized asthmatic children.
Randomised controlled trial of aminophylline for severe acute asthma.
OBJECTIVES: To determine whether children with severe acute asthma treated with large doses of inhaled salbutamol, inhaled ipratropium, and intravenous steroids are conferred any further benefits by the addition of aminophylline given intravenously.
STUDY DESIGN: Randomised, double blind, placebo controlled trial of 163 children admitted to hospital with asthma who were unresponsive to nebulised salbutamol.
RESULTS: The placebo and treatment groups of children were similar at baseline. The 48 children in the aminophylline group had a greater improvement in spirometry at six hours and a higher oxygen saturation in the first 30 hours. Five subjects in the placebo group were intubated and ventilated after enrollment compared with none in the aminophylline group.
CONCLUSIONS: Aminophylline continues to have a place in the management of severe acute asthma in children unresponsive to initial treatment.
Options:
A: It significantly improves lung function within 6 hours of treatment but does not reduce symptoms, number of nebulised treatments, or length of hospital stay.
B: It significantly reduces the length of hospital stay and the number of nebulised treatments required.
C: It has no significant impact on lung function, symptoms, or length of hospital stay.
D: It significantly reduces the need for mechanical ventilation and improves oxygenation. | A |
422 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What were the findings regarding the effects of different surgical approaches and ancillary techniques in the internal fixation of intracapsular hip fractures? Please answer this question based on the information provided below:
Osteosynthesis of femoral neck fracture. The sliding-screw-plate with or without compression.
In a prospective study of 220 displaced femoral neck fractures treated with a sliding-screw-plate, the cases were allocated to osteosynthesis with or without compression. In surviving patients followed for at least 1 year, union occurred in 57/85 with compression and 58/71 without compression. At 2 years, necrosis was radiographically evident in 9/37 and 7/36 united fractures. Thus, compression cannot be recommended when displaced femoral neck fractures are treated with a sliding-screw-plate.
Factors influencing the incidence of reoperation after femoral neck fractures.
This investigation compares two groups of patients with fractures of the femoral neck: 22 required a further operation and 72 did not. Special attention was paid to osteoporosis, the displacement of the fracture, viability of the femoral head, operative impaction and osteosynthesis with a Thornton nail or three Scand hip pins. There was a significant (p less than 0.01) difference between the two groups with regard to osteoporosis, fracture displacement and viability of the femoral head. Scand hip pins, as compared to Thornton nails, showed a tendency (p less than 0.1) to need a smaller number of reoperations. Operative impaction compared with no impaction showed no difference.
Femoral head vitality after peroperative impaction of hip fractures.
In 94 patients with femoral neck fracture the vitality of the femoral head was determined pre- and postoperatively with 99mTc-MDP-scintimetry. In half of the fractures a Thornton nail was used, in the other half three Scand hip pins. Irrespective of the displacement, no difference was noted in the two groups. In half of the operations in each group the fracture was impacted by hammer at the end of the operation. In displaced fractures, impaction caused a decrease in femoral head vitality.
Delayed internal fixation of fractures of the neck of the femur in young adults. A prospective, randomised study comparing closed and open reduction.
We have compared the results and complications after closed and open reduction with ternal fixation in young adults with displaced intracapsular fractures (Garden grades III and IV) of the neck of the femur. We also studied the risk factors which influenced nonunion and the development of avascular necrosis (AVN). A total of 102 patients aged between 15 and 50 years was randomised to receive either closed or open reduction. Both groups were compared for age, gender, time to surgery and posterior comminution as well as for union and complications. Using univariate and multivariate analysis the factors influencing nonunion and AVN were assessed. Of the 102 patients, 92 were available for review. There was no significant difference between the groups in terms of union (p = 0.93) and AVN at two years (p = 0.85). Posterior comminution, poor reduction and improper placement of the screws were the major factors contributing to nonunion. The overall incidence of AVN was 16.3% (15 of 92 patients) and it was not influenced by these factors. A delay of more than 48 hours before surgery did not influence the rate of union or the development of AVN when compared with operation within 48 hours of injury.
Options:
A: Impaction of the fracture during surgery significantly improved blood flow to the femoral head.
B: Compression of the fracture showed a higher incidence of non-union compared to no compression.
C: Open reduction significantly decreased the length of surgery compared to closed reduction.
D: There is insufficient evidence to confirm the relative effects of open versus closed reduction, or the effects of intra-operative impaction or compression. | D |
423 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What were the findings regarding the efficacy and safety of colchicine in patients with alcoholic or non-alcoholic liver fibrosis or cirrhosis? Please answer this question based on the information provided below:
Failure of colchicine to improve short-term survival in patients with alcoholic hepatitis.
Colchicine treatment was used in this randomized placebo-controlled trial in patients with severe acute alcoholic hepatitis [serum bilirubin greater than or equal to 5 mg/dL (85.5 mumol/L) mean, 17.5 +/- 7.5 mg/dL (299.25 +/- 128.25 mumol/L)]. Hospitalization mortality and morbidity and the effect on biochemical test results were the end points of the treatment. Patients in the two groups were evenly matched by demographics and laboratory test results. Mean time to study entry was less than 7 days from admission. The duration of the trial was 30 days. Thirty-six patients (24 men, 12 women) received colchicine (1 mg orally every morning) and 36 (25 men, 11 women) received an identical placebo. Seven (19%) colchicine-treated and six (17%) control patients died during the index hospitalization after a mean of 17.4 +/- 10.8 and 17.8 +/- 5.3 days, respectively (NS). During a 4-month follow-up period from entry into the trial, there were two additional deaths in each group. No differences between placebo- and colchicine-treated patients were observed in any of the laboratory parameters (serum bilirubin, aspartate transaminase, alanine transaminase, prothrombin activity, albumin, white blood cell count, hemoglobin, and creatinine) that were followed up over the 30-day treatment period. The frequency of complications did not differ statistically between the two groups. This study showed no effect of colchicine treatment on mortality and morbidity of severe alcoholic hepatitis. Colchicine cannot be recommended for the treatment of patients with alcoholic hepatitis.
Failure of colchicine to improve short-term survival in patients with alcoholic hepatitis.
Colchicine treatment was used in this randomized placebo-controlled trial in patients with severe acute alcoholic hepatitis [serum bilirubin greater than or equal to 5 mg/dL (85.5 mumol/L) mean, 17.5 +/- 7.5 mg/dL (299.25 +/- 128.25 mumol/L)]. Hospitalization mortality and morbidity and the effect on biochemical test results were the end points of the treatment. Patients in the two groups were evenly matched by demographics and laboratory test results. Mean time to study entry was less than 7 days from admission. The duration of the trial was 30 days. Thirty-six patients (24 men, 12 women) received colchicine (1 mg orally every morning) and 36 (25 men, 11 women) received an identical placebo. Seven (19%) colchicine-treated and six (17%) control patients died during the index hospitalization after a mean of 17.4 +/- 10.8 and 17.8 +/- 5.3 days, respectively (NS). During a 4-month follow-up period from entry into the trial, there were two additional deaths in each group. No differences between placebo- and colchicine-treated patients were observed in any of the laboratory parameters (serum bilirubin, aspartate transaminase, alanine transaminase, prothrombin activity, albumin, white blood cell count, hemoglobin, and creatinine) that were followed up over the 30-day treatment period. The frequency of complications did not differ statistically between the two groups. This study showed no effect of colchicine treatment on mortality and morbidity of severe alcoholic hepatitis. Colchicine cannot be recommended for the treatment of patients with alcoholic hepatitis.
Unfavourable effects of colchicine in combination with interferon-alpha in the treatment of chronic hepatitis C.
BACKGROUND: The prognosis of chronic hepatitis depends on the progression of hepatic fibrosis.
AIM: To investigate whether the antifibrotic drug colchicine, in combination with interferon-alpha has a role in the treatment of chronic hepatitis C.
METHODS: Sixty-five HCV-RNA positive patients with chronic hepatitis were randomized to receive interferon-alpha, 6 MU t.i.w. for 6 months followed by 3 MU t.i.w. for further 6 months, with or without the adjunct of colchicine, 1 mg o.d., 6 days a week, for 3 years. We report an interim analysis after the first 18 months.
RESULTS: Thirty-four patients received interferon-alpha and 31 received interferon-alpha and colchicine. The two groups were comparable for baseline data, including HCV-RNA levels, genotypes and histological grading/staging. Drop-outs and side-effects were similar. The proportion of patients who achieved alanine transaminase normalization or undetectable HCV-RNA at month 6 was higher in the interferon-alpha (68% and 47%, respectively) than in the interferon-alpha plus colchicine group (32% and 23%, P=0.004 and P=0. 04, respectively). End-of-treatment biochemical and virological response occurred in 41% and 29% of the interferon-alpha and 19% and 10% of the combination group, respectively (P=0.05 and P=0.05). Sustained biochemical response occurred in 26% of the interferon-alpha and 6% of the interferon-alpha plus colchicine group (P=0.03), corresponding percentages of sustained HCV-RNA loss being 21% and 3% (P=0.04).
CONCLUSIONS: The combination of colchicine and interferon-alpha worsens the effectiveness of interferon-alpha alone in HCV chronic hepatitis. These alarming findings prompted us to interrupt the trial at this stage.
Lack of effect of colchicine in alcoholic cirrhosis: final results of a double blind randomized trial.
BACKGROUND: Colchicine, an inhibitor of collagen synthesis, has been suggested as potentially beneficial in cirrhosis.
OBJECTIVE: This long-term, randomized, double blind, placebo controlled trial was conducted in order to evaluate the efficacy of colchicine in alcoholic cirrhosis.
METHODS: Ambulatory patients with biopsy proven alcoholic cirrhosis, presenting from 1989 to 1997, with no exclusion criteria (e.g. Child-Pugh C, bilirubin > 10 mg/dl and gastrointestinal bleeding in the previous 15 days), were randomized to receive orally, 5 days/week, 1 mg/day of colchicine or placebo.
MAIN OUTCOME MEASURES: Results were analysed on an intention to treat basis, for survival, incidence of complications, biochemical liver tests and safety.
RESULTS: Twenty-nine patients received colchicine and 26 placebo; characteristics of both groups were similar. The median follow-up was 40.6 (1.4-126.3) months in the colchicine versus 42.4 (5.7-118.2) months in the placebo group (NS). No significant side effects were reported. During follow-up, there were no significant differences in compliance and alcohol abstinence (86% vs 85%). Overall survival was not statistically different (P = 0.38). Cumulative 3-year survival rates were 74.9% in the colchicine versus 91.4% in placebo group (NS). The annual incidence rate of complications was similar with colchicine or placebo: gastrointestinal bleeding, 1.5% vs 1.2%; ascites, 3.7% vs 3.7%; and encephalopathy, 1.0% vs 0.9%. The comparison of changes in biochemical parameters between groups did not show any significant difference.
CONCLUSIONS: Although well tolerated, colchicine does not appear to overcome the progression and natural history of long-established alcoholic cirrhosis.
Lack of effect of colchicine in alcoholic cirrhosis: final results of a double blind randomized trial.
BACKGROUND: Colchicine, an inhibitor of collagen synthesis, has been suggested as potentially beneficial in cirrhosis.
OBJECTIVE: This long-term, randomized, double blind, placebo controlled trial was conducted in order to evaluate the efficacy of colchicine in alcoholic cirrhosis.
METHODS: Ambulatory patients with biopsy proven alcoholic cirrhosis, presenting from 1989 to 1997, with no exclusion criteria (e.g. Child-Pugh C, bilirubin > 10 mg/dl and gastrointestinal bleeding in the previous 15 days), were randomized to receive orally, 5 days/week, 1 mg/day of colchicine or placebo.
MAIN OUTCOME MEASURES: Results were analysed on an intention to treat basis, for survival, incidence of complications, biochemical liver tests and safety.
RESULTS: Twenty-nine patients received colchicine and 26 placebo; characteristics of both groups were similar. The median follow-up was 40.6 (1.4-126.3) months in the colchicine versus 42.4 (5.7-118.2) months in the placebo group (NS). No significant side effects were reported. During follow-up, there were no significant differences in compliance and alcohol abstinence (86% vs 85%). Overall survival was not statistically different (P = 0.38). Cumulative 3-year survival rates were 74.9% in the colchicine versus 91.4% in placebo group (NS). The annual incidence rate of complications was similar with colchicine or placebo: gastrointestinal bleeding, 1.5% vs 1.2%; ascites, 3.7% vs 3.7%; and encephalopathy, 1.0% vs 0.9%. The comparison of changes in biochemical parameters between groups did not show any significant difference.
CONCLUSIONS: Although well tolerated, colchicine does not appear to overcome the progression and natural history of long-established alcoholic cirrhosis.
Lack of effect of colchicine in alcoholic cirrhosis: final results of a double blind randomized trial.
BACKGROUND: Colchicine, an inhibitor of collagen synthesis, has been suggested as potentially beneficial in cirrhosis.
OBJECTIVE: This long-term, randomized, double blind, placebo controlled trial was conducted in order to evaluate the efficacy of colchicine in alcoholic cirrhosis.
METHODS: Ambulatory patients with biopsy proven alcoholic cirrhosis, presenting from 1989 to 1997, with no exclusion criteria (e.g. Child-Pugh C, bilirubin > 10 mg/dl and gastrointestinal bleeding in the previous 15 days), were randomized to receive orally, 5 days/week, 1 mg/day of colchicine or placebo.
MAIN OUTCOME MEASURES: Results were analysed on an intention to treat basis, for survival, incidence of complications, biochemical liver tests and safety.
RESULTS: Twenty-nine patients received colchicine and 26 placebo; characteristics of both groups were similar. The median follow-up was 40.6 (1.4-126.3) months in the colchicine versus 42.4 (5.7-118.2) months in the placebo group (NS). No significant side effects were reported. During follow-up, there were no significant differences in compliance and alcohol abstinence (86% vs 85%). Overall survival was not statistically different (P = 0.38). Cumulative 3-year survival rates were 74.9% in the colchicine versus 91.4% in placebo group (NS). The annual incidence rate of complications was similar with colchicine or placebo: gastrointestinal bleeding, 1.5% vs 1.2%; ascites, 3.7% vs 3.7%; and encephalopathy, 1.0% vs 0.9%. The comparison of changes in biochemical parameters between groups did not show any significant difference.
CONCLUSIONS: Although well tolerated, colchicine does not appear to overcome the progression and natural history of long-established alcoholic cirrhosis.
Lack of effect of colchicine in alcoholic cirrhosis: final results of a double blind randomized trial.
BACKGROUND: Colchicine, an inhibitor of collagen synthesis, has been suggested as potentially beneficial in cirrhosis.
OBJECTIVE: This long-term, randomized, double blind, placebo controlled trial was conducted in order to evaluate the efficacy of colchicine in alcoholic cirrhosis.
METHODS: Ambulatory patients with biopsy proven alcoholic cirrhosis, presenting from 1989 to 1997, with no exclusion criteria (e.g. Child-Pugh C, bilirubin > 10 mg/dl and gastrointestinal bleeding in the previous 15 days), were randomized to receive orally, 5 days/week, 1 mg/day of colchicine or placebo.
MAIN OUTCOME MEASURES: Results were analysed on an intention to treat basis, for survival, incidence of complications, biochemical liver tests and safety.
RESULTS: Twenty-nine patients received colchicine and 26 placebo; characteristics of both groups were similar. The median follow-up was 40.6 (1.4-126.3) months in the colchicine versus 42.4 (5.7-118.2) months in the placebo group (NS). No significant side effects were reported. During follow-up, there were no significant differences in compliance and alcohol abstinence (86% vs 85%). Overall survival was not statistically different (P = 0.38). Cumulative 3-year survival rates were 74.9% in the colchicine versus 91.4% in placebo group (NS). The annual incidence rate of complications was similar with colchicine or placebo: gastrointestinal bleeding, 1.5% vs 1.2%; ascites, 3.7% vs 3.7%; and encephalopathy, 1.0% vs 0.9%. The comparison of changes in biochemical parameters between groups did not show any significant difference.
CONCLUSIONS: Although well tolerated, colchicine does not appear to overcome the progression and natural history of long-established alcoholic cirrhosis.
Relationship between blood lactic acid and serum proline in alcoholic liver cirrhosis.
Treatment of cirrhosis with colchicine. A double-blind randomized trial.
As part of a double-blind, randomized, controlled trial to evaluate the effect of colchicine on liver cirrhosis, 43 cirrhotic patients were assigned to either a placebo (20 patients) or a colchicine (23 patients) treatment group. Colchicine 1 mg and an indistinguishable placebo were administered orally on a daily dose 5 days a week. In the colchicine group, 12 were males and 11 females, while in the control group 13 were males and 7 females. The time elapsed between diagnosis and inclusion in the study was 14.1 mo for the controls and 14.5 mo for the patients on colchicine. Mortality related to the liver disease occurred in 4 patients on colchicine and 8 patients on placebo. Although the probability of surviving in the colchicine group was greater than that of the placebo, the difference did not reach statistically significant levels. Of the colchicine-treated patients, in three a remarkable decrease in liver fibrosis was observed in serial biopsies. In two other patients, carcinoma of the liver developed. Six of the survivors on colchicine have improved clinically, noticing disappearance of ascites and edema, as well as a decrease in the size of the spleen. All the survivors on placebo continue to show clinical deterioration. In contrast to the usual drop of serum albumin seen in the cirrhotic patients, those receiving colchicine increased and maintained their serum albumin levels throughout the study. Serum proline values were elevated only in the alcohol cirrhotic patients. Serum alkaline phosphatase increased only in those patients receiving colchicine. The results indicate that in some cases, liver fibrosis could be modified by treatment with antifibrotic drugs. The use of colchicine at present should remain within controlled studies.
Colchicine, serum albumin, and alkaline phosphatase.
Treatment of cirrhosis with colchicine. A double-blind randomized trial.
As part of a double-blind, randomized, controlled trial to evaluate the effect of colchicine on liver cirrhosis, 43 cirrhotic patients were assigned to either a placebo (20 patients) or a colchicine (23 patients) treatment group. Colchicine 1 mg and an indistinguishable placebo were administered orally on a daily dose 5 days a week. In the colchicine group, 12 were males and 11 females, while in the control group 13 were males and 7 females. The time elapsed between diagnosis and inclusion in the study was 14.1 mo for the controls and 14.5 mo for the patients on colchicine. Mortality related to the liver disease occurred in 4 patients on colchicine and 8 patients on placebo. Although the probability of surviving in the colchicine group was greater than that of the placebo, the difference did not reach statistically significant levels. Of the colchicine-treated patients, in three a remarkable decrease in liver fibrosis was observed in serial biopsies. In two other patients, carcinoma of the liver developed. Six of the survivors on colchicine have improved clinically, noticing disappearance of ascites and edema, as well as a decrease in the size of the spleen. All the survivors on placebo continue to show clinical deterioration. In contrast to the usual drop of serum albumin seen in the cirrhotic patients, those receiving colchicine increased and maintained their serum albumin levels throughout the study. Serum proline values were elevated only in the alcohol cirrhotic patients. Serum alkaline phosphatase increased only in those patients receiving colchicine. The results indicate that in some cases, liver fibrosis could be modified by treatment with antifibrotic drugs. The use of colchicine at present should remain within controlled studies.
Colchicine in the treatment of cirrhosis of the liver.
There is preliminary evidence that colchicine, an inhibitor of collagen synthesis, may be beneficial in the treatment of cirrhosis of the liver. To evaluate the use of colchicine (1 mg per day, five days per week) in the treatment of hepatic cirrhosis, we performed a randomized, double-blind, placebo-controlled trial in which 100 patients were followed for up to 14 years. Forty-five patients had alcoholic cirrhosis, 41 had posthepatitic cirrhosis, and the remaining 14 had cirrhosis with various other causes. Histologic studies were available for 92 percent of patients. Seventy-three patients were in Child-Turcotte class A, 26 were in class B, and one was in class C. Fifty-four patients received colchicine, and 46 received placebo. The overall survival in the colchicine group was markedly better than in the placebo group (median survival, 11 and 3.5 years, respectively; P less than 0.001). The cumulative 5-year survival rates were 75 percent in the colchicine group and 34 percent in the placebo group; the corresponding 10-year survival rates were 56 percent and 20 percent. Among the 30 patients treated with colchicine who underwent repeated liver biopsies, histologic improvement was seen in 9; the liver appeared normal in 2, and 7 had minimal portal fibrosis. No histologic improvement was observed in the 14 members of the placebo group who had two or more biopsies. Few side effects were observed in either group.
A prospective randomized trial of colchicine in prevention of liver cirrhosis in chronic hepatitis B patients.
BACKGROUND: The clinical course of chronic hepatitis B is variable. Patients with hepatic decompensation, bridging necrosis or an alpha-fetoprotein level greater than 100 ng/mL during an exacerbation of hepatitis have a high risk of developing cirrhosis. This study was conducted to evaluate the effect of colchicine in the prevention of cirrhosis in such patients.
METHODS: Patients with risk factor(s) were randomized to receive either colchicine 5 mg/week or no specific treatment, the end point being development of cirrhosis.
RESULTS: After a follow up period of 4 years, the treatment group had a marked reduction in exacerbations of acute hepatitis (32% vs. 63%/patient/year, P < 0.005). Seven out of 38 patients in the treatment group and 10 out of 27 patients in the control group developed cirrhosis. The calculated cumulative incidence of cirrhosis by the end of first, second, third and fourth years in the treatment group was 8.7, 18.6, 32 and 32%, respectively. The corresponding figures in the control group were 30, 35.5, 46.3 and 73.2%, respectively, with a P-value of 0.057.
CONCLUSIONS: The results suggest that colchicine may prevent cirrhosis in chronic hepatitis B patients with risk factor(s), possibly by suppressing exacerbations of hepatitis through an anti-inflammatory effect.
[Colchicine in chronic liver disease of alcoholic etiology. Double-blind, randomized study of its effects on blood levels of plasma proteins and clinical course in patients].
UNLABELLED: Patients with alcoholic chronic liver disease when treated with colchicine during a 12 month-period improved significantly the plasmatic levels of albumin and prothrombin when compared with a similar group of patients who took placebo. No differences in the mortality rate and in number of patients admitted at the hospital could be detected among those groups during this period.
PURPOSE: To evaluate the clinical outcome and the plasmatic levels of albumin, pre-albumin, prothrombin and transferrin in patients presenting alcoholic chronic liver disease taking colchicine or placebo, during a 12-month period.
METHODS: In a double-blind, randomized, controlled trial, 41 patients with alcoholic chronic liver disease were assigned to either placebo (20 patients) or a colchicine (21 patients) treatment group, assessing their clinical course (mortality rate and hospital admission) and plasmatic protein levels during a 12-month period. Albumin, pre-albumin and transferrin plasmatic levels were assessed through a immunodiffusion radial method and prothrombin time and activity was assessed by a one stage Quick modified method.
RESULTS: At the end of the trial, only 7.3% of the patients were lost during follow-up. No statistical differences could be found in mortality and number of patients admitted at the hospital among placebo and colchicine groups. Comparatively to the placebo group, a significant increase in the mean of percentage variation was found in patients of the colchicine group for serum albumin levels (17.9% colchicine x 3.6% placebo, p < 0.05) and for prothrombin activity (19.2% colchicine x 2.1% placebo, p < 0.05). A similar pattern of response was found in pre-albumin serum levels, but such differences were not statistically different. No differences were found in serum transferrin levels among both groups.
CONCLUSION: These results suggest that colchicine intake has a positive effect on plasmatic protein levels in patients with alcoholic chronic liver disease.
[Colchicine therapy of fibrosing liver diseases--report of a randomized double-blind study].
It is reported on results of a double blind study of colchicine therapy in fibrotic liver diseases over a period of three years. The study includes 74 probands; 37 of them had been treated after randomization for five days a week with 4 X 0,25 mg/d colchicine, 37 with placebo. 53 probands attained the 12th month of treatment, 43 of them 24th, 24 probands were in the study for 36 months. 3 diagnoses groups had been formed with regard to the histological grades of fibrosis: chronic hepatitis (without structural transformation); structural liver transformation/moderate liver cirrhosis; severe liver cirrhosis. In 38 cases the disease was caused by alcohol. 45 data had been studied (clinical results, paraclinical data concerning hepatological diagnostic and connective tissue metabolism and morphologic data). The biometric evaluation was carried out with the stage variant analysis by Friedman. Rebiopsies have been carried out in 40 probands after 1 year, in 4 probands after 2 years. 4 data (Serumalbumine, Gamma-GT, ALAT, KP) showed significant changes in the colchicine-group as well as in the placebo-group. In both therapy groups the morphologic supervisions of the fibrosis grades (rebiopsies) showed improvements, no changes, and deterioration about in the same frequency. In this study there was no effectiveness of colchicine on the course of fibrotic liver diseases to be stated. Concerning the contradictions in the recent literature and probable the insufficient colchicine dose, the authors recommend further studies on colchicine therapy in liver diseases with incipient i.e. reversible fibrosis.
Treatment of alcoholic hepatitis with colchicine. Results of a randomized double blind trial.
A randomized double-blind trial of colchicine vs placebo was conducted in 67 patients with histologically proven alcoholic hepatitis, 33 of whom had cirrhosis. Patients with hepatic encephalopathy, ascites, protracted prothrombin time, severe thrombocytopenia, hepatocellular carcinoma, evident lack of discipline or refusal to participate in the trial were not included. Thirty-three patients received colchicine (1 mg/day) and 34 received placebo for 6 months. Blood parameters including N-terminal peptide of type III procollagen were assessed in the serum, and a percutaneous liver biopsy was performed at the start of the trial and after 3 and 6 months. Alcoholic hepatitis and fibrosis scores were established for each biopsy specimen. Twenty-eight percent of patients were lost to follow-up at 3 months, and fifty-two percent at 6 months. One patient died of liver failure. Fifty-eight percent of patients were abstaining from alcohol at 3 months and fifty percent at 6 months. No significant effect of treatment was noted. Nevertheless, improvement in alcoholic hepatitis core at 3 months was more important in the colchicine group than in the placebo group. No side-effects were noted except transient diarrhea. Our results suggest that colchicine has no important effect on the course of alcoholic hepatitis. A trial including of at least 260 patients might be necessary for the observed alcoholic hepatitis score difference at 3 months, favoring colchicine, to be statistically significant.
A double-blind randomized controlled trial of colchicine in patients with hepatitis B virus-related postnecrotic cirrhosis.
The preliminary results of a prospective double-blind controlled trial of colchicine in 100 patients with hepatitis B virus-related cirrhosis are reported. The patients, 94 males and 6 females, aged 32-80, were assigned to receive either 1 mg of colchicine or an identical placebo orally on a daily basis. The duration of the follow up ranged from 15 to 51 months (median 26 months). Seventy percent had histological proof of cirrhosis. On entry, 80 patients were in Child-Pugh class A, 19 were in class B, and one was in class C. Compared to the placebo group, there was no improvement in the colchicine group after a 24-month follow up in any of the biochemistry data, for example, serum albumin, alkaline phosphatase, alanine and aspartate aminotransferase, bilirubin, and prothrombin time. The difference in the cumulative survival rates at 51 months did not reach statistical significance (p = 0.8) in either group. There was no histological improvement in 30 patients who were willing to undergo repeated liver biopsies. No trend toward improvement of the hepatic pressure gradient was observed in these patients. The serum levels of aminopropeptide of type III procollagen increased significantly in patients in both groups after 24 months of therapy (1.07 +/- 0.06 vs. 1.36 +/- 0.06 U/ml in the colchicine group, 0.93 +/- 0.09 vs. 1.25 +/- 0.07 U/ml in the placebo group; p < 0.05). In addition, neither the clinical deterioration of cirrhosis nor death was prevented in patients receiving colchicine therapy. This report indicates that colchicine has no effect in the treatment of HBV-related postnecrotic cirrhosis.
A double-blind randomized controlled trial of colchicine in patients with hepatitis B virus-related postnecrotic cirrhosis.
The preliminary results of a prospective double-blind controlled trial of colchicine in 100 patients with hepatitis B virus-related cirrhosis are reported. The patients, 94 males and 6 females, aged 32-80, were assigned to receive either 1 mg of colchicine or an identical placebo orally on a daily basis. The duration of the follow up ranged from 15 to 51 months (median 26 months). Seventy percent had histological proof of cirrhosis. On entry, 80 patients were in Child-Pugh class A, 19 were in class B, and one was in class C. Compared to the placebo group, there was no improvement in the colchicine group after a 24-month follow up in any of the biochemistry data, for example, serum albumin, alkaline phosphatase, alanine and aspartate aminotransferase, bilirubin, and prothrombin time. The difference in the cumulative survival rates at 51 months did not reach statistical significance (p = 0.8) in either group. There was no histological improvement in 30 patients who were willing to undergo repeated liver biopsies. No trend toward improvement of the hepatic pressure gradient was observed in these patients. The serum levels of aminopropeptide of type III procollagen increased significantly in patients in both groups after 24 months of therapy (1.07 +/- 0.06 vs. 1.36 +/- 0.06 U/ml in the colchicine group, 0.93 +/- 0.09 vs. 1.25 +/- 0.07 U/ml in the placebo group; p < 0.05). In addition, neither the clinical deterioration of cirrhosis nor death was prevented in patients receiving colchicine therapy. This report indicates that colchicine has no effect in the treatment of HBV-related postnecrotic cirrhosis.
Options:
A: Colchicine significantly reduced mortality and liver-related complications without increasing adverse events.
B: Colchicine had no significant effect on mortality, liver-related mortality, complications, liver biochemistry, liver histology, or alcohol consumption, but was associated with an increased risk of adverse events.
C: Colchicine significantly improved liver biochemistry and histology, but had no effect on mortality or complications.
D: Colchicine had no significant effect on any outcomes and did not increase the risk of adverse events. | B |
424 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What were the findings regarding the use of hormone replacement therapy (HRT) for the prevention of cardiovascular diseases in post-menopausal women? Please answer this question based on the information provided below:
Estrogen in the prevention of atherosclerosis. A randomized, double-blind, placebo-controlled trial.
BACKGROUND: Although observational studies suggest that estrogen replacement therapy (ERT) reduces cardiovascular morbidity and mortality in postmenopausal women, use of unopposed ERT for prevention of coronary heart disease in healthy postmenopausal women remains untested.
OBJECTIVE: To determine the effects of unopposed ERT on the progression of subclinical atherosclerosis in healthy postmenopausal women without preexisting cardiovascular disease.
DESIGN: Randomized, double-blind, placebo-controlled trial.
SETTING: University-based clinic.
PATIENTS: 222 postmenopausal women 45 years of age or older without preexisting cardiovascular disease and with low-density lipoprotein cholesterol levels of 3.37 mmol/L or greater (>/=130 mg/dL).
INTERVENTION: Unopposed micronized 17beta-estradiol (1 mg/d) or placebo. All women received dietary counseling. Women received lipid-lowering medication if their low-density lipoprotein cholesterol level exceeded 4.15 mmol/L (160 mg/dL).
MEASUREMENTS: The rate of change in intima-media thickness of the right distal common carotid artery far wall in computer image processed B-mode ultrasonograms obtained at baseline and every 6 months during the 2-year trial.
RESULTS: In a multivariable mixed-effects model, among women who had at least one follow-up measurement of carotid intima-media thickness (n = 199), the average rate of progression of subclinical atherosclerosis was lower in those taking unopposed estradiol than in those taking placebo (-0.0017 mm/y vs. 0.0036 mm/y); the placebo-estradiol difference between average progression rates was 0.0053 mm/y (95% CI, 0.0001 to 0.0105 mm/y) (P = 0.046). Among women who did not receive lipid-lowering medication (n = 77), the placebo-estradiol difference between average rates of progression was 0.0147 mm/y (CI, 0.0055 to 0.0240) (P = 0.002). Average rates of progression did not differ between estradiol and placebo recipients who took lipid-lowering medication (n = 122) (P > 0.2).
CONCLUSIONS: Overall, the average rate of progression of subclinical atherosclerosis was slower in healthy postmenopausal women taking unopposed ERT with 17beta-estradiol than in women taking placebo. Reduction in the progression of subclinical atherosclerosis was seen in women who did not take lipid-lowering medication but not in those who took these medications.
Effects of estrogen replacement on the progression of coronary-artery atherosclerosis.
BACKGROUND: Heart disease is a major cause of illness and death in women. To understand better the role of estrogen in the treatment and prevention of heart disease, more information is needed about its effects on coronary atherosclerosis and the extent to which concomitant progestin therapy may modify these effects.
METHODS: We randomly assigned a total of 309 women with angiographically verified coronary disease to receive 0.625 mg of conjugated estrogen per day, 0.625 mg of conjugated estrogen plus 2.5 mg of medroxyprogesterone acetate per day, or placebo. The women were followed for a mean (+/-SD) of 3.2+/-0.6 years. Base-line and follow-up coronary angiograms were analyzed by quantitative coronary angiography.
RESULTS: Estrogen and estrogen plus medroxyprogesterone acetate produced significant reductions in low-density lipoprotein cholesterol levels (9.4 percent and 16.5 percent, respectively) and significant increases in high-density lipoprotein cholesterol levels (18.8 percent and 14.2 percent, respectively); however, neither treatment altered the progression of coronary atherosclerosis. After adjustment for measurements at base line, the mean (+/-SE) minimal coronary-artery diameters at follow-up were 1.87+/-0.02 mm, 1.84+/-0.02 mm, and 1.87+/-0.02 mm in women assigned to estrogen, estrogen plus medroxyprogesterone acetate, and placebo, respectively. The differences between the values for the two active-treatment groups and the value for the placebo group were not significant. Analyses of several secondary angiographic outcomes and subgroups of women produced similar results. The rates of clinical cardiovascular events were also similar among the treatment groups.
CONCLUSIONS: Neither estrogen alone nor estrogen plus medroxyprogesterone acetate affected the progression of coronary atherosclerosis in women with established disease. These results suggest that such women should not use estrogen replacement with an expectation of cardiovascular benefit.
The estrogen replacement and atherosclerosis (ERA) study: study design and baseline characteristics of the cohort.
The Estrogen Replacement and Atherosclerosis (ERA) trial is a three-arm, randomized, placebo-controlled, double-blind trial to evaluate the effects of estrogen replacement therapy (0.625 mg/day oral conjugated estrogen) with or without continuous low-dose progestin (2.5 mg oral medroxyprogesterone acetate/day) versus placebo on progression of atherosclerosis. A total of 309 postmenopausal women at five sites underwent baseline coronary angiography and were randomized. Participants will have repeat coronary angiography after an average of 3.25 years of treatment. The primary outcome of interest will be change in minimum diameter of the major epicardial segments, as assessed by quantitative coronary angiography. The primary aim is to test the hypothesis that either form of hormone therapy will slow the progression or induce regression of coronary atherosclerosis compared to placebo. The secondary aims are to assess the effects of the two treatments versus placebo on endothelial function (measured using flow-mediated vasodilator responses), on several presumed mediators of estrogen's effect on atherosclerosis (i.e., plasma lipids and lipoproteins, blood pressure, glucose metabolism, hemostatic factors, and antioxidant activity), on other factors that influence the development of coronary heart disease (i.e., diet, smoking status, exercise, weight, and health-related quality of life issues), and on clinical cardiovascular events. The ERA trial is the first angiographic endpoint clinical trial to examine the effects of postmenopausal hormone replacement on coronary atherosclerosis in women. It will provide an unparalleled opportunity to determine if either regimen of hormone therapy is effective in slowing the progress of angiographically defined coronary atherosclerosis. This study will complement other estrogen replacement trials, such as the PEPI, HERS, and Women's Health Initiative studies, to provide a more comprehensive examination of the effects of estrogen replacement on cardiovascular risk factors, anatomic and functional manifestations of atherosclerosis, and risk for coronary heart disease in postmenopausal women. Control Clin Trials 2000;21:257-285
Increased risk of recurrent venous thromboembolism during hormone replacement therapy--results of the randomized, double-blind, placebo-controlled estrogen in venous thromboembolism trial (EVTET).
Recent observational studies suggest a 2-4 fold increased risk of venous thromboembolism (VTE) in women taking hormone replacement therapy (HRT). The present study was started before publication of these studies, and the aim was to determine if HRT alters the risk of VTE in high risk women. The study was a randomized. double-blind, and placebo-controlled clinical trial with a double-triangular sequential design. Females with previously verified VTE were randomized to 2 mg estradiol plus 1 mg norethisterone acetate, 1 tablet daily (n = 71) or placebo (n = 69). The primary outcome was recurrent deep venous thrombosis (DVT) or pulmonary embolism (PE). Between 1996 and 1998 a total of 140 women were included. The study was terminated prematurely based on the results of circumstantial evidence emerging during the trial. Eight women in the HRT group and one woman in the placebo group developed VTE. The incidence of VTE was 10.7% in the HRT group and 2.3% in the placebo group. In the HRT group, all events happened within 261 days after inclusion. The sequential design did not stop the study, but strongly indicated a difference between the two groups. Our data strongly suggests that women who have previously suffered a VTE have an increased risk of recurrence on HRT. This treatment should therefore be avoided in this patient group if possible. The results also support those of recent epidemiological studies, which also indicate increased risk of VTE in non-selected female populations during HRT.
Long-term effects of hormone replacement therapy on symptoms of angina pectoris, quality of life and compliance in women with coronary artery disease.
OBJECTIVE: The aim of the present study was to evaluate the effects of HRT on symptoms of angina pectoris, quality of life and factors of importance for compliance in women with ischemic heart disease.
METHODS: Sixty postmenopausal women with coronary artery disease were randomized into three groups: one group received transdermal 17 beta-estradiol at a dose of 50 micrograms per 24 h alone for 18 days followed by 10 days of combined treatment with medroxyprogesterone acetate (MPA) 5 mg orally; the second group received placebo and the third group received conjugated estrogens orally for 18 days followed by a combined treatment with MPA for 10 days. Clinical evaluations were performed at baseline, after 3, 6 and 12 months. The investigations included gynecological history. occurrence of climacteric symptoms, quality of life evaluation, cardiac history and symptoms of angina pectoris.
RESULTS: Forty-six women (77%) completed the study during 1 year. The following cardiac events occurred in the women who completed the study: one patient was hospitalized because of congestive heart failure (patch), two patients because of angina pectoris, one patient because of coronary bypass operation (CEE) and three patients underwent balloon dilatation (placebo), all three on CEE. Among the 14 women who discontinued, two patients had TIA (patch), one experienced palpitations (CEE) and one woman died from myocardial infarction (placebo). Overall improvement in mood and cognitive functions were reported in all three treatment groups.
CONCLUSIONS: HRT does not seem to have negative effects on symptoms of angina pectoris and seems to increase quality of life in older women with coronary heart disease. It also seems safe from the cardiovascular point of view.
Heart and Estrogen/progestin Replacement Study (HERS): design, methods, and baseline characteristics.
The Heart and Estrogen/progestin Replacement Study (HERS) is a randomized, double-blind, placebo-controlled trial designed to test the efficacy and safety of estrogen plus progestin therapy for prevention of recurrent coronary heart disease (CHD) events in women. The participants are postmenopausal women with a uterus and with CHD as evidenced by prior myocardial infarction, coronary artery bypass graft surgery, percutaneous transluminal coronary angioplasty, or other mechanical revascularization or at least 50% occlusion of a major coronary artery. Between February 1993 and September 1994, 20 HERS centers recruited and randomized 2763 women. Participants ranged in age from 44 to 79 years, with a mean age of 66.7 (SD 6.7) years. Most participants were white (89%), married (57%), and had completed high school or some college (80%). As expected, the prevalence of coronary risk factors was high: 62% were past or current smokers, 59% had hypertension, 90% had serum LDL-cholesterol of 100 mg/dL or higher, and 23% had diabetes. Each woman was randomly assigned to receive one tablet containing 0.625 mg conjugated estrogens plus 2.5 mg medroxyprogesterone acetate daily or an identical placebo. Participants will be evaluated every 4 months for an average of 4.2 years for the occurrence of CHD events (CHD death and nonfatal myocardial infarction). We will also assess other major CHD endpoints, including revascularization and hospitalization for unstable angina. The primary analysis will compare the rate of CHD events in women assigned to active treatment with the rate in those assigned to placebo. The trial was designed to have power greater than 90% to detect a 35% reduction in the incidence of CHD events, assuming a 50% lag in effect for 2 years and a 5% annual event rate in the placebo group. The design, analysis, and conduct of the study are controlled by the Steering Committee of Principal Investigators and coordinated at the University of California, San Francisco. HERS is the largest trial of any intervention to reduce the risk of recurrent CHD events in women with heart disease and is the first controlled trial to seek evidence of the efficacy and safety of postmenopausal hormone therapy to prevent recurrent CHD events.
Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group.
CONTEXT: Observational studies have found lower rates of coronary heart disease (CHD) in postmenopausal women who take estrogen than in women who do not, but this potential benefit has not been confirmed in clinical trials.
OBJECTIVE: To determine if estrogen plus progestin therapy alters the risk for CHD events in postmenopausal women with established coronary disease.
DESIGN: Randomized, blinded, placebo-controlled secondary prevention trial.
SETTING: Outpatient and community settings at 20 US clinical centers.
PARTICIPANTS: A total of 2763 women with coronary disease, younger than 80 years, and postmenopausal with an intact uterus. Mean age was 66.7 years.
INTERVENTION: Either 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate in 1 tablet daily (n = 1380) or a placebo of identical appearance (n = 1383). Follow-up averaged 4.1 years; 82% of those assigned to hormone treatment were taking it at the end of 1 year, and 75% at the end of 3 years.
MAIN OUTCOME MEASURES: The primary outcome was the occurrence of nonfatal myocardial infarction (MI) or CHD death. Secondary cardiovascular outcomes included coronary revascularization, unstable angina, congestive heart failure, resuscitated cardiac arrest, stroke or transient ischemic attack, and peripheral arterial disease. All-cause mortality was also considered.
RESULTS: Overall, there were no significant differences between groups in the primary outcome or in any of the secondary cardiovascular outcomes: 172 women in the hormone group and 176 women in the placebo group had MI or CHD death (relative hazard [RH], 0.99; 95% confidence interval [CI], 0.80-1.22). The lack of an overall effect occurred despite a net 11% lower low-density lipoprotein cholesterol level and 10% higher high-density lipoprotein cholesterol level in the hormone group compared with the placebo group (each P<.001). Within the overall null effect, there was a statistically significant time trend, with more CHD events in the hormone group than in the placebo group in year 1 and fewer in years 4 and 5. More women in the hormone group than in the placebo group experienced venous thromboembolic events (34 vs 12; RH, 2.89; 95% CI, 1.50-5.58) and gallbladder disease (84 vs 62; RH, 1.38; 95% CI, 1.00-1.92). There were no significant differences in several other end points for which power was limited, including fracture, cancer, and total mortality (131 vs 123 deaths; RH, 1.08; 95% CI, 0.84-1.38).
CONCLUSIONS: During an average follow-up of 4.1 years, treatment with oral conjugated equine estrogen plus medroxyprogesterone acetate did not reduce the overall rate of CHD events in postmenopausal women with established coronary disease. The treatment did increase the rate of thromboembolic events and gallbladder disease. Based on the finding of no overall cardiovascular benefit and a pattern of early increase in risk of CHD events, we do not recommend starting this treatment for the purpose of secondary prevention of CHD. However, given the favorable pattern of CHD events after several years of therapy, it could be appropriate for women already receiving this treatment to continue.
Postmenopausal hormone therapy and risk of stroke: The Heart and Estrogen-progestin Replacement Study (HERS).
BACKGROUND: Observational studies have shown that postmenopausal hormone therapy may increase, decrease, or have no effect on the risk of stroke. To date, no clinical trial has examined this question. To investigate the relation between estrogen plus progestin therapy and risk of stroke among postmenopausal women, we analyzed data collected from the Heart & Estrogen-progestin Replacement Study (HERS), a secondary coronary heart disease prevention trial.
METHODS AND RESULTS: Postmenopausal women (n=2763) were randomly assigned to take conjugated estrogen plus progestin or placebo. Primary outcomes for these analyses were stroke incidence and stroke death during a mean follow-up of 4.1 years. The number of women with strokes was compared with the number of women without strokes. A total of 149 women (5%) had 1 or more strokes, 85% of which were ischemic, resulting in 26 deaths. Hormone therapy was not significantly associated with risk of nonfatal stroke (relative hazard [RH] 1.18; 95% CI 0.83 to 1.66), fatal stroke (RH 1.61; 95% CI 0.73 to 3.55), or transient ischemic attack (RH 0.90; 95% CI 0.57 to 1.42). Independent predictors of stroke events included increasing age, hypertension, diabetes, current cigarette smoking, and atrial fibrillation. Black women were at increased risk compared with white women, and unexpectedly, body mass index was inversely associated with stroke risk.
CONCLUSIONS: Hormone therapy with conjugated equine estrogen and progestin had no significant effect on the risk for stroke among postmenopausal women with coronary disease.
Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II).
CONTEXT: The Heart and Estrogen/progestin Replacement Study (HERS) found no overall reduction in risk of coronary heart disease (CHD) events among postmenopausal women with CHD. However, in the hormone group, findings did suggest a higher risk of CHD events during the first year, and a decreased risk during years 3 to 5.
OBJECTIVE: To determine if the risk reduction observed in the later years of HERS persisted and resulted in an overall reduced risk of CHD events with additional years of follow-up.
DESIGN AND SETTING: Randomized, blinded, placebo-controlled trial of 4.1 years' duration (HERS) and subsequent unblinded follow-up for 2.7 years (HERS II) conducted at outpatient and community settings at 20 US clinical centers.
PARTICIPANTS: A total of 2763 postmenopausal women with CHD and average age of 67 years at enrollment in HERS; 2321 women (93% of those surviving) consented to follow-up in HERS II.
INTERVENTION: Participants were randomly assigned to receive 0.625 mg/d of conjugated estrogens and 2.5 mg of medroxyprogesterone acetate (n = 1380), or placebo (n = 1383) during HERS; open-label hormone therapy was prescribed at personal physicians' discretion during HERS II. The proportions with at least 80% adherence to hormones declined from 81% (year 1) to 45% (year 6) in the hormone group, and increased from 0% (year 1) to 8% (year 6) in the placebo group.
MAIN OUTCOME MEASURES: The primary outcome was nonfatal myocardial infarction and CHD death. Secondary cardiovascular events were coronary revascularization, hospitalization for unstable angina or congestive heart failure, nonfatal ventricular arrhythmia, sudden death, stroke or transient ischemic attack, and peripheral arterial disease.
RESULTS: There were no significant decreases in rates of primary CHD events or secondary cardiovascular events among women assigned to the hormone group compared with the placebo group in HERS, HERS II, or overall. The unadjusted relative hazard (RH) for CHD events in HERS was 0.99 (95% confidence interval [CI], 0.81-1.22); HERS II, 1.00 (95% CI, 0.77-1.29); and overall, 0.99 (0.84-1.17). The overall RHs were similar after adjustment for potential confounders and differential use of statins between treatment groups (RH, 0.97; 95% CI, 0.82-1.14), and in analyses restricted to women who were adherent to randomized treatment assignment (RH, 0.96; 95% CI, 0.77-1.19).
CONCLUSIONS: Lower rates of CHD events among women in the hormone group in the final years of HERS did not persist during additional years of follow-up. After 6.8 years, hormone therapy did not reduce risk of cardiovascular events in women with CHD. Postmenopausal hormone therapy should not be used to reduce risk for CHD events in women with CHD.
Noncardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II).
CONTEXT: The Heart and Estrogen/progestin Replacement Study (HERS) was a randomized trial of estrogen plus progestin therapy after menopause.
OBJECTIVE: To examine the effect of long-term postmenopausal hormone therapy on common noncardiovascular disease outcomes.
DESIGN AND SETTING: Randomized, blinded, placebo-controlled trial of 4.1 years' duration (HERS) and subsequent open-label observational follow-up for 2.7 years (HERS II), carried out between 1993 and 2000 in outpatient and community settings at 20 US clinical centers.
PARTICIPANTS: A total of 2763 postmenopausal women with coronary disease and average age of 67 years at enrollment in HERS; 2321 women (93% of those surviving) consented to follow-up in HERS II.
INTERVENTION: Participants were randomly assigned to receive 0.625 mg/d of conjugated estrogens plus 2.5 mg of medroxyprogesterone acetate (n = 1380) or placebo (n = 1383) during HERS; open-label hormone therapy was prescribed at personal physicians' discretion during HERS II. The proportions with at least 80% adherence to hormones declined from 81% (year 1) to 45% (year 6) in the hormone group and increased from 0% (year 1) to 8% (year 6) in the placebo group.
MAIN OUTCOME MEASURES: Thromboembolic events, biliary tract surgery, cancer, fracture, and total mortality.
RESULTS: Comparing women assigned to hormone therapy with those assigned to placebo, the unadjusted intention-to-treat relative hazard (RH) for venous thromboembolism declined from 2.66 (95% confidence interval [CI], 1.41-5.04) during HERS to 1.40 (95% CI, 0.64-3.05) during HERS II (P for time trend =.08); it was 2.08 overall for the 6.8 years (95% CI, 1.28-3.40), and 3 of the 73 women with thromboembolism died within 30 days due to pulmonary embolism. The overall RH for biliary tract surgery was 1.48 (95% CI, 1.12-1.95); for any cancer, 1.19 (95% CI, 0.95-1.50); and for any fracture, 1.04 (95% CI, 0.87-1.25). There were 261 deaths among those assigned to hormone therapy and 239 among those assigned to placebo (RH, 1.10; 95% CI, 0.92-1.31). Adjusted and as-treated analyses did not alter our conclusions.
CONCLUSIONS: Treatment for 6.8 years with estrogen plus progestin in older women with coronary disease increased the rates of venous thromboembolism and biliary tract surgery. Trends in other disease outcomes were not favorable and should be assessed in larger trials and in broader populations.
Oestrogen therapy for prevention of reinfarction in postmenopausal women: a randomised placebo controlled trial.
BACKGROUND: Results of observational studies suggest that hormone replacement therapy (HRT) could reduce the risk of coronary heart disease (CHD), but those of randomised trials do not indicate a lower risk in women who use oestrogen plus progestagen. The aim of this study was to ascertain whether or not unopposed oestrogen reduces the risk of further cardiac events in postmenopausal women who survive a first myocardial infarction.
METHODS: The study was a randomised, blinded, placebo controlled, secondary prevention trial of postmenopausal women, age 50-69 years (n=1017) who had survived a first myocardial infarction. Individuals were recruited from 35 hospitals in England and Wales. Women received either one tablet of oestradiol valerate (2 mg; n=513) or placebo (n=504), daily for 2 years. Primary outcomes were reinfarction or cardiac death, and all-cause mortality. Analyses were by intention-to-treat. Secondary outcomes were uterine bleeding, endometrial cancer, stroke or other embolic events, and fractures.
FINDINGS: Frequency of reinfarction or cardiac death did not differ between treatment groups at 24 months (rate ratio 0.99, 95% CI 0.70-1.41, p=0.97). Similarly, the reduction in all-cause mortality between those who took oestrogen and those on placebo was not significant (0.79, 0.50-1.27, p=0.34). The relative risk of any death (0.56, 0.23-1.33) and cardiac death (0.33, 0.11-1.01) was lowest at 3 months post-recruitment.
INTERPRETATION: Oestradiol valerate does not reduce the overall risk of further cardiac events in postmenopausal women who have survived a myocardial infarction.
Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women: a randomized controlled trial.
CONTEXT: Hormone replacement therapy (HRT) and antioxidant vitamins are widely used for secondary prevention in postmenopausal women with coronary disease, but no clinical trials have demonstrated benefit to support their use.
OBJECTIVE: To determine whether HRT or antioxidant vitamin supplements, alone or in combination, influence the progression of coronary artery disease in postmenopausal women, as measured by serial quantitative coronary angiography.
DESIGN, SETTING, AND PATIENTS: The Women's Angiographic Vitamin and Estrogen (WAVE) Trial, a randomized, double-blind trial of 423 postmenopausal women with at least one 15% to 75% coronary stenosis at baseline coronary angiography. The trial was conducted from July 1997 to January 2002 in 7 clinical centers in the United States and Canada.
INTERVENTIONS: Patients were randomly assigned in a 2 x 2 factorial design to receive either 0.625 mg/d of conjugated equine estrogen (plus 2.5 mg/d of medroxyprogesterone acetate for women who had not had a hysterectomy), or matching placebo, and 400 IU of vitamin E twice daily plus 500 mg of vitamin C twice daily, or placebo.
MAIN OUTCOME MEASURE: Annualized mean (SD) change in minimum lumen diameter (MLD) from baseline to concluding angiogram of all qualifying coronary lesions averaged for each patient. Patients with intercurrent death or myocardial infarction (MI) were imputed the worst rank of angiographic outcome.
RESULTS: The mean (SD) interval between angiograms was 2.8 (0.9) years. Coronary progression, measured in mean (SD) change, worsened with HRT by 0.047 (0.15) mm/y and by 0.024 (0.15) mm/y with HRT placebo (P =.17); and for antioxidant vitamins by 0.044 (0.15) mm/y and with vitamin placebo by 0.028 (0.15) mm/y (P =.32). When patients with intercurrent death or MI were included, the primary outcome showed an increased risk for women in the active HRT group (P =.045), and suggested an increased risk in the active vitamin group (P =.09). Fourteen patients died in the HRT group and 8 in the HRT placebo group (hazard ratio [HR], 1.8; 95% confidence interval [CI], 0.75-4.3), and 16 in the vitamin group and 6 in the vitamin placebo group (HR, 2.8; 95% CI, 1.1-7.2). Death, nonfatal MI, or stroke occurred in 26 HRT patients vs 15 HRT controls (HR, 1.9; 95% CI, 0.97-3.6) and in 26 vitamin patients and 18 vitamin controls (HR, 1.5; 95% CI, 0.80-2.9). There was no interaction between the 2 treatment interventions.
CONCLUSION: In postmenopausal women with coronary disease, neither HRT nor antioxidant vitamin supplements provide cardiovascular benefit. Instead, a potential for harm was suggested with each treatment.
A clinical trial of estrogen-replacement therapy after ischemic stroke.
BACKGROUND: Observational studies have suggested that estrogen-replacement therapy may reduce a woman's risk of stroke and death.
METHODS: We conducted a randomized, double-blind, placebo-controlled trial of estrogen therapy (1 mg of estradiol-17beta per day) in 664 postmenopausal women (mean age, 71 years) who had recently had an ischemic stroke or transient ischemic attack. Women were recruited from 21 hospitals in the United States and were followed for the occurrence of stroke or death.
RESULTS: During a mean follow-up period of 2.8 years, there were 99 strokes or deaths among the women in the estradiol group, and 93 among those in the placebo group (relative risk in the estradiol group, 1.1; 95 percent confidence interval, 0.8 to 1.4). Estrogen therapy did not reduce the risk of death alone (relative risk, 1.2; 95 percent confidence interval, 0.8 to 1.8) or the risk of nonfatal stroke (relative risk, 1.0; 95 percent confidence interval, 0.7 to 1.4). The women who were randomly assigned to receive estrogen therapy had a higher risk of fatal stroke (relative risk, 2.9; 95 percent confidence interval, 0.9 to 9.0), and their nonfatal strokes were associated with slightly worse neurologic and functional deficits.
CONCLUSIONS: Estradiol does not reduce mortality orthe recurrence of stroke in postmenopausal women with cerebrovascular disease. This therapy should not be prescribed for the secondary prevention of cerebrovascular disease.
The evolution of the Women's Health Initiative: perspectives from the NIH.
The Women's Health Initiative (WHI) addresses some of the major health concerns of postmenopausal women. It is designed to test whether long-term preventive measures will decrease the incidence of cardiovascular disease, certain cancers, and fractures, and it seeks to find better predictors of future health and disease in older women. This report traces the evolution of the clinical trial and observational study (CT/OS) components of WHI from early planning in the 1980s to the current status of the WHI CT/OS as an integrated, ongoing clinical study. Particular attention is directed to the antecedent planning meetings and feasibility studies that formed the underpinnings of the WHI. The issues of hormone replacement therapy and of the optimal diet for postmenopausal women were investigated for almost a decade prior to WHI. However, no studies of sufficient size and duration to confidently test the value and risks of these approaches were initiated because of the cost and insufficient political commitment. The initiation of WHI in 1991 represents the confluence of scientific need and capability with the social priorities to improve the health and welfare of women.
Design of the Women's Health Initiative clinical trial and observational study. The Women's Health Initiative Study Group.
The Women's Health Initiative (WHI) is a large and complex clinical investigation of strategies for the prevention and control of some of the most common causes of morbidity and mortality among postmenopausal women, including cancer, cardiovascular disease, and osteoporotic fractures. The WHI was initiated in 1992, with a planned completion date of 2007. Postmenopausal women ranging in age from 50 to 79 are enrolled at one of 40 WHI clinical centers nationwide into either a clinical trial (CT) that will include about 64,500 women or an observational study (OS) that will include about 100,000 women. The CT is designed to allow randomized controlled evaluation of three distinct interventions: a low-fat eating pattern, hypothesized to prevent breast cancer and colorectal cancer and, secondarily, coronary heart disease; hormone replacement therapy, hypothesized to reduce the risk of coronary heart disease and other cardiovascular diseases and, secondarily, to reduce the risk of hip and other fractures, with increased breast cancer risk as a possible adverse outcome; and calcium and vitamin D supplementation, hypothesized to prevent hip fractures and, secondarily, other fractures and colorectal cancer. Overall benefit-versus-risk assessment is a central focus in each of the three CT components. Women are screened for participation in one or both of the components--dietary modification (DM) or hormone replacement therapy (HRT)--of the CT, which will randomize 48,000 and 27,500 women, respectively. Women who prove to be ineligible for, or who are unwilling to enroll in, these CT components are invited to enroll in the OS. At their 1-year anniversary of randomization, CT women are invited to be further randomized into the calcium and vitamin D (CaD) trial component, which is projected to include 45,000 women. The average follow-up for women in either CT or OS is approximately 9 years. Concerted efforts are made to enroll women of racial and ethnic minority groups, with a target of 20% of overall enrollment in both the CT and OS. This article gives a brief description of the rationale for the interventions being studied in each of the CT components and for the inclusion of the OS component. Some detail is provided on specific study design choices, including eligibility criteria, recruitment strategy, and sample size, with attention to the partial factorial design of the CT. Some aspects of the CT monitoring approach are also outlined. The scientific and logistic complexity of the WHI implies particular leadership and management challenges. The WHI organization and committee structure employed to respond to these challenges is also briefly described.
Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial.
CONTEXT: Despite decades of accumulated observational evidence, the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain.
OBJECTIVE: To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States.
DESIGN: Estrogen plus progestin component of the Women's Health Initiative, a randomized controlled primary prevention trial (planned duration, 8.5 years) in which 16608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993-1998.
INTERVENTIONS: Participants received conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102).
MAIN OUTCOMES MEASURES: The primary outcome was coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome. A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, and death due to other causes.
RESULTS: On May 31, 2002, after a mean of 5.2 years of follow-up, the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits. This report includes data on the major clinical outcomes through April 30, 2002. Estimated hazard ratios (HRs) (nominal 95% confidence intervals [CIs]) were as follows: CHD, 1.29 (1.02-1.63) with 286 cases; breast cancer, 1.26 (1.00-1.59) with 290 cases; stroke, 1.41 (1.07-1.85) with 212 cases; PE, 2.13 (1.39-3.25) with 101 cases; colorectal cancer, 0.63 (0.43-0.92) with 112 cases; endometrial cancer, 0.83 (0.47-1.47) with 47 cases; hip fracture, 0.66 (0.45-0.98) with 106 cases; and death due to other causes, 0.92 (0.74-1.14) with 331 cases. Corresponding HRs (nominal 95% CIs) for composite outcomes were 1.22 (1.09-1.36) for total cardiovascular disease (arterial and venous disease), 1.03 (0.90-1.17) for total cancer, 0.76 (0.69-0.85) for combined fractures, 0.98 (0.82-1.18) for total mortality, and 1.15 (1.03-1.28) for the global index. Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures. The absolute excess risk of events included in the global index was 19 per 10 000 person-years.
CONCLUSIONS: Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women. All-cause mortality was not affected during the trial. The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD.
Options:
A: HRT significantly reduced the risk of all-cause mortality, cardiovascular death, non-fatal myocardial infarction, venous thromboemboli, and stroke.
B: HRT had no protective effect on cardiovascular outcomes and was associated with higher risks of venous thromboembolic events, pulmonary embolus, and stroke.
C: HRT significantly reduced the risk of cardiovascular death and non-fatal myocardial infarction but increased the risk of venous thromboembolic events and stroke.
D: HRT had a protective effect on all cardiovascular outcomes but increased the risk of venous thromboembolic events. | B |
425 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | In newborn infants requiring resuscitation, what are the comparative effects of using room air versus 100% oxygen on mortality and neurological outcomes? Please answer this question based on the information provided below:
Resuscitation of asphyxic newborn infants with room air or 100% oxygen.
To test the hypothesis that room air is superior to 100% oxygen when asphyxiated newborns are resuscitated, 84 neonates (birth weight > 999 g) with heart rate < 80 and/or apnea at birth were allocated to be resuscitated with either room air (n = 42) or 100% oxygen (n = 42). Serial, unblinded observations of heart rates at 1, 3, 5, and 10 min and Apgar scores at 1 min revealed no significant differences between the two groups. At 5 min, median (25th and 75th percentile) Apgar scores were higher in the room air than in the oxygen group [8 (7-9) versus 7 (6-8), p = 0.03]. After the initial resuscitation, arterial partial pressure of oxygen, pH, and base excess were comparable in the two groups. Assisted ventilation was necessary for 2.4 (1.5-3.4) min in the room air group and 3.0 (2.0-4.0) min in the oxygen group (p = 0.14). The median time to first breath was 1.5 (1.0-2.0) min in both the room air and oxygen groups (p = 0.59), and the time to first cry was 3.0 (2.0-4.0) min and 3.5 (2.5-5.5) min in the room air and oxygen groups, respectively (p = 0.19). Three neonates in the room air group and four in the oxygen group died in the neonatal period. At 28 d, 72 of the 77 surviving neonates were available for follow-up (36 in each group), and none had any neurologic sequelae.(ABSTRACT TRUNCATED AT 250 WORDS)
Resuscitation of asphyxiated newborns with room air or 100% oxygen at birth: a multicentric clinical trial.
OBJECTIVE: To compare the short-term efficacy of room air versus 100% oxygen for resuscitation of asphyxic newborns at birth.
DESIGN: Multicentric quasi randomized controlled trial.
SETTING: Teaching hospitals.
INCLUSION CRITERIA: Asphyxiated babies weighing greater than 1000 grams, with heart rate less than 100 per min and/or apnea, unresponsive to nasopharyngeal suction and tactile stimuli and having no lethal abnormalities.
INTERVENTION: Asphyxiated neonates born on odd dates were given oxygen and those on even dates room air for resuscitation.
OUTCOME MEASURES: Primary: Apgar score at 5 minutes; Secondary: Mortality and Hypoxic ischaemic encephalopathy (HIE) during first 7 days of life.
RESULTS: A total of 431 asphyxiated babies, 210 in the room air and 221 in 100% oxygen group were enrolled for the study. Both the groups were comparable for maternal, intrapartum and neonatal characteristics. The heart rates in room air and 100% oxygen groups were comparable at 1 minute (94 bpm and 88 bpm), 5 minutes (131 bpm and 131 bpm) and 10 minutes (135 bpm and 136 bpm). Median apgar scores at 5 min [7 versus 7] and 10 minutes [8 versus 8 ], in the room air and oxygen groups respectively, were found to be comparable. Median time to first breath (1.5 versus 1.5 minutes) was similar in the room air and oxygen group. Median time to first cry (2.0 versus 3.0 minutes) and median duration of resuscitation (2.0 versus 3 minutes) were significantly shorter in the room air group. The number of babies with HIE during first seven days of life in the two treatment groups (35.7% babies in room air and 37.1% in the 100% oxygen group) were similar. There was also no statistically significant difference in the overall and asphyxia related mortality in the two treatment groups (12.4% and 10.0% in room air versus 18.1% and 13.6% in oxygen group).
CONCLUSION: Room air appears as good as 100% oxygen for resuscitation of asphyxic newborn babies at birth.
Resuscitation of newborn infants with 21% or 100% oxygen: follow-up at 18 to 24 months.
OBJECTIVE: To follow-up children who had been resuscitated at birth with either 21% or 100% oxygen (O2).
METHODS: A multicenter study with 10 participating centers recruited 609 infants to the Resair 2 study where resuscitation was performed with either 21% or 100% O2. A follow-up between ages 18 and 24 months was performed. However, during follow-up registration, it was found that 18 infants had been enrolled twice in the original Resair 2 study with different registration numbers, leaving 591 enrolled in the Resair 2 study and 410 enrolled in the 7 centers participating in the follow-up. Of these 410 infants, 79 died (76 in the neonatal and 3 in the postneonatal period). Furthermore, for 8 infants informed consent was not obtained, leaving 323 eligible for follow-up. Of these, 213 infants (66%) were followed-up: 91 (62%) had been resuscitated with 21% O2, and 122 (69%) with 100% O2. At a median age of 22 and 20 months (not significant) in the 21% and 100% groups, respectively, a simple questionnaire was filled out and neurologic assessment was performed in addition to measuring anthropometric data.
RESULTS: There were no significant differences in weight, height, or head circumference between the 2 groups. Cerebral palsy developed in 10% and 7%, respectively, in the 2 groups (not significant). In total, 11 cases (12%) in the 21% versus 11 cases (9%) in the 100% O(2) group (odds ratio: 1.39, 95% confidence interval: 0.57-3.36) developed cerebral palsy and/or mental or other delay. Furthermore, it was concluded that 14 (15%) in the 21% group and 12 (10%) in the 100% group were not normal (odds ratio: 1.67, 95% confidence interval: 0.73-3.80).
CONCLUSIONS: There were no significant differences in somatic growth or neurologic handicap at an age of 18 to 24 months in infants resuscitated with either 21% or 100% O2 at birth. Based on these data, resuscitation with ambient air seems to be safe, at least in most cases. More studies are needed to settle this issue.
Resuscitation of asphyxiated newborn infants with room air or oxygen: an international controlled trial: the Resair 2 study.
OBJECTIVE: Birth asphyxia represents a serious problem worldwide, resulting in approximately 1 million deaths and an equal number of serious sequelae annually. It is therefore important to develop new and better ways to treat asphyxia. Resuscitation after birth asphyxia traditionally has been carried out with 100% oxygen, and most guidelines and textbooks recommend this; however, the scientific background for this has never been established. On the contrary, theoretic considerations indicate that resuscitation with high oxygen concentrations could have detrimental effects. We have performed a series of animal studies as well as one pilot study indicating that resuscitation can be performed with room air just as efficiently as with 100% oxygen. To test this more thoroughly, we organized a multicenter study and hypothesized that room air is superior to 100% oxygen when asphyxiated newborn infants are resuscitated.
METHODOLOGY: In a prospective, international, controlled multicenter study including 11 centers from six countries, asphyxiated newborn infants with birth weight >999 g were allocated to resuscitation with either room air or 100% oxygen. The study was not blinded, and the patients were allocated to one of the two treatment groups according to date of birth. Those born on even dates were resuscitated with room air and those born on odd dates with 100% oxygen. Informed consent was not obtained until after the initial resuscitation, an arrangement in agreement with the new proposal of the US Food and Drug Administration's rules governing investigational drugs and medical devices to permit clinical research on emergency care without the consent of subjects. The protocol was approved by the ethical committees at each participating center. Entry criterion was apnea or gasping with heart rate <80 beats per minute at birth necessitating resuscitation. Exclusion criteria were birth weight <1000 g, lethal anomalies, hydrops, cyanotic congenital heart defects, and stillbirths. Primary outcome measures were death within 1 week and/or presence of hypoxic-ischemic encephalopathy, grade II or III, according to a modification of Sarnat and Sarnat. Secondary outcome measures were Apgar score at 5 minutes, heart rate at 90 seconds, time to first breath, time to first cry, duration of resuscitation, arterial blood gases and acid base status at 10 and 30 minutes of age, and abnormal neurologic examination at 4 weeks. The existing routines for resuscitation in each participating unit were followed, and the ventilation techniques described by the American Heart Association were used as guidelines aiming at a frequency of manual ventilation of 40 to 60 breaths per minute.
RESULTS: Forms for 703 enrolled infants from 11 centers were received by the steering committee. All 94 patients from one of the centers were excluded because of violation of the inclusion criteria in 86 of these. Therefore, the final number of infants enrolled in the study was 609 (from 10 centers), with 288 in the room air group and 321 in the oxygen group. Median (5 to 95 percentile) gestational ages were 38 (32.0 to 42.0) and 38 (31.1 to 41.5) weeks (NS), and birth weights were 2600 (1320 to 4078) g and 2560 (1303 to 3900) g (NS) in the room air and oxygen groups, respectively. There were 46% girls in the room air and 41% in the oxygen group (NS). Mortality in the first 7 days of life was 12.2% and 15.0% in the room air and oxygen groups, respectively; adjusted odds ratio (OR) = 0.82 with 95% confidence intervals (CI) = 0.50-1.35. Neonatal mortality was 13.9% and 19.0%; adjusted OR = 0. 72 with 95% CI = 0.45-1.15. Death within 7 days of life and/or moderate or severe hypoxic-ischemic encephalopathy (primary outcome measure) was seen in 21.2% in the room air group and in 23.7% in the oxygen group; OR = 0.94 with 95% CI = 0.63-1.40. (ABSTRACT TRUNCATED)
Resuscitation with room air instead of 100% oxygen prevents oxidative stress in moderately asphyxiated term neonates.
BACKGROUND: Traditionally, asphyxiated newborn infants have been ventilated using 100% oxygen. However, a recent multinational trial has shown that the use of room air was just as efficient as pure oxygen in securing the survival of severely asphyxiated newborn infants. Oxidative stress markers in moderately asphyxiated term newborn infants resuscitated with either 100% oxygen or room air have been studied for the first time in this work.
METHODS: Eligible term neonates with perinatal asphyxia were randomly resuscitated with either room air or 100% oxygen. The clinical parameters recorded were those of the Apgar score at 1, 5, and 10 minutes, the time of onset of the first cry, and the time of onset of the sustained pattern of respiration. In addition, reduced and oxidized glutathione concentrations and antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase) were determined in blood from the umbilical artery during delivery and in peripheral blood at 72 hours and at 4 weeks' postnatal age.
RESULTS: Our results show that the room-air resuscitated (RAR) group needed significantly less time to first cry than the group resuscitated with 100% oxygen (1.2 +/- 0.6 minutes vs 1.7 +/- 0.5). Moreover, the RAR group needed less time undergoing ventilation to achieve a sustained respiratory pattern than the group resuscitated with pure oxygen (4.6 +/- 0.7 vs 7.5 +/- 1.8 minutes). The reduced-to-oxidized-glutathione ratio, which is an accurate index of oxidative stress, of the RAR group (53 +/- 9) at 28 days of postnatal life showed no differences with the control nonasphyxiated group (50 +/- 12). However, the reduced-to-oxidized-glutathione ratio of the 100% oxygen-resuscitated group (OxR) (15 +/- 5) was significantly lower and revealed protracted oxidative stress. Furthermore, the activities of superoxide dismutase and catalase in erythrocytes were 69% and 78% higher, respectively, in the OxR group than in the control group at 28 days of postnatal life. Thus, this shows that these antioxidant enzymes, although higher than in controls, could not cope with the ongoing generation of free radicals in the OxR group. However, there were no differences in antioxidant enzyme activities between the RAR group and the control group at this stage.
CONCLUSIONS: There are no apparent clinical disadvantages in using room air for ventilation of asphyxiated neonates rather than 100% oxygen. Furthermore, RAR infants recover more quickly as assessed by Apgar scores, time to the first cry, and the sustained pattern of respiration. In addition, neonates resuscitated with 100% oxygen exhibit biochemical findings reflecting prolonged oxidative stress present even after 4 weeks of postnatal life, which do not appear in the RAR group. Thus, the current accepted recommendations for using 100% oxygen in the resuscitation of asphyxiated newborn infants should be further discussed and investigated.
Oxidative stress in asphyxiated term infants resuscitated with 100% oxygen.
OBJECTIVE: To test the hypothesis that resuscitation of asphyxiated infants with pure oxygen causes hyperoxemia and oxidative stress.Study design Asphyxiated term newborn infants (n = 106) were randomly resuscitated with room air (RAR = 51) or 100% oxygen (OxR = 55). The Apgar score, time of the first cry, and establishment of a sustained pattern of respiration were recorded. Assays performed included: blood gases; reduced glutathione (GSH) and oxidized glutathione (GSSG) in whole blood; glutathione-related enzyme activities; and superoxide dismutase activity (SOD) in erythrocytes.
RESULTS: The RAR group needed less time of ventilation for resuscitation (5.3 +/- 1.5 vs 6.8 +/- 1.2 min; P <.05). Pure oxygen caused hyperoxemia (PO(2), 126.3 +/- 21.8 mm Hg) that did not occur with the use of room air (PO(2), 72.2 +/- 6.8 mm Hg). GSH was decreased and GSSG, the glutathione cycle enzymes, and SOD activities were increased in both asphyxiated groups. However, the 100% oxygen-resuscitated group showed significantly greater alterations that correlated positively with hyperoxemia.
CONCLUSIONS: Asphyxia causes oxidative stress in the perinatal period, and resuscitation with 100% oxygen causes hyperoxemia and increased oxidative stress. Because there are no advantages to resuscitation with 100% oxygen, room air may be preferred under certain circumstances for the resuscitation of asphyxiated neonates.
Options:
A: Room air significantly reduces mortality compared to 100% oxygen, with no significant differences in neurological outcomes.
B: 100% oxygen significantly reduces mortality compared to room air, with no significant differences in neurological outcomes.
C: There is no significant difference in mortality between room air and 100% oxygen, but room air significantly improves neurological outcomes.
D: There is no significant difference in mortality or neurological outcomes between room air and 100% oxygen. | A |
426 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What was the conclusion regarding the effectiveness of different disease management interventions for patients with chronic heart failure (CHF) in terms of reducing all-cause mortality and hospital admissions? Please answer this question based on the information provided below:
Randomised controlled trial of specialist nurse intervention in heart failure.
OBJECTIVES: To determine whether specialist nurse intervention improves outcome in patients with chronic heart failure.
DESIGN: Randomised controlled trial.
SETTING: Acute medical admissions unit in a teaching hospital.
PARTICIPANTS: 165 patients admitted with heart failure due to left ventricular systolic dysfunction. The intervention started before discharge and continued thereafter with home visits for up to 1 year.
MAIN OUTCOME MEASURES: Time to first event analysis of death from all causes or readmission to hospital with worsening heart failure.
RESULTS: 31 patients (37%) in the intervention group died or were readmitted with heart failure compared with 45 (53%) in the usual care group (hazard ratio=0.61, 95% confidence interval 0.33 to 0.96). Compared with usual care, patients in the intervention group had fewer readmissions for any reason (86 v 114, P=0.018), fewer admissions for heart failure (19 v 45, P<0.001) and spent fewer days in hospital for heart failure (mean 3.43 v 7.46 days, P=0.0051).
CONCLUSIONS: Specially trained nurses can improve the outcome of patients admitted to hospital with heart failure.
Cost/utility ratio in chronic heart failure: comparison between heart failure management program delivered by day-hospital and usual care.
OBJECTIVE: This study compared the effectiveness and cost/utility ratio between a heart failure (HF) management program delivered by day-hospital (DH) and usual care in chronic heart failure (CHF) outpatients.
BACKGROUND: Previous studies showed that about 50% of readmissions for CHF can be prevented by a multidisciplinary approach. However, the performance, effectiveness, and cost/utility ratio of a process of HF outpatient management related to evidence-based medicine have not been considered.
METHODS: A total of 234 prospective patients discharged by a HF Unit were randomized to two management strategies: 122 patients to usual community care and 112 patients to a HF management program delivered by the DH. Management (rate of readmissions, therapeutic interventions), functional parameters (New York Heart Association [NYHA] functional class, left ventricular diameters, and ejection fraction, deceleration time of early diastolic mitral flow, peak oxygen uptake, and mitral regurgitation) and hard outcomes (cardiac death and urgent cardiac transplantation) were evaluated. The cost/utility ratios of the two strategies were compared.
RESULTS: After 12 +/- 3 months of follow-up, the individual rate access in DH was 5.5 +/- 3.8 days. The DH subjects were readmitted to the hospital less frequently than were the usual-care group patients (13 vs. 78, p < 0.00001). Patients allocated to usual-care management showed heterogeneous changes in NYHA functional class (13% improved and 16% worsened p = NS); In contrast, the DH group showed significant changes in NYHA functional class (23% improved and 11% worsened, p < 0.009). Hard cardiac events in the one-year follow-up occurred in 25/234 (10.6%) patients; cardiac death occurred in 21/122 (17.2%) of the community group and in 3/112 (2.7%) in the DH group (p < 0.0007). One DH patient underwent urgent transplantation. Comparison of the two managerial models by Cox regression analysis showed that DH management significantly protected against the appearance of hard events (relative risk [RR] 0.17; confidence interval [CI] 0.06 to 0.66). The cost/utility ratio of the two management strategies was similar (usual care $2,409 vs. DH $2,244). The incremental analysis revealed a cost savings of $1,068 for each quality-adjusted life year gained. The cost/utility ratio for the integration of DH management of CHF was $19,462 (CI $13,904 to $34,048).
CONCLUSIONS: A heart failure outpatient management program delivered by a DH can reduce mortality and morbidity of CHF patients. This management strategy is cost-effective and has an equitable value from a societal point of view.
Cost effective management programme for heart failure reduces hospitalisation.
OBJECTIVE: To study the effects of a management programme on hospitalisation and health care costs one year after admission for heart failure.
DESIGN: Prospective, randomised trial.
SETTING: University hospital with a primary catchment area of 250,000 inhabitants.
PATIENTS: 190 patients (aged 65-84 years, 52.3% men) hospitalised because of heart failure.
INTERVENTION: Two types of patient management were compared. The intervention group received education on heart failure and self management, with follow up at an easy access, nurse directed outpatient clinic for one year after discharge. The control group was managed according to routine clinical practice.
MAIN OUTCOME MEASURES: Time to readmission, days in hospital, and health care costs during one year.
RESULTS: The one year survival rate was 71.8% (n = 79) in the control group and 70.0% (n = 56) in the intervention group (NS). The mean time to readmission was longer in the intervention group than in the control group (141 (87) v 106 (101); p < 0.05) and number of days in hospital tended to be fewer (4.2 (7.8) v 8.2 (14.3); p = 0.07). There was a trend towards a mean annual reduction in health care costs per patient of US$1300 (US $1 = SEK 7.76) in the intervention group compared with costs in the controls (US$3594 v 2294; p = 0.07).
CONCLUSIONS: A management programme for patients with heart failure discharged after hospitalisation reduces health care costs and the need for readmission.
Randomized, controlled trial of integrated heart failure management: The Auckland Heart Failure Management Study.
AIMS: To determine the effect of an integrated heart failure management programme, involving patient and family, primary and secondary care, on quality of life and death or hospital readmissions in patients with chronic heart failure.
METHODS AND RESULTS: This trial was a cluster randomized, controlled trial of integrated primary/secondary care compared with usual care for patients with heart failure. The intervention involved clinical review at a hospital-based heart failure clinic early after discharge, individual and group education sessions, a personal diary to record medication and body weight, information booklets and regular clinical follow-up alternating between the general practitioner and heart failure clinic. Follow-up was for 12 months. One hundred and ninety-seven patients admitted to Auckland Hospital with an episode of heart failure were enrolled in the study. There was no significant difference between the intervention and control groups for the combined end-point of death or hospital readmission. The physical dimension of quality of life showed a greater improvement in the intervention group from baseline to 12 months compared with the control group (-11.1 vs -5.8 respectively, 2 P=0.015). The main effect of the intervention was attributable to the prevention of multiple admissions (56 intervention group vs 95 control group, 2 P=0.015) and associated reduction in bed days.
CONCLUSIONS: This integrated management programme for patients with chronic heart failure improved quality of life and reduced total hospital admissions and total bed days.
Feasibility of a nurse-monitored, outpatient-care programme for elderly patients with moderate-to-severe, chronic heart failure.
AIMS: To evaluate the feasibility of a nurse-monitored, outpatient-care program for elderly patients previously hospitalized with chronic heart failure.
METHODS AND RESULTS: Patients with chronic heart failure hospitalized in the medical wards were screened to find those eligible for a randomized study to compare the effect of a nurse-monitored, outpatient-care programme aiming at symptom management, with conventional care. The inclusion criteria were patients classified in New York Heart Association classes III-IV, age 65 years, and eligibility for an outpatient follow-up programme. The total in-hospital population of patients discharged with a heart-failure diagnosis was surveyed. Eighty-nine per cent of all the hospitalized patients (n=1541) were 65 years old. Of these, 69% (n=1058) were treated in the medical wards which were screened. The study criteria were met by 158 patients (15%). No visits to the nurse occurred in 23 cases among the 79 patients randomized to the structured-care group (29%), mainly on account of death or fatigue. The numbers of hospitalizations and hospital days did not differ between the structured-care and the usual-care groups.
CONCLUSIONS: Given the selection criteria and the outline of the interventions, the outpatient, nurse-monitored, symptom-management programme was not feasible for the majority of these elderly patients with moderate-to-severe, chronic heart failure, mainly because of the small proportion of eligible patients and the high drop-out rate. Management of these patients would have to be more adjusted to their home situation.
Outpatient care programmes for the elderly.
Quality of life of individuals with heart failure: a randomized trial of the effectiveness of two models of hospital-to-home transition.
BACKGROUND: The growing number of patients with congestive heart failure has increased both the pressure on hospital resources and the need for community management of the condition. Improving hospital-to-home transition for this population is a logical step in responding to current practice guidelines' recommendations for coordination and education. Positive outcomes have been reported from trials evaluating multiple interventions, enhanced hospital discharge, and follow-up through the addition of a case management role. The question remains if similar gains could be achieved working with usual hospital and community nurses.
METHODS: A 12-week, prospective, randomized controlled trial was conducted of the effect of transitional care on health-related quality of life (disease-specific and generic measures), rates of readmission, and emergency room use. The nurse-led intervention focused on the transition from hospital-to-home and supportive care for self-management 2 weeks after hospital discharge.
RESULTS: At 6 weeks after hospital discharge, the overall Minnesota Living with Heart Failure Questionnaire (MLHFQ) score was better among the Transitional Care patients (27.2 +/- 19.1 SD) than among the Usual Care patients (37.5 +/- 20.3 SD; P = 0.002). Similar results were found at 12 weeks postdischarge for the overall MLHFQ and at 6- and 12-weeks postdischarge for the MLHFQ's Physical Dimension and Emotional Dimension subscales. Differences in generic quality life, as assessed by the SF-36 Physical component, Mental Component, and General Health subscales, were not significantly different between the Transition and Usual Care groups. At 12 weeks postdischarge, 31% of the Usual Care patients had been readmitted compared with 23% of the Transitional Care patients (P = 0.26), and 46% of the Usual Care group visited the emergency department compared with 29% in the Transitional Care group (chi2 = 4.86, df 1, P = 0.03).
CONCLUSIONS: There were significant improvements in health-related quality of life (HRQL) associated with Transitional Care and less use of emergency rooms.
Self-care and quality of life in patients with advanced heart failure: the effect of a supportive educational intervention.
OBJECTIVE: The goal of this study was to determine the effects of a supportive educational nursing intervention on self-care abilities, self-care behavior, and quality of life of patients with advanced heart failure.
DESIGN: The study design was an experimental, random assignment.
SETTING: The study was located at the University Hospital in Maastricht, The Netherlands.
PATIENTS: The study included 179 patients (mean age 73 years, 58% men, New York Heart Association classification III and IV) admitted to a university hospital with symptoms of heart failure.
OUTCOME MEASURES: Outcome measures included self-care abilities (Appraisal of Self-care Agency Scale), self-care behavior (Heart Failure Self-care Behavior Scale), 3 dimensions of quality of life (functional capabilities, symptoms, and psychosocial adjustment to illness), and overall well-being (Cantril's ladder of life).
INTERVENTION: The intervention patients received systematic education and support by a nurse in the hospital and at home. Control patients received routine care.
RESULTS: Self-care abilities did not change as a result of the intervention, but the self-care behavior in the intervention group was higher than the self-care behavior in the control group during follow-up. The effect of the supportive educational intervention on quality of life was limited. The 3 dimensions of quality of life improved after hospitalization in both groups, with no differences between intervention and control group as measured at each follow-up measurement. However, there was a trend indicating differences between the 2 groups in decrease in symptom frequency and symptom distress during the 9 months of follow-up.
CONCLUSION: A supportive educational nursing intervention is effective in improving self-care behavior in patients with advanced (New York Heart Association class III-IV) heart failure; however, a more intensive intervention is needed to show effectiveness in improving quality of life.
Effects of education and support on self-care and resource utilization in patients with heart failure.
AIMS: To test the effect of education and support by a nurse on self-care and resource utilization in patients with heart failure.
METHODS: A total of 179 patients (mean age 73, 58% male, NYHA III-IV) hospitalized with heart failure were evaluated prospectively. Patients were randomized to the study intervention or to 'care as usual'. The supportive educative intervention consisted of intensive, systematic and planned education by a study nurse about the consequences of heart failure in daily life, using a standard nursing care plan developed by the researchers for older patients with heart failure. Education and support took place during the hospital stay and at a home visit within a week of discharge. Data were collected on self-care abilities, self-care behaviour, readmissions, visits to the emergency heart centre and use of other health care resources.
RESULTS: Education and support from a nurse in a hospital setting and at home significantly increases self-care behaviour in patients with heart failure. Patients from both the intervention and the control group increased their self-care behaviour within 1 month of discharge, but the increase in the intervention group was significantly more after 1 month. Although self-care behaviour in both groups decreased during the following 8 months, the increase from baseline remained statistically significant in the intervention group, but not in the control group. No significant effects on resource utilization were found.
CONCLUSIONS: Intensive, systematic, tailored and planned education and support by a nurse results in an increase in patients' self-care behaviour. No significant effects were found on use of health care resources. Additional organisational changes, such as longer follow-up and the availability of a heart failure specialist would probably enhance the effects of education and support.
A randomized trial of the efficacy of multidisciplinary care in heart failure outpatients at high risk of hospital readmission.
OBJECTIVES: We sought to determine whether a multidisciplinary outpatient management program decreases chronic heart failure (CHF) hospital readmissions and mortality over a six-month period.
BACKGROUND: Hospital admission for CHF is an important problem amenable to improved outpatient management.
METHODS: Two hundred patients hospitalized with CHF at increased risk of hospital readmission were randomized to a multidisciplinary program or usual care. A study cardiologist and a CHF nurse evaluated each patient and made recommendations to the patient's primary physician before randomization. The intervention team consisted of a cardiologist, a CHF nurse, a telephone nurse coordinator and the patient's primary physician. Contact with the patient was on a prespecified schedule. The CHF nurse followed an algorithm to adjust medications. Patients in the nonintervention group were followed as usual. The primary outcome was the composite of the number of CHF hospital admissions and deaths over six months, compared by using a log transformation t test by intention-to-treat analysis.
RESULTS: The median age of the study patients was 63.5 years, and 39.5% were women. There were 43 CHF hospital admissions and 7 deaths in the intervention group, as compared with 59 CHF hospital admissions and 13 deaths in the nonintervention group (p = 0.09). The quality-of-life score, percentage of patients on target vasodilator therapy and percentage of patients compliant with diet recommendations were significantly better in the intervention group. Cost per patient, in 1998 U.S. dollars, was similar in both groups.
CONCLUSIONS: This study demonstrates that a six-month, multidisciplinary approach to CHF management can improve important clinical outcomes at a similar cost in recently hospitalized high-risk patients with CHF.
Randomized trial of an education and support intervention to prevent readmission of patients with heart failure.
OBJECTIVES: We determined the effect of a targeted education and support intervention on the rate of readmission or death and hospital costs in patients with heart failure (HF).
BACKGROUND: Disease management programs for patients with HF including medical components may reduce readmissions by 40% or more, but the value of an intervention focused on education and support is not known.
METHODS: We conducted a prospective, randomized trial of a formal education and support intervention on one-year readmission or mortality and costs of care for patients hospitalized with HF.
RESULTS: Among the 88 patients (44 intervention and 44 control) in the study, 25 patients (56.8%) in the intervention group and 36 patients (81.8%) in the control group had at least one readmission or died during one-year follow-up (relative risk = 0.69, 95% confidence interval [CI]: 0.52, 0.92; p = 0.01). The intervention was associated with a 39% decrease in the total number of readmissions (intervention group: 49 readmissions; control group: 80 readmissions, p = 0.06). After adjusting for clinical and demographic characteristics, the intervention group had a significantly lower risk of readmission compared with the control group (hazard ratio = 0.56, 95% CI: 0.32, 0.96; p = 0.03) and hospital readmission costs of $7,515 less per patient.
CONCLUSIONS: A formal education and support intervention substantially reduced adverse clinical outcomes and costs for patients with HF.
Case management in a heterogeneous congestive heart failure population: a randomized controlled trial.
BACKGROUND: Both randomized and nonrandomized controlled studies have linked congestive heart failure (CHF) case management (CM) to decreased readmissions and improved outcomes in mostly homogeneous settings. The objective of this randomized controlled trial was to test the effect of CHF CM on the 90-day readmission rate in a more heterogeneous setting.
METHODS: A total of 287 patients admitted to the hospital with the primary or secondary diagnosis of CHF, left ventricular dysfunction of less than 40%, or radiologic evidence of pulmonary edema for which they underwent diuresis were randomized. The intervention consisted of 4 major components: early discharge planning, patient and family CHF education, 12 weeks of telephone follow-up, and promotion of optimal CHF medications.
RESULTS: The 90-day readmission rates were equal for the CM and usual care groups (37%). Total inpatient and outpatient median costs and readmission median cost were reduced 14% and 26%, respectively, for the intervention group. Patients in the CM group were more likely to be taking CHF medication at target doses, but dosages did not increase significantly throughout 12 weeks. Although both groups took their medications as prescribed equally well, the rest of the adherence to treatment plan was significantly better in the CM group. Subgroup analysis of patients who lived locally and saw a cardiologist showed a significant decrease in CHF readmissions for the intervention group (P =.03).
CONCLUSIONS: These results suggest several limitations to the generalizability of the CHF CM-improved outcome link in a heterogeneous setting. One explanation is that the lack of coordinated system supports and varied accessibility to care in an extended, nonnetworked physician setting limits the effectiveness of the CM.
Elimination of early rehospitalization in a randomized, controlled trial of multidisciplinary care in a high-risk, elderly heart failure population: the potential contributions of specialist care, clinical stability and optimal angiotensin-converting enzyme inhibitor dose at discharge.
BACKGROUND: Despite a growing body of data demonstrating the benefits of multidisciplinary care in heart failure, persistently high rates of readmission, especially within the first month of discharge, continue to be documented.
AIMS: As part of an ongoing randomized study on the value of multidisciplinary care in a high risk (NYHA Class IV), elderly (mean age 69 years) heart failure population, we examined the effects of this intervention on previously high (20%) 1-month readmission rates.
METHODS: Unlike previous studies of this approach, both multidisciplinary (MC) and routine care (RC) populations were cared for by the cardiology service, complied with adherence to clinical stability criteria prior to discharge (100% of patients) and received at least target dose angiotensin-converting enzyme (ACE) inhibition with perindopril prior to discharge (94% of indicated patients). We analysed death and unplanned readmission for heart failure at 1 month.
RESULTS: This early report from the first 70 patients (67% male, 71% systolic dysfunction with a mean ejection fraction of 31.0+/-6.7%) enrolled in this study demonstrates elimination of 1-month hospital readmission in both RC and MC groups. This unexpected result represents a dramatic improvement both for this patient cohort (20% 30-day readmission rate prior to enrollment reduced to 0% following the index admission in both care groups) and in comparison with available data.
CONCLUSIONS: Critical contributors to this improvement appear to be specialist cardiology care, adherence to clinical stability criteria prior to discharge and routine use of target or high-dose ACE inhibitor therapy prior to discharge. Widespread application of this approach may have a dramatic improvement in morbidity of CHF while limiting the escalating costs of this condition.
Heart failure management: multidisciplinary care has intrinsic benefit above the optimization of medical care.
PURPOSE: This work addresses the unanswered question of whether multidisciplinary care (MDC) of heart failure (HF) can reduce readmissions when optimal medical care is applied in both intervention and control groups.
METHODS: In a randomized, controlled study, 98 patients (mean age, 70.8 +/- 10.5 years) admitted to hospital with left ventricular failure (New York Heart Association Class IV) were assigned to routine care (RC, n = 47) or MDC (n = 51). All patients received the same components of inpatient, optimal medical care of HF: specialist-led inpatient care; titration to maximum tolerated dose of angiotensin-converting enzyme inhibitor before discharge; attainment of predetermined discharge criteria (weight stable, off all intravenous therapy, and no change in oral regimen for 2 days). Only those in the MDC group received inpatient and outpatient education and close telephone and clinic follow-up. The primary study endpoint was rehospitalization or death for a HF-related issue at 3 months.
MAIN FINDINGS: At 3 months, four people had events in the MDC group (7.8% rate over 3 months) compared with 12 people (25.5% rate over 3 months) in the RC group (P = 0.04).
CONCLUSION: These data demonstrate for the first time the intrinsic benefit of MDC in the setting of protocol-driven, optimal medical management of HF. Moreover, the event rate of 7.8% at 3 months, as the lowest reported rate for such a high-risk group, underlines the value of this approach to the management of heart failure.
Impact of pharmacist interventions on hospital readmissions for heart failure.
Prevention of readmission in elderly patients with congestive heart failure: results of a prospective, randomized pilot study.
OBJECTIVE: To determine the feasibility and potential impact of a non-pharmacologic multidisciplinary intervention for reducing hospital readmissions in elderly patients with congestive heart failure.
DESIGN: Prospective, randomized clinical trial, with 2:1 assignment to the study intervention or usual care.
SETTING: 550-bed secondary and tertiary care university teaching hospital.
PATIENTS AND PARTICIPANTS: 98 patients > or = 70 years of age (mean 79 +/- 6 years) admitted with documented congestive heart failure.
INTERVENTIONS: Comprehensive multidisciplinary treatment strategy consisting of intensive teaching by a geriatric cardiac nurse, a detailed review of medications by a geriatric cardiologist with specific recommendations designed to improve medication compliance and reduce side effects, early consultation with social services to facilitate discharge planning, dietary teaching by a hospital dietician, and close follow-up after discharge by home care and the study team.
MEASUREMENTS AND MAIN RESULTS: All patients were followed for 90 days after initial hospital discharge. The primary study endpoints were rehospitalization within the 90-day interval and the cumulative number of days hospitalized during follow-up. The 90-day readmission rate was 33.3% (21.7%-44.9%) for the patients receiving the study intervention (n = 63) compared with 45.7% (29.2%-62.2%) for the control patients (n = 35). The mean number of days hospitalized was 4.3 +/- 1.1 (2.1-6.5) for the treated patients vs 5.7 +/- 2.0 (1.8-9.6) for the usual-care patients. In a prospectively defined subgroup of patients at intermediate risk for readmission (n = 61), readmissions were reduced by 42.2% (from 47.6% to 27.5%; p = 0.10), and the average number of hospital days during follow-up decreased from 6.7 +/- 3.2 days to 3.2 +/- 1.2 days (p = NS).
CONCLUSIONS: These pilot data suggest that a comprehensive, multidisciplinary approach to reducing repetitive hospitalizations in elderly patients with congestive heart failure may lead to a reduction in readmissions and hospital days, particularly in patients at moderate risk for early rehospitalization. Further evaluation of this treatment strategy, including an assessment of the cost-effectiveness, is warranted.
A multidisciplinary intervention to prevent the readmission of elderly patients with congestive heart failure.
BACKGROUND: Congestive heart failure is the most common indication for admission to the hospital among older adults. Behavioral factors, such as poor compliance with treatment, frequently contribute to exacerbations of heart failure, a fact suggesting that many admissions could be prevented.
METHODS: We conducted a prospective, randomized trial of the effect of a nurse-directed, multidisciplinary intervention on rates of readmission within 90 days of hospital discharge, quality of life, and costs of care for high-risk patients 70 years of age or older who were hospitalized with congestive heart failure. The intervention consisted of comprehensive education of the patient and family, a prescribed diet, social-service consultation and planning for an early discharge, a review of medications, and intensive follow-up.
RESULTS: Survival for 90 days without readmission, the primary outcome measure, was achieved in 91 of the 142 patients in the treatment group, as compared with 75 of the 140 patients in the control group, who received conventional care (P = 0.09). There were 94 readmissions in the control group and 53 in the treatment group (risk ratio, 0.56; P = 0.02). The number of readmissions for heart failure was reduced by 56.2 percent in the treatment group (54 vs. 24, P = 0.04), whereas the number of readmissions for other causes was reduced by 28.5 percent (40 vs. 29, P not significant). In the control group, 23 patients (16.4 percent) had more than one readmission, as compared with 9 patients (6.3 percent) in the treatment group (risk ratio, 0.39; P = 0.01). In a subgroup of 126 patients, quality-of-life scores at 90 days improved more from base line for patients in the treatment group (P = 0.001). Because of the reduction in hospital admissions, the overall cost of care was $460 less per patient in the treatment group.
CONCLUSIONS: A nurse-directed, multidisciplinary intervention can improve quality of life and reduce hospital use and medical costs for elderly patients with congestive heart failure.
Effect of a multidisciplinary intervention on medication compliance in elderly patients with congestive heart failure.
PURPOSE: The objectives of this investigation were to prospectively assess medication compliance rates in elderly patients with congestive heart failure, to identify factors associated with reduced compliance, and to evaluate the effect of a multidisciplinary treatment approach on medication adherence.
PATIENTS AND METHODS: A total of 156 patients > or = 70 years of age (mean, 79.4 +/- 6.0; 67% female, 65% nonwhite) hospitalized with congestive heart failure were evaluated prospectively. Prior to discharge, patients were randomized to the study intervention (n = 80) or conventional care (n = 76). The intervention consisted of comprehensive patient education, dietary and social service consultations, medication review, and intensive postdischarge follow-up. Detailed data were collected on all prescribed medications at the time of discharge, and compliance was assessed by pill counts 30 +/- 2 days later.
RESULTS: The overall compliance rate during the first 30 days after discharge was 84.6 +/- 15.1% (range, 23.1-100%). Compliance was 87.9 +/- 12.0% in patients randomized to the study intervention, compared with 81.1 +/- 17.2% in the control group (P = 0.003). A compliance rate of > or = 80% was achieved by 85.0% of the treatment group versus 69.7% of the control group (P = 0.036). By multivariate analysis, assignment to the treatment group was the strongest independent predictor of compliance (P = 0.008). Other variables included in the model were Caucasian race (P = 0.044) and not living alone (P = 0.09).
CONCLUSIONS: A multidisciplinary treatment strategy is associated with improved medication compliance during the first 30 days following hospital discharge in elderly patients with congestive heart failure. Improved compliance may contribute to improved outcomes in these patients.
Effect of a standardized nurse case-management telephone intervention on resource use in patients with chronic heart failure.
BACKGROUND: Case management is believed to promote continuity of care and decrease hospitalization rates, although few controlled trials have tested this approach.
OBJECTIVE: To assess the effectiveness of a standardized telephonic case-management intervention in decreasing resource use in patients with chronic heart failure.
METHODS: A randomized controlled clinical trial was used to assess the effect of telephonic case management on resource use. Patients were identified at hospitalization and assigned to receive 6 months of intervention (n = 130) or usual care (n = 228) based on the group to which their physician was randomized. Hospitalization rates, readmission rates, hospital days, days to first rehospitalization, multiple readmissions, emergency department visits, inpatient costs, outpatient resource use, and patient satisfaction were measured at 3 and 6 months.
RESULTS: The heart failure hospitalization rate was 45.7% lower in the intervention group at 3 months (P =.03) and 47.8% lower at 6 months (P =.01). Heart failure hospital days (P =.03) and multiple readmissions (P =.03) were significantly lower in the intervention group at 6 months. Inpatient heart failure costs were 45.5% lower at 6 months (P =.04). A cost saving was realized even after intervention costs were deducted. There was no evidence of cost shifting to the outpatient setting. Patient satisfaction with care was higher in the intervention group.
CONCLUSIONS: The reduction in hospitalizations, costs, and other resource use achieved using standardized telephonic case management in the early months after a heart failure admission is greater than that usually achieved with pharmaceutical therapy and comparable with other disease management approaches.
Effects of a multidisciplinary, home-based intervention on unplanned readmissions and survival among patients with chronic congestive heart failure: a randomised controlled study.
BACKGROUND: Hospital admissions among patients with congestive heart failure (CHF) are a major contributor to health-care costs. Previous investigations suggest that the therapeutic efficacy of pharmacotherapy in CHF may be improved by strategies incorporating home visits to identify and address factors precipitating deterioration and resultant readmission.
METHODS: Chronic CHF patients discharged home after acute hospital admission were randomly assigned usual care (n=100) or a multidisciplinary, home-based intervention (n=100), consisting of a home visit by a cardiac nurse 7-14 days after discharge. The primary endpoint of the study was frequency of unplanned readmission plus out-of-hospital death within 6 months.
FINDINGS: During 6 months' follow-up there were 129 primary endpoint events in the usual-care group and 77 in the intervention group (p=0.02). More intervention-group than usual-care patients remained event-free (38 vs 51; p=0.04). Overall, there were fewer unplanned readmissions (68 vs 118; p=0.03) and associated days in hospital (460 vs 1173; p=0.02) among intervention-group patients. Hospital-based costs were Australian $490,300 for the intervention group and A$922,600 for the usual-care group (p=0.16); the mean cost of the intervention was A$350 per patient, and other community-based costs were similar for both groups.
INTERPRETATION: A home-based intervention has the potential to decrease the rate of unplanned readmissions and associated health-care costs, prolong event-free and total survival, and improve quality of life among patients with chronic CHF.
Options:
A: Case management interventions significantly reduced all-cause mortality and hospital admissions for heart failure.
B: Multidisciplinary interventions showed strong evidence of reducing all-cause mortality and hospital admissions for heart failure.
C: Clinic-based interventions were found to be the most effective in reducing all-cause mortality and hospital admissions for heart failure.
D: There was weak evidence that case management interventions may reduce all-cause mortality and hospital admissions for heart failure, but the data were insufficient to form strong recommendations. | D |
427 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What were the findings regarding the use of routine neuromuscular paralysis with pancuronium in ventilated preterm infants with evidence of asynchronous respiratory efforts? Please answer this question based on the information provided below:
Pancuronium prevents pneumothoraces in ventilated premature babies who actively expire against positive pressure inflation.
Preterm infants who were making expiratory efforts against ventilator inflation were randomised to be paralysed with pancuronium or to receive no paralysing agent during ventilation. Pneumothoraces developed in all 11 unparalysed babies but in only 1 of 11 (p less than 0.0004) of those managed with pancuronium, which had no serious side-effects. In 34 infants excluded from the trial because they were not breathing against the ventilator, no pneumothoraces developed.
Reduction in intraventricular hemorrhage by elimination of fluctuating cerebral blood-flow velocity in preterm infants with respiratory distress syndrome.
In a previous study of preterm infants requiring mechanical ventilation for the respiratory distress syndrome, we demonstrated a striking association of fluctuating cerebral blood-flow velocity in the first day of life with the subsequent occurrence of intraventricular hemorrhage. Because this fluctuating pattern could be eliminated by muscle paralysis, we conducted a prospective study of preterm infants receiving mechanical ventilation for the respiratory distress syndrome in which we evaluated the effect of paralysis and this flow-velocity pattern on the incidence and severity of intraventricular hemorrhage. Twenty-four infants with the fluctuating pattern in the first hours of life were identified and randomly selected to serve as controls (10) or to be subjected to muscle paralysis (14). Intraventricular hemorrhage developed in all 10 control infants but in only 5 of the 14 infants subjected to muscle paralysis. Moreover, in 4 of the 5 paralyzed infants in whom hemorrhage developed, it did so after cessation of the paralysis. Seven of the 10 control infants had Grade III hemorrhage, the most severe variety of intraventricular hemorrhage, whereas none of the paralyzed infants had Grade III hemorrhage. We conclude that elimination of fluctuating cerebral blood-flow velocity in preterm infants with respiratory distress syndrome markedly reduces the incidence and severity of intraventricular hemorrhage.
Pancuronium during mechanical ventilation speeds recovery of lungs of infants with hyaline membrane disease.
Spontaneous breathing during mechanical ventilation in newborn infants may damage the lung. To find out whether the prevalence of lesions which might be due to trauma was reduced by muscle relaxation, fifty infants who required mechanical ventilation of hyaline membrane disease were randomly assigned to treated and control groups. The treated infants were kept muscle relaxed with pancuronium bromide until they needed a FiO2 of 0.40 or less during ventilation. The mean birthweight, gestational age, age at entry to the trial, duration of intubation and ventilation, FiO2 during the acute phase of the illness, and ventilator pressures were closely comparable in the two groups. Two of twenty-six treated infants and one of twenty-four controls died. Four treated and five control infants acquired pneumothoraces and/or interstitial emphysema. The length of time that the treated infants required added oxygen was significantly less than in the control infants. All treated infants were breathing room air spontaneously by one month of age whereas seven control infants were still dependent on added oxygen, needing an average FiO2 of 0.35 to achieve a mean PaO2 of 6.5 kPa (49 mm Hg). These seven infants required added oxygen until they were 5-18 (mean 10) weeks old. Muscle relaxation during mechanical ventilation for hyaline membrane disease speeds recovery of the lungs, probably owing to a reduction in traumatic damage.
Effect of morphine and pancuronium on the stress response in ventilated preterm infants.
Ninety-five premature newborns who had hyaline membrane disease and were struggling against the ventilator were randomised to one of three treatment groups: morphine (group M), pancuronium (group P) or morphine with pancuronium (group M+P). The dose of morphine was 50 micrograms/kg per h but was increased to 100 micrograms/kg per h in group M infants if they continued to struggle. The dosage of pancuronium was 100 micrograms/kg given as required to inhibit spontaneous respiration. Plasma catecholamine levels were measured on entry and at 24 h. Blood pressure and ventilatory requirements were determined on entry and at 6 h. The clinical outcome of the infants was documented. Group M infants (n = 29) showed a significant reduction in noradrenaline levels (median change -2.2 nmols/l (range -47.2 to +7.2 nmols/l), although seven were withdrawn from this group because of failure to settle. Group P (n = 28) and group M+P (n = 38) showed no significant change in noradrenaline levels. Comparison between the groups showed that group M infants had a significant reduction in noradrenaline levels compared with group P. The immediate effects of treatment on blood pressure and ventilatory requirements were similar in the three groups. The clinical outcome did not differ for any of the measured parameters. When adequate sedation is achieved, morphine may reduce the stress of newborn intensive care.
Randomised trial of routine versus selective paralysis during ventilation for neonatal respiratory distress syndrome.
The strategy of non-selective neuromuscular paralysis was compared with that of synchronised (fast rate) ventilation and selective paralysis in infants receiving mechanical ventilation for respiratory distress syndrome with chronic lung disease as the primary outcome measure. One hundred and ninety three infants weighing under 2000 g were randomly allocated to receive either pancuronium during mechanical ventilation in the acute phase of respiratory distress syndrome (non-selective group) or synchronised ventilation (initial ventilatory rate at or above that of the infant's) (selective group). Infants in the selective group received pancuronium if they were consistently expiring during the inspiratory phase of the ventilator cycle. There was no significant difference between the groups with respect to birth weight, gestation, and sex distribution. There was no significant difference between the group with respect to death (selective 19%, non-selective 16%), pneumothorax (selective 14%, non-selective 14%), chronic lung disease (selective 49%), non-selective 47%), and oxygen dependency at 36 weeks' postmenstrual age (selective 32%, non-selective 39%). Routine paralysis of ventilated infants has potential complications that may be avoided by using synchronised ventilation. As the latter is not associated with an increased incidence of long term respiratory complications, it is concluded that it is the optimum strategy of the two for ventilating infants with respiratory distress syndrome.
Options:
A: It significantly reduced intraventricular hemorrhage and showed a trend towards less air leak.
B: It significantly increased mortality and chronic lung disease.
C: It had no significant effect on any clinical outcomes.
D: It significantly increased the risk of pneumothorax and barotrauma. | A |
428 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What is the efficacy of glucocorticosteroids or adrenocorticotrophic hormone (ACTH) medication in the treatment of autoimmune myasthenia gravis? Please answer this question based on the information provided below:
Randomized trial of azathioprine or prednisone for initial immunosuppressive treatment of myasthenia gravis.
Ten patients with myasthenia gravis were randomized to azathioprine or prednisone as the initial immunomodulating drug and followed for over one year. Of five patients randomized to azathioprine, two had idiosyncratic reactions and were immediately crossed over to prednisone. Two patients completed one year on azathioprine with little or no change in level of function and were crossed over to prednisone and showed greater improvement. The fifth patient on azathioprine had a satisfactory improvement and continued on it during the second year. All patients initially randomized to prednisone improved, but the degree varied among patients. The side effects of azathioprine were idiosyncratic reactions. The side effects of prednisone were manageable.
A randomised clinical trial comparing prednisone and azathioprine in myasthenia gravis. Results of the second interim analysis. Myasthenia Gravis Clinical Study Group.
From January 1983 to October 1990, 41 patients with generalised myasthenia gravis were randomly given either prednisone or azathioprine. The main goal was to record the time to the occurrence of the first episode of deterioration. During a mean follow-up of 30 months, 21 patients showed deterioration, 12 in the prednisone group and nine in the azathioprine group (p = 0.40). No difference was observed between the two groups in muscular score and functional grade, assessed at the end of each treatment year, or in tolerance. Treatment failure occurred in 17 patients, 12 in the prednisone group and five in the azathioprine group (p = 0.02); even after adjustment for imbalances in prognostic features, the failure rate remained 2.8 times higher in the prednisone group than in the azathioprine group (p = 0.5). In the patients in whom treatment failed, symptoms were initially more severe than in the others, but the combination of prednisone and azathioprine resulted in clinical improvement, consisting of remission or only minor deficits in half of the patients after two years of treatment. These findings indicate that azathioprine increases treatment response compared with prednisone, although no difference in the duration of improvement was demonstrated. Nevertheless, it appears that the most severe forms of the disease, often resistant to prednisone or azathioprine alone, could benefit from the combination of both drugs.
Alternate-day prednisone: preliminary report of a double-blind controlled study.
Thirteen patients with moderately severe myasthenia gravis participated in a double-blind study using either 100 mg of prednisone or an equivalen numbder of placebo tablets on alternate days. Anticholinesterase therapy was continued on a demand basis. At the end of 6 months the code was broken. Seven patients were on placebo and three of these had improved to such a degree that steroid therapy was not indicated. Four of these patients ultimately were started on prednisone and improved. Of the six patients on prednisone, three showed no improvement and three were improved. At the end of 2 years, the seven patients still taking prednisone were on maintenance dosage of this drug. Three of this group had experienced relapses when the dosage was cut to 15 to 25 mg on alternate days, and they again improved when the prednisone dosage was increased. No statistical evaluation is possible because of the small number of patients. It can be stated that seven patients improved with steroid therapy. Conversely, not all patients treated with alternate-day prednisone improved. Finally, any evaluation of treatment of myasthenia gravis must take into consideration the potential for spontaneous improvement, as demonstrated by three of the patients treated with placebo.
Treatment of myasthenia gravis with methylprednisolone pulse: a double blind study.
OBJECTIVES: To evaluate the efficacy and safety of one single intravenous methylprednisolone (IVMP) pulse therapy in myasthenia gravis.
MATERIAL AND METHODS: We performed a double blind placebo controlled study (2+2 g IVMP vs placebo) in patients with moderate MG.
RESULTS: A mean increase in muscle function of 27 points was found in the treatment group after one IVMP pulse as compared with a 0.7 point increase in the placebo group (P<0.01). In the IVMP group 8 of 10 patients showed a positive treatment response. The mean duration of improvement after IVMP was 8 weeks (range 4-14 weeks). No severe side effects were found. Acetylcholine receptor antibody concentrations were unchanged in spite of the positive treatment response.
CONCLUSIONS: We conclude that a single IVMP treatment is efficacious and safe in the treatment of moderate MG.
CORTICOTROPIN IN TREATMENT OF OCULAR MYASTHENIA; A CONTROLLED CLINICAL TRIAL.
Options:
A: Glucocorticosteroids offer significant short-term benefit compared with placebo, but there is no difference in efficacy between glucocorticosteroids and either azathioprine or intravenous immunoglobulin.
B: Adrenocorticotrophic hormone (ACTH) shows significant benefit over placebo for the treatment of ocular myasthenia gravis.
C: Glucocorticosteroids are less effective than azathioprine and intravenous immunoglobulin in treating myasthenia gravis.
D: There is no evidence to support the use of glucocorticosteroids or ACTH in the treatment of myasthenia gravis. | A |
429 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What treatment combination was found to significantly reduce pregnancy loss in women with a history of miscarriage and antiphospholipid antibody (APL)? Please answer this question based on the information provided below:
A multicenter, placebo-controlled pilot study of intravenous immune globulin treatment of antiphospholipid syndrome during pregnancy. The Pregnancy Loss Study Group.
OBJECTIVE: Treatment with heparin and low-dose aspirin improves fetal survival among women with antiphospholipid syndrome. Despite treatment, however, these pregnancies are frequently complicated by preeclampsia, fetal growth restriction, and placental insufficiency, often with the result of preterm birth. Small case series suggest that intravenous immune globulin may reduce the rates of these obstetric complications, but the efficacy of this treatment remains unproven. This pilot study was undertaken to determine the feasibility of a multicenter trial of intravenous immune globulin and to assess the impact on obstetric and neonatal outcomes among women with antiphospholipid syndrome of the addition of intravenous immune globulin to a heparin and low-dose aspirin regimen.
STUDY DESIGN: This multicenter, randomized, double-blind pilot study compared treatment with heparin and low-dose aspirin plus intravenous immune globulin with heparin and low-dose aspirin plus placebo in a group of women who met strict criteria for antiphospholipid syndrome. All patients had lupus anticoagulant, medium to high levels of immunoglobulin G anticardiolipin antibodies, or both. Patients with a single live intrauterine fetus at </=12 weeks' gestation were randomly assigned to receive either intravenous immune globulin (1 g/kg body weight) or an identical-appearing placebo for 2 consecutive days each month until 36 weeks' gestation in addition to a heparin and low-dose aspirin regimen. Maternal characteristics, obstetric complications, and neonatal outcomes were compared with the Student t test and the Fisher exact test as appropriate.
RESULTS: Sixteen women were enrolled during a 2-year period; 7 received intravenous immune globulin and 9 were given placebo. The groups were similar with respect to age, gravidity, number of previous pregnancy losses, and gestational age at the initiation of treatment. Obstetric outcomes were excellent in both groups, with all women being delivered of live-born infants after 32 weeks' gestation. The rates of antepartum complications such as preeclampsia, fetal growth restriction, and placental insufficiency (as manifested by fetal growth restriction or fetal distress) were similar between the 2 groups. Gestational age at delivery (intravenous immune globulin group, 34.6 +/- 1.1 weeks; placebo group, 36.7 +/- 2.1 weeks) and birth weights (intravenous immune globulin group, 2249.7 +/- 186.1 g; placebo group; 2604.4 +/- 868.9 g) were similar between the 2 groups. There were fewer cases of fetal growth restriction (intravenous immune globulin group, 0%; placebo group, 33%) and neonatal intensive care unit admission (intravenous immune globulin group, 20%; placebo group, 44%) among the infants in the intravenous immune globulin group than those in the placebo group, but these differences were not significant.
CONCLUSION: A multicenter treatment trial of intravenous immune globulin is feasible. In this pilot study intravenous immune globulin did not improve obstetric or neonatal outcomes beyond those achieved with a heparin and low-dose aspirin regimen. Although not statistically significant, the findings of fewer cases of fetal growth restriction and neonatal intensive care unit admissions among the intravenous immune globulin-treated pregnancies may warrant expansion of the study.
Repeated fetal losses associated with antiphospholipid antibodies: a collaborative randomized trial comparing prednisone with low-dose heparin treatment.
OBJECTIVE: We attempted to compare the use of low-dose heparin with a standard dose of 40 mg prednisone daily (both plus low-dose aspirin) for treatment of pregnant women with antiphospholipid antibody-associated recurrent fetal loss with respect to maternal and perinatal morbidity and efficacy in prevention of fetal death.
STUDY DESIGN: A multicenter randomized trial included 20 patients. Generalizability of results from randomized patients was evaluated by means of additional data from 13 women refusing and 12 women ineligible for randomization. Data from study groups were compared with Fisher's exact test, and generalizability was evaluated with a chi 2 test for trend.
RESULTS: Live birth rates were the same (75%) with either treatment, but "serious" maternal morbidity and the frequency of preterm delivery were significantly higher among women randomly assigned to prednisone (p = 0.02 vs p = 0.006). Preterm delivery among prednisone-treated women was usually associated with premature rupture of the membranes or preeclampsia. These results could be generalized to the other groups of women ascertained during the course of the study.
CONCLUSIONS: Low-dose heparin should be preferred to prednisone when treatment is indicated for high-risk pregnant women with antiphospholipid antibodies.
Do low-risk pregnant women with antiphospholipid antibodies need to be treated? Organizing Group of the Antiphospholipid Antibody Treatment Trial.
We identified 19 women who had persistently positive test results for antiphospholipid antibodies who were considered to be at low risk because they had none of the associated signs or symptoms of the antiphospholipid antibody syndrome. They had had no (10/19, 53%) or just one prior spontaneous abortion and did not have a history of thrombosis or thrombocytopenia. Many (8/19, 42%) had had a prior uncomplicated pregnancy ending in a live birth. These women were randomly assigned to receive low-dose aspirin (81 mg daily) or usual care. There were few obstetric complications recorded in either treatment group. One woman in the aspirin group had a fetal death, and one in the usual care group had a low-birth-weight infant. The frequency of complications was so low that > 600 such women would need to be entered into a randomized trial to evaluate whether low-dose aspirin would be beneficial treatment during a pregnancy. We concluded that treatment of pregnant women with antiphospholipid antibodies who are otherwise at low risk cannot be justified on the basis of the available evidence.
Antiphospholipid syndrome in pregnancy: a randomized, controlled trial of treatment.
OBJECTIVE: To compare the efficacy of low-dose aspirin alone versus low-dose aspirin plus low molecular weight heparin in pregnant women with antiphospholipid syndrome and recurrent miscarriage as prophylaxis against pregnancy loss.
METHODS: From a regional miscarriage clinic, 119 consecutive women with persistently positive tests for lupus anticoagulant and/or anticardiolipin immunoglobulin G and M antibody were invited to participate in a randomized, controlled trial between 1997 and 2000. After ethical approval and adherence to a written protocol, 12 women were unwilling to participate, five failed exclusion/inclusion criteria, and four were nonpregnant. Laboratory analysis was performed by Sheffield University Coagulation Department, electronically generated randomization by Manchester University Centre for Cancer Epidemiology, and data collection and analysis by a research officer at Leeds University. Viability ultrasound every 2 weeks was provided until 12 weeks' gestation before transfer to the pregnancy support antenatal clinic.
RESULTS: Ninety-eight women were randomized before 12 weeks' gestation. Forty-seven received low-dose aspirin 75 mg daily (group A), and 51 received low-dose aspirin plus low molecular weight heparin 5000 U subcutaneously daily (group B) throughout pregnancy. There were 13 pregnancy losses and 34 live births in group A and 11 losses and 40 live births in group B. The live-birth rate was 72% in group A and 78% in group B (odds ratio 1.39, 95% confidence interval 0.55, 3.47). There were no cases of maternal thrombosis in either group.
CONCLUSION: A high success rate is achieved when low-dose aspirin is used for antiphospholipid syndrome in pregnancy. The addition of low molecular weight heparin does not significantly improve pregnancy outcome.
Antiphospholipid syndrome in pregnancy: a randomized, controlled trial of treatment.
Antiphospholipid antibody-associated recurrent pregnancy loss: treatment with heparin and low-dose aspirin is superior to low-dose aspirin alone.
OBJECTIVE: The purpose of this study was to compare the use of low-dose aspirin alone with heparin and low-dose aspirin in the treatment of the antiphospholipid antibody syndrome.
STUDY DESIGN: A prospective, single-center trial included 50 patients who were alternately assigned to treatment. Each patient had at least three consecutive spontaneous pregnancy losses, positive antiphospholipid antibodies on two occasions, and a complete evaluation. Data were compared by chi(2) analysis and Fisher's exact test.
RESULTS: Viable infants were delivered of 11 of 25 (44%) women treated with aspirin and 20 of 25 (80%) women treated with heparin and aspirin (p < 0.05). There were no significant differences between the low-dose aspirin and the heparin plus low-dose aspirin groups with respect to gestational age at delivery (37.8 +/- 2.1 vs 37.2 +/- 3.4 weeks), number of cesarean sections (18% vs 20%), or complications.
CONCLUSION: Heparin plus low-dose aspirin provides a significantly better pregnancy outcome than low-dose aspirin alone does for antiphospholipid antibody-associated recurrent pregnancy loss.
A clinical trial for the treatment of antiphospholipid antibody-associated recurrent pregnancy loss with lower dose heparin and aspirin.
This study was conducted to determine if lower dose heparin (LD Heparin) combined with aspirin is as efficacious as higher dose heparin (HD Heparin) for the treatment of the antiphospholipid antibody syndrome in women seeking pregnancy. The method of the study was a prospective, single center trial including 50 patients who were consecutively assigned to treatment. Each patient had at least three consecutive, spontaneous pregnancy losses, positive antiphospholipid antibodies on two occasions, and a complete evaluation. Data were compared using Fisher's exact test. Viable infants were delivered from 20/25 (80%) women treated with higher dose heparin vs. 19/25 (76%) of women treated with lower dose heparin. There were no significant differences between groups with respect to gestational age at the time of delivery (37.2 +/- 3.4 versus 37.7 +/- 1.6 weeks), maternal complications, or fetal complications. A lower dose of heparin plus aspirin was as effective as higher dose heparin for the treatment of antiphospholipid antibody-associated recurrent pregnancy loss.
Prednisone and aspirin in women with autoantibodies and unexplained recurrent fetal loss.
BACKGROUND: Recurrent fetal loss has been well described in women with antiphospholipid antibodies. Such women also often have other autoantibodies commonly found in patients with systemic lupus erythematosus. Treating them with prednisone and aspirin may reduce the risk of fetal loss.
METHODS: We screened 773 nonpregnant women who had the unexplained loss of at least two fetuses for antinuclear, anti-DNA, antilymphocyte, and anticardiolipin antibodies and for the lupus anticoagulant. Of 385 women with at least one autoantibody, 202 who later became pregnant were randomly assigned in equal numbers to receive either prednisone (0.5 to 0.8 mg per kilogram of body weight per day) and aspirin (100 mg per day) or placebo for the duration of the pregnancy. The women were stratified according to age (18 to 34 years or 35 to 39 years) and the week of gestation at which the previous fetal losses had occurred (< or = 12 or > 12 weeks). The primary outcome measure was a successful pregnancy.
RESULTS: Live infants were born to 66 women in the treatment group (65 percent) and 57 women in the placebo group (56 percent, P=0.19). More infants were born prematurely in the treatment group than in the placebo group (62 percent vs. 12 percent, P<0.001). The major side effects of therapy in the mothers were hypertension (treatment group, 13 percent; placebo group, 5 percent; P=0.05) and diabetes mellitus (15 percent and 5 percent, P=0.02).
CONCLUSIONS: Treating women who have autoantibodies and recurrent fetal loss with prednisone and aspirin is not effective in promoting live birth, and it increases the risk of prematurity.
Appropriate management of antiphospholipid-related pregnancy in women without lupus who have low titer autoantibodies.
Does aspirin have a role in improving pregnancy outcome for women with the antiphospholipid syndrome? A randomized controlled trial.
OBJECTIVE: This pilot investigation was undertaken to assess the efficacy of low-dose aspirin therapy for the treatment of women with antiphospholipid antibodies when recurrent miscarriage is the only sequela.
STUDY DESIGN: A double-blind, randomized, placebo-controlled trial was conducted in the setting of the recurrent miscarriage clinic of a tertiary referral obstetric hospital. The participants were 50 women with a history of recurrent miscarriages (>/=3) and antiphospholipid antibodies. Women with systemic lupus erythematosus or a history of thrombosis were excluded. Women were recruited after full investigative screening at the recurrent miscarriage clinic. Women with >/=3 fetal losses and persistently positive results for antiphospholipid antibodies were randomly allocated to receive either aspirin (75 mg daily) or placebo. Investigators, clinicians, and patients were blinded to the treatment. Rates of live births, antenatal complications, and delivery and neonatal outcomes were recorded prospectively. Data were compared by chi(2) analysis with Yates' correction, the Fisher exact test, or the Student t test as appropriate.
RESULTS: There were 10 exclusions after random assignment because of inappropriate inclusion. Eighty-five percent of the placebo (17/20) group and 80% of the aspirin-treated group (16/20) were delivered of live infants. This difference was not significant. There were no significant differences in antenatal complications or neonatal morbidity between the groups.
CONCLUSIONS: This preliminary study suggests that low-dose aspirin has no additional benefit when added to supportive care for women for whom recurrent early fetal loss is the only sequela of the antiphospholipid syndrome. This live birth rate with supportive care alone exceeds the published live birth rates for women with antiphospholipid antibody-mediated recurrent fetal loss who were treated with heparin or corticosteroids. This trial, like all other trials in this field, is small, but its results bring into question the need for pharmacologic intervention for women with antiphospholipid syndrome for whom recurrent fetal loss is the only sequela. Our results highlight the need for a large randomized controlled trial to identify the optimal treatment for this group of women and justify the inclusion of a placebo arm in any such trial.
Randomized trial of aspirin versus aspirin and heparin in pregnant women with the antiphospholipid syndrome.
Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies)
OBJECTIVE: To determine whether treatment with low dose aspirin and heparin leads to a higher rate of live births than that achieved with low dose aspirin alone in women with a history of recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies), lupus anticoagulant, and cardiolipin antibodies (or anticardiolipin antibodies).
DESIGN: Randomised controlled trial.
SETTING: Specialist clinic for recurrent miscarriages.
SUBJECTS: 90 women (median age 33 (range 22-43)) with a history of recurrent miscarriage (median number 4 (range 3-15)) and persistently positive results for phospholipid antibodies.
INTERVENTION: Either low dose aspirin (75 mg daily) or low dose aspirin and 5000 U of unfractionated heparin subcutaneously 12 hourly. All women started treatment with low dose aspirin when they had a positive urine pregnancy test. Women were randomly allocated an intervention when fetal heart activity was seen on ultrasonography. Treatment was stopped at the time of miscarriage or at 34 weeks' gestation.
MAIN OUTCOME MEASURES: Rate of live births with the two treatments.
RESULTS: There was no significant difference in the two groups in age or the number and gestation of previous miscarriages. The rate of live births with low dose aspirin and heparin was 71% (32/45 pregnancies) and 42% (19/45 pregnancies) with low dose aspirin alone (odds ratio 3.37 (95% confidence interval 1.40 to 8.10)). More than 90% of miscarriages occurred in the first trimester. There was no difference in outcome between the two treatments in pregnancies that advanced beyond 13 weeks' gestation. Twelve of the 51 successful pregnancies (24%) were delivered before 37 weeks' gestation. Women randomly allocated aspirin and heparin had a median decrease in lumbar spine bone density of 5.4% (range -8.6% to 1.7%).
CONCLUSION: Treatment with aspirin and heparin leads to a significantly higher rate of live births in women with a history of recurrent miscarriage associated with phospholipid antibodies than that achieved with aspirin alone.
Comparative trial of prednisone plus aspirin versus aspirin alone in the treatment of anticardiolipin antibody-positive obstetric patients.
OBJECTIVE: We compared the use of aspirin alone with combined therapy (prednisone plus aspirin) in antiphospholipid antibody-positive obstetric patients with prior adverse pregnancy outcome.
STUDY DESIGN: Thirty-nine patients meeting specific laboratory and clinical inclusion criteria were randomized to receive either combined therapy (prednisone plus low-dose aspirin, n = 17) or aspirin alone (n = 22). The daily aspirin dose was 81 mg; prednisone was begun at 20 mg/day and increased or decreased on the basis of observed changes in serial antibody levels. Perinatal outcomes were compared between groups. Evaluation of treatment-related maternal complications and serial antibody titers was also accomplished.
RESULTS: Thirty-four randomized subjects were evaluable (prednisone plus low-dose aspirin, n = 12 vs aspirin only, n = 22); no perinatal losses were observed in the study cohort. Preterm delivery was experienced by significantly more patients receiving prednisone plus low-dose aspirin than aspirin only (8/12 vs 3/22, respectively; p = 0.003), and prednisone exposure appeared to be an independent risk factor for preterm birth.
CONCLUSIONS: The use of prednisone therapy in conjunction with low-dose aspirin does not appear to improve outcome and may provoke obstetric complications in antiphospholipid antibody-positive patients.
Randomized study of subcutaneous low molecular weight heparin plus aspirin versus intravenous immunoglobulin in the treatment of recurrent fetal loss associated with antiphospholipid antibodies.
OBJECTIVE: To compare the 2 most efficacious therapeutic regimens, intravenous immunoglobulin (IVIG) and anticoagulation with low molecular weight (LMW) heparin plus low-dose aspirin, in women with recurrent pregnancy loss associated with antiphospholipid antibodies (aPL).
METHODS: We examined 40 women with recurrent abortion (at least 3 occurrences) and repeatedly positive test results for anticardiolipin or lupus anticoagulant. The subjects were randomly assigned to treatment with IVIG or LMW heparin plus low-dose aspirin. Both therapies were started when the women were pregnant as documented by a positive urine test. IVIG was stopped at the thirty-first week of gestation, aspirin at the thirty-fourth week, and heparin at the thirty-seventh week. The primary outcome of interest was the rate of live births with the 2 treatments.
RESULTS: The characteristics of the 2 groups were similar at the time of randomization. The women treated with LMW heparin plus low-dose aspirin had a higher rate of live births (84%) than those treated with IVIG (57%).
CONCLUSION: Treatment with LMW heparin plus low-dose aspirin should be considered as the standard therapy for recurrent pregnancy loss due to aPL.
Low-dose aspirin in prevention of miscarriage in women with unexplained or autoimmune related recurrent miscarriage: effect on prostacyclin and thromboxane A2 production.
Early pregnancies in women with a history of recurrent spontaneous abortion (RSA) are accompanied by a deficiency in vasodilatory and anti-aggregatory prostacyclin (PGI2) and/or overproduction of its endogenous antagonist thromboxane A2 (TXA2). We evaluated the effect of a low-dose aspirin (LDA) on PGI2 and TXA2 production and on pregnancy outcome in RSA women with and without detectable anticardiolipin antibodies (ACA). Of 82 RSA women studied, 66 became pregnant, and of them, 33 (six with elevated and 27 with normal ACA concentrations) were randomized to receive LDA (50 mg/day) and 33 (six with elevated and 27 with normal ACA concentrations) to receive placebo (PLA) from a mean of 6.6 days after the missed period to delivery. Treatment with LDA inhibited platelet TXA2 production similarly in RSA women with and without detectable ACA and with continuing pregnancies (7.0 +/- 0.7 ng/ml, LDA group versus 254.5 +/- 37.8 ng/ml, PLA group, mean +/- SEM, P < 0.0001) or miscarrying pregnancies (13.8 +/- 3.8 ng/ml compared with 233.6 +/- 59.8 ng/ml, P < 0.0001 respectively). Furthermore, LDA decreased urinary excretion of the TXA2 metabolite (2,3-dinor-TXB2) both in pregnancies which went to term (6.1 +/- 0.6 ng/mmol creatinine, LDA group versus 19.3 +/- 3.0 ng/mmol creatinine, PLA group, P < 0.0001) or again ended in miscarriage (4.7 +/- 0.8 ng/mmol creatinine versus 17.3 +/- 4.4 ng/mmol creatinine, P < 0.0001 respectively), but did not affect the excretion of the prostacyclin metabolite (2,3-dinor-6-keto-PGF1alpha). Early pregnancy ultrasound examination revealed a living fetus in 58 women. Of these, seven in the LDA group (23.3%, four with elevated and three with normal ACA concentrations) and five in the PLA group (17.9%, two with elevated and three with normal ACA concentrations; not significant) experienced a miscarriage. All infants were healthy, and the frequency of growth retardation was similar in both groups (13.0%). One woman in the LDA group (4.3%) and three women receiving PLA (13.0%) developed pre-eclampsia (not significant). Therefore, although treatment with LDA caused a desirable biochemical effect, it did not improve pregnancy outcome in RSA women with or without detectable ACA.
Low-dose aspirin in prevention of miscarriage in women with unexplained or autoimmune related recurrent miscarriage: effect on prostacyclin and thromboxane A2 production.
Early pregnancies in women with a history of recurrent spontaneous abortion (RSA) are accompanied by a deficiency in vasodilatory and anti-aggregatory prostacyclin (PGI2) and/or overproduction of its endogenous antagonist thromboxane A2 (TXA2). We evaluated the effect of a low-dose aspirin (LDA) on PGI2 and TXA2 production and on pregnancy outcome in RSA women with and without detectable anticardiolipin antibodies (ACA). Of 82 RSA women studied, 66 became pregnant, and of them, 33 (six with elevated and 27 with normal ACA concentrations) were randomized to receive LDA (50 mg/day) and 33 (six with elevated and 27 with normal ACA concentrations) to receive placebo (PLA) from a mean of 6.6 days after the missed period to delivery. Treatment with LDA inhibited platelet TXA2 production similarly in RSA women with and without detectable ACA and with continuing pregnancies (7.0 +/- 0.7 ng/ml, LDA group versus 254.5 +/- 37.8 ng/ml, PLA group, mean +/- SEM, P < 0.0001) or miscarrying pregnancies (13.8 +/- 3.8 ng/ml compared with 233.6 +/- 59.8 ng/ml, P < 0.0001 respectively). Furthermore, LDA decreased urinary excretion of the TXA2 metabolite (2,3-dinor-TXB2) both in pregnancies which went to term (6.1 +/- 0.6 ng/mmol creatinine, LDA group versus 19.3 +/- 3.0 ng/mmol creatinine, PLA group, P < 0.0001) or again ended in miscarriage (4.7 +/- 0.8 ng/mmol creatinine versus 17.3 +/- 4.4 ng/mmol creatinine, P < 0.0001 respectively), but did not affect the excretion of the prostacyclin metabolite (2,3-dinor-6-keto-PGF1alpha). Early pregnancy ultrasound examination revealed a living fetus in 58 women. Of these, seven in the LDA group (23.3%, four with elevated and three with normal ACA concentrations) and five in the PLA group (17.9%, two with elevated and three with normal ACA concentrations; not significant) experienced a miscarriage. All infants were healthy, and the frequency of growth retardation was similar in both groups (13.0%). One woman in the LDA group (4.3%) and three women receiving PLA (13.0%) developed pre-eclampsia (not significant). Therefore, although treatment with LDA caused a desirable biochemical effect, it did not improve pregnancy outcome in RSA women with or without detectable ACA.
Pregnancy outcome in recurrent spontaneous abortion associated with antiphospholipid antibodies: a comparative study of intravenous immunoglobulin versus prednisone plus low-dose aspirin.
PROBLEM: To compare the use of intravenous immunoglobulins (IVIG) with prednisone plus low-dose aspirin (LDA) in treating pregnant women with a history of recurrent fetal loss having the antiphospholipid antibody (aPL), in terms of live-birth rate and maternal and perinatal morbidity.
METHOD: A prospective, two-centers trial study included 82 recurrent aborters with aPL syndrome. Twenty-nine were treated with prednisone and LDA in one center, 53 received IVIG in the other center. Maternal and fetal outcomes and pregnancy complications were compared between groups.
RESULTS: Live-birth rates were equivalent between groups (78 vs 76%). Mean birth weight was higher in the IVIG group than in the prednisone plus LDA group. In the prednisone- plus LDA-treated patients, gestational hypertension and gestational diabetes were found significantly more often than in the IVIG-treated group (14 vs 5% and 14 vs 5%, respectively).
CONCLUSION: In patients with aPL syndrome, IVIG treatment improved pregnancy outcome, with significantly lower pregnancy complication rates, when compared with prednisone plus LDA therapy.
Options:
A: Aspirin alone
B: Low molecular weight heparin (LMWH) combined with aspirin
C: Unfractionated heparin combined with aspirin
D: Prednisone and aspirin | C |
430 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What were the main findings regarding the efficacy of tiotropium in the treatment of stable chronic obstructive pulmonary disease (COPD) compared to placebo and other bronchodilators? Please answer this question based on the information provided below:
[Efficacy of tiotropium bromide (Spiriva) in patients with chronic-obstructive pulmonary disease (COPD) of different severities].
BACKGROUND: Aim of this study was to evaluate the efficacy of inhaled Tiotropium bromide in COPD patients of different severities in pneumological practices during a three months clinical trial.
METHODS: A randomized, double blind, placebo controlled study including COPD-patients (FEV1/FVC < 70 %, FEV1 < or = 70 % predicted; age > or = 40 years; > or = 10 pack years) of different severities was performed. The efficacy of 18 microg Tiotropium bromide once daily on lung function and exacerbations over 12 weeks was evaluated by respective pulmonary function tests (spirometry) before (trough value) and 2 hours after inhalation of study medication.
RESULTS: 1639 patients (1236 Tiotropium bromide, 403 placebo; FEV1 reversibility after 200 microg Ipratropium bromide + 200 microg Fenoterol: 7.9 +/- 7.5 % predicted [mean +/- sd]) were randomized. After 12 weeks of treatment Tiotropium bromide led to significant increases of trough FEV1 (23 - 24 h after last inhalation; + 79 +/- 17 ml), and 2 h after Tiotropium bromide inhalation (+ 128 +/- 19 ml) (all values vs. placebo, adjusted mean +/- se, p < 0.0001). FVC and IVC were also improved significantly. In mild COPD (FEV1 > or = 50 - 70 %) improvements were most pronounced (trough FEV1 + 113 +/- 29 ml, 2 h post-inhalation + 181 +/- 33 ml; all values vs. placebo., p < 0.0001). 14.6 % of patients treated with Tiotropium bromide had a COPD exacerbation vs. 19.9 % of patients treated with placebo (p = 0.0151). The time to first exacerbation was prolonged (p = 0.0092 vs. placebo).
CONCLUSION: Tiotropium bromide 18 microg once daily led to a persistent improvement of lung function and a reduction of exacerbations in patients with COPD of different severities.
Health outcomes following treatment for six months with once daily tiotropium compared with twice daily salmeterol in patients with COPD.
BACKGROUND: A study was undertaken to record exacerbations and health resource use in patients with COPD during 6 months of treatment with tiotropium, salmeterol, or matching placebos.
METHODS: Patients with COPD were enrolled in two 6-month randomised, placebo controlled, double blind, double dummy studies of tiotropium 18 micro g once daily via HandiHaler or salmeterol 50 micro g twice daily via a metered dose inhaler. The two trials were combined for analysis of heath outcomes consisting of exacerbations, health resource use, dyspnoea (assessed by the transitional dyspnoea index, TDI), health related quality of life (assessed by St George's Respiratory Questionnaire, SGRQ), and spirometry.
RESULTS: 1207 patients participated in the study (tiotropium 402, salmeterol 405, placebo 400). Compared with placebo, tiotropium but not salmeterol was associated with a significant delay in the time to onset of the first exacerbation. Fewer COPD exacerbations/patient year occurred in the tiotropium group (1.07) than in the placebo group (1.49, p<0.05); the salmeterol group (1.23 events/year) did not differ from placebo. The tiotropium group had 0.10 hospital admissions per patient year for COPD exacerbations compared with 0.17 for salmeterol and 0.15 for placebo (not statistically different). For all causes (respiratory and non-respiratory) tiotropium, but not salmeterol, was associated with fewer hospital admissions while both groups had fewer days in hospital than the placebo group. The number of days during which patients were unable to perform their usual daily activities was lowest in the tiotropium group (tiotropium 8.3 (0.8), salmeterol 11.1 (0.8), placebo 10.9 (0.8), p<0.05). SGRQ total score improved by 4.2 (0.7), 2.8 (0.7) and 1.5 (0.7) units during the 6 month trial for the tiotropium, salmeterol and placebo groups, respectively (p<0.01 tiotropium v placebo). Compared with placebo, TDI focal score improved in both the tiotropium group (1.1 (0.3) units, p<0.001) and the salmeterol group (0.7 (0.3) units, p<0.05). Evaluation of morning pre-dose FEV(1), peak FEV(1) and mean FEV(1) (0-3 hours) showed that tiotropium was superior to salmeterol while both active drugs were more effective than placebo.
CONCLUSIONS: Exacerbations of COPD and health resource usage were positively affected by daily treatment with tiotropium. With the exception of the number of hospital days associated with all causes, salmeterol twice daily resulted in no significant changes compared with placebo. Tiotropium also improved health related quality of life, dyspnoea, and lung function in patients with COPD.
Effect of tiotropium bromide on circadian variation in airflow limitation in chronic obstructive pulmonary disease.
BACKGROUND: In chronic obstructive pulmonary disease (COPD), the degree of circadian variation in forced expiratory volume in 1 second (FEV1) and the influence of anticholinergic blockade is not known. Tiotropium is a long acting inhaled anticholinergic bronchodilator that increases daytime FEV1 in COPD. We hypothesised that tiotropium would modify the overnight change in FEV1, and this would be unaffected by the timing of drug administration.
METHODS: A double blind, randomised, placebo controlled trial was conducted with tiotropium 18 mg once daily in the morning (09.00 hours), evening (21.00 hours), or an identical placebo. Patients with stable COPD (n=121, FEV1=41% predicted) underwent spirometric tests every 3 hours for 24 hours at baseline and after 6 weeks of treatment.
RESULTS: There were no significant differences at baseline between the groups. Tiotropium improved mean (SE) FEV1 (over 24 hours) in the morning (1.11 (0.03) l) and evening (1.06 (0.03) l) groups compared with placebo (0.90 (0.03) l), and nocturnal FEV1 (mean of 03.00 and 06.00 hours) in the morning (1.03 (0.03) l) and evening (1.04 (0.03) l) groups compared with placebo (0.82 (0.03) l) at the 6 week visit (p<0.01). FEV1 before morning or evening dosing was similar, while the peak FEV1 moved later in the day with active treatment. The mean percentage change in FEV1 from 09.00 hours to 03.00 hours (the nocturnal decline in FEV1) was -2.8% in the morning group, -1.0% in the evening group, and -12.8% in the placebo group. The magnitude of the peak to trough change in FEV1 was not statistically different.
CONCLUSIONS: Tiotropium produced sustained bronchodilation throughout the 24 hour day without necessarily abolishing circadian variation in airway calibre.
The spirometric efficacy of once-daily dosing with tiotropium in stable COPD: a 13-week multicenter trial. The US Tiotropium Study Group.
STUDY OBJECTIVE: To compare the bronchodilator efficacy and safety of tiotropium and placebo.
DESIGN: A 3-month, randomized, double-blind, placebo-controlled, multicenter trial.
SETTING: Outpatient.
PATIENTS: Four hundred seventy patients with stable COPD (mean FEV(1) = 38.6% predicted).
INTERVENTIONS: Tiotropium 18 microg (N = 279) or placebo (N = 191) given once daily via a lactose-based dry-powder inhaler device.
MEASUREMENTS AND RESULTS: Spirometry was evaluated on days 1, 8, 50, and 92. Data were expressed as the mean trough (ie, before morning dose; 23 to 24 h after previous dose) and average response observed in the 3 h after the dose was received. Tiotropium produced significant improvement in trough FEV(1) and FVC, averaging 12% greater than baseline on day 8; these improvements were maintained on days 50 and 92. The average postdose FEV(1) was 16% greater than baseline on day 1 and 20% greater than baseline on day 92; FVC was 17% greater than baseline on day 1 and 19% greater than baseline on day 92. Tiotropium was significantly more effective than placebo in both trough and average FEV(1) and FVC response (p < 0.001). These spirometric effects were corroborated by significant improvements in daily morning and evening peak expiratory flow rate, as well as a reduction in "as-needed" albuterol use. Symptoms of wheezing and shortness of breath were significantly less in patients receiving tiotropium, and the physician global assessment noted overall improvements with those treated with tiotropium relative to placebo. The most common reported adverse event after tiotropium was dry mouth (9.3% vs 1.6% relative to placebo; p < 0.05).
CONCLUSIONS: These data demonstrate that tiotropium is a safe and effective once-daily anticholinergic bronchodilator and should prove useful as first-line maintenance therapy in COPD.
A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive pulmonary disease.
Currently available inhaled bronchodilators used as therapy for chronic obstructive pulmonary disease (COPD) necessitate multiple daily dosing. The present study evaluates the long-term safety and efficacy of tiotropium, a new once-daily anticholinergic in COPD. Patients with stable COPD (age 65.2+/-8.7 yrs (mean+/-SD), n=921) were enrolled in two identical randomized double-blind placebo-controlled 1-yr studies. Patients inhaled tiotropium 18 microg or placebo (mean screening forced expiratory volume in one second (FEV1) 1.01 versus 0.99 L, 39.1 and 38.1% of the predicted value) once daily as a dry powder. The primary spirometric outcome was trough FEV1 (i.e. FEV1 prior to dosing). Changes in dyspnoea were measured using the Transition Dyspnea Index, and health status with the disease-specific St. George's Respiratory Questionnaire and the generic Short Form 36. Medication use and adverse events were recorded. Tiotropium provided significantly superior bronchodilation relative to placebo for trough FEV1 response (approximately 12% over baseline) (p<0.01) and mean response during the 3 h following dosing (approximately 22% over baseline) (p<0.001) over the 12-month period. Tiotropium recipients showed less dyspnoea (p<0.001), superior health status scores, and fewer COPD exacerbations and hospitalizations (p<0.05). Adverse events were comparable with placebo, except for dry mouth incidence (tiotropium 16.0% versus placebo 2.7%, p<0.05). Tiotropium is an effective, once-daily bronchodilator that reduces dyspnoea and chronic obstructive pulmonary disease exacerbation frequency and improves health status. This suggests that tiotropium will make an important contribution to chronic obstructive pulmonary disease therapy.
Improvement in resting inspiratory capacity and hyperinflation with tiotropium in COPD patients with increased static lung volumes.
BACKGROUND: In patients with COPD, changes in inspiratory capacity (IC) have shown a higher correlation to patient-focused outcomes, such as dyspnea with exercise, than other standard spirometric measurements. Changes in IC reflect changes in hyperinflation. Tiotropium is a once-daily inhaled anticholinergic that has its effect through prolonged M3 muscarinic receptor antagonism and has demonstrated sustained improvements in spirometric and health outcomes. We sought to evaluate changes in resting IC and lung volumes after long-term administration of tiotropium.
METHODS: To evaluate the effect of tiotropium, 18 micro g/d, on IC, a 4-week, randomized, double-blind, placebo-controlled study was conducted in 81 patients with stable COPD. At each of the visits (weeks 0, 2, and 4) FEV(1), FVC, IC, slow vital capacity (SVC), and thoracic gas volume (TGV) were measured prior to study drug (- 60 and - 15 min) and after study drug (30 min, 60 min, 120 min, and 180 min).
RESULTS: Mean age was 64 years; 62% were men. Mean baseline FEV(1) was 1.12 L (43% predicted). The mean differences (tiotropium - placebo) in FEV(1) trough (morning before drug), peak, and area under the curve over 3 h values (adjusted for baseline and center differences) at week 4 were 0.16 L, 0.22 L, and 0.22 L, respectively (p < 0.01 for all); differences in IC for these variables were 0.22 L, 0.35 L, and 0.30 L (p < 0.01 for all). Differences in TGV were - 0.54 L, - 0.60 L, and - 0.70 L, respectively (p < 0.01 for all). The percentage improvement in area under the curve above baseline with tiotropium was similar among FEV(1) and lung volumes (FEV(1), 18%; FVC, 20%; SVC, 16%; IC, 16%; TGV, 14%).
CONCLUSIONS: Observed improvements in IC and reductions in TGV with once-daily tiotropium reflect improvements in hyperinflation that are maintained over 24 h.
A 6-month, placebo-controlled study comparing lung function and health status changes in COPD patients treated with tiotropium or salmeterol.
BACKGROUND: Tiotropium, a once-daily anticholinergic, and salmeterol represent two inhaled, long-acting bronchodilators from different pharmacologic classes. A trial was designed to examine the efficacy and safety of both compounds with multiple outcome measures, including lung function, dyspnea, and health-related quality of life (HRQoL) in patients with COPD.
METHODS: A 6-month, randomized, placebo-controlled, double-blind, double-dummy, parallel-group study of tiotropium, 18 microg once daily via dry-powder inhaler, compared with salmeterol, 50 microg bid via metered-dose inhaler, was conducted in patients with COPD. Efficacy was assessed by 12-h monitoring of spirometry, transition dyspnea index (TDI), and the St. George's Respiratory Questionnaire (SGRQ).
RESULTS: A total of 623 patients participated (tiotropium, n= 209; salmeterol, n = 213; and placebo, n = 201). The groups were similar in age (mean, 65 years), gender (75% men), and baseline FEV(1) (mean, 1.08 +/- 0.37 L; percent predicted, 40 +/- 12% [+/- SD]). Compared with placebo treatment, the mean predose morning FEV(1) following 6 months of therapy increased significantly more for the tiotropium group (0.14 L) than the salmeterol group (0.09 L; p < 0.01). The average FEV(1) (0 to 12 h) for tiotropium was statistically superior to salmeterol (difference, 0.08 L; p < 0.001). Tiotropium improved TDI focal score by 1.02 U compared with placebo (p = 0.01), whereas there was no significant change in TDI focal score with salmeterol (0.24 U). Tiotropium was superior to salmeterol in improving TDI focal score (p < 0.05). At 6 months, the mean improvement in SGRQ total score vs baseline was tiotropium, - 5.14 U (p < 0.05 vs placebo); salmeterol, - 3.54 U (p = 0.4 vs placebo); and placebo, - 2.43 U. A statistically higher proportion of patients receiving tiotropium achieved at least a 4-U change in SGRQ score compared to patients receiving placebo. Both active drugs reduced the need for rescue albuterol (p < 0.0001).
CONCLUSIONS: Tiotropium once daily produces superior bronchodilation, improvements in dyspnea, and proportion of patients achieving meaningful changes in HRQoL compared to twice-daily salmeterol in patients with COPD.
Long-acting bronchodilation with once-daily dosing of tiotropium (Spiriva) in stable chronic obstructive pulmonary disease.
Tiotropium (Spiriva; Ba679BR) is a new-generation, long-acting anticholinergic bronchodilator that has muscarinic M(1) and M(3) receptor subtype selectivity. A multicenter, randomized, double-blind, parallel group, placebo-controlled study was conducted to evaluate the dose-response characteristics of tiotropium inhalation powder given once daily to stable patients with chronic obstructive pulmonary disease (COPD). Patients (mean FEV(1) = 1.08 L [42% predicted]) were randomized to receive 0, 4.5, 9, 18, or 36 microg tiotropium once daily at noon for 4 wk, with spirometry done before and hourly for 6 h after dosing. Patients measured and recorded their peak expiratory flow rates (PEFRs) three times each day. Significant dose-related improvement in FEV(1) and significant improvement in FVC occurred within 1 h after the first dose of tiotropium as compared with placebo. Over the 29 d of the study, all doses of tiotropium produced significant increases over placebo in trough (i.e., as measured spirometrically at 20 to 24 h after the previous dose and just before the next dose of tiotropium), peak, and 6-h postdose average FEV(1) and FVC, and in PEFR, without a significant difference among the different doses investigated. PEFR gradually returned to pretreatment baseline levels over a 3-wk evaluation period following the discontinuation of tiotropium. The overall safety profile for the tiotropium doses was similar to that for placebo. In summary, tiotropium was shown to be safe and effective in doses ranging from 4.5 to 36 microg delivered once daily. The improvements in spirometry with once-daily dosing confirm the long duration of action of tiotropium reported in single-dose studies, and its sustained improvement of spirometric measures over the 1 mo of testing in the study points to utility of tiotropium as a maintenance bronchodilator for patients with COPD. On the basis of the comparable bronchodilator response at doses from 9 to 36 microg, and advantages suggested by the safety profile at doses below 36 microg in this study, a dose of 18 microg once daily was selected for use in long-term studies of the safety and efficacy of tiotropium.
Prevention of exacerbations of chronic obstructive pulmonary disease with tiotropium, a once-daily inhaled anticholinergic bronchodilator: a randomized trial.
BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) frequently develop exacerbations, leading to major clinical and health resource use ramifications.
OBJECTIVE: To prospectively evaluate the effectiveness of a long-acting inhaled anticholinergic bronchodilator, tiotropium, in reducing COPD exacerbations and exacerbation-related health care utilization.
DESIGN: Randomized, double-blind study.
SETTING: 26 Veterans Affairs medical centers.
PATIENTS: 1829 patients with moderate to severe COPD (mean baseline FEV(1), 36% predicted).
INTERVENTION: Once-daily tiotropium (18 microg) or placebo for 6 months. Patients otherwise received usual care, except for other anticholinergic bronchodilators.
MEASUREMENTS: The coprimary end points were the percentage of patients with a COPD exacerbation and the percentage of patients with a COPD-related hospitalization.
RESULTS: Tiotropium significantly reduced the percentage of patients experiencing 1 or more exacerbations compared with placebo (27.9% vs. 32.3%, respectively; difference, -5.7 percentage points [95% CI, -10.4 to -1.0 percentage points]; P = 0.037). Fewer tiotropium patients were hospitalized because of COPD exacerbation (7.0% vs. 9.5%, respectively; difference, -3.0 percentage points [CI, -5.9 to -0.1 percentage points]; P = 0.056), although this difference was of borderline statistical significance. Analysis of secondary outcomes indicates that tiotropium may lengthen the time to first COPD exacerbation (P = 0.028) and reduce health care utilization for exacerbations, including the frequency of hospitalizations (P = 0.047), unscheduled clinic visits (P = 0.019), and days of antibiotic treatment (P = 0.015). Tiotropium did not statistically significantly reduce all-cause hospitalization rates.
LIMITATIONS: Trial participants were enrolled from 1 health care system, and 99% were men. The follow-up period extended for only 6 months.
CONCLUSIONS: Tiotropium reduces COPD exacerbations and may reduce related health care utilization in patients with moderate to severe COPD.
Effects of tiotropium on lung hyperinflation, dyspnoea and exercise tolerance in COPD.
The aim of this study was to test the hypothesis that use of tiotropium, a new long-acting anticholinergic bronchodilator, would be associated with sustained reduction in lung hyperinflation and, thereby, would improve exertional dyspnoea and exercise performance in patients with chronic obstructive pulmonary disease. A randomised, double-blind, placebo-controlled, parallel-group study was conducted in 187 patients (forced expiratory volume in one second 44 +/- 13% pred): 96 patients received 18 microg tiotropium and 91 patients received placebo once daily for 42 days. Spirometry, plethysmographic lung volumes, cycle exercise endurance and exertional dyspnoea intensity at 75% of each patient's maximal work capacity were compared. On day 42, the use of tiotropium was associated with the following effects at pre-dose and post-dose measurements as compared to placebo: vital capacity and inspiratory capacity (IC) increased, with inverse decreases in residual volume and functional residual capacity. Tiotropium increased post-dose exercise endurance time by 105 +/- 40 s (21%) as compared to placebo on day 42. At a standardised time near end-exercise (isotime), IC, tidal volume and minute ventilation all increased, whilst dyspnoea decreased by 0.9 +/- 0.3 Borg scale units. In conclusion, the use of tiotropium was associated with sustained reductions of lung hyperinflation at rest and during exercise. Resultant increases in inspiratory capacity permitted greater expansion of tidal volume and contributed to improvements in both exertional dyspnoea and exercise endurance.
A randomised controlled comparison of tiotropium nd ipratropium in the treatment of chronic obstructive pulmonary disease. The Dutch Tiotropium Study Group.
BACKGROUND: A study was undertaken to evaluate and compare the efficacy and safety of tiotropium and ipratropium during long term treatment in patients with stable chronic obstructive pulmonary disease (COPD).
METHODS: 288 patients of mean (SD) age 65 (8) years and forced expiratory volume in one second (FEV(1)) 41 (12)% predicted participated in a 14 centre, double blind, double dummy, parallel group study and were randomised after a run in period of two weeks to receive either tiotropium 18 microg once daily from a dry powder inhaler (HandiHaler; two thirds of patients) or ipratropium 40 microg four times daily from a metered dose inhaler (one third of patients) for a period of 13 weeks. Outcome measures were lung function, daily records of peak expiratory flow (PEF), and the use of concomitant salbutamol. FEV(1) and forced vital capacity (FVC) were measured one hour before and immediately before inhalation (mean value of the two measurements on test day 1 was the baseline value while on all other test days it was known as the trough FEV(1) and FVC), and 0.5, 1, 2, 3, 4, 5, and 6 hours after inhalation of the study drug on days 1, 8, 50, and 92.
RESULTS: During treatment tiotropium achieved a significantly greater improvement than ipratropium (p<0.05) in trough, average, and peak FEV(1) levels and in trough and average FVC levels. The trough FEV(1) response on days 8, 50, and 92 ranged between 0.15 l (95% CI 0.11 to 0.19) and 0.16 l (95% CI 0.12 to 0.20) for tiotropium and between 0.01 l (95% CI -0.03 to 0.05) and 0.03 l (95% CI 0.01 to 0. 07) for ipratropium. The trough FVC response on days 8, 50, and 92 ranged between 0.34 l (95% CI 0.28 to 0.40) and 0.39 l (95% CI 0.31 to 0.47) for tiotropium and between 0.08 l (95% CI 0.00 to 0.16) and 0.18 l (95% CI 0.08 to 0.28) for ipratropium. On all test days tiotropium produced a greater improvement in FEV(1) than ipratropium starting three hours after inhalation (p<0.05). During treatment weekly mean morning and evening peak expiratory flow (PEF) was consistently better in the tiotropium group than in the ipratropium group, the difference in morning PEF being significant up through week 10 and in evening PEF up through week 7 of treatment (p<0.05). The use of concomitant salbutamol was also lower in the tiotropium group (p<0.05). The only drug related adverse event was dry mouth (tiotropium 14.7%, ipratropium 10.3% of patients).
CONCLUSIONS: Tiotropium in a dose of 18 microg inhaled once daily using the HandiHaler was significantly more effective than 40 microg ipratropium four times daily in improving trough, average, and peak lung function over the 13 week period. The safety profile of tiotropium was similar to ipratropium. These data support the use of tiotropium as first line treatment for the long term maintenance treatment of patients with airflow obstruction due to COPD.
Improved health outcomes in patients with COPD during 1 yr's treatment with tiotropium.
Tiotropium, a novel once-daily inhaled anticholinergic, has been shown to improve lung function over a 24-h period. In order to extend these findings, health-outcomes were evaluated over 1 yr in chronic obstructive pulmonary disease (COPD) patients. Spirometric results, peak expiratory flow rate (PEFR), salbutamol use and effects on dyspnoea, health-related quality of life and COPD exacerbations were assessed in two identical 1-yr randomized double-blind double-dummy studies of tiotropium 18 microg once daily (n=356) compared with ipratropium 40 microg q.i.d. (n=179). Screening forced expiratory volume in one second (FEV1) were 1.25+/-0.43 L (41.9+/-12.7% of the predicted value) (tiotropium) and 1.18+/-0.37 L (39.4+/-10.7% pred) (ipratropium). Trough FEV1 at 1 yr improved by 0.12+/-0.01 L with tiotropium and declined by 0.03+/-0.02 L with ipratropium (p<0.001). Significant improvement in PEFR, salbutamol use, Transition Dyspnea Index focal score, and the St George's Respiratory Questionnaire total and impact scores were seen with tiotropium (p<0.01). Tiotropium reduced the number of exacerbations (by 24%, p<0.01), and increased time to first exacerbation (p<0.01) and time to first hospitalization for a COPD exacerbation (p<0.05) compared with ipratropium. Apart from an increased incidence of dry mouth in the tiotropium group, adverse events were similar between treatments. Tiotropium was effective in improving dyspnoea, exacerbations, health-related quality of life and lung function in patients with chronic obstructive pulmonary disease, and exceeds the benefits seen with ipratropium. The data support the use of tiotropium once-daily as first-line maintenance treatment in patients with chronic obstructive pulmonary disease.
Options:
A: Tiotropium significantly reduced COPD exacerbations and related hospitalisations compared to placebo and ipratropium, and improved health-related quality-of-life and symptom scores.
B: Tiotropium had no significant effect on COPD exacerbations, hospitalisations, or quality-of-life compared to placebo and other bronchodilators.
C: Tiotropium increased the frequency of COPD exacerbations and hospitalisations compared to placebo and ipratropium, but improved quality-of-life and symptom scores.
D: Tiotropium had a significant effect on reducing COPD exacerbations and hospitalisations compared to long-acting ss2-agonists, but no effect on quality-of-life or symptom scores. | A |
431 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What are the potential benefits of using intravenous prostacyclin in adults with idiopathic primary pulmonary hypertension? Please answer this question based on the information provided below:
Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial.
BACKGROUND: Pulmonary hypertension is a progressive and often fatal complication of the scleroderma spectrum of disease for which no treatment has been proven effective in a randomized trial.
OBJECTIVE: To determine the effect of epoprostenol on pulmonary hypertension secondary to the scleroderma spectrum of disease.
DESIGN: Randomized, open-label, controlled trial.
SETTING: 17 pulmonary hypertension referral centers.
PATIENTS: 111 patients with moderate to severe pulmonary hypertension.
INTERVENTION: Epoprostenol plus conventional therapy or conventional therapy alone.
MEASUREMENTS: The primary outcome measure was exercise capacity. Other measures were cardiopulmonary hemodynamics, signs and symptoms of pulmonary hypertension and scleroderma, and survival.
RESULTS: Exercise capacity improved with epoprostenol (median distance walked in 6 minutes, 316 m at 12 weeks compared with 270 m at baseline) but decreased with conventional therapy (192 m at 12 weeks compared with 240 m at baseline). The difference between treatment groups in the median distance walked at week 12 was 108 m (95% CI, 55.2 m to 180.0 m) (P < 0.001). Hemodynamics improved at 12 weeks with epoprostenol. The changes in mean pulmonary artery pressure for the epoprostenol and conventional therapy groups were -5.0 and 0.9 mm Hg, respectively (difference, -6.0 mm Hg [CI, -9.0 to -3.0 mm Hg), and the mean changes in pulmonary vascular resistance were -4.6 and 0.9 mm Hg/L per minute, respectively (difference, -5.5 mm Hg/L per minute [CI, -7.3 to -3.7 mm Hg/L per minute). Twenty-one patients treated with epoprostenol and no patients receiving conventional therapy showed improved New York Heart Association functional class. Borg Dyspnea Scores and Dyspnea-Fatigue Ratings improved in the epoprostenol group. Trends toward greater improvement in severity of the Raynaud phenomenon and fewer new digital ulcers were seen in the epoprostenol group. Four patients in the epoprostenol group and five in the conventional therapy group died (P value not significant). Side effects of epoprostenol therapy included jaw pain, nausea, and anorexia. Adverse events related to the epoprostenol delivery system included sepsis, cellulitis, hemorrhage, and pneumothorax (4% incidence for each condition).
CONCLUSIONS: Continuous epoprostenol therapy improves exercise capacity and cardiopulmonary hemodynamics in patients with pulmonary hypertension due to the scleroderma spectrum of disease.
Survival in primary pulmonary hypertension with long-term continuous intravenous prostacyclin.
OBJECTIVE: To evaluate the effects of long-term-intravenous infusion of prostacyclin on exercise capacity, hemodynamics, and survival in patients with primary pulmonary hypertension.
DESIGN: Open, multicenter, uncontrolled trial.
SETTING: Four referral centers.
PATIENTS: 18 patients with primary pulmonary hypertension: 1 New York Heart Association (NYHA) class II patient, 13 NYHA class III patients, and 4 NYHA class IV patients.
INTERVENTIONS: Continuous intravenous prostacyclin administered by portable infusion pumps. All patients were treated with anticoagulant agents.
MEASUREMENTS AND MAIN RESULTS: With the 6-minute walk used to evaluate exercise capacity, patients could walk on average more than 100 meters farther after prostacyclin therapy was initiated (distance at 6 months, 370 +/- 119 meters compared with 264 +/- 160 meters at baseline; P < 0.001; distance at 18 months, 408 +/- 138 meters; P = 0.02 compared with baseline). Hemodynamics were improved at 6 months: The cardiac index increased 18% (95% CI, 0.1% to 36.7%; P = 0.02), and mean pulmonary artery pressure and total pulmonary resistance decreased 9% (CI, 1.4% to 15.7%; P = 0.03) and 26% (CI, 6.1% to 46.3%; P = 0.02), respectively, compared with baseline. The improvements in cardiac index and total pulmonary resistance were maintained at 12 months (27% increase [CI, 1.3% to 51.9%; P = 0.05] and 32% decrease [CI, 9.7% to 53.6%; P = 0.02] compared with baseline, respectively). Survival was improved in NYHA class III and IV patients who received continuous prostacyclin (n = 17; follow-up, 37 to 69 months) when compared with historical controls who received standard therapy (National Institutes of Health Primary Pulmonary Hypertension Registry, n = 31, P = 0.045). Kaplan-Meier estimates of 1-, 2-, and 3-year survival rates for the patients treated with prostacyclin were 86.9%, 72.4%, and 63.3%, respectively, compared with 77.4%, 51.6%, and 40.6% for the historical control group (hazard ratio, 2.9 [CI, 1.0 to 8.0; P = 0.045]). Serious complications attributable to the drug and delivery system included two deaths and seven episodes of nonfatal sepsis in three patients.
CONCLUSIONS: Continuous intravenous prostacyclin resulted in sustained clinical and hemodynamic improvement and probably in improved survival in patients with severe primary pulmonary hypertension. Despite potentially serious complications, long-term prostacyclin may be especially helpful in seriously ill patients awaiting transplantation.
Beraprost therapy for pulmonary arterial hypertension.
OBJECTIVES: The purpose of this study was to assess the safety and efficacy of the oral prostacyclin analogue beraprost sodium during a 12-month double-blind, randomized, placebo-controlled trial in patients with pulmonary arterial hypertension (PAH).
BACKGROUND: Pulmonary arterial hypertension is a progressive disease that ultimately causes right heart failure and death. Despite the risks from its delivery system, continuous intravenous epoprostenol remains the most efficacious treatment currently available.
METHODS: A total of 116 patients with World Health Organization (WHO) functional class II or III primary pulmonary hypertension or PAH related to either collagen vascular diseases or congenital systemic to pulmonary shunts were enrolled. Patients were randomized to receive the maximal tolerated dose of beraprost sodium (median dose 120 microg four times a day) or placebo for 12 months. The primary end point was disease progression; i.e., death, transplantation, epoprostenol rescue, or >25% decrease in peak oxygen consumption (VO(2)). Secondary end points included exercise capacity assessed by 6-min walk test and peak VO(2), Borg dyspnea score, hemodynamics, symptoms of PAH, and quality of life.
RESULTS: Patients treated with beraprost exhibited less evidence of disease progression at six months (p = 0.002), but this effect was not evident at either shorter or longer follow-up intervals. Similarly, beraprost-treated patients had improved 6-min walk distance at 3 months by 22 m from baseline and at 6 months by 31 m (p = 0.010 and 0.016, respectively) compared with placebo, but not at either 9 or 12 months. Drug-related adverse events were common and were related to the disease and/or expected prostacyclin adverse events.
CONCLUSIONS: These data suggest that beneficial effects may occur during early phases of treatment with beraprost in WHO functional class II or III patients but that this effect attenuates with time.
Effects of beraprost sodium, an oral prostacyclin analogue, in patients with pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled trial.
OBJECTIVES: The purpose of this study was to assess the efficacy and safety of beraprost sodium, an orally active prostacyclin analogue, in New York Heart Association (NYHA) functional class II and III patients with pulmonary arterial hypertension (PAH).
BACKGROUND: Pulmonary arterial hypertension is a life-threatening disease for which continuous intravenous infusion of prostacyclin has been proven effective. However, this treatment is associated with serious complications arising from the complex delivery system.
METHODS: In this double-blind, placebo-controlled study, 130 patients with PAH were randomized to the maximal tolerated dose of beraprost (median dose 80 microg four times a day) or to placebo for 12 weeks. The primary end point was the change in exercise capacity assessed by the 6-min walk test. Secondary end points included changes in Borg dyspnea index, cardiopulmonary hemodynamics and NYHA functional class.
RESULTS: Patients treated with beraprost improved exercise capacity and symptoms. The difference between treatment groups in the mean change of 6-min walking distance at week 12 was 25.1 m (95% confidence interval [CI]: 1.8 to 48.3, p = 0.036). The difference in the mean change of Borg dyspnea index was -0.94 (95% CI: -1.63 to -0.24, p = 0.009). In the sub-group of patients with primary pulmonary hypertension, the difference in the mean change of 6-min walking distance was 46.1 m (95% CI: 3.0 to 89.3, p = 0.035). Cardiopulmonary hemodynamics and NYHA functional class had no statistically significant changes. Drug-related adverse events were common in the titration phase and decreased in the maintenance period.
CONCLUSIONS: Beraprost improves exercise capacity and symptoms in NYHA functional class II and III patients with PAH and, in particular, in those with primary pulmonary hypertension.
Effects of beraprost sodium, an oral prostacyclin analogue, in patients with pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled trial.
OBJECTIVES: The purpose of this study was to assess the efficacy and safety of beraprost sodium, an orally active prostacyclin analogue, in New York Heart Association (NYHA) functional class II and III patients with pulmonary arterial hypertension (PAH).
BACKGROUND: Pulmonary arterial hypertension is a life-threatening disease for which continuous intravenous infusion of prostacyclin has been proven effective. However, this treatment is associated with serious complications arising from the complex delivery system.
METHODS: In this double-blind, placebo-controlled study, 130 patients with PAH were randomized to the maximal tolerated dose of beraprost (median dose 80 microg four times a day) or to placebo for 12 weeks. The primary end point was the change in exercise capacity assessed by the 6-min walk test. Secondary end points included changes in Borg dyspnea index, cardiopulmonary hemodynamics and NYHA functional class.
RESULTS: Patients treated with beraprost improved exercise capacity and symptoms. The difference between treatment groups in the mean change of 6-min walking distance at week 12 was 25.1 m (95% confidence interval [CI]: 1.8 to 48.3, p = 0.036). The difference in the mean change of Borg dyspnea index was -0.94 (95% CI: -1.63 to -0.24, p = 0.009). In the sub-group of patients with primary pulmonary hypertension, the difference in the mean change of 6-min walking distance was 46.1 m (95% CI: 3.0 to 89.3, p = 0.035). Cardiopulmonary hemodynamics and NYHA functional class had no statistically significant changes. Drug-related adverse events were common in the titration phase and decreased in the maintenance period.
CONCLUSIONS: Beraprost improves exercise capacity and symptoms in NYHA functional class II and III patients with PAH and, in particular, in those with primary pulmonary hypertension.
Efficacy and safety of treprostinil: an epoprostenol analog for primary pulmonary hypertension.
Intravenous epoprostenol is currently FDA approved for management of primary pulmonary hypertension, but it requires intravenous infusion and is associated with adverse effects. The objective of this study was to evaluate the effects of an epoprostenol analog, treprostinil, for management of pulmonary hypertension. Ten tertiary care academic institutions with pulmonary hypertension programs participated in these pilot trials. In the first trial, intravenous epoprostenol and intravenous treprostinil were compared. In the second trial, intravenous treprostinil and subcutaneous treprostinil were compared. In the third trial, subcutaneous treprostinil was compared with placebo infusion during an 8-week period. Intravenous epoprostenol and intravenous treprostinil resulted in a similar reduction in pulmonary vascular resistance acutely (22% and 20%, respectively). Intravenous treprostinil and subcutaneous treprostinil also demonstrated comparable short-term decrease in pulmonary vascular resistance (23% and 28%, respectively). The placebo-controlled 8-week trial demonstrated a mean improvement of 37 +/- 17 m as measured by the 6-minute walk distance in patients receiving treprostinil compared with a 6 +/- 28 m reduction in those receiving placebo. There were trends toward an improvement in cardiac index and pulmonary vascular resistance index in the treprostinil group. Subcutaneous treprostinil has favorable hemodynamic effects when given acutely and in the short term. Treprostinil can be given safely to an ambulatory patient with a novel subcutaneous delivery pump system.
Inhaled iloprost for severe pulmonary hypertension.
BACKGROUND: Uncontrolled studies suggested that aerosolized iloprost, a stable analogue of prostacyclin, causes selective pulmonary vasodilatation and improves hemodynamics and exercise capacity in patients with pulmonary hypertension.
METHODS: We compared repeated daily inhalations of 2.5 or 5.0 microg of iloprost (six or nine times per day; median inhaled dose, 30 microg per day) with inhalation of placebo. A total of 203 patients with selected forms of severe pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (New York Heart Association [NYHA] functional class III or IV) were included. The primary end point was met if, after week 12, the NYHA class and distance walked in six minutes were improved by at least one class and at least 10 percent, respectively, in the absence of clinical deterioration according to predefined criteria and death.
RESULTS: The combined clinical end point was met by 16.8 percent of the patients receiving iloprost, as compared with 4.9 percent of the patients receiving placebo (P=0.007). There were increases in the distance walked in six minutes of 36.4 m in the iloprost group as a whole (P=0.004) and of 58.8 m in the subgroup of patients with primary pulmonary hypertension. Overall, 4.0 percent of patients in the iloprost group (including one who died) and 13.7 percent of those in the placebo group (including four who died) did not complete the study (P=0.024); the most common reason for withdrawal was clinical deterioration. As compared with base-line values, hemodynamic values were significantly improved at 12 weeks when measured after iloprost inhalation (P<0.001), were largely unchanged when measured before iloprost inhalation, and were significantly worse in the placebo group. Further significant beneficial effects of iloprost treatment included an improvement in the NYHA class (P=0.03), dyspnea (P=0.015), and quality of life (P=0.026). Syncope occurred with similar frequency in the two groups but was more frequently rated as serious in the iloprost group, although this adverse effect was not associated with clinical deterioration.
CONCLUSIONS: Inhaled iloprost is an effective therapy for patients with severe pulmonary hypertension.
Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol). Results of a randomized trial.
STUDY OBJECTIVE: To determine the efficacy of continuous intravenous infusion of prostacyclin (epoprostenol) in primary pulmonary hypertension.
DESIGN: Randomized trial with 8-week treatment periods and nonrandomized treatment for up to 18 months.
SETTING: Four referral centers.
PATIENTS: Sequential sample of 24 patients with primary pulmonary hypertension. Nineteen patients completed the study. Four patients died and one left the study because of adverse effects (pulmonary edema).
INTERVENTIONS: Continuous intravenous prostacyclin administered by portable infusion pump at doses determined by acute responses during baseline catheterization in ten patients. Nine patients were treated with anticoagulants, oral vasodilators, and diuretics.
MEASUREMENTS AND MAIN RESULTS: Starting with a baseline value for total pulmonary resistance of 21.6 units, there was a decrease of 7.9 units (95% CI, -13.1 to -2.2; P = 0.022) in the prostacyclin-treated group after 8 weeks; there was virtually no change in the conventional therapy group (from 20.6 to 20.4 units, not significant). Six of ten prostacyclin-treated patients who completed the 8-week study period had reductions in mean pulmonary artery pressure of greater than 10 mm Hg, whereas only one of nine in the conventional treatment group had a similar response (P = 0.057). Nine patients receiving prostacyclin for up to 18 months have persistent hemodynamic effects, although dose requirements have increased with time. Complications have been attributable to the drug delivery system.
CONCLUSIONS: Prostacyclin produces substantial and sustained hemodynamic and symptomatic responses in severe primary pulmonary hypertension and may be useful in the management of some patients with this disease.
Treprostinil, a prostacyclin analogue, in pulmonary arterial hypertension associated with connective tissue disease.
STUDY OBJECTIVES: To assess the efficacy and safety of continuous subcutaneous infusion of treprostinil, a stable prostacyclin analogue, for treating pulmonary arterial hypertension (PAH) in patients with connective tissue disease (CTD).
DESIGN: Two multicenter, randomized, double-blind, placebo-controlled, prospective trials of treprostinil vs placebo in 470 patients with PAH.
PATIENTS: A subset of 90 patients with PAH and CTD, including systemic lupus erythematosus, diffuse scleroderma, limited scleroderma, and mixed CTD/overlap syndrome.
INTERVENTIONS: Patients received either treprostinil (initiated at 1.25 ng/kg/min, and titrated upward) or placebo via continuous subcutaneous infusion. The maximum dose of treprostinil allowed was 22.5 ng/kg/min.
MEASUREMENTS: Six-minute walk (6MW) distance and dyspnea-fatigue scores were determined at baseline, and at 6 weeks and 12 weeks. Hemodynamic measures were obtained at baseline and at 12 weeks.
RESULTS: At baseline, most patients had New York Heart Association class III symptoms. The mean baseline 6MW distance was 289 m (range, 60 to 448 m). The mean dose of treprostinil at week 12 was 8.4 ng/kg/min (range, 1.25 to 17.5 ng/kg/min). After 12 weeks, the change in cardiac index from baseline was + 0.2 +/- 0.08 L/min/m(2) in the treprostinil group and - 0.07 +/- 0.07 L/min/m(2) in the placebo group (p = 0.007). The pulmonary vascular resistance index decreased by 4 +/- 2 U x m(2) in the treprostinil group and increased by 1 +/- 1 U x m(2) in the placebo group (p = 0.006). The placebo-corrected median improvement from baseline in 6MW distance was 25 m in treprostinil-treated patients (p = 0.055); this improvement appeared to be dose related. Dyspnea fatigue scores also improved in the treprostinil group compared with the placebo group (p = 0.014). Adverse events included infusion site pain and typical side effects related to prostaglandins, and were tolerated by most patients.
CONCLUSIONS: Continuous subcutaneous infusion of treprostinil in patients with PAH associated with CTD improved exercise capacity, symptoms of PAH, and hemodynamics.
Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double-blind, randomized, placebo-controlled trial.
Pulmonary arterial hypertension is a life-threatening disease for which continuous intravenous prostacyclin has proven to be effective. However, this treatment requires a permanent central venous catheter with the associated risk of serious complications such as sepsis, thromboembolism, or syncope. Treprostinil, a stable prostacyclin analogue, can be administered by a continuous subcutaneous infusion, avoiding these risks. We conducted a 12-week, double-blind, placebo-controlled multicenter trial in 470 patients with pulmonary arterial hypertension, either primary or associated with connective tissue disease or congenital systemic-to-pulmonary shunts. Exercise capacity improved with treprostinil and was unchanged with placebo; the between treatment group difference in median six-minute walking distance was 16 m (p = 0.006). Improvement in exercise capacity was greater in the sicker patients and was dose-related, but independent of disease etiology. Concomitantly, treprostinil significantly improved indices of dyspnea, signs and symptoms of pulmonary hypertension, and hemodynamics. The most common side effect attributed to treprostinil was infusion site pain (85%) leading to premature discontinuation from the study in 8% of patients. Three patients in the treprostinil treatment group presented with an episode of gastrointestinal hemorrhage. We conclude that chronic subcutaneous infusion of treprostinil is an effective treatment with an acceptable safety profile in patients with pulmonary arterial hypertension.
Failure of vasoldilator infusion to alter pulmonary diffusing capacity in systemic sclerosis.
PURPOSE: Patients with systemic sclerosis (SSc) do not exhibit a normal increase in the diffusing capacity for carbon monoxide (DLCO) on assuming the supine position. We sought to determine whether a potent prostacyclin derivative and vasodilator, iloprost, would reverse this defect.
PATIENTS AND METHODS: Fourteen patients with SSc were enrolled in a randomized, double-blind, placebo-controlled study of iloprost. Patients were tested before and during 3 days of iloprost or placebo infusion with both upright and supine pulmonary function studies.
RESULTS: The results of baseline pulmonary function studies including DLCO were not significantly altered by iloprost. Furthermore, iloprost did not alter the abnormal postural DLCO response.
CONCLUSION: These results suggest that the pulmonary vascular defects seen in this group of patients are not a consequence of reversible pulmonary vasospasm.
Options:
A: Significant improvements in exercise capacity, NYHA functional class, and cardiopulmonary haemodynamics over short-term treatment.
B: No significant improvements in any measured outcomes over short-term treatment.
C: Significant improvements in exercise capacity only, with no changes in NYHA functional class or cardiopulmonary haemodynamics.
D: Significant improvements in NYHA functional class only, with no changes in exercise capacity or cardiopulmonary haemodynamics. | A |
432 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What is the conclusion regarding the effectiveness of base infusion or fluid bolus in reducing morbidity and mortality in preterm infants with metabolic acidosis? Please answer this question based on the information provided below:
Controlled trial of bicarbonate therapy in high-risk premature newborn infants.
Sixty-two high-risk acidemic premature newborn infants, given maintenance intravascular infusions of 10% glucose, were assigned to liberal or restricted sodium bicarbonate treatment groups. Those infants in the liberal group received 5 to 15 mEq bicarbonate/dl 10% glucose, depending on the degree of acidosis. Among infants given bicarbonate, correction of pH was not more rapid and mortality was not decreased. Instead, there was a small increase in the number of deaths, but the incidence of intraventricular hemorrhage was similar to that in infants not given bicarbonate.
Comparison of albumin versus bicarbonate treatment for neonatal metabolic acidosis.
UNLABELLED: In this study the effectiveness of 4.5% human albumin was compared with 4.2% sodium bicarbonate for neonatal metabolic acidosis, using a randomised controlled trial. The change in median pH following bicarbonate was more than twice that in the albumin group. This was statistically significant.
CONCLUSION: In normotensive infants, use of bicarbonate to correct metabolic acidosis may be more effective than use of albumin.
Options:
A: Base infusion significantly reduces mortality and adverse neurodevelopmental outcomes.
B: Fluid bolus significantly reduces mortality and adverse neurodevelopmental outcomes.
C: Both base infusion and fluid bolus significantly reduce mortality and adverse neurodevelopmental outcomes.
D: There is insufficient evidence to determine whether base infusion or fluid bolus reduces morbidity and mortality. | D |
433 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What are the most effective first-line therapies for the emergency management of hyperkalaemia, and what combination of treatments may be considered when hyperkalaemia is severe? Please answer this question based on the information provided below:
Nebulized albuterol for acute hyperkalemia in patients on hemodialysis.
STUDY OBJECTIVE: To determine the efficacy and safety of nebulized albuterol in the acute treatment of hyperkalemia in patients on chronic hemodialysis.
DESIGN: Prospective, double-blind, and placebo-controlled study.
SETTING: Outpatient hemodialysis clinic at a university medical center.
PATIENTS: Ten patients on maintenance hemodialysis who had chronic hyperkalemia.
INTERVENTIONS: Patients received nebulized albuterol therapy (10 mg or 20 mg) or placebo (saline) on three separate occasions, serial measurements of plasma potassium levels, blood pressure, and pulse were then taken for a 2-hour period.
MEASUREMENTS AND MAIN RESULT: Patients had a significant decrease in plasma potassium concentrations that was evident by 30 minutes and sustained for at least 2 hours after albuterol treatment. After the administration of 10- and 20-mg doses of albuterol, the maximal decrease in the plasma potassium levels was 0.62 +/- 0.09 and 0.98 +/- 0.14 mmol/L (SE), respectively. Nebulized saline administration did not produce a significant change in the plasma potassium concentrations. Patients did not develop symptoms or significant changes in blood pressure or heart rate with albuterol treatment.
CONCLUSIONS: In the doses used, nebulized albuterol therapy resulted in a prompt and significant decrease in the plasma potassium concentrations in patients on hemodialysis, and caused no adverse cardiovascular effects. This treatment should be considered as an important adjunct for acute treatment of serious hyperkalemia in this population of patients.
Albuterol and insulin for treatment of hyperkalemia in hemodialysis patients.
We evaluated in maintenance hemodialysis patients the potassium lowering effects of intravenous insulin with glucose, nebulized albuterol, and a regimen combining both modalities. There was a similar decrease in plasma potassium following either insulin with glucose (0.65 +/- 0.09 mmol/liter) or albuterol (0.66 +/- 0.12 mmol/liter), and a substantially greater fall with the combined regimen (1.21 +/- 0.19 mmol/liter, P less than 0.02 vs. either drug alone). Baseline plasma glucose concentrations were similar (about 4.8 mmol/liter) prior to all three treatments. Following insulin with glucose, plasma glucose increased transiently. but then fell to 2.8 +/- 0.3 mmol/liter at one hour, with concentrations below 3 mmol/liter in 9 of 12 patients. None of the patients had symptoms of hypoglycemia. Plasma glucose increased to 6.8 +/- 0.5 mmol/liter with albuterol. After the combined drug regimen plasma glucose rose transiently and was back to baseline (4.7 +/- 0.7 mmol/liter) at one hour. Treatment with insulin or albuterol produced trivial increases in heart rate, whereas the combined drug regimen was associated with a significant rise (15.1 +/- 6.0 min-1). These observations suggest that albuterol and insulin with glucose are equally efficacious in lowering plasma potassium in uremic patients, and that the hypokalemic effects of the two drugs is additive. The hypoglycemic effect of insulin is attenuated by coadministration albuterol. Combined therapy with insulin, glucose and albuterol is efficacious and safe for the acute treatment of hyperkalemia in hemodialysis patients.
Effect of albuterol treatment on subsequent dialytic potassium removal.
End-stage renal disease patients presenting with severe hyperkalemia are frequently treated with albuterol to lower their plasma potassium acutely, until emergent hemodialysis can be initiated. Such treatment stimulates potassium shifts from the extracellular to the intracellular fluid compartments. The resulting reduction of potassium concentration gradient between the blood and dialysate may potentially attenuate the efficacy of potassium removal during the ensuing hemodialysis treatment. To evaluate the effect of prior albuterol treatment on dialytic potassium removal, seven chronic hemodialysis patients were studied prospectively on two separate occasions. In one study the patients received 20 mg nebulized albuterol 30 minutes before dialysis; in the control study, albuterol treatment was omitted. Plasma potassium decreased 30 minutes after albuterol treatment (-0.84 +/- 0.06 mmol/L; P < 0.001) and remained unchanged in the corresponding period of the control experiment. Plasma potassium decreased during dialysis in both experimental protocols, but was significantly lower throughout dialysis in the albuterol study, as compared with the control study. Cumulative dialytic potassium removal was significantly lower following albuterol pretreatment compared with the control experiment (29.0 +/- 5.7 mmol v 49.6 +/- 7.0 mmol; P < 0.001). These observations suggest that acute albuterol therapy in patients with end-stage renal disease may substantially decrease potassium removal in the ensuing hemodialysis session. This may lead to rebound hyperkalemia several hours after the dialysis treatment.
Effect of bicarbonate administration on plasma potassium in dialysis patients: interactions with insulin and albuterol.
Acute treatment of hyperkalemia in patients with end-stage renal disease requires temporizing measures to shift potassium rapidly from the extracellular to the intracellular fluid compartments until hemodialysis can be initiated. Whereas insulin and albuterol are effective in lowering plasma potassium acutely, bicarbonate by itself is not. Bicarbonate administration may, however, potentiate the effects of insulin and albuterol on plasma potassium. Using a prospective cross-over design, we investigated the acute effects of (1) isotonic bicarbonate, (2) isotonic saline, (3) insulin + bicarbonate, (4) insulin + saline, (5) albuterol + bicarbonate, and (6) albuterol + saline on plasma potassium as well as blood bicarbonate and pH in nondiabetic hemodialysis patients. After obtaining a baseline blood sample, the subjects received one of the six treatment protocols, with plasma potassium measured every 15 minutes over 1 hour. Neither isotonic bicarbonate nor isotonic saline decreased plasma potassium significantly (-0.03 +/- 0.06 mmol/L v -0.01 +/- 0.10 mmol/L at 60 minutes; P = 0.60). Intravenous insulin decreased plasma potassium by a similar degree when given in conjunction with bicarbonate or saline (-0.81 +/- 0.05 mmol/L v -0.85 +/- 0.06 mmol/L at 60 minutes; P = 0.65). Likewise, nebulized albuterol decreased plasma potassium by a similar degree when given with bicarbonate or saline (-0.71 +/- 0.16 mmol/L v -0.53 +/- 0.15 mmol/L at 60 minutes; P = 0.18). The three protocols that included bicarbonate administration resulted in significant increases in blood bicarbonate (P < 0.005) and pH (P < 0.01), whereas the three protocols that included saline did not affect blood bicarbonate or pH. These observations suggest that bicarbonate administration does not potentiate the potassium-lowering effects of insulin or albuterol in hemodialysis patients.
Effect of single dose resin-cathartic therapy on serum potassium concentration in patients with end-stage renal disease.
Hyperkalemia in patients with renal failure is frequently treated with a cation exchange resin (sodium polystyrene sulfonate, hereafter referred to as resin) in combination with a cathartic, but the effect of such therapy on serum potassium concentration has not been established. This study evaluates the effect of four single-dose resin-cathartic regimens and placebo on 5 different test days in six patients with chronic renal failure. Dietary intake was controlled. Fecal potassium output and serum potassium concentration were measured for 12 h. Phenolphthalein alone caused an average fecal potassium output of 54 mEq. The addition of resin caused an increase in insoluble potassium output but a decrease in soluble potassium output; therefore, there was no significant effect of resin on total potassium output. Sorbitol plus resin caused less potassium output than phenolphthalein plus resin. On placebo therapy, the average serum potassium concentration increased slightly (0.4 mEq/L) during the 12-h experiment. This rise was apparently abrogated by some of the regimens that included resin; this may have been due in part to extracellular volume expansion caused by absorption of sodium released from resin. Phenolphthalein regimens were associated with a slight rise in serum potassium concentrations (similar to placebo); this may have been due to extracellular volume contraction produced by high volume and sodium-rich diarrhea and acidosis secondary to bicarbonate losses. None of the regimens reduced serum potassium concentrations, compared with baseline levels. Because single-dose resin-cathartic therapy produces no or only trivial reductions in serum potassium concentration, and because this therapy is unpleasant and occasionally is associated with serious complications, this study questions the wisdom of its use in the management of acute hyperkalemic episodes.
Increasing blood flow increases kt/V(urea) and potassium removal but fails to improve phosphate removal.
BACKGROUND: Hyperphosphatemia and hyperkalemia are major determinants of morbidity and mortality in hemodialysis patients. Half of the dialysis population suffers from hyperphosphatemia which is now recognized as an important cardiovascular disease risk factor. It is, therefore, necessary to improve the removal of these molecules. In this study, we investigated the effect of enhancing blood flow on Kt/V for urea (Kt/Vu), potassium and phosphate removal.
METHODS: Thirteen patients were investigated in a randomized, cross-over, prospective study using 3 blood flows (Qb) of 200,250 and 300 ml/min which gave 39 standardized high-flux hemodialysis treatments. Effective blood flows were measured by ultrasonic flow meter. Quantification of delivered dialysis dose was performed by partial dialysate and ultrafiltrate collection for the determination of potassium and phosphate removal and by blood urea concentrations for determination of Kt/Vu.
RESULTS: Kt/Vu rose significantly from 1.10 +/- 0.14 to 1.22 +/- 0.14 and finally to 1.39 +/- 0.16 (p = 0.0001) with increasing Qb similar to the increase in potassium removal from 53.0 +/- 2.4 to 63.4 +/- 2.6 and to 74.2 +/- 3.8 mMol (p = 0.01). Phosphate removal only improved from 28.1 +/- 1.3 to 31.4 +/- 1.5 (p = 0.050) when Qb was increased from 200 to 250 ml/min but remained unchanged at 31.2 +/- 1.5 mMol (NS compared to phosphate removal at Qb = 250 ml/min) when Qb was increased to 300 ml/min.
CONCLUSIONS: Increasing delivered Kt/Vu and potassium removal with higher Qb fails to produce the same desired effect with phosphate removal during high-flux hemodialysis.
Comparison of aminophylline and insulin-dextrose infusions in acute therapy of hyperkalemia in end-stage renal disease patients.
OBJECTIVE: This study was performed to compare the efficacy of aminophylline and insulin-dextrose infusion as acute treatment modality of hyperkalemia in patients with end-stage renal disease (ESRD).
METHODS: This study was conducted on 30 ESRD patients with serum potassium > 6.0 mEq/L. These patients were divided in two groups of 15 each. Group A patients were treated with aminophylline infusion, whereas group B patients were treated with insulin-dextrose infusion. Serum potassium and other biochemical parameters such as blood sugar were measured at beginning of treatment followed by at 60 minutes, 180 minutes, and 360 minutes after treatment.
RESULTS: Intervenous infusion of aminophylline lowered plasma potassium from 6.48 +/- 0.39 mEq/L to 5.92 +/- 0.40 mEq/L at 180 minutes (p < 0.001 Vs basal) and 6.05 +/- 0.53 mEq/L at 360 minutes (p < 0.01 Vs basal). Whereas, intravenous infusion of insulin-dextrose decreased plasma potassium from 6.59 +/- 0.31 mEq/L to 5.76 +/- 0.32 mEq/L (p < 0.001 Vs basal) and 5.84 +/- 0.21 mEq/L (p < 0.001 Vs basal). Thus in both groups, plasma potassium levels were significantly less than basal levels throughout the study. The decrease in plasma potassium was significantly more in group B patients (p value is < 0.001 after 60 minutes, < 0.05 after 180 minutes and < 0.05 after 360 minutes) when compared to group A patients. There was one episode of hypoglycemia (blood sugar < 60 mg%) in insulin-dextrose infusion group. No other side effects were observed throughout the study.
CONCLUSION: Aminophylline is an effective modality for acute treatment of hyperkalemia, though it is less effective than insulin-dextrose infusion. However, more studies are required to confirm these results.
Salbutamol metered-dose inhaler with spacer for hyperkalemia: how fast? How safe?
OBJECTIVE: To determine the efficacy of inhaled salbutamol (rapidly delivered, using a metered-dose inhaler with a spacer device [MDI-S]) in lowering the serum potassium levels in patients with hyperkalemia.
DESIGN: A randomized, double-blind, placebo-controlled trial.
PATIENTS: Seventeen chronic renal failure patients referred to the Nephrology Unit between October 1, 1997 and March 31, 1998 for hemodialysis were randomized.
INTERVENTION AND RESULTS: Group 1 received salbutamol followed by a placebo. Group 2 received a placebo followed by salbutamol. Each patient inhaled 1,200 microg salbutamol or a placebo through an MDI-S within 2 min. Blood samples were obtained repeatedly before inhalation and after 1, 3, 5, 10, and 60 min. The pulse rate and blood pressure were repeatedly measured. Insulin levels were examined in a subset of patients (n = 10) before, and 1 and 5 min following inhalation. Salbutamol's known side effects, palpitation, tachycardia tremor, and headache, were recorded. Potassium levels rose after 1 min following the completion of treatment and then decreased steadily thereafter. A rise of > or = 0.1 mEq/L was seen in 10 of 17 patients (59%) during the treatment period and there was no change (0%) seen during the placebo period (p < 0.0001). Within 3 min after inhalation of salbutamol, potassium levels declined as a function of time. Potassium levels in those patients taking the placebo did not change as a function of time (p < 0.001). The difference between the placebo and the salbutamol-treated periods reached significance after 5 min (p < 0.05). The serum glucose levels rose following inhalation of salbutamol, with a significant rise after 3 min. The heart rate rose significantly within the first 5 min following inhalation. Serum insulin levels remained unchanged 1 min after inhalation; however, after 5 min, a significant elevation was detected.
CONCLUSION: Salbutamol inhalation of 1,200 microg, using an MDI-S, has a relatively rapid onset of action that induces a consistent reduction in serum potassium levels, starting 3 to 5 min following delivery. Unexpectedly, a paradoxical elevation was detected in serum potassium levels in the first minutes following inhalation. This effect, although minor (0.15 mEq/L above baseline), may cast some doubt on the role of salbutamol inhalation as the first treatment for excessive hyperkalemia.
Treatment of hyperkalaemia using intravenous and nebulised salbutamol.
In 11 children (aged 5-18 years) with end stage chronic renal failure, the effect on plasma potassium of two doses of salbutamol (separated by two hours) given intravenously (4 micrograms/kg) and on a separate date, of salbutamol administered by nebuliser (2.5 mg if the child weighed below 25 kg, 5 mg if above) was observed. Within 30 minutes of the first dose, the mean plasma potassium concentration fell significantly by 0.87 and 0.61 mmol/l after intravenous and nebulised administration respectively. Sixty minutes after the second dose the plasma potassium was significantly reduced by a further 0.28 and 0.53 mmol/l respectively. There was a significant difference between the two methods of administration at 300 minutes after the first dose favouring nebulisation. No major side effects were observed. Nebulised salbutamol should be the first choice emergency treatment of hyperkalaemia.
Treatment of hyperkalaemia by altering the transcellular gradient in patients with renal failure: effect of various therapeutic approaches.
Ten patients with acute and 60 with chronic renal failure (both groups having hyperkalaemia), were managed at Kenyatta National Hospital in the medical wards and Renal Unit between August, 1995 and January, 1996. They were divided into seven different treatment groups, each consisting of ten patients. Treatment A glucose 25g i.v. with insulin 10 units i.v., treatment B 50 mmol of 8.4% sodium bicarbonate infusion, treatment C 0.5mg of salbutamol i.v. in 50mls 5% dextrose, treatment D was a combination of treatments A and B, treatment E was a combination of treatment B and C, treatment F was a combination of treatments A and C while treatment G was a combination of treatments A and B and C. Serum potassium was measured, 30 minutes, 1 hour, 2 hours, 4 hours and 8 hours after treatment. Plasma glucose concentration was measured before treatment was given and 1 hour after in all patients. Electrocardiography was done before treatment on all patients and repeated 30 minutes and 1 hour after treatment for the patients with hyperkalaemic changes on the initial recording. All treatment modalities had satisfactory potassium lowering effects. Of the single therapeutic approaches, treatment A and C were equieffective, but better than treatment B (P < 0.001). Amongst the two regimen combinations, treatment D and F were more efficacious than treatment E and all the single therapeutic approaches (P < 0.001). Treatment G was the most efficacious in lowering serum potassium in this study. All treatment modalities had maximum serum potassium lowering effect at 1-2 hours. A fall in plasma glucose concentration was a notable feature of treatments A and D, but significant hypoglycaemia occurred in 20% of patients receiving treatment A and in none on treatment D. The ECG changes of hyperkalaemia did not correlate with serum potassium levels. The normalisation of hyperkalaemic ECG alteration occurred within the first 30 minutes after treatment. In conclusion, combination therapies for hyperkalaemia appear to be more efficacious than single therapeutic approaches. Inclusion of salbutamol seems to protect against insulin induced hypoglycaemia. The maximum potassium lowering effect is observed 1-2 hours of administration of either agents. The potassium reducing effect remains significant compared to baseline values even after 8 hours. If dialysis cannot be instituted early enough it seems reasonable to repeat treatment every 4-6 hours to sustain the effect. Repeated administration of glucose with insulin may not be safe because of the hypoglycaemic effect. Other single and combination therapies can theoretically be repeated regularly until dialysis is initiated although this requires further clinical evaluation.
Levalbuterol is as effective as racemic albuterol in lowering serum potassium.
Albuterol is an effective treatment for hyperkalemia through beta-adrenergic induction of potassium (K+) uptake. Levalbuterol, the R-enantiomer of racemic albuterol, is used for the treatment of asthma and 0.63 mg of levalbuterol has the same therapeutic efficacy as 2.5 mg of albuterol but with a decreased adverse effects profile. We hypothesized that levalbuterol can reduce serum K+ levels similarly to albuterol when used in equipotent doses. In a randomized, double blind, placebo-controlled prospective study, we compared the K+-lowering effects of nebulized saline and equipotent bronchodilatory doses of albuterol (10 mg) and levalbuterol (2.5 mg) in healthy adult volunteers. Nine subjects entered each of the three study groups. Serum K+ was measured at baseline, at 30 min (immediately after treatment), at 60 min, and at 90 min. All adverse effects were recorded. The three groups had similar baseline K+ values. Immediately after nebulization, only levalbuterol showed a significant decrease in potassium level (p = 0.024). At 30 and 60 min after treatment, both albuterol and levalbuterol groups had significantly lower K+ values compared to placebo. No significant difference occurred between the albuterol and levalbuterol groups. Levalbuterol caused fewer reported adverse effects compared to albuterol.
Low-potassium and glucose-free dialysis maintains urea but enhances potassium removal.
BACKGROUND: The influence of potassium (K) removal on dialysis efficiency as measured by urea elimination is not clear. In this prospective, randomized, cross-over study we investigated the magnitude of K removal and its effect on urea (u) elimination during high-flux haemodialysis (HD).
METHODS: Twelve stable, non-diabetic HD patients were investigated during three one-week standardized HD periods (1.8 m(2) high-flux polysulphone dialyser, treatment time 240 min, Qb = 300 ml/min, Qd = 500 ml/min, dialysate without glucose, bicarbonate 40 mmol/l), using dialysates containing 0 (0K), 1 (1K), and 2 (2K) mmol/l of K. Mass removal of K (M(K)) and u (M(U)) were measured during the mid-week treatment by partial dialysate collection. Urea reduction rate (URR) and Kt/V were determined.
RESULTS: 0K, 1K and 2K treatments were perfectly comparable. Plasma K (PK) continuously declined reaching stable concentrations after 180 min. While 0K dialysate removed 117.1 mmol, 80.2 and 63.3 mmol (P < 0.001) were removed by 1K and 2K baths respectively. M(U) was not influenced by M(K) (r = 0.22) and amounted to 491.1 (0K), 508.6 (1K), and 506.2 (2K) mmol (NS) respectively. Accordingly, urea clearance, URR and Kt/V were constant during 0K, 1K and 2K treatments.
CONCLUSIONS: Potassium-free dialysate significantly enhances potassium elimination. Potassium removal has no influence on urea elimination. High potassium removal, when needed, does not impair dialysis efficiency as measured by urea kinetics in high-flux, glucose-free, 40 mmol/l bicarbonate HD.
Options:
A: Nebulised or inhaled salbutamol, or IV insulin-and-glucose; their combination may be more effective than either alone.
B: IV bicarbonate and K-absorbing resin; their combination may be more effective than either alone.
C: Oral potassium binders and dietary potassium restriction; their combination may be more effective than either alone.
D: Oral potassium binders and IV calcium; their combination may be more effective than either alone. | A |
434 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What is the effect of prescribing bed rest during pregnancy on the prevention of miscarriage in women at high risk of miscarriage? Please answer this question based on the information provided below:
The management of bleeding in early pregnancy.
Ultrasound scan findings were analysed for 187 women referred to an emergency gynaecological scanning clinic during a seven month period, with bleeding in early pregnancy. One sixth of the women were not pregnant, one third had non-viable pregnancies and one half had viable pregnancies; 9% of this latter group subsequently miscarried. For the majority of women referred to the clinic, bed rest would have been inappropriate. In this study the value of bed rest and hospitalisation was considered uncertain for women with viable singleton pregnancies of 7-14 weeks gestation and bleeding in the previous 24 hours. Only 23 women with otherwise uncomplicated pregnancies met these criteria and consented to recruitment to a randomized controlled trial: three subsequently miscarried. Emergency scanning as a routine part of the gynaecological service is recommended, thus confining bed rest to those women with viable pregnancies. Reliable evaluation of bed rest and hospitalisation for such women will require a multicentre study.
A comparative study of human chorionic gonadotropin, placebo, and bed rest for women with early threatened abortion.
OBJECTIVE: To compare the effect of hCG therapy with placebo or bed rest in women with threatened abortion.
DESIGN: Random assignment, double-blind.
SETTING: Community hospitals.
PATIENTS AND INTERVENTIONS: Sixty-one women with viable pregnancies under 8 weeks' gestation on admission to hospital were randomly allocated to receive injections of hCG or placebo, or were advised to rest in bed.
MAIN OUTCOME MEASURES: Abortion vs. continuation of pregnancy at 16 weeks' gestation.
RESULTS: Thirty-one aborted: 6/20 on hCG, 10/21 on placebo, 15/20 on bed rest. hCG vs. bed rest, P < .01; placebo vs. bed rest, hCG vs. placebo--not significant. Plasma progesterone: continuing pregnancy > abortion, P < .01; continued with hCG vs. aborted on placebo, P < .001; continued with hCG vs. aborted with bed rest, P < .001. No significant differences in pregnancy/birth complications or infants' birth weight. Female/male ratio was 2:1.
CONCLUSIONS: hCG is significantly better than bed rest.
Options:
A: Bed rest significantly reduces the risk of miscarriage compared to no intervention.
B: Bed rest significantly increases the risk of miscarriage compared to no intervention.
C: There is no statistically significant difference in the risk of miscarriage between women prescribed bed rest and those who are not.
D: Bed rest is more effective than human chorionic gonadotrophin therapy in preventing miscarriage. | C |
435 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What was the conclusion regarding the effectiveness of interventions aimed at improving adherence to treatment recommendations in people with type 2 diabetes mellitus? Please answer this question based on the information provided below:
Intervention study for smoking cessation in diabetic patients: a randomized controlled trial in both clinical and primary care settings.
OBJECTIVE: To evaluate the effectiveness of a nurse-managed smoking cessation intervention in diabetic patients.
RESEARCH DESIGN AND METHODS: This randomized controlled clinical trial involved 280 diabetic smokers (age range 17-84 years) who were randomized either into control (n = 133) or intervention (n = 147) groups at 12 primary care centers and 2 hospitals located in Navarre, Spain. The intervention consisted of a 40-min nurse visit that included counseling, education, and contracting information (a negotiated cessation date). The follow-up consisted of telephone calls, letters, and visits. The control group received the usual care for diabetic smokers. Baseline and 6-month follow-up measurements included smoking status (self-reported cessation was verified by urine cotinine concentrations), mean number of cigarettes smoked per day, and stage of change.
RESULTS: At the 6-month follow-up, the smoking cessation incidence was 17.0% in the intervention group compared with 2.3% in the usual care group, which was a 14.7% difference (95% CI 8.2-21.3%). Among participants who continued smoking, a significant reduction was evident in the average cigarette consumption at the 6-month follow-up. The mean number of cigarettes per day decreased from 20.0 at baseline to 15.5 at 6 months for the experimental group versus from 19.7 to 18.1 for the control group (P < 0.01).
CONCLUSIONS: A structured intervention managed by a single nurse was shown to be effective in changing the smoking behavior of diabetic patients.
Management of patients with type 2 diabetes by pharmacists in primary care clinics.
OBJECTIVE: To determine the impact of clinical pharmacists involved in direct patient care on the glycemic control of patients with type 2 diabetes mellitus.
DESIGN: Eligible patients included those with type 2 diabetes who received insulin or were initiated on insulin therapy by the pharmacists and were willing to perform self-monitoring of blood glucose. The pharmacists provided diabetes education, medication counseling, monitoring, and insulin initiation and/or adjustments. All initial patient interactions with the pharmacists were face-to-face. Thereafter, patient-pharmacist interactions were either face-to-face or telephone contacts.
SETTING: Two primary care clinics in a university-affiliated Veterans Affairs Medical Center.
PARTICIPANTS: Study subjects were patients with type 2 diabetes who were referred to the pharmacists by their primary care providers for better glycemic control.
OUTCOME MEASURES: Primary outcome variables were changes from baseline in glycosylated hemoglobin, fasting blood glucose, and random blood glucose measurements. Secondary outcomes were the number and severity of symptomatic episodes of hypoglycemia, and the number of emergency room visits or hospitalizations related to diabetes. Twenty-three veterans aged 65-9.4 years completed the study. Fifteen (65%) patients were initiated on insulin by the pharmacists; 8 (35%) were already using insulin. Patients were followed for a mean-SD of 27-10 weeks. Glycosylated hemoglobin, fasting blood glucose concentrations, and random blood glucose concentrations significantly decreased from baseline by 2.2% (p = 0.00004), 65 mg/dL (p < 0.01), and 82 mg/dL (p = 0.00001), respectively. Symptomatic hypoglycemic episodes occurred in 35% of patients. None of these episodes required physician intervention.
CONCLUSIONS: This study demonstrates that pharmacists working as members of interdisciplinary primary care teams can positively impact glycemic control in patients with type 2 diabetes requiring insulin.
Effect of a pharmacist-managed diabetes care program in a free medical clinic.
Diabetes care, morbidity, and mortality are usually worse in poor minority populations compared with non-minority ones. This report evaluates evidence-based process and outcome measures of diabetes care in diabetic patients followed in a free medical clinic and compares them to published results. The following process measures compared favorably with measures of the general population: dilated eye and foot exams and measurements of glycated hemoglobin levels; concentrations of total cholesterol; fasting triglycerides and low density lipoprotein (LDL) cholesterol; and proteinuria (by dipstick). Process and outcome measures in 89 diabetic patients referred to a Diabetes Management Program in which diabetes care was delivered by pharmacists following detailed algorithms (experimental group) were compared with measures in 92 diabetic patients who received diabetes care in the general clinic setting (control group). The patients in the experimental group had a slightly longer duration of diabetes and more microvascular and neuropathic complications, and more diabetic patients were taking insulin than were patients in the control group. All of the process measures listed above were more frequent in the experimental group. Compared with the control group, the initial glycated hemoglobin level (% +/- SE) in the experimental group was significantly (P < .001) higher (8.8 +/- 0.2 versus 7.9 +/- 0.2) but fell significantly (P < .03) more (-0.8 +/- 0.2 versus -0.05 +/- 0.3). The lack of a greater decrease in the glycated hemoglobin levels in the experimental group was not related to the inability of the pharmacists to follow the algorithms, the patients' refusal to follow the recommended medication adjustments, or the lack of appropriate self-monitoring of blood glucose in insulin-requiring patients. It was inversely related (r = -0.36, P < .03) to the number of missed visits, i.e., the greater the number of broken appointments, the less the glycated hemoglobin fell. In conclusion, diabetes care for a poor minority population in a free clinic setting can compare favorably to care in the general population. Pharmacists following detailed algorithms can enhance this care further. Administrative and support system changes that minimize the number of missed visits might further improve diabetes care in this population.
Medication compliance in non-insulin-dependent diabetes: a randomized comparison of chlorpropamide and insulin.
Medication compliance may be a problem in the management of patients with diabetes. Some physicians initially treat patients having non-insulin-dependent diabetes with oral sulfonylureas because they fear greater compliance problems with insulin therapy. We compared compliance with insulin and chlorpropamide in patients newly beginning medication for NIDDM. Seventy-seven adults with hyperglycemia despite diet therapy were randomly assigned to chlorpropamide or insulin. Compliance was measured four times over 24 wk. Patients then crossed over to the other medication and were followed for 24 additional weeks. Overall, there were no differences in compliance with the two medications in terms of percent of prescription used, proportion taking at least 80% of prescribed medication, self-report of medication or diet compliance, or protocol dropout rates. However, treatment satisfaction was higher with chlorpropamide, and most patients preferred chlorpropamide to insulin (P less than 0.0001). While such differences in satisfaction may affect long-term compliance, physicians should not assume that their patients will be less compliant with insulin than with oral sulfonylureas.
A randomized study of the impact of home health aides on diabetic control and utilization patterns.
Home health aides were offered to half of a group of 227 low-income diabetic clinic patients; in the group offered aides, fasting blood sugar (FBS) declined when compared to control group (10.1 mg/dl vs an increase of 5.1 mg/dl), and missed clinic appointments and emergency room use also decreased. The group of 44, who, upon offer of an aide actually accepted one, showed a significant increase in eye clinic appointments as well as the greatest decline in FBS (13.9 mg/dl).
Evaluation of a pharmaceutical care model on diabetes management.
OBJECTIVE: To assess the effectiveness of a pharmaceutical care model on the management of non-insulin-dependent diabetes mellitus (NIDDM) in urban African-American patients.
DESIGN: Eligible patients were randomized to either a pharmacist intervention or control group and followed over a 4-month period. Patients in the intervention group received diabetes education, medication counseling, instructions on dietary regulation, exercise, and home blood glucose monitoring, and evaluation and adjustment of their hypoglycemic regimen. Patients in the control group continued to receive standard medical care provided by their physicians.
SETTING: A university-affiliated internal medicine outpatient clinic.
PARTICIPANTS: The study population consisted of urban African American patients with NIDDM currently attending the clinic.
MAIN OUTCOME MEASURES: Primary outcome measures included fasting plasma glucose and glycated hemoglobin concentrations. Secondary outcome endpoints included blood pressure, serum creatinine, creatinine clearance, microalbumin to creatinine ratio, total cholesterol, triglycerides, high-density lipoprotein, and low density lipoprotein concentrations. Quality-of-life assessments were performed in both groups at baseline and at the end of the study.
RESULTS: Thirty-nine patients (17 intervention, 22 control) completed the study. The intervention group consisted of 12 women and 5 men with a mean +/- SD age of 59 +/- 12 years, total body weight (TBW) of 93 +/- 22 kg, body mass index (BMI) of 34 +/- 7 kg/m2, and duration of NIDDM 6.8 +/- 6.5 years. The control group consisted of 15 women and 7 men with a mean age of 65 +/- 12 years, TBW of 88 +/- 19 kg, BMI of 33 + 7 kg/m2, and a duration of NIDDM of 6.2 +/- 4.8 y. Significant improvement in glycated hemoglobin (p = 0.003) and fasting plasma glucose (p =0.015) was achieved in the intervention group. No change in glycemia was observed in the control subjects. Statistically significant differences in the final glycated hemoglobin (p = 0.003) and fasting plasma glucose (p = 0.022) concentrations were noted between groups. No significant changes in blood pressure control, lipid profile, renal function parameters, weight, or quality-of-life measures were noted within or between groups.
CONCLUSIONS: Our data demonstrate the effectiveness of pharmaceutical care in the reduction of hyperglycemia associated with NIDDM in a group of urban African-American patients.
Assessment of the function and effect of diabetes education programs in Taiwan.
A multi-center prospective study was conducted to assess the function and impact of diabetic education programs on diabetic control. A total of 208 subjects with type 2 diabetes were recruited. Diabetes self-care, assessed by questionnaire, was evaluated before, and 4 months after attending a diabetes education course. A total of 121 subjects who received advanced diabetes education courses were designated as the experimental group. A second group of 87 cases receiving a basic course served as controls. In addition to basic knowledge, the advanced education programs included dietary control, blood glucose monitoring, management of hypoglycemia, medication compliance, foot care and exercise. Diabetes self-care techniques were significantly improved in the experimental group. The overall score for diabetes self-care techniques improved in both groups at the 4th month over baseline values. The change was significant with the controls' (P < 0.001). Multiple regression analysis confirmed the intensity of diabetic education was the only significant variable correlated with the decrease of fasting blood glucose and systolic blood pressure. In conclusion, integrated and intensive diabetes education program in diabetes education centers provides an effective method for improving diabetes self-care techniques and metabolic outcome.
Effect of diabetes education on glucose control.
After diabetes education, 39 adult diabetic patients were randomized to either an education group or control group. The two groups received identical medical care and follow-up, except that the education group met with their diabetes educator on at least a quarterly basis. Neither group showed any statistically significant change in their glycosylated hemoglobin values, although the education group did have a 4% drop after initial education compared to a 6% rise in the control group. The education group had a lower attrition rate and a better improvement in self-rated dietary compliance. Education remains the cornerstone of diabetes management. Our team identified some trends between the two groups as well as some ideas to improve motivating and developing a stronger and more effective relationship with our patients.
Pharmacists' interventions using an electronic medication-event monitoring device's adherence data versus pill counts.
OBJECTIVE: To compare adherence data from an electronic medication-event monitoring device (MEMS, Aprex) with pill counts in assisting pharmacists in making recommendations regarding diabetes therapy.
DESIGN: Two-month, double-blind, randomized, controlled trial.
SETTING: Veterans Affairs Medical Center ambulatory care clinics.
PATIENTS: Forty-seven patients with poor to fair metabolic control of diabetes mellitus were enrolled. Patients were excluded if they were receiving insulin, had a concurrent infection, required child-resistant caps or medication remainder devices, or could not return for followup visits. Twenty patients were randomized to the MEMS and 27 to the control group (pill counts). Fasting plasma glucose concentrations were measured monthly and glycohemoglobin concentrations were measured at baseline and 60 days. Thirty-two patients were evaluable: 15 using MEMS and 17 using pill counts.
INTERVENTION: Investigators made pharmacologic or educational recommendations to the patient's healthcare provider based on both laboratory data and MEMS readings in the treatment group or laboratory data and pill counts in the control group.
MAIN OUTCOME MEASURE: Quantities and types of recommendations regarding diabetes therapy made by pharmacists using adherence data from the two methods were tabulated.
RESULTS: In the MEMS group, 47 percent of the recommendations related to patient education compared with 12 percent in the control group (p = 0.028). MEMS data would have changed four recommendations in the control group to involve patient education.
CONCLUSIONS: MEMS data resulted in different numbers and types of recommendations than pill counts. Pharmacists then could make specific recommendations regarding patient education before resorting to pharmacologic manipulations.
Telemedicine improved diabetic management.
Effective control of diabetes is known to delay or prevent the end-organ complications of this disease. Can telemedicine improve a patient's ability to self-manage diabetes? Twenty-eight patients entered a study comparing home telemedicine consultation with standard outpatient care. A nurse case manager contacted the telemedicine group once a week under the direction of a primary care physician, who contacted the telemedicine group once a month. Laboratory studies and total body weight were measured at the beginning and at the end of the 3-month study. The hemoglobin A1c (HbA1c) and total body weight improved significantly in the intervention (telemedicine) group, as shown by a 16% reduction in mean HbA1c level (from 9.5 to 8.2%) and a 4% mean weight reduction (from 214.3 to 206.7 pounds). Based on our experience, we present a functionally based telemedicine classification system to improve the application of electronic medicine in future studies.
Impact of dosage frequency on patient compliance.
OBJECTIVE: To evaluate the impact of dosage frequency on the compliance of patients who receive their medicines from community pharmacies.
RESEARCH DESIGN AND METHODS: Each month, patients received a supply of their medication in a Medication Event Monitoring Systems container, which registered each opening of the package. At the end of the study, the patients received a short questionnaire. The subjects were 91 diabetic patients using oral antidiabetic agents. Patients taking insulin and those who were unable to collect their medicines from the pharmacy were excluded from the study. Compliance was defined as the percentage of doses taken during the observation period. Another parameter used was compliance with the prescribed regimen, defined as the percentage of days in which the number of tablets were taken as prescribed. As a last parameter, compliance with the prescribed dose intervals was used.
RESULTS: Compliance is influenced by the frequency of doses. The compliance for this group of patients is 74.8%, with an average of 79% in the case of a dose once daily and 38% in the case of a dose three times daily. The predominant type of noncompliance in all groups was dose omissions. However, more than one-third of the patients used more doses than prescribed. Overconsumption is a frequently made mistake by patients on a one-dose daily schedule.
CONCLUSIONS: The reduction of dose frequency may decrease total noncompliance, but at the same time, it increases the risk of overconsumption. Reducing the frequency does not automatically result in a better therapeutic schedule. The choice of once or twice daily should depend on the therapeutic range of the drug.
Impact of automated calls with nurse follow-up on diabetes treatment outcomes in a Department of Veterans Affairs Health Care System: a randomized controlled trial.
OBJECTIVE: We evaluated automated telephone disease management (ATDM) with telephone nurse follow-up as a strategy for improving diabetes treatment processes and outcomes in Department of Veterans Affairs (VA) clinics. We also compared the results with those of a prior ATDM trial conducted in a county health care system.
RESEARCH DESIGN AND METHODS: A total of 272 VA patients with diabetes using hypoglycemic medications were randomized. During the 1-year study period, intervention patients received biweekly ATDM health assessment and self-care education calls, and a nurse educator followed up with patients based on their ATDM assessment reports. Telephone surveys were used to measure patients' self-care, symptoms, and satisfaction with care. Outpatient service use was evaluated using electronic databases and self-reports, and glycemic control was measured by HbA1c and serum glucose testing.
RESULTS: At 12 months, intervention patients reported more frequent glucose self-monitoring and foot inspections than patients receiving usual care and were more likely to be seen in podiatry and diabetes specialty clinics. Intervention patients also were more likely than control patients to have had a cholesterol test. Among patients with baseline HbA1c levels > or =8%, mean end-point values were lower among intervention patients than control patients (8.7 vs. 9.2%, respectively; P = 0.04). Among intervention and control patients with baseline values > or =9%, mean end-point values were 9.1 and 10.2%, respectively (P = 0.04). At follow-up, intervention patients reported fewer symptoms of poor glycemic control than control patients and greater satisfaction with their health care.
CONCLUSIONS: This intervention improved the quality of VA diabetes care. Intervention effects for most end points replicated findings from the prior county clinic trial, although intervention-control differences in the current study were smaller because of the relatively good self-care and health status among the current study's enrollees.
Use of a pharmacologic indicator to compare compliance with tablets prescribed to be taken once, twice, or three times daily.
By use of an interview, return tablet count, and a pharmacologic indicator (low-dose phenobarbital), we compared compliance with tablets prescribed to be taken once, twice, or three times daily. One hundred seventy-nine patients with type II diabetes were randomly allocated to take one 2 mg phenobarbital tablet once, twice, or three times daily for 28 days. Phenobarbital level/dose ratios indicated that compliance was similar with once- and twice-daily regimens, and both were better than thrice-daily dosing. Mean return tablet counts suggested that compliance was best with the once-daily regimen; both twice- and thrice-daily regimens were similarly inferior. This difference between the techniques may be explained by the inadequacies of the residual tablet count, which identified only 13% of cases identified by phenobarbital. We conclude that compliance with the once-daily regimen was best, but that compliance with a twice-daily regimen was very similar, and both were superior to dosing three times a day.
Teaching patients to monitor their risk factors retards the progression of vascular complications in high-risk patients with Type 2 diabetes mellitus--a randomized prospective study.
AIMS: Intensive management of risk parameters in diabetic patients may retard the progression of both micro- and macrovascular complications. Intensified care requires expert staff and is expensive. The aim of the present study was to examine whether sharing the therapeutic responsibility with the patients will improve the outcome.
METHODS: A randomized prospective study of 165 patients with diabetes mellitus Type 2, hypertension (> 140/90 mmHg) and hyperlipidaemia (LDL-C > 120 mg/dl). Patients were randomly allocated to standard annual consultation (SC) or to a patient participation programme (PP). The medical care for both groups was administered by primary care physicians, who were unaware of the nature of the intervention.
RESULTS: At 4 years the mean blood pressure was 148/88 (+/- 6.1/1.7) mmHg in the SC patients vs. 142/84 (+/- 5.8/1.8) mmHg in the PP group (P = 0.02). The mean LDL-C was 124 +/- 8 and 114 +/- 6 mg/dl (P = 0.01) and the mean HbA1c was 8.9 +/- 1.2% and 8.2 +/- 1.5% (P = 0.04) in the SC and PP groups, respectively. The average annual fall in estimated glomerular filtration rate was 3.5 ml/min per year in the SC group vs. 2.25 in the PP group (P < 0.05). Albumin/creatinine ratio > 300 mg/g developed in four SC patients vs. none of the PP patients. There was a total of 36 cardiovascular events in the SC group vs. 23 in the PP group (P = 0.04). All patients in the PP group received ACE inhibitors (or AII blockers) and statins vs. 52% and 43%, respectively, in the SC group. Glucose-lowering regimens were similar.
CONCLUSIONS: Well-informed and motivated patients were more insistent to reach and maintain target values of the main risk factors of diabetic complications. The differences between the PP and SC groups were of the same order of magnitude as those between intensive and standard care groups in other studies albeit with, comparatively, a very modest cost.
Can medication packaging improve glycemic control and blood pressure in type 2 diabetes? Results from a randomized controlled trial.
OBJECTIVE: To assess the impact of calendar blister pack (CBP) use on glycemic and blood pressure control.
RESEARCH DESIGN AND METHODS: We conducted an 8-month randomized controlled double-blind study among diabetic patients with poor glucose control (HbA1c >9.0%) in an urban area of South Auckland, New Zealand, with a high proportion of Maori and Pacific Islands people. Subjects included 68 consecutive patients, of whom 50% were prescribed three or more medications per day
RESULTS: HbA1c was reduced by 0.95+/-0.22% in the CBP group and 0.15+/-0.25% in the control group (P = 0.026). Diastolic blood pressure decreased 5.8+/-1.5 mm Hg in the CBP group and increased 0.1+/-1.9 mm Hg in the control group (P = 0.0041). Systolic blood pressure did not change significantly
CONCLUSIONS: CBPs should be considered among diabetic patients with poor glycemic control receiving multiple medications.
Effect of value-added utilities on prescription refill compliance and Medicaid health care expenditures--a study of patients with non-insulin-dependent diabetes mellitus.
An estimated 20 million Americans suffer from diabetes. Patients with non-insulin-dependent diabetes mellitus (NIDDM) comprise approximately 90% of the diabetic population. An estimated 10-30% of patients with NIDDM withdraw from their prescribed regimen within 1 year of diagnosis, and of the remainder, nearly 20% administer insufficient medication to facilitate an adequate reduction in blood glucose. A randomized trial was undertaken to discern the effect of pharmacy-based value-added utilities on prescription-refill compliance with sulfonylurea therapy and health service utilization. The subjects were 258 Medicaid beneficiaries from the state of South Carolina, previously untreated for NIDDM, prescribed 5 mg of the second-generation sulfonylurea glyburide twice daily, and monitored with regard to prescription-refill compliance and health service utilization for 1 year. Subjects provided informed consent and were randomly assigned to one of four experimental groups: (i) the control cohort received standard pharmaceutical care with each dispensing of glyburide; (ii) the second cohort received standard pharmaceutical care and was mailed a medication-refill reminder 10 days prior to each sequential refill date; (iii) the third cohort received standard pharmaceutical care and was provided unit-of-use packaging with each prescription-refill request; (iv) the fourth cohort received standard pharmaceutical care, mailed medication-refill reminders, and unit-of-use packaging. Analysis of variance (ANOVA) procedures revealed that patients receiving mailed prescription-refill reminders, unit-of-use packaging, or a combination of both interventions achieved a significant (P < or = 0.05) increase in the Medication Possession Ratio (MPR) for sulfonylurea therapy relative to controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Increasing prescribed office visits. A controlled trial in patients with diabetes mellitus.
Patients who fail to show for scheduled visits or who fail to contact their provider when warning symptoms occur pose important problems for the primary care physician. A group of interventions was examined to determine the effectiveness in increasing the number of prescribed office visits in patients with diabetes mellitus. This group of interventions included mailed packets with information on how to use the clinic, providers' names and phone numbers, after-hours phone numbers, a list of early warning signs, and a booklet on managing diabetes mellitus; mailed appointment reminders; and intense follow-up of visit failures for prompt rescheduling. Eight hundred fifty-nine patients on drug therapy for diabetes mellitus were stratified by risk of hospitalization and randomly assigned within strata to control and intervention groups. The intervention group received all interventions. After 1 year, the intervention group averaged 12% more total contacts than the control group (5.8 vs. 5.2, P = 0.01), due largely to an increase in kept scheduled visits (4.1 vs. 3.6, P = 0.006). These effects were greatest in those patients at higher risk of hospitalization. Also, visit failures were reduced only in high-risk patients. The effect of the interventions did not diminish during the year of study. This systematic and repetitive intervention appears effective in increasing prescribed office visits and is especially effective in patients requiring more frequent care.
Management of obese patients with diabetes mellitus: comparison of advice education with group management.
The purpose of our study was to compare the effect on diabetes control of group management with the advice-educational technique traditionally used in managing obese outpatients with poorly controlled non-insulin-dependent diabetes mellitus (NIDDM). Forty-one patients were randomly assigned to these two treatment programs, and 32 patients completed the 6-mo study. Initially, patients were seen for 1-h sessions at 1- and 2-wk intervals and later at 1-mo intervals. Patients were asked to do home blood glucose monitoring, decrease caloric intake, increase exercise, and if they were taking insulin, to adjust the dose to attain approximate euglycemia and to stabilize food and exercise patterns. The combined groups reduced mean +/- SD glycohemoglobin from 10.9 +/- 3.1 to 9.4 +/- 2.4% (P less than .05). Internal Health Locus of Control Scale was negatively and significantly correlated with initial and subsequent glycohemoglobin values (the more internal, the lower the glycohemoglobin). At the end of the study the patients in the group management program had significantly lower blood glucose levels than those given advice and education, but no significant differences in glycohemoglobin values or percentage overweight were observed. One patient had a normal initial glycohemoglobin, and only 4 patients had values in the normal range of 4-6.8% at the end of the study. Better management programs need to be developed for treating obese outpatients with NIDDM.
Options:
A: Interventions showed significant improvements in adherence and reduced complications.
B: Interventions had a small effect on various outcomes, but no significant overall impact on adherence.
C: Interventions led to significant improvements in quality of life and reduced mortality and morbidity.
D: Interventions were found to be harmful and decreased adherence to treatment recommendations. | B |
436 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What are the comparative effects of intramuscular olanzapine versus other treatments for managing acute agitation or aggression in people with severe mental illness? Please answer this question based on the information provided below:
A double-blind, randomized comparison of the efficacy and safety of intramuscular injections of olanzapine, lorazepam, or placebo in treating acutely agitated patients diagnosed with bipolar mania.
There are no rapid-acting intramuscular formulations of atypical antipsychotics available for quickly calming an agitated patient with bipolar disorder. In this study, 201 agitated patients with bipolar mania were randomly assigned to receive one to three injections of the atypical antipsychotic olanzapine (10 mg, first two injections; 5 mg, third injection), the benzodiazepine lorazepam (2 mg, first two injections; 1 mg, third injection), or placebo (placebo, first two injections; olanzapine, 10 mg, third injection) within a 24-hour period. Agitation was measured at baseline, every 30 minutes for the first 2 hours, and at 24 hours after the first injection using the Positive and Negative Syndrome Scale-Excited Component subscale and two additional agitation scales. At 2 hours after the first injection, patients treated with olanzapine showed a significantly greater reduction in scores on all agitation scales compared with patients treated with either placebo or lorazepam. At 24 hours after the first injection, olanzapine remained statistically superior to placebo in reducing agitation in patients with acute mania, whereas patients treated with lorazepam were not significantly different from those treated with placebo or olanzapine. Furthermore, no significant differences among the three treatment groups were observed in safety measures, including treatment-emergent extrapyramidal symptoms, the incidence of acute dystonia, or QTc interval changes. These findings suggest that intramuscular olanzapine is a safe and effective treatment for reducing acute agitation in patients with bipolar mania.
Comparison of rapidly acting intramuscular olanzapine, lorazepam, and placebo: a double-blind, randomized study in acutely agitated patients with dementia.
This double-blind study investigated the efficacy and safety of rapid-acting intramuscular olanzapine in treating agitation associated with Alzheimer's disease and/or vascular dementia. At 2 h, olanzapine (5.0 mg, 2.5 mg) and lorazepam (1.0 mg) showed significant improvement over placebo on the PANSS Excited Component (PANSS-EC) and Agitation-Calmness Evaluation Scale (ACES), and both 5.0 mg olanzapine and lorazepam showed superiority to placebo on the Cohen-Mansfield Agitation Inventory. At 24 h, both olanzapine groups maintained superiority over placebo on the PANSS-EC; lorazepam did not. Olanzapine (5.0 mg) and lorazepam improved ACES scores more than placebo. Simpson-Angus and Mini-Mental State Examination scores did not change significantly from baseline. Sedation (ACES > or =8), adverse events, and laboratory analytes were not significantly different from placebo for any treatment. No significant differences among treatment groups were seen in extrapyramidal symptoms or in corrected QT interval at either 2 h or 24 h, and no significant differences among treatment groups were seen in vital signs, including orthostasis. Intramuscular injection of olanzapine may therefore provide substantial benefit in rapidly treating inpatients with acute dementia-related agitation.
Double-blind, placebo-controlled comparison of intramuscular olanzapine and intramuscular haloperidol in the treatment of acute agitation in schizophrenia.
OBJECTIVE: The authors evaluated the comparative efficacy and safety of intramuscular olanzapine, intramuscular haloperidol, and intramuscular placebo for the treatment of acute agitation in schizophrenia.
METHOD: Hospitalized patients with schizophrenia received one to three injections of intramuscular olanzapine, 10 mg, intramuscular haloperidol, 7.5 mg, or intramuscular placebo over a 24-hour period. Agitation was measured with the excited component of the Positive and Negative Syndrome Scale and two additional scales.
RESULTS: According to scores on the excited component of the Positive and Negative Syndrome Scale, both intramuscular olanzapine and intramuscular haloperidol reduced agitation significantly more than intramuscular placebo 2 and 24 hours following the first injection. Intramuscular olanzapine reduced agitation significantly more than intramuscular haloperidol 15, 30, and 45 minutes following the first injection. No patients treated with intramuscular olanzapine experienced acute dystonia, compared with 7% of those who were treated with intramuscular haloperidol. No significant QT(c) interval changes were observed in any patients.
CONCLUSIONS: Intramuscular olanzapine represents a rapid, effective, and safe treatment for acute agitation in schizophrenia.
Options:
A: Intramuscular olanzapine is less effective than placebo in reducing the need for additional injections within 24 hours.
B: Intramuscular olanzapine is more likely to cause movement disorders compared to haloperidol.
C: Intramuscular olanzapine is as effective as haloperidol in achieving an important clinical response within 2 hours.
D: Intramuscular olanzapine is more likely to cause treatment-emergent adverse events compared to lorazepam. | C |
437 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What were the findings regarding the use of glucocorticosteroids for patients with primary biliary cirrhosis in terms of mortality, liver inflammation markers, and adverse events? Please answer this question based on the information provided below:
Oral budesonide and ursodeoxycholic acid for treatment of primary biliary cirrhosis: results of a prospective double-blind trial.
BACKGROUND & AIMS: Ursodeoxycholic acid (UDCA) is used for treatment of primary biliary cirrhosis. Previous studies showed that, compared with UDCA monotherapy, bile salts plus prednisolone had no further effect on laboratory data but improved liver histology. Thirty percent of these patients had prednisolone-related side effects. Budesonide is a glucocorticoid with a high receptor affinity and a high first-pass metabolism. In this study we investigated whether budesonide and UDCA are superior to UDCA monotherapy.
METHODS: A 2-year prospective, controlled double-blind trial was performed. Twenty patients (mainly with early-stage disease) were treated with UDCA at a dose of 10-15 mg/kg daily in addition to 3 mg budesonide 3 times daily (group A), and 19 patients (1 dropped out for personal reasons) were treated with UDCA plus placebo (group B). Liver biopsy specimens were taken before, after 12 months, and at the end of study. Glucose tolerance tests, serum cortisol levels, and adrenocorticotropin-stimulated cortisol secretion were assessed at regular intervals. Bone mass density was measured by dual-energy photon absorptiometry.
RESULTS: Compared with pretreatment values, liver enzyme and immunoglobulin M and G levels decreased significantly in both groups. Improvement in group A was significantly more pronounced (P < 0.05) than in group B. Titers of antimitochondrial antibodies did not change. In group A, the point score of liver histology improved by 30.3%; in group B, it deteriorated by 3.5% (P < 0.001). Changes in bone mineral density after 2 years were -1.747% in group A and -0.983% in group B (P = 0.43). Budesonide had little influence on the hypothalamic-pituitary-adrenal axis. One patient in group A had budesonide-related side effects; in 3 patients in group B, complications of liver disease developed.
CONCLUSIONS: Combination therapy with UDCA and budesonide is superior to UDCA and placebo.
Oral budesonide and ursodeoxycholic acid for treatment of primary biliary cirrhosis: results of a prospective double-blind trial.
BACKGROUND & AIMS: Ursodeoxycholic acid (UDCA) is used for treatment of primary biliary cirrhosis. Previous studies showed that, compared with UDCA monotherapy, bile salts plus prednisolone had no further effect on laboratory data but improved liver histology. Thirty percent of these patients had prednisolone-related side effects. Budesonide is a glucocorticoid with a high receptor affinity and a high first-pass metabolism. In this study we investigated whether budesonide and UDCA are superior to UDCA monotherapy.
METHODS: A 2-year prospective, controlled double-blind trial was performed. Twenty patients (mainly with early-stage disease) were treated with UDCA at a dose of 10-15 mg/kg daily in addition to 3 mg budesonide 3 times daily (group A), and 19 patients (1 dropped out for personal reasons) were treated with UDCA plus placebo (group B). Liver biopsy specimens were taken before, after 12 months, and at the end of study. Glucose tolerance tests, serum cortisol levels, and adrenocorticotropin-stimulated cortisol secretion were assessed at regular intervals. Bone mass density was measured by dual-energy photon absorptiometry.
RESULTS: Compared with pretreatment values, liver enzyme and immunoglobulin M and G levels decreased significantly in both groups. Improvement in group A was significantly more pronounced (P < 0.05) than in group B. Titers of antimitochondrial antibodies did not change. In group A, the point score of liver histology improved by 30.3%; in group B, it deteriorated by 3.5% (P < 0.001). Changes in bone mineral density after 2 years were -1.747% in group A and -0.983% in group B (P = 0.43). Budesonide had little influence on the hypothalamic-pituitary-adrenal axis. One patient in group A had budesonide-related side effects; in 3 patients in group B, complications of liver disease developed.
CONCLUSIONS: Combination therapy with UDCA and budesonide is superior to UDCA and placebo.
Prednisolone for primary biliary cirrhosis--good news, bad news.
A pilot, double-blind, controlled 1-year trial of prednisolone treatment in primary biliary cirrhosis: hepatic improvement but greater bone loss.
A randomized, double-blind, 1-year pilot study of prednisolone treatment for primary biliary cirrhosis was undertaken. Nineteen patients received 30 mg prednisolone per day initially, with a maintenance dose of 10 mg per day. Seventeen patients received placebo. The groups were matched for age, menopausal status, hepatic histological stage and bilirubin. Treatment was well tolerated without dropouts. Two patients receiving prednisolone developed diabetes, one a duodenal ulcer and one depression. One patient receiving placebo died for liver failure after 3 months. Cholestatic symptoms (itch and fatigue) improved on prednisolone. There was significant (prednisolone vs. placebo) improvement in transaminase (p = 0.0214), alkaline phosphatase (p = 0.0032), procollagen III peptide (p = 0.0103), immunoglobulin G (p = 0.0012) and liver histology (p = 0.016); these changes were greatest among noncirrhotic patients. No patient developed skeletal symptoms. Fifty-seven per cent had abnormal triolein breath tests prior to treatment, and 65% had abnormally low calcium absorption tests. Calcium absorption increased significantly in the treated group vs. placebo at 2 weeks (p less than 0.02), but not at 1 year. Femoral photon absorptiometry fell in the prednisolone group after 1 year (-3.5% vs. placebo +0.5%, p less than 0.05), as did trabecular bone volume (-6% vs. -2.8%, p less than 0.005) and resorption surface (-11% vs. +2%, p less than 0.02) on serial bone biopsy. Prednisolone seems to exert a favorable hepatic effect in primary biliary cirrhosis but at the expense of increased bone loss to approximately twice the expected rate. Prednisolone treatment merits further assessment in primary biliary cirrhosis over a longer period, with attention to selection of patients most likely to benefit and continuing observation of bone mass to better establish the "cost/benefit" ratio.
A controlled trial of prednisolone treatment in primary biliary cirrhosis. Three-year results.
The results of a 3-year, placebo-controlled trial of prednisolone treatment in primary biliary cirrhosis (PBC) are presented. The active (n = 19) and placebo (n = 17) arms were initially well matched for age, menopausal status and disease severity. At 3 years hepatic symptoms were relatively improved in the prednisolone group. Hepatic mortality was 3/19 (prednisolone), 5/17 (placebo) (p = n.s.). For all liver blood tests the trend favoured prednisolone treatment, though the differences were only significant for alkaline phosphatase and protein. All immunoglobulins fell significantly. Quantitative ELISA determination of antimitochondrial antibody showed a significant fall in the prednisolone group compared with placebo (p less than 0.001 at 1 year, p less than 0.05 at 3 years). Deterioration in histology (appearance of cirrhosis) was more common in the placebo group. Overall hepatic function (hepatic mortality, doubling in bilirubin, 6 milligrams fall in albumin, de novo appearance of cirrhosis or symptoms of portal hypertension) was significantly worse in the placebo group (p less than 0.01). After 3 years no significant differences could be detected in bone mineral content (single photon absorptiometry of radius and femur) between the two groups or in comparison with other PBC patients. Thus, after 3 years, prednisolone treatment was associated with a better overall hepatic outcome and little evidence of increased bone loss.
A controlled trial of prednisolone treatment in primary biliary cirrhosis. Three-year results.
The results of a 3-year, placebo-controlled trial of prednisolone treatment in primary biliary cirrhosis (PBC) are presented. The active (n = 19) and placebo (n = 17) arms were initially well matched for age, menopausal status and disease severity. At 3 years hepatic symptoms were relatively improved in the prednisolone group. Hepatic mortality was 3/19 (prednisolone), 5/17 (placebo) (p = n.s.). For all liver blood tests the trend favoured prednisolone treatment, though the differences were only significant for alkaline phosphatase and protein. All immunoglobulins fell significantly. Quantitative ELISA determination of antimitochondrial antibody showed a significant fall in the prednisolone group compared with placebo (p less than 0.001 at 1 year, p less than 0.05 at 3 years). Deterioration in histology (appearance of cirrhosis) was more common in the placebo group. Overall hepatic function (hepatic mortality, doubling in bilirubin, 6 milligrams fall in albumin, de novo appearance of cirrhosis or symptoms of portal hypertension) was significantly worse in the placebo group (p less than 0.01). After 3 years no significant differences could be detected in bone mineral content (single photon absorptiometry of radius and femur) between the two groups or in comparison with other PBC patients. Thus, after 3 years, prednisolone treatment was associated with a better overall hepatic outcome and little evidence of increased bone loss.
Options:
A: Significant improvement in mortality, no change in liver inflammation markers, and no increase in adverse events.
B: No significant improvement in mortality, improvements in liver inflammation markers, and a significant increase in adverse events.
C: Significant improvement in mortality, improvements in liver inflammation markers, and a significant increase in adverse events.
D: No significant improvement in mortality, no change in liver inflammation markers, and no increase in adverse events. | B |
438 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What is the impact of red-light cameras on the incidence and severity of road crashes and casualties, and the incidence of red-light violations? Please answer this question based on the information provided below:
Evaluation of red light camera enforcement in Oxnard, California.
Red light cameras are increasingly being used to supplement police efforts to enforce against noncompliance with traffic signals--a substantial contributing factor in urban motor vehicle crashes. Camera enforcement is intended to modify driver behavior through both general deterrence and punishment of individual violators. A before/after quasi-experimental design with controls was employed to evaluate the influence of a red light camera enforcement program on red light violation rates in the city of Oxnard, CA. A total of 14 intersections (nine camera sites, three non-camera sites, and two control sites) were studied. Overall, the red light violation rate was reduced approximately 42% several months after the enforcement program began. Increases in driver compliance with red lights were not limited to the camera-equipped intersections but spilled over to nonequipped intersections as well. Results of public opinion surveys conducted approximately 6 weeks before, 6 weeks after, and 6 months after the camera enforcement program began indicated that nearly 80% of Oxnard residents support using red light cameras as a supplement to police efforts to enforce traffic signal laws.
Reductions in injury crashes associated with red light camera enforcement in oxnard, california.
OBJECTIVES: This study estimated the impact of red light camera enforcement on motor vehicle crashes in one of the first US communities to employ such cameras-Oxnard, California.
METHODS: Crash data were analyzed for Oxnard and for 3 comparison cities. Changes in crash frequencies were compared for Oxnard and control cities and for signalized and nonsignalized intersections by means of a generalized linear regression model.
RESULTS: Overall, crashes at signalized intersections throughout Oxnard were reduced by 7% and injury crashes were reduced by 29%. Right-angle crashes, those most associated with red light violations, were reduced by 32%; right-angle crashes involving injuries were reduced by 68%.
CONCLUSIONS: Because red light cameras can be a permanent component of the transportation infrastructure, crash reductions attributed to camera enforcement should be sustainable.
Options:
A: Red-light cameras significantly reduce total casualty crashes, but the evidence is less conclusive for total collisions, specific casualty collision types, and violations.
B: Red-light cameras have no significant impact on total casualty crashes, total collisions, specific casualty collision types, or violations.
C: Red-light cameras significantly increase total casualty crashes and total collisions, but reduce specific casualty collision types and violations.
D: Red-light cameras have a significant impact on reducing total collisions and violations, but no impact on total casualty crashes or specific casualty collision types. | A |
439 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What are the comparative benefits and disadvantages of using NSAIDs versus opioids for managing pain in acute renal colic? Please answer this question based on the information provided below:
Comparative study of the efficacy of lysine acetylsalicylate, indomethacin and pethidine in acute renal colic.
The aim of this study was to compare the analgesic efficacy of intravenous lysine acetylsalicylate 1.8 g, indomethacin 100 mg and pethidine 100 mg in acute renal colic in a randomized double-blind clinical trial. One hundred and fifty patients with acute renal colic were divided into three groups. The first group received lysine acetylsalicylate 1.8 g, the second group received indomethacin 100 mg and the third group received pethidine 100 mg. The degree of pain relief was recorded 5, 15, 30 and 60 min after intravenous administration of the drugs. There was no statistically significant difference between the degree of analgesia provided by pethidine and indomethacin. Lysine acetylsalicylate was less effective than indomethacin and pethidine. It is concluded that intravenous indomethacin is an effective alternative to intravenous pethidine in the treatment of acute renal colic. Intravenous lysine acetylsalicylate is inferior to intravenous indomethacin in treatment of acute renal colic.
Comparative study of the efficacy of dipyrone, diclofenac sodium and pethidine in acute renal colic. Collaborative Group of the Spanish Society of Clinical Pharmacology.
A randomized, double-blind, multicentre clinical trial was designed to compared the analgesic efficacy of i.m. dipyrone 1 and 2 g, i.m. diclofenac sodium and i.m. pethidine in acute renal colic. The study was carried out in 451 patients in 13 Spanish hospitals. Ureteric colic was diagnosed by the clinical features, urinalysis, or when the presence of a ureteric calculus was confirmed. The severity of pain was assessed by the physicians and by patients using visual analogue scales. The main parameter of drug efficacy was the need for rescue treatment-pethidine 100 mg i.m. 30 min after the experimental treatment. Rescue treatment was required in 93 patients: they represented 24.1% of the group given dipyrone 1 g; 22.3% of those on dipyrone 2 g; 16.4% of those given diclofenac sodium; and 19.5% of those on pethidine. The differences between the groups were not significant. In the remaining 358 patients, no difference between treatments was observed. The results suggest that in acute renal colic the use of dipyrone 2 g is unjustified as dipyrone 1 g is equally effective. Diclofenac sodium is a valid alternative, which shows similar analgesic efficacy.
Indomethacin suppositories versus intravenously titrated morphine for the treatment of ureteral colic.
STUDY OBJECTIVES: To develop a protocol for the blinded IV titration of morphine and to compare the analgesic efficacy and side effect profile of indomethacin suppositories versus IV morphine in the treatment of acute ureteral colic.
DESIGN: Randomized, double-blind, double-dummy, two-period crossover study.
SETTING: Emergency department of a central-city, teaching hospital.
PARTICIPANTS: Patients 18 to 75 years of age with pain suggestive of ureteral colic. Exclusions included pregnancy, adverse reactions to the study drugs, chronic nonsteroidal anti-inflammatory drug (NSAID) therapy, or any pain medicine taken within four hours of ED admission.
INTERVENTIONS: Patients were randomized to one of two groups: indomethacin 100-mg rectal suppository or morphine by IV titration (5-mg loading dose and up to two additional 2.5-mg doses if needed). At the end of 30 minutes, if adequate pain relief had not been obtained, treatment was crossed over.
MEASUREMENTS: Verbal analog scale (initial pain) and visual analog pain relief scale.
MAIN RESULTS: Seventy-five patients were entered into the study. Only data from those patients with stone presence confirmed by IV pyelogram or stone passage were analyzed. Twenty-four could not be evaluated (23 who did not meet criteria for stone presence and one whose pain resolved spontaneously before study medications could be administered). Of the remaining 51 patients, 31 received indomethacin first and 20 received morphine first. Morphine recipients reported more pain relief at ten minutes (P = .02), but at 20 and 30 minutes, no significant difference (P = .17 and .74, respectively) existed between the two groups.
CONCLUSION: IV morphine produced more rapid analgesia than rectally administered indomethacin. There were no significant differences in vital sign changes or number of side effects between the two treatment groups. This study is the first to compare an NSAID with morphine administered by IV titration, considered by many to be the "gold standard" for relief of acute, severe pain. Future studies could evaluate the simultaneous administration of an opioid combined with an NSAID or compare an IV titrated opioid with an IV NSAID.
Comparison of intravenous ketorolac, meperidine, and both (balanced analgesia) for renal colic.
STUDY OBJECTIVE: To compare the analgesic efficacy and safety of IV ketorolac, the only nonsteroidal antiinflammatory drug indicated for parenteral use in acute pain in the United States, with IV meperidine and with a combination of the two agents in renal colic.
METHODS: We carried out a double-blind, randomized, multicenter clinical trial in the emergency departments of four urban tertiary care teaching hospitals. Our study subjects were 154 patients with suspected renal colic. Each subject received an initial IV dose of ketorolac 60 mg, meperidine 50 mg, or both supplemented as needed beyond 30 minutes with additional doses of meperidine.
RESULTS: The main outcome measures were changes in pain-intensity and pain-relief scores, amount of supplemental meperidine required, end-of-study drug tolerability, and adverse events. Analyses of 106 subjects with confirmed renal colic indicated that ketorolac and the combination were significantly better than meperidine alone by all efficacy measures, including pain relief and time elapsed before the need for supplemental meperidine. By 30 minutes, 75% of the ketorolac group and 74% of the combination group had a 50% reduction in pain scores, compared with 23% of the meperidine group (P < .001). The ketorolac and combination groups did not differ significantly in any of the efficacy measures.
CONCLUSION: IV ketorolac, alone or in combination with meperidine, was superior to IV meperidine alone in moderate and severe renal colic. Because many subjects in all three treatment groups received supplemental meperidine and because response to ketorolac alone cannot be predicted, clinicians may choose to initiate treatment with a ketorolac-meperidine combination.
Intravenous tenoxicam for the treatment of renal colic.
Diclofenac sodium versus pethidine in acute renal colic.
Intravenous indomethacin and oxycone-papaverine in the treatment of acute renal colic. A double-blind study.
In a prospective double-blind, cross-over study, 61 patients with acute renal colic were treated with either indomethacin (50 mg) or oxycone-papaverine (5 mg + 50 mg) administered intravenously. For those patients requiring a second injection the drugs were reversed. The intensity of pain was evaluated before and 20 min after each injection according to an analogue visual scale 0 to 100. Both drug regimens provided comparable and significant pain relief; a pain score of less than 20 appeared to be satisfactory and was achieved in almost all cases.
Efficacy of ketorolac tromethamine versus meperidine in the ED treatment of acute renal colic.
To compare the efficacy of intramuscular ketorolac and meperidine in the emergency department (ED) treatment of renal colic, a prospective, controlled, randomized, double-blind trial was conducted in an academic ED with 76,000 annual visits. Participants were volunteer ED patients with a diagnosis of ureterolithiasis confirmed by intravenous pyelogram. Subjects were randomized 1:1 to receive a single intramuscular injection of either 60 mg ketorolac or 100 to 150 mg meperidine, based on weight. Of the 70 patients completing the trial, 33 received ketorolac and 37 received meperidine. Demographic characteristics and baseline pain scores of both groups were comparable (P = NS, Mann Whitney U). Ketorolac was significantly (P < .05) more effective than meperidine in reducing renal colic at 40, 60, and 90 minutes as measured on a 10-cm visual analogue scale. Similar proportions of patients in each group were given rescue analgesia and admitted. Of patients who were discharged home without rescue, those treated with ketorolac left the ED significantly earlier than those treated with meperidine (3.46 v 4.33 h, P < .05). These results show that intramuscular ketorolac as a single agent for renal colic is more effective than meperidine and promotes earlier discharge of renal colic patients from the ED.
Intravenous indomethacin in the treatment of ureteric colic. A clinical multicentre study with pethidine and metamizol as the control preparations.
The analgesic effects of intravenously administered indomethacin, pethidine and metamizol were compared in a series of 169 patients with ureteric colic. Complete pain relief was obtained in 59% in the indomethacin group, in 52% in the pethidine group and in 44% in the metamizol group. The observed side effects were not serious. On the basis of the study results indomethacin can be recommended as an alternative drug in the treatment of ureteric colic.
Prostaglandin-synthetase inhibition with diclofenac sodium in treatment of renal colic: comparison with use of a narcotic analgesic.
A multi-centre comparative study of diclofenac sodium and a dipyrone/spasmolytic combination, and a single-centre comparative study of diclofenac sodium and pethidine in renal colic patients in India.
A single-blind, randomized clinical trial was carried out to compare the analgesic effectiveness in patients with renal colic of single intramuscular doses of diclofenac sodium (75 mg) versus a dipyrone (1 g)/spasmolytics combination, and diclofenac sodium (75 mg) versus pethidine (75 mg). The first study involved three centres, the second study one centre. In total, 107 patients were treated with diclofenac sodium, 85 with dipyrone/spasmolytics, and 25 with pethidine. Assessments were made during the first hour after drug administration of the degree of pain relief, the severity of pain using a visual analogue scale, and the duration of analgesia. A global assessment of treatment efficacy was made by the participating physicians at the end of the study period. Patients treated with diclofenac sodium showed an earlier onset of analgesia and a higher incidence of total pain relief compared to those treated with dipyrone/spasmolytics or pethidine. Although the mean duration of analgesia was only slightly greater in the diclofenac sodium group than in the dipyrone/spasmolytics group, a significantly longer effect was seen when diclofenac sodium was compared with pethidine (p less than 0.01). Pain severity assessments revealed that diclofenac sodium caused a significantly greater improvement in pain after 60 minutes compared to dipyrone/spasmolytics (p less than 0.05) and after 30 minutes compared to pethidine (p less than 0.05). Global efficacy assessments by the physician rated diclofenac sodium as significantly superior to dipyrone/spasmolytics (p less than 0.01) and pethidine (p less than 0.001). Moreover, diclofenac sodium was better tolerated than either of the comparative treatments. The results indicate that intramuscular diclofenac sodium is a useful alternative to the drugs commonly used in India in the treatment of renal colic.
A double-blind single dose comparison of intramuscular ketorolac tromethamine and pethidine in the treatment of renal colic.
The efficacy of a single dose of intramuscular ketorolac 10 mg or 90 mg was compared with pethidine 100 mg in a randomized double-blind study in 121 patients reporting at least moderate pain due to renal colic. Pain was assessed before drug administration, and then at 1 hour and 12 hours after the dose. Sedation was also assessed at these times, and additionally at the 12 hour assessment the time of the next analgesic dose was recorded. At 1 hour after dosing, pain scores had decreased in all groups; the largest decrease was seen in the ketorolac 90 mg group. The difference in the decrease was significant between the two ketorolac groups, but the differences between ketorolac and pethidine were not significant. Fewer patients in the ketorolac 90 mg group (17%) required a further dose of analgesic within 10 hours than in either the ketorolac 10 mg group (39%) or the pethidine 100 mg group (47%). The difference between ketorolac 90 mg and pethidine 100 mg was statistically significant. At both assessment times the proportion of patients with no sedation was higher in the two ketorolac groups than in the pethidine group. The overall incidence of adverse events was low with all drugs, notably so for the occurrence of vomiting after ketorolac. The results of the study show that intramuscular ketorolac is efficacious in the treatment of renal colic.
Comparison of a narcotic (oxicone) and a non-narcotic anti-inflammatory analgesic (indoprofen) in the treatment of renal colic.
Intravenous indoprofen (400 mg), a cyclooxygenase inhibitor, was compared with intramuscular oxicodone hydrochloride (= oxicone 10 mg), a narcotic analgesic agent, in regard to efficacy and side effects in the treatment of renal colic. Oxicone was combined with papaverine (20 mg). Patients were randomized to either treatment, and the drugs were given in double-dummy fashion, i.e. one injection of active drug plus one placebo injection. Pain intensity before and after treatment was registered by the patient (visual analog scale) and by a nurse, who also registered side effects. Oxicone was given to 46 patients and indoprofen to 48. The groups did not differ in body weight, age, sex distribution, or pretreatment intensity of pain. More patients required additional treatment in the oxicone than in the indoprofen group (19 v. 10). At 2-5 min after injection, pain reduction was greater with indoprofen, and more patients in this group had pain relief after 3-5 hours. Side effects were less frequent with indoprofen than with oxicone (1 v. 20 patients), in particular from the central nervous system. This difference probably was related to indoprofen's slow and poor penetration of the blood-brain barrier. The study affirmed that non-narcotic cyclooxygenase inhibitors can replace narcotic analgesics for acute pain alleviation in renal colic. Indoprofen seems to be a useful alternative, with low risk of central nervous side effects.
[Usefulness of a non-steroid anti-inflammatory, sodium diclofenac, in the treatment of renal colic. Comparative study with a spasmolytic and an opiate analgesic].
A comparison of intramuscular ketorolac and pethidine in the alleviation of renal colic.
OBJECTIVE: To compare the analgesic efficacy of a single 30 mg intramuscular dose of ketorolac with that of intramuscular pethidine 100 mg, in a double-blind, parallel-group investigation of patients presenting with pain suggestive of renal colic.
PATIENTS AND METHODS: Seventy-six patients (17 women, 15 men; mean age 45.2 years, range 20-80) were allocated by means of a pre-determined randomization schedule to receive ketorolac and 78 patients (20 women, 58 men; mean age 42.1, years range 18-70) to receive pethidine. Data from eight patients in the ketorolac group and six in the pethidine group were excluded from the efficacy analyses because of protocol violations. The severity of each patient's pain was assessed on a four-point verbal rating scale (VRS) and a 10 cm visual analogue scale at pre-dose and at 15 min intervals for the first hour post dosing. The time to first administration of rescue analgesic, up to 24 h following dosing with the study medication, was recorded. Adverse events were elicited by general questioning.
RESULTS: Eighty-eight per cent of patients in each treatment group had improved according to the VRS of pain severity 1 h after dosing; the summed pain intensity differences up to 1 h were statistically significantly different in favour of ketorolac (P < 0.05). Fifty-six per cent of patients who were receiving ketorolac required rescue analgesia during the study period compared with 74% receiving pethidine. The incidences of adverse events were lower in the ketorolac group (28%) than the pethidine group (51%).
CONCLUSION: Ketorolac can be considered a viable alternative to pethidine for the treatment of renal colic.
Analgesic effect and tolerance of Voltaren and Ketogan in acute renal or ureteric colic.
Fifty-six patients with renal or ureteric colic were entered into a randomised, prospective, double-blind investigation of the analgesic efficacy and tolerance of Voltaren versus Ketogan, both administered intramuscularly. There were no significant differences regarding pain-relief but side effects were fewer in patients treated with Voltaren.
Rectal diclofenac compared with pethidine injection in acute renal colic.
[Intramuscular ketorolac compared to subcutaneous tramadol in the initial emergency treatment of renal colic].
OBJECTIVE: To compare the efficacy and safety of two analgesics (tramadol and ketorolac) for initial emergency treatment of renal colic.
METHODS: A prospective study on 48 patients randomly assigned to treatment with ketorolac 30 mg i.m. and tramadol 1 mg/kg s.c. Pain intensity was evaluated by a simple analogic scale ranging from 0-4 (0 = no pain, 1 = mild, 2 = moderate, 3 = severe and 4 = very severe pain). Statistical analyses were performed with Student's test and the chi square test for numerical and qualitative data, respectively.
RESULTS: No significant differences were found for the overall efficacy (> 80%) or side effects in both groups. However, a difference was found between both groups for pain score 15 minutes post-injection, which showed i.m. ketorolac to be more effective.
CONCLUSION: Both ketorolac (30 mg i.m.) and tramadol (1 mg/kg s.c.) are effective in the initial treatment of renal colic. Both drugs have an efficacy greater than 80% when used separately and almost 100% when used in combination. The analgesic effect of ketorolac is observed earlier than that of tramadol.
A comparative study on the analgesic effects of indomethacin and hydromorphinechloride-atropine in acute, ureteral-stone pain.
In a prospective study, including fifty consecutive patients with acute ureteral-stone pain, the patients were randomly distributed into two groups for treatment. There were given either an intravenous injection of indomethacin (Confortid) 50 mg, or a subcutaneous injection of 2 mg hydromorphine chloride-atropine (Dilaudid-atropin 1 ml). Patients in the latter group also received a suppository of prochlorperazine (Stemetil) 25 mg. The analgesic effect of the two drugs did not differ significantly. Indomethacin was quicker acting, probably due to the intravenous route of administration. The side effects were alike but those caused by indomethacin had a tendency to be milder and of shorter duration.
Options:
A: Both NSAIDs and opioids provide effective pain relief, but NSAIDs are associated with fewer adverse events and a lower likelihood of requiring rescue medication.
B: Opioids provide more effective pain relief than NSAIDs, but NSAIDs are associated with fewer adverse events.
C: NSAIDs provide more effective pain relief than opioids, but opioids are associated with fewer adverse events.
D: Both NSAIDs and opioids provide effective pain relief, but opioids are associated with fewer adverse events and a lower likelihood of requiring rescue medication. | A |
440 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What were the findings regarding the impact of clinical decision support systems (CDSS) on neonatal care, specifically in terms of mortality, morbidity, and physician performance? Please answer this question based on the information provided below:
[Usefulness of a software package to reduce medication errors in neonatal care].
BACKGROUND: Many treatment errors in neonatal intensive care units are caused by the need to carry out a sequence of calculations to determine the dose and dilution of the drugs used.
OBJECTIVES: To help in this task, we designed a spreadsheet (Neodosis) that helps clinicians and nurses to calculate the doses and standardize the dilutions of some of the drugs most commonly used in resuscitation and neonatal intensive care units. The aim of this study was to verify the usefulness and reliability of this software package.
METHODS: A randomized, cross-over, controlled trial was conducted through simulated clinical cases in which the number of errors in the prescription data and the amount of time spent in making calculations, with and without the program, were evaluated. Fifty-four tests were performed by pediatricians, third- and fourth-year pediatric residents, and nurses.
RESULTS: Without computer support, all three groups made errors (residents, pediatricians and nurses in descending order). When Neodosis was used, all the medical staff made significantly fewer errors. The greatest reduction was found in errors made by pediatric residents: minor errors decreased from 16 % to 2 % and major errors from 1.6 % to zero. When using the spreadsheet, the time spent by all groups in making the calculations was reduced by between one-third and one-half.
CONCLUSIONS: The tests performed with simulated clinical cases revealed that the number of errors made by the healthcare personnel who participated in this study was not inconsiderable. The use of Neodosis helped physicians and nurses to make markedly fewer errors and also saved them time.
A randomized, controlled trial of computerized physiologic trend monitoring in an intensive care unit.
OBJECTIVE: To assess whether the provision of computerized physiologic trend data could improve outcome in newborn infants requiring intensive care.
DESIGN: Randomized, controlled trial, with subsidiary questionnaire studies.
SETTING: Tertiary neonatal intensive care unit with 12 intensive care cots.
PATIENTS: All infants admitted between January 1991 and September 1993 who were < or =32 wks gestation or >32 wks gestation, and ventilated for >4 hrs or asphyxiated.
INTERVENTIONS: Randomization to one of four groups for first 7 days of life: A) no display of trend data; B) continuous display of trend data; C1) alternating 24-hr display of trend data, starting with display in first 24 hrs; and C2) alternating 24-hr display of trend data, starting with no display in first 24 hrs.
MEASUREMENTS AND MAIN RESULTS: The short-term effects of monitoring on patient outcome was judged by volume of colloid given, number of blood gases taken, and by measurement taken from cranial Doppler ultrasound. Medium-term measures included time ventilated, time given supplemental oxygen, death, time to death or discharge, and cranial ultrasound at discharge. Long-term outcome was assessed by neurodevelopmental status at age 1 to 4 yrs of age. Staff and parent questionnaires assessed their respective attitudes to the introduction of this technology. None of the patient outcome measures, short-, medium-, or long-term, demonstrated any significant benefit from the provision of computerized physiologic trend monitoring. Staff questionnaires demonstrated an acceptance of the system and an improved understanding of neonatal physiology as a result of computerized physiologic trends. Parent questionnaires demonstrated increased anxiety caused by the system in 11% of parents, although only 1% of parents continued to have concerns if the system were able to help their child.
CONCLUSIONS: A randomized, controlled trial was unable to demonstrate any benefit to patients resulting from the introduction of a computerized physiologic trend monitoring system. Benefits of the system have been recognized, however, in subsidiary studies, staff education, and research studies.
Options:
A: CDSS significantly reduced mortality and morbidity in newborn infants and improved physician performance.
B: CDSS had no significant effect on mortality and morbidity in newborn infants, but improved physician performance by reducing calculation errors and time taken for dosage calculations.
C: CDSS significantly improved both short-term and long-term outcomes for newborn infants, including reducing mortality and morbidity.
D: CDSS had no significant effect on mortality, morbidity, or physician performance in neonatal care. | B |
441 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What conclusions can be drawn about the effectiveness and safety of gangliosides in treating acute spinal cord injury based on the available evidence? Please answer this question based on the information provided below:
Recovery of motor function after spinal-cord injury--a randomized, placebo-controlled trial with GM-1 ganglioside.
BACKGROUND: Spinal-cord injury is devastating; until recently, there was no medical treatment to improve recovery of the initial neurologic deficit. Studies in animals have shown that monosialotetrahexosylganglioside (GM-1) ganglioside enhances the functional recovery of damaged neurons.
METHODS: A prospective, randomized, placebo-controlled, double-blind trial of GM-1 ganglioside was conducted in patients with spinal-cord injuries. Of 37 patients entered into the study, 34 (23 with cervical injuries and 11 with thoracic injuries) completed the test-drug protocol (100 mg of GM-1 sodium salt or placebo intravenously per day for 18 to 32 doses, with the first dose taken within 72 hours of the injury) and a one-year follow-up period. Neurologic recovery was assessed with the Frankel scale (comprising five categories) and the American Spinal Injury Association (ASIA) motor score (a scale of scores from 0 to 100, derived from strength tests of 20 specific muscles, each scored from 0 to 5).
RESULTS: There was a significant difference between groups in the distribution of improvement of Frankel grades from base line to the one-year follow-up (improvement of 0, 1, 2, and 3 grades in 13, 4, 1, and 0 patients, respectively, in the placebo group and 8, 1, 6, and 1 patients, respectively, in the GM-1 group; P = 0.034 by the Cochran-Mantel-Haenszel chi-square test). The GM-1-treated patients also had a significantly greater mean improvement in ASIA motor score from base line to the one-year follow-up than the placebo-treated patients (36.9 vs. 21.6 points; P = 0.047 by analysis of covariance with the base-line ASIA motor score as the covariate). An analysis of individual muscle recoveries revealed that the increased recovery in the GM-1 group was attributable to initially paralyzed muscles that regained useful motor strength rather than to strengthening of paretic muscles.
CONCLUSIONS: This small study provides evidence that GM-1 enhances the recovery of neurologic function after one year. A larger study must be conducted, however, before GM-1 is considered efficacious and safe in treating spinal-cord injury.
The Sygen multicenter acute spinal cord injury study.
STUDY DESIGN: Randomized, double-blind, sequential, multicenter clinical trial of two doses of Sygen versus placebo.
OBJECTIVES: To determine efficacy and safety of Sygen in acute spinal cord injury.
SUMMARY OF BACKGROUND DATA: An earlier, single-center trial in 28 patients showed an improvement (50.0% vs. 7.1%, P = 0.034) in marked recovery with Sygen.
METHODS: Standard clinical trial techniques.
RESULTS: The prospectively planned analysis at the prespecified endpoint time for all patients was negative. There was a significant effect in all patients in the primary outcome variable (the percentage of marked recovery) at week 8, the end of the dosing period. There was a significant effect in all patients in the time at which marked recovery is first achieved. Restricted to severity Group B, which has small sample size, the primary efficacy analysis showed a trend but did not reach significance. There is a large, consistent and, at some time points, significant effect in the primary outcome variable in the nonoperated patients through week 26. The American Spinal Injury Association motor, light touch, and pinprick scores showed a consistent trend in favor of Sygen, as also did bowel function, bladder function, sacral sensation, and anal contraction. The less severely injured patients appeared to have a greater beneficial drug effect. Evidence against an effect of Sygen was minimal and scattered.
CONCLUSIONS: Although not proven in the primary efficacy analysis of this trial, Sygen appears to be beneficial in patients with severe spinal cord injury.
Measurements and recovery patterns in a multicenter study of acute spinal cord injury.
STUDY DESIGN: Post hoc, secondary analysis of data from 1992 to 1998 in the trial of Sygen in acute spinal cord injury.
OBJECTIVES: Quasi-epidemiologic understanding of measurement tools and of recovery patterns. No drug efficacy results.
SUMMARY OF BACKGROUND DATA: Many authors have studied individual scales for measuring the severity of spinal cord injury.
METHODS: Emphasis on descriptive, rather than inferential, statistics: consistent with secondary analysis.
RESULTS: Of the 760 patients, 43 died within 365 days. The rate was higher for complete injuries (7.1% vs. 3.2%, P = 0.017). Marked recovery at 26 weeks was more frequent in those with better baseline American Spinal Injury Association (ASIA) Impairment Scale (AIS) scores, but was not different for methylprednisolone within versus after 3 hours. Light touch scores improved at each visit, more so in those with higher scores at baseline. Bladder control similarly improved. Motor and sensory scores exhibited departures from assumptions underlying normal-theory statistical techniques: t test and analysis of variance. Furthermore, they were mixtures of differing distributions from different study strata, so that overall conclusions depend on the mixture of patients seen.
CONCLUSIONS: The prognosis of these patients with spinal cord injury seen at 28 centers in North America during the mid-1990s appears better than was often assumed earlier. The general patterns are similar across different measurement scales, although there are intriguing differences. The patterns in different strata are different in specifics, and complete injuries do less well. Pooling data from different strata may result in probability distributions that depart from normal-theory assumptions and give misleading results depending on recruitment patterns.
Recruitment and early treatment in a multicenter study of acute spinal cord injury.
STUDY DESIGN: Post hoc secondary analysis of data from 1992 to 1998 in the trial of Sygen in Acute Spinal Cord Injury.
OBJECTIVES: Quasi-epidemiologic understanding of injury and treatment patterns and of recruitment in an SCI trial. No drug efficacy results.
SUMMARY OF BACKGROUND DATA: The most recent large epidemiologic study was the National SCI Database by Stover and colleagues around 1980.
METHODS: Emphasis on descriptive, rather than inferential, statistics: consistent with secondary analysis.
RESULTS: The study involved 760 patients at 28 centers in North America. Cervical injuries were more common than thoracic, and complete injuries were more common than incomplete injuries. Recruitment in the complete cervical stratum was 332, but the incomplete thoracic strata had only 31 patients combined. Vital signs at arrival and on randomization show fair stability. Clock times show more injuries on weekends and nights but suggest immediate attention was given. Elapsed times to treatment (especially EMT and Medevac arrival) are short. The rate of direct admission to tertiary centers, traction weight, and time to surgery vary among centers. Inpatient rehabilitation appeared driven by insurance in addition to severity.
CONCLUSIONS: The imbalances in favor of cervical and of complete injuries would make it hard for studies to attain results for SCI in general. The vital signs and time patterns suggest local protocol-driven stabilization to prevent secondary physiologic injury early after SCI. Some features of care vary among centers, but the sparseness of prospective data in specific injury and treatment categories suggests that treatment guidelines have limited empirical support and should be made cautiously.
Options:
A: Ganglioside treatment significantly reduces the death rate in SCI patients.
B: Ganglioside treatment improves recovery and quality of life in SCI survivors.
C: The evidence does not support the use of ganglioside treatment to reduce the death rate or improve recovery and quality of life in SCI patients.
D: Ganglioside treatment has been proven to be harmful and increases the death rate in SCI patients. | C |
442 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What is the impact of unit-dose packaged antimalarial drugs on treatment adherence and treatment failure in people with uncomplicated malaria? Please answer this question based on the information provided below:
Improving adherence to malaria treatment for children: the use of pre-packed chloroquine tablets vs. chloroquine syrup.
Malaria is a major cause of morbidity and mortality among children under five in sub-Saharan Africa. Prompt diagnosis and adequate treatment of acute clinical episodes are essential to reduce morbidity and prevent complications and mortality. In many countries, chloroquine syrup is the mainstay of malaria treatment for children under five. Not only is syrup more expensive than tablets, adherence to the prescribed dose at home is a problem because mothers use wrongly sized measuring devices or have difficulty with the instructions. We investigated the impact of introducing pre-packed tablets for children on adherence to treatment and compared the total cost of the tablets with that of syrup. Children aged 0--5 years diagnosed with malaria at the clinic over a 6-week period received either pre-packed tablets or syrup by random assignment. The principal caregivers were interviewed at home on day 4 after attending the clinic. Of the 155 caregivers given pre-packed tablets, 91% (n=141) adhered to the recommended dosage, while only 42% (n=61) of 144 who were provided syrup did. Only 20% of caregivers who received syrup used an accurate 5 ml measure. The cost of treatment with tablets was about one-quarter that of syrup and 62% (n=96) of caregivers preferred tablets. Pre-packed chloroquine tablets are a viable alternative to syrup.
Impact of pre-packaging antimalarial drugs and counselling on compliance with malaria treatment at Port Moresby General Hospital Adult Outpatient Department.
We investigated the impact of pre-packaging antimalarial drugs and counselling on compliance with treatment of malaria at the Adult Outpatient Department of Port Moresby General Hospital. Adult patients who were prescribed standard antimalarial drugs following clinical and microscopic diagnosis of malaria were randomly assigned to one of three groups: an intervention group, where pre-packaging and counselling instructions were applied; control group A, with counselling but no pre-packaging; and control group B, with neither counselling nor pre-packaging. Patients were interviewed on two occasions, day 1 of treatment and day 4 post treatment. Of a total of 436 patients, 322 patients (179 males and 143 females) completed the study. Our data indicate an increase of 18% in compliance with treatment in the intervention group and 16% in control group A, when compared with control group B. While compliance with treatment was gender independent, the language spoken and used for giving instructions and counselling may have influenced patients' behaviour on prescribed medication. The results of our study indicate that a simple pre-packaging system and proper counselling could improve compliance with antimalarial drug treatment. As an additional beneficial observation, pre-packaging is likely to eliminate errors and possible contamination of the products during dispensing.
The effect of drug packaging on patients' compliance with treatment for Plasmodium vivax malaria in China.
A study conducted in 1994 showed that the use of blister packs containing antimalarial drugs significantly increased patients' compliance, compared with traditional means of dispensing drugs in a paper envelope. The present study assessed patients' compliance and compared the difference between 3-day chloroquine and 8-day primaquine courses of treatment for vivax malaria. The level of real compliance was determined by making the drugs with phenobarbital, and measuring its level in the blood following treatment. The results show that blister packaging significantly improved patients' compliance (p < 0.001) over traditional means of dispensing antimalarial drugs; there was no difference in treatment compliance between 3-day and 8-day courses when the drugs were in blister packs. However, with ordinary packaging the treatment compliance rate for an 8-day course was significantly less than for a 3-day course (P < 0.05).
The effect of drug packaging on patients' compliance with treatment for Plasmodium vivax malaria in China.
A study conducted in 1994 showed that the use of blister packs containing antimalarial drugs significantly increased patients' compliance, compared with traditional means of dispensing drugs in a paper envelope. The present study assessed patients' compliance and compared the difference between 3-day chloroquine and 8-day primaquine courses of treatment for vivax malaria. The level of real compliance was determined by making the drugs with phenobarbital, and measuring its level in the blood following treatment. The results show that blister packaging significantly improved patients' compliance (p < 0.001) over traditional means of dispensing antimalarial drugs; there was no difference in treatment compliance between 3-day and 8-day courses when the drugs were in blister packs. However, with ordinary packaging the treatment compliance rate for an 8-day course was significantly less than for a 3-day course (P < 0.05).
Impact of prepackaging antimalarial drugs on cost to patients and compliance with treatment.
OBJECTIVE: To examine the extent to which district health teams could reduce the burden of malaria, a continuing major cause of mortality and morbidity, in a situation where severe resource constraints existed and integrated care was provided.
METHODS: Antimalarial drugs were prepackaged into unit doses in an attempt to improve compliance with full courses of chemotherapy.
FINDINGS: Compliance improved by approximately 20% in both adults and children. There were 50% reductions in cost to patients, waiting time at dispensaries and drug wastage at facilities. The intervention, which tended to improve both case and drug management at facilities, was well accepted by health staff and did not involve them in additional working time.
CONCLUSION: The prepackaging of antimalarials at the district level offers the prospect of improved compliance and a reduction in the spread of resistance.
Options:
A: Unit-dose packaged drugs significantly reduce treatment failure and improve treatment adherence.
B: Unit-dose packaged drugs have no significant impact on treatment adherence or treatment failure.
C: Unit-dose packaged drugs improve treatment adherence but there is insufficient evidence to determine their effect on treatment failure.
D: Unit-dose packaged drugs significantly increase treatment failure and reduce treatment adherence. | C |
443 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What were the findings regarding the effectiveness of psychological treatments for anxiety and depressive disorders performed by paraprofessionals compared to professionals and control conditions? Please answer this question based on the information provided below:
Professional and non-professional intervention for highly anxious primiparous mothers.
Primiparous women (n = 627) were screened on state and trait anxiety measures in the post-partum period; sub-groups of highly anxious (n = 89), moderately anxious (n = 29), and minimally anxious (n = 29) mothers were derived and subsequently interviewed. The high-anxiety mothers were randomly assigned to a professional intervention, to a non-professional intervention, and to a control group, and their progress was reviewed over the following 12 months. Compliance, both in responding to progressive assessments and in accepting therapeutic intervention, was extremely high. Changes in anxiety levels for mothers not receiving an intervention were minimal over the study. In the high-anxiety sub-groups, there was a 19% reduction in state anxiety levels for those receiving a professional intervention, a 12% reduction for those receiving a non-professional intervention, and a 3% reduction in the controls. A planned contrast analysis determined that only professional intervention had a significant effect, intervention successfully lowering state anxiety levels to a value comparable with the moderately anxious mothers.
Professional and paraprofessional group treatments for depression: a comparison of cognitive-behavioral and mutual support interventions.
The relative efficacy of professional and paraprofessional therapists in providing group cognitive-behavioral therapy (CBT) and mutual support group therapy (MSG) was examined. Depressed outpatients (N = 98) were randomly assigned to CBT or MSG led by either 2 professional or 2 paraprofessional therapists. Results suggest that nonprofessionals were as effective as professionals in reducing depressive symptoms and that clients in the CBT and MSG conditions improved equally. Clinically significant improvement was demonstrated for both conditions. However, following treatment, more patients in the professionally led CBT groups were classified as nondepressed and alleviated than in the paraprofessionally led CBT groups. Additionally, therapist adherence to manual-based treatments was associated with greater improvement in clinician-rated depressive symptoms in both conditions and skills in cognitive restructuring were associated with greater improvement among clients in CBT.
Professional and paraprofessional group treatments for depression: a comparison of cognitive-behavioral and mutual support interventions.
The relative efficacy of professional and paraprofessional therapists in providing group cognitive-behavioral therapy (CBT) and mutual support group therapy (MSG) was examined. Depressed outpatients (N = 98) were randomly assigned to CBT or MSG led by either 2 professional or 2 paraprofessional therapists. Results suggest that nonprofessionals were as effective as professionals in reducing depressive symptoms and that clients in the CBT and MSG conditions improved equally. Clinically significant improvement was demonstrated for both conditions. However, following treatment, more patients in the professionally led CBT groups were classified as nondepressed and alleviated than in the paraprofessionally led CBT groups. Additionally, therapist adherence to manual-based treatments was associated with greater improvement in clinician-rated depressive symptoms in both conditions and skills in cognitive restructuring were associated with greater improvement among clients in CBT.
The effect of peer support on postpartum depression: a pilot randomized controlled trial.
OBJECTIVE: To evaluate the effect of peer support (mother-to-mother) on depressive symptomatology among mothers identified as high-risk for postpartum depression (PPD).
METHOD: Forty-two mothers in British Columbia were identified as high-risk for PPD according to the Edinburgh Postnatal Depression Scale (EPDS) and randomly assigned to either a control group (that is, to standard community postpartum care) or an experimental group. The experimental group received standard care plus telephone-based peer support, initiated within 48 to 72 hours of randomization, from a mother who previously experienced PPD and attended a 4-hour training session. Research assistants blind to group allocation conducted follow-up assessments on diverse outcomes, including depressive symptomatology, at 4 and 8 weeks postrandomization.
RESULTS: Significant group differences were found in probable major depressive symptomatology (EPDS > 12) at the 4-week (chi 2 = 5.18, df = 1; P = 0.02) and 8-week (chi 2 = 6.37, df = 1; P = 0.01) assessments. Specifically, at the 4-week assessment 40.9% (n = 9) of mothers in the control group scored > 12 on the EPDS, compared with only 10% (n = 2) in the experimental group. Similar findings were found at the 8-week assessment, when 52.4% (n = 11) of mothers in the control group scored > 12 on the EPDS, compared with 15% (n = 3) of mothers in the experimental group. Of the 16 mothers in the experimental group who evaluated the intervention, 87.5% were satisfied with their peer-support experience.
CONCLUSIONS: Telephone-based peer support may effectively decrease depressive symptomatology among new mothers. The high maternal satisfaction with, and acceptance of, the intervention suggests that a larger trial is feasible.
Befriending as an intervention for chronic depression among women in an inner city. 1: Randomised controlled trial.
BACKGROUND: Earlier work on the protective role of social support in onset and course of depressive disorder suggested that its provision might be relevant for outcome.
AIMS: To evaluate volunteer befriending as an intervention among women with chronic depression in inner London.
METHOD: A randomised controlled trial, with a waiting list control design, with outcome measured as Present State Examination (PSE)-based full or partial remission after one year.
RESULTS: A statistically significant effect upon remission was found for befriending. Other treatments monitored naturalistically did not relate to remission, nor did initial duration of chronic episode or comorbidity, but there was an association with initial PSE score. The findings are discussed in relation to standard drug-trial results and to another befriending intervention with the elderly.
CONCLUSIONS: The results are not unpromising. Additional trials with less restricted intake conditions, and in more naturalistic general practice settings, might confirm volunteer befriending as a useful adjunct to current treatments.
Options:
A: Paraprofessionals were significantly more effective than professionals in treating anxiety and depressive disorders.
B: Paraprofessionals were significantly less effective than professionals in treating anxiety and depressive disorders.
C: There was no significant difference between paraprofessionals and professionals in treating anxiety and depressive disorders.
D: Paraprofessionals were significantly less effective than control conditions in treating anxiety and depressive disorders.
E: Paraprofessionals were significantly more effective than control conditions in treating anxiety and depressive disorders. | C |
444 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What is the role of prophylactic cranial irradiation (PCI) in the management of patients with non-small cell lung cancer (NSCLC) treated with radical intent? Please answer this question based on the information provided below:
Prophylactic cranial irradiation for lung cancer patients at high risk for development of cerebral metastasis: results of a prospective randomized trial conducted by the Radiation Therapy Oncology Group.
Beginning in February 1984, 187 evaluable patients with adenocarcinoma or large cell carcinoma of the lung clinically confined to the chest were randomized to receive either conventionally fractionated thoracic irradiation alone or thoracic irradiation with concurrent, prophylactic cranial irradiation. The study population included 161 patients treated for medically or surgically inoperable primary cancers, and 26 patients undergoing adjuvant postoperative mediastinal irradiation following attempted curative resection of primary cancers found to have metastasized to hilar or mediastinal lymph nodes. Elective brain irradiation was not effective in preventing the clinical appearance of brain metastases, although the time to develop brain metastases appears to have been delayed. Eighteen of 94 patients (19%) randomized to chest irradiation alone have developed brain metastases as opposed to 8/93 patients (9%) randomized to receive prophylactic cranial irradiation (p = .10). No survival difference was observed between the treatment arms. Among the 26 patients undergoing prior resection of all gross intrathoracic disease, brain metastases were observed in 3/12 patients (25%) receiving adjuvant chest irradiation alone, compared to none of 14 receiving prophylactic cranial irradiation (p = .06). In the absence of fully reliable therapy for the primary disease, and without effective systemic therapy preventing dissemination to other, extrathoracic sites, prophylactic cranial irradiation for inoperable non-small cell lung cancer cannot be justified in routine clinical practice. Further investigation in the adjuvant, postoperative setting may be warranted.
Combined chemoradiotherapy in limited-disease, inoperable non-small cell lung cancer.
Forty-three patients with limited-disease, inoperable non-small cell lung cancer received two intravenous courses of cyclophosphamide, Adriamycin, and cisplatin (CAP) chemotherapy over a 6-week period. This was followed by 5 weeks of combined chemoradiotherapy (CCRT) consisting of low weekly doses of CAP for 5 weeks plus 50 Gy continuous X ray therapy (XRT) to the primary tumor site. Chemotherapy was continued until disease progression occurred or until the total dose of Adriamycin reached 450 mg/m2, whichever came first. CCRT improved the response rate [complete response (CR) plus partial responses (PR)] from 25% after two courses of CAP alone to 65% after CCRT. Previous response to two courses of CAP influences response subsequent to CAP plus XRT. A pretherapy weight loss of 6% or greater had a significant adverse effect on both response and survival time. The median survival time for all patients was 50 weeks; patients whose disease responded to treatment survived significantly longer than patients with nonresponding disease. The median time until disease progression was 37 weeks. Twenty-seven patients relapsed. The first sites of relapse were local in 30% of the patients, distant in 56% of them, and both local and distant in 15%. Severe esophagitis occurred in 30% of the patients and was dose-limiting. The administration of CCRT resulted in an improved response rate compared with the rates reported in previous studies of chemotherapy or radiotherapy alone. Further improvement of the CCRT program is needed to increase long-term survival time and to decrease esophageal toxicity.
Role of elective brain irradiation during combined chemoradiotherapy for limited disease non-small cell lung cancer.
We have studied the clinical impact of elective brain irradiation (EBI) in patients with locally advanced, non-small cell lung cancer (LA-NSC). All patients received combination chemotherapy (cyclophosphamide + doxorubicin (Adriamycin) + cisplatin = CAP) or CAP plus radiotherapy as the initial treatment for their active tumor or as an adjuvant therapy. Of 97 evaluable patients, 46 were randomized to receive EBI (3 000 rad in 10 fractions given over two weeks). The characteristics of both groups were comparable by sex, age, performance status, pretherapy weight loss, histologic cell type, clinical staging, and type of prior therapy. EBI significantly decreased the incidence of central nervous system (CNS) metastasis in the treated group compared to the control group (4% vs 27%, p = .002). CNS involvement occurred in the treated group after failure at other sites whereas 12 of 14 control patients had CNS metastases as the first site of relapse. EBI decreased the incidence of CNS metastasis in all prognostic categories. Using multivariate analysis, the beneficial effect was shown to be significant in females, patients with good performance status, weight loss less than 6%, squamous cell histology, state III disease or no prior therapy. EBI significantly increased CNS metastasis-free interval with a beneficial effect that was significant in males, patients with weight loss less than 6%, squamous cell histology or responders. Although no survival benefit was observed for the treated group because of the adverse effect from other relapses, EBI will become more important as better treatment programs are developed.(ABSTRACT TRUNCATED AT 250 WORDS)
Cranial irradiation in cancer of the lung of all cell types.
The Veterans Administration Lung Group conducted a prospective study of irradiation for subclinical brain metastases in patients with inoperable carcinoma of the lung between 1975 and 1978. Patients were randomized to receive whole-brain irradiation (2,000 rads in two weeks) or no brain treatment, and to receive one of two regimens of thoracic irradiation. Three hundred twenty-three patients with normal radionuclide brain scans were able to be evaluated. The rate of clinical brain metastasis was 26% for patients with small cell carcinoma vs 10% for the "non-small-cell" group. A statistically insignificant decrease in the rate of brain metastasis was found among irradiated patients with small cell carcinoma. The frequency of brain metastasis in the non-small-cell patients was reduced from 13% to 6% by irradiation. Prophylactic cranial irradiation can decrease morbidity from non-small-cell carcinoma of the lung.
Options:
A: PCI significantly reduces the incidence of brain metastases and improves overall survival.
B: PCI reduces the incidence of brain metastases but does not provide a survival benefit.
C: PCI has no effect on the incidence of brain metastases or overall survival.
D: PCI improves quality of life and overall survival in NSCLC patients. | B |
445 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What was the effect of neoadjuvant chemotherapy on survival in patients with invasive bladder cancer? Please answer this question based on the information provided below:
Improved local control of invasive bladder cancer by concurrent cisplatin and preoperative or definitive radiation. The National Cancer Institute of Canada Clinical Trials Group.
PURPOSE: A prospective randomized trial was conducted to determine whether the addition of concurrent cisplatin to preoperative or definitive radiation therapy in patients with muscle-invasive bladder cancer improved local control or survival.
PATIENTS AND METHODS: Ninety-nine eligible patients with T2 to T4b transitional cell bladder cancer participated, 64% with cT3b or cT4. Patients and their physicians selected either definitive radiotherapy or precystectomy radiotherapy; patients were then randomly allocated to receive intravenous cisplatin 100 mg/m2 at 2-week intervals for three cycles concurrent with pelvic radiation, or to receive radiation without chemotherapy. Patients were stratified by clinical tumor stage and by radiation plan. The median follow-up duration is 6.5 years.
RESULTS: The occurrence of distant metastases was the same in both study arms. However, 25 of 48 control patients have had a first recurrence in the pelvis, compared with 15 of 51 cisplatin-treated patients (P = .036). The pelvic relapse rate in the two groups was significantly reduced by concurrent cisplatin (P = .038, log-rank test) and this effect was preserved in a stepwise Cox regression model of prognostic factors (hazards ratio, 0.50; 90% confidence interval [CI], 0.29 to 0.86; P = .036). The hazard reduction was similar for both radiation plans. Pretreatment leukocytosis and high clinical stage were independent adverse factors in a Cox model of overall survival, but the effect of cisplatin was not significant.
CONCLUSION: Concurrent cisplatin may improve pelvic control of locally advanced bladder cancer with preoperative or definitive radiation, but has not been shown to improve overall survival. The use of concurrent cisplatin had no detectable effect on distant metastases.
Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer.
BACKGROUND: Despite aggressive local therapy, patients with locally advanced bladder cancer are at significant risk for metastases. We evaluated the ability of neoadjuvant chemotherapy to improve the outcome in patients with locally advanced bladder cancer who were treated with radical cystectomy.
METHODS: Patients were enrolled if they had muscle-invasive bladder cancer (stage T2 to T4a) and were to be treated with radical cystectomy. They were stratified according to age (less than 65 years vs. 65 years or older) and stage (superficial muscle invasion vs. more extensive disease) and were randomly assigned to radical cystectomy alone or three cycles of methotrexate, vinblastine, doxorubicin, and cisplatin followed by radical cystectomy.
RESULTS: We enrolled 317 patients over an 11-year period, 10 of whom were found to be ineligible; thus, 154 were assigned to receive surgery alone and 153 to receive combination therapy. According to an intention-to-treat analysis, the median survival among patients assigned to surgery alone was 46 months, as compared with 77 months among patients assigned to combination therapy (P=0.06 by a two-sided stratified log-rank test). In both groups, improved survival was associated with the absence of residual cancer in the cystectomy specimen. Significantly more patients in the combination-therapy group had no residual disease than patients in the cystectomy group (38 percent vs. 15 percent, P<0.001).
CONCLUSIONS: As compared with radical cystectomy alone, the use of neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin followed by radical cystectomy increases the likelihood of eliminating residual cancer in the cystectomy specimen and is associated with improved survival among patients with locally advanced bladder cancer.
Five-year followup of a prospective trial of radical cystectomy and neoadjuvant chemotherapy: Nordic Cystectomy Trial I. The Nordic Cooperative Bladder Cancer Study Group.
PURPOSE: Chemotherapy is widely used in patients with locally advanced bladder cancer but until now there has been no conclusive evidence that this therapy improves survival. The Nordic Cooperative Bladder Cancer Study Group conducted a randomized phase III study to assess the possible benefit of neoadjuvant chemotherapy in patients with bladder cancer undergoing radical cystectomy after short-term radiotherapy.
MATERIALS AND METHODS: Our trial included 325 patients with locally advanced stage T1 grade 3 or stages T2 to T4aNXM0 bladder cancer allocated randomly into a chemotherapy or no chemotherapy group (control). The chemotherapy schedule consisted of 2 cycles of 70 mg./m.2 cisplatin and 30 mg./m.2 doxorubicin with a 3-week interval between the cycles.
RESULTS: After 5 years the overall survival rate was 59% in the chemotherapy group and 51% in the control group (p = 0.1). The corresponding cancer specific survival rate was 64 and 54%, respectively. In regard to treatment, no difference was observed for stages T1 and T2 disease, while there was a 15% difference in overall survival for patients with stages T3 to T4a disease (p = 0.03). In a multivariate analysis only chemotherapy and T category emerged as independent prognostic factors. The relative death risk for patients who received chemotherapy was 0.69 (95% confidence interval 0.49 to 0.98) compared to the control group after adjustment for the other tested factors.
CONCLUSIONS: Neoadjuvant chemotherapy seems to improve long-term survival after cystectomy in patients with stages T3 to T4a bladder carcinoma, while no survival benefit was found for stages T1 to T2 disease.
Neoadjuvant cisplatin chemotherapy before radical cystectomy in invasive transitional cell carcinoma of the bladder: a prospective randomized phase III study.
From November 1984 to April 1989, 122 patients with clinical T2-4a Nx-2 M0 transitional cell carcinoma of the bladder were entered in a prospective randomized trial to compare survival between a control group of 60 patients treated only with radical cystectomy (arm A) and a group of 62 patients treated with 3 cycles of 100 mg./m.2 neoadjuvant cisplatin before radical cystectomy (arm B). Secondary objectives of the trial were comparison of the disease-free interval and time to death, significance of response of the primary tumor to cisplatin, pattern of relapse and toxicity. As of April 1993 after a median followup of 78.2 months (range 48 to 101) no difference in survival between the control patients and those who received neoadjuvant cisplatin has been observed. The overall direct survival is 37.3% for arm A and 35.5% for arm B. The survival rate of the 109 patients who complied with the protocol is 38.2% for 55 patients of the control group and 40.7% for 54 patients of the cisplatin group. Survival rates of patients theoretically rendered free of disease by radical cystectomy (complete response pT0-4a, pN0-2, M0) is 43.7% for 40 control patients and 47.8% for 41 cisplatin treated patients. The time to relapse in complete response patients was significantly longer (p = 0.0298) for those who received cisplatin (arm A 13.1 months versus arm B 30.3 months). The time to death (cause specific) did not differ significantly between both groups overall (p = 0.1349) but it was significantly different between controls and responders (p = 0.0501). Preoperative cisplatin downstaged the primary tumor in 19 patients (33.9%), of whom 11 (19.6%) had no tumor in the cystectomy specimen (pT0) and 8 (14.3%) had superficial tumor (pTis pTa pT1). In 6 patients (9.7%) disease progressed during chemotherapy. The survival of the responders was significantly better than that of nonresponders (p = 0.0142), with specific death rate of 26.3% and 62.5%, respectively, and a median time to death of 43 months for responders and 30.5 months for nonresponders. Patients without nodal involvement (pN0) or with only 1 micrometastasis (pN1) fared significantly better (p = 0.0001) than those with major node invasion (pN2-4), irrespective of the treatment received. The survival rate is 48.6% for patients with pN0 disease, 37.5% for pN1 and 5% for pN2-4. Toxicity of cisplatin was minimal and there were no differences in perioperative morbidity between the arms.(ABSTRACT TRUNCATED AT 400 WORDS)
Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. International collaboration of trialists.
BACKGROUND: Several non-randomised trials have shown that transitional-cell carcinoma of the bladder is a moderately chemosensitive tumour. We investigated whether the addition of neoadjuvant cisplatin-based chemotherapy to radical surgery or radiotherapy would improve survival.
METHODS: Patients with T2 G3, T3, T4a, N0-NX, or M0 transitional-cell carcinoma of the bladder undergoing curative cystectomy or full-dose external-beam radiotherapy were randomly assigned three cycles of neoadjuvant chemotherapy (cisplatin, methotrexate, and vinblastine, with folinic acid rescue, n=491) or no chemotherapy (n=485). When possible, clinical tumour response was assessed cytoscopically after completion of chemotherapy but before cystectomy or radiotherapy; histopathologically assessed response was on cystectomy samples. We recorded every 6 months locoregional persistence or relapse of tumour, appearance of distant metastases, survival, and cause of death.
FINDINGS: Median follow-up of patients still alive was 4.0 years. 485 patients died, and 78.6% of deaths were due to transitional-cell carcinoma. Chemotherapy mortality was 1% and operative (cystectomy) mortality was 3.7%. Kaplan-Meier curves compared by means of the log-rank test gave a calculated absolute difference between groups in 3-year survival of 5.5% (95% CI -0.5 to 11.0, p=0.075; 55.5% for chemotherapy, 50.0% for no chemotherapy). Median survival in the chemotherapy group was 44 months compared with 37.5 months for the no-chemotherapy group. 32.5% of cystectomy samples contained no tumour after neoadjuvant chemotherapy.
INTERPRETATION: Three cycles of neoadjuvant chemotherapy before cystectomy or radiotherapy did not give the 10% improvement in 3-year survival that was judged to be necessary for introduction into routine use. The chemotherapy regimen was associated with a higher pathological complete-response rate in primary tumours, but there was no clear evidence that it would increase survival.
Plenary debate of randomized phase III trial of neoadjuvant MVAC plus cystectomy versus cystectomy alone in patients with locally advanced bladder cancer.
Neo-adjuvant (pre-emptive) cisplatin therapy in invasive transitional cell carcinoma of the bladder.
Following 2 pilot studies which showed 57 and 61% response rates to intravenous cisplatin for transitional cell carcinoma of the bladder prior to definitive treatment, the West Midlands Urological Research Group (WMURG) and the Australian Bladder Cancer Study Group (ABCSG) independently began randomised trials to test the survival benefit of neo-adjuvant intravenous cisplatin prior to radiotherapy in T2-T4 M0 transitional cell carcinoma of the bladder. Both trials failed to recruit their target numbers of 250 patients in the West Midlands and 320 in Australia. Since they had similar treatment protocols and eligibility criteria, they were combined in an overview analysis, achieving a total number of 255 patients. Each treatment group was compared with its own control group and the differences were pooled to give an overall result. There was no difference in survival between treated and control patients. The odds ratio was 1.13 with the control groups faring marginally better than the chemotherapy groups. Even with 255 patients the 95% confidence interval of the odds ratio was wide (0.80-1.57). Although there is no clear evidence of a clinically worthwhile benefit from neo-adjuvant cisplatin, this approach must be tested in a larger study using combination treatments with greater activity in metastatic disease.
Neoadjuvant chemotherapy with cisplatin and methotrexate in patients with muscle-invasive bladder tumours.
This prospective, randomized study based on two associated trials was designed to evaluate the effect of neoadjuvant chemotherapy with cisplatin and methotrexate with folinic acid rescue or no chemotherapy prior to local treatment in patients with T2-T4b, NX-3, MO transitional cell carcinoma of the bladder. In the first trial, local treatment consisted of cystectomy (DAVECA 8901) and in the other trial the treatment was radiotherapy (DAVECA 8902); 153 eligible patients were randomized. The majority of the patients (89%) completed the protocol. The overall time to progression for all 153 patients was 12.9 months. Median time to progression was 14.2 months with chemotherapy and 11.4 months without chemotherapy. The actuarial 5-year overall survival rate for all 153 patients was 29%, and 29% for both treatment groups. Multivariate analyses showed that T-stage, tumour size and serum creatinine were independent prognostic factors for survival. The cystectomy trial included 33 patients. Median survival was 78.9 months, 82.5 months with chemotherapy and 45.8 months without chemotherapy (p = 0.76). The radiotherapy trial included 120 patients. The median survival was 17.6 months. Median survival was 19.2 months in the group receiving chemotherapy and 16.3 in the group not receiving chemotherapy. The 5-year survival rate was 19% in the group receiving chemotherapy and 24% in the groups not receiving chemotherapy (p = 0.98). Late toxicity grade 3 or 4 of the bladder was recorded in 25% of the patients (actuarial rate). Neoadjuvant chemotherapy with cisplatin and methotrexate did not significantly improve disease-free or overall survival in 153 randomized patients with invasive bladder cancer.
Adjuvant chemotherapy in T3 carcinoma of the bladder. A prospective trial: preliminary report.
We report the early results of a multi-centre, randomised prospective trial of neoadjuvant and maintenance chemotherapy with methotrexate (MTX) in 376 patients with advanced (T3) carcinoma of the bladder. In patients under 65 years of age, treatment consisted of radical radiotherapy (64 Gy) or, in some centres, pre-operative radiotherapy (44 Gy) and elective cystectomy. All patients over 65 had radical radiotherapy. MTX was administered to 188 patients. There was no increase in toxicity attributable to the MTX. MTX did not significantly increase the proportion of patients whose tumours responded to radiotherapy; 50% (70/141) responded to radiotherapy and 56% (76/136) to MTX radiotherapy. The development of metastases and survival was also similar in both groups (3-year survival: radiotherapy 37.3%, MTX + radiotherapy 38.6%). We report the logistic difficulties of the administration of prolonged courses of maintenance chemotherapy. Further controlled trials of neo-adjuvant chemotherapy in advanced bladder cancer are required, involving more active regimes.
Neoadjuvant cisplatin-methotrexate chemotherapy for invasive bladder cancer -- Nordic cystectomy trial 2.
BACKGROUND: In the first Nordic cystectomy trial (1986-1989) a chemotherapy combination of cisplatin-doxorubicin and external radiation seemed to improve the long-term survival after cystectomy in patients with stage T3-T4a bladder carcinomas. The aim of this study was to investigate if solely neoadjuvant chemotherapy could influence survival in patients with advanced urothelial bladder cancer undergoing cystectomy.
METHODS: The study (1991-1997) recruited 317 patients with T2-T4aNXM0 urothelial bladder tumours. The patients were randomly allocated to three courses of cisplatin-methotrexate or no pretreatment before cystectomy, eight were subsequently excluded due to protocol violation.
RESULTS: Chemotherapy according to protocol was administered to 74% (115/155) of the patients in the experimental arm. No chemotherapy related mortality was observed. Of remaining patients in the experimental arm, 14 did not receive any chemotherapy, nine discontinued after one course and 14 after two courses due to side effects. Median follow-up time among censored patients was 5.3 years. Estimated 5-year overall survival was 53% in the experimental arm and 46% in the control arm (n.s. log-rank test). The proportion of patients with pathological stage pT0 was 26.4% in the experimental arm and 11.5% in the control arm (p = 0.001). Risk of locoregional relapse and distant metastases was similar in the study arms.
CONCLUSIONS: The chemotherapy regimen was well tolerated. Despite substantial downstaging no statistically significant survival benefit with the neoadjuvant therapy could be seen after 5 years of follow-up.
Neo-adjuvant (pre-emptive) cisplatin therapy in invasive transitional cell carcinoma of the bladder.
Following 2 pilot studies which showed 57 and 61% response rates to intravenous cisplatin for transitional cell carcinoma of the bladder prior to definitive treatment, the West Midlands Urological Research Group (WMURG) and the Australian Bladder Cancer Study Group (ABCSG) independently began randomised trials to test the survival benefit of neo-adjuvant intravenous cisplatin prior to radiotherapy in T2-T4 M0 transitional cell carcinoma of the bladder. Both trials failed to recruit their target numbers of 250 patients in the West Midlands and 320 in Australia. Since they had similar treatment protocols and eligibility criteria, they were combined in an overview analysis, achieving a total number of 255 patients. Each treatment group was compared with its own control group and the differences were pooled to give an overall result. There was no difference in survival between treated and control patients. The odds ratio was 1.13 with the control groups faring marginally better than the chemotherapy groups. Even with 255 patients the 95% confidence interval of the odds ratio was wide (0.80-1.57). Although there is no clear evidence of a clinically worthwhile benefit from neo-adjuvant cisplatin, this approach must be tested in a larger study using combination treatments with greater activity in metastatic disease.
Options:
A: Neoadjuvant chemotherapy had no significant effect on overall survival.
B: Neoadjuvant chemotherapy significantly reduced the risk of death and improved overall survival.
C: Neoadjuvant chemotherapy was only beneficial for certain subgroups of patients.
D: Single-agent platinum chemotherapy showed a significant benefit on overall survival. | B |
446 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What were the findings regarding the effectiveness of the sequential combination of glucocorticosteroids and alfa interferon compared to alfa interferon alone in patients with HBeAg-positive chronic hepatitis B? Please answer this question based on the information provided below:
[Treatment of chronic hepatitis B with interferon alpha (Wellferon) with and without previous corticosteroid therapy -- results of a multicenter, double blind study].
The present study was aimed to test the efficacy and safety of interferon alpha (Wellferon-Wellcome Foundation Ltd.) either alone, or in combination with short-term corticosteroid pretreatment in the therapy of chronic hepatitis B. 44 patients with documented chronic hepatitis type B (12 women and 32 men; mean age 37.5 years, range 23-59 years) and satisfying the entry criteria were subjects of the study. 30 patients had chronic active hepatitis on liver biopsy, while 14 had chronic persistent hepatitis. Consecutive patients were given either placebo or prednisone in a double-blinded manner for 4 weeks (0.6 mg/kg/day in the first two weeks, 0.45 mg/kg/day in the third week and 0.25 mg/kg/day in the last week), and then, after a 2 week pause, therapy with interferon was instituted for a total of 12 weeks. Interferon was given by intramuscular injection in a single daily dose of 10 x 10(6) IU for 5 days and three times weekly thereafter. However, because of side effects, the dose of interferon was occasionally reduced to 5 x 10(6) IU in most patients. Interferon induced a sustained cessation of HBV replication as judged by loss of DNA-polymerase activity in 26 (59%) patients, 20 (45%) patients seroconverted to anti-HBe. Additionally, 6 (14%) cases lost HBsAg and seroconverted to anti-HBs. Prednisone pretreatment did not seem to improve the efficacy of interferon therapy. The outcome of the treatment was unrelated to gender and pretreatment activity of transaminases, however, patients with low activity of HBV replication were more likely to respond to therapy than patients with high HBV replication.
Treatment of children with chronic hepatitis B with a combination of steroids and human lymphoblastoid interferon.
The efficacy of human lymphoblastoid interferon (Wellferon) therapy was measured in 20 children with chronic hepatitis B with or without pretreatment with prednisolone. Patients were randomised to receive 0.6 mg/kg/day prednisolone for 3 weeks, then at 0.3 mg/kg for a fourth week or placebo. All patients then received interferon 5 MU/m2 i.m. for 12 weeks; daily for 5 days then three times a week for the remaining 11 weeks. Preliminary results show that 25% of children had a permanent loss of viral markers of replication. However, response to interferon varied widely between individuals and a prolonged follow-up is required in order to determine the influence of prednisolone pretreatment on the efficacy of interferon therapy.
Dual-centre, double-blind, randomised trial of lymphoblastoid interferon alpha with or without steroid pretreatment in children with chronic hepatitis B.
Thirty-five children with chronic HBV infection, HBV-DNA and eAg serum positivity, and HBcAg in liver tissue were treated with lymphoblastoid human interferon alpha with (16 cases) or without (19 cases) prednisolone pretreatment. The patients were double-blind randomized to receive steroid or placebo for 4 weeks, followed after 2 weeks by 5 or 10 MU/m2 interferon for 12 weeks. The e anti-e seroconversion rate reached 48%, which is much higher than the spontaneous seroconversion rate. The influence of "prednisolone priming" was not statistically significant. HBeAg clearance was similar in both groups (44% after prednisolone/interferon and 53% after interferon alone). The response to either treatment did not correlate with the pretreatment serum transaminase. HBV-DNA or degree of histological activity. Interferon was well tolerated, the side effects being less severe than in adults, and never led to suspension of the treatment.
Lymphoblastoid interferon alfa with or without steroid pretreatment in children with chronic hepatitis B: a multicenter controlled trial.
The comparative efficacy of prednisolone followed by interferon alfa (IFN-alpha) versus IFN-alpha alone in enhancing the rate of antibody to hepatitis B e antigen (anti-HBe) seroconversion has not been evaluated in a large cohort of white children. To determine this, a multicenter-controlled trial was conducted in 95 hepatitis B virus (HBV)-DNA/hepatitis B e antigen (HBeAg)-positive children (median age, 9 years [range, 2-16 years]; 56 boys; 84 [89 percent] white), all having inflammatory changes on liver biopsy. Patients were randomized to receive either prednisolone followed by IFN-alpha (n = 34); placebo followed by IFN-alpha (n = 30); or no treatment (n = 31). The prednisolone/placebo was given on a double-blind basis. Lymphoblastoid IFN-alpha was given at 5 MU/m(2) three times a week for 12 weeks. Baseline clinical, biochemical, and histological features were similar for the three groups. The majority (85 percent) had a baseline aspartate aminotransferase (AST) level < or = 100 IU/L. On follow-up between 12 and 18 months (median, 15 months) after treatment, the loss of HBeAg with anti-HBe seroconversion was more common in patients pretreated with steroids (12 of 34 [35 percent]) or placebo [12 of 30 (40 percent)] as against controls (4 of 31 [13 percent], P< .05). Factors predictive of anti-HBe seroconversion were baseline HBV-DNA concentration of < or = 1,000 pg/mL and a greater degree of portal tract inflammation on pretrial biopsy. Our results show that in white children treatment with IFN-alpha, at the dose and duration used in this study, improves the rate of anti-HBe seroconversion. Steroid priming does not potentiate the effect of IFN-alpha.
Autoantibody prevalence in chronic hepatitis B virus infection: effect in interferon alfa.
The most effective treatment of chronic hepatitis B virus (HBV) infection is interferon alfa (IFN-alpha), a potentially severe side effect of which is the induction of autoimmunity. To assess whether IFN-alpha causes clinical or serological autoimmune manifestations, we studied 61 children randomized to receive 5 MU/m2 of IFN-alpha three times per week for 12 weeks, with or without steroid priming or no treatment. Autoantibodies to antinuclei (ANA), smooth muscle (SMA), gastric parietal cell (GPC), liver kidney microsomal type 1, mitochondrial, liver cytosolic antigen, thyroid microsomal, and thyroid globulin were detected by standard techniques. Over a median of 4 years (range, 1-5 years) from randomization, no clinical signs of autoimmunity were observed. Autoantibody positivity for nuclei, smooth muscle, and/or gastric parietal cells was observed on at least one occasion in 42 of 61 children (69%), with no overall difference in the prevalence between patients treated with interferon alone (19 of 24 [79%]), steroids plus interferon (13 of 20 [65%]), or untreated controls (10 of 17 [59%]). There was also no difference in the autoantibody prevalence before, during, and at follow-up after cessation of treatment in both interferon-treated and interferon-untreated patients. Autoantibodies are common in chronic HBV infection, and their prevalence is uninfluenced by IFN-alpha.
Prednisolone withdrawal therapy enhances the effect of human lymphoblastoid interferon in chronic hepatitis B. INTERPRED Trial Group.
BACKGROUND/AIMS: The aim of this multicentre, randomised, controlled, clinical trial was to evaluate the effect of prednisolone followed by lymphoblastoid interferon treatment in chronic hepatitis B.
METHODS: Two hundred and thirteen patients with chronic hepatitis B were randomised to either prednisolone (2 weeks of 0.6 mg/kg/day, 1 week of 0.45 mg/kg/day and 1 week of 0.25 mg/kg/day) or matching placebo followed by a 2-week rest phase and then human lymphoblastoid interferon 10 MU daily for 5 days followed by 10 MU thrice weekly for 11 weeks. Of 200 evaluable patients, 33 (16.5%) were females, and 50 (25%) were male homosexuals. Thirty three patients (16.5%) had chronic persistent hepatitis, 145 (72.5%) had chronic active hepatitis and 22 (11%) had active cirrhosis.
RESULTS: Survival analysis disclosed statistically significant effects of prednisolone pre-treatment on both HBeAg disappearance and HBeAg to anti-HBe seroconversion (log-rank test statistics 5.43; p = 0.02 and 4.75; p = 0.03). Observed HBeAg disappearance and HBeAg to anti-HBe seroconversion rates (placebo vs. prednisolone patients) were 28% vs. 44% and 23% vs. 38%. Six months after stopping interferon, HBV DNA was negative in 51% of prednisolone patients vs. 28% of placebo patients (Chi-square test statistic 6.13; p = 0.013). Prednisolone pre-treatment tended to be more effective in patients with higher transaminase levels and in patients with low levels of HBV DNA. Fifteen patients (7.5%) (13 within 1 year of follow-up) eventually lost HBsAg; 14 of these subsequently developed anti-HBs. Interferon treatment was modified in 102 patients (51%). Three out of 22 patients with cirrhosis (14%), one of whom received prednisolone pre-treatment, developed hepatic decompensation with a fatal outcome while on interferon treatment.
CONCLUSIONS: Prednisolone pre-treatment significantly enhanced the treatment effect of lymphoblastoid interferon in terms of HBeAg clearance and seroconversion to anti-HBe. Treatment should be used with caution in patients with cirrhosis and avoided in patients showing signs, or with a history, of decompensated cirrhosis.
Effect of recombinant alpha 2 interferon with or without prednisone in Chinese HBsAg carrier children.
Ninety Chinese hepatitis B surface antigen (HBsAg) carrier children, aged 2-17 years, positive for hepatitis B e antigen (HBeAg) and hepatitis B virus DNA on at least three occasions in 6 months, were randomized into 3 groups. Thirty children received syrup vitamin B complex as control, 29 received 6 weeks of placebo syrup followed by 16 weeks of recombinant alpha 2b-interferon [intron A (rIFN2b)], 5 x 10(6) u/m2 subcutaneously thrice weekly; and 31 received 6 weeks of syrup prednisone (0.6 mg/kg tailed to 0.2 mg/kg) followed by 16 weeks of recombinant alpha 2b-interferon as above. The placebo/prednisone syrup was given on a double-blind basis. At 24 months of follow-up, persistent loss of hepatitis B virus DNA occurred in none of the children in the control group, in one child receiving recombinant alpha 2b-interferon alone, who also seroconverted to anti-HBe and anti-HBs and in five children receiving interferon with steroid priming (p = 0.0571 compared with controls), with four seroconverting to anti-HBe and one also seroconverting to anti-HBs. A rise of transaminases to above twice the upper limit of normal levels during the first 7 months of follow-up occurred in one subject in the control group, four in the group receiving alpha 2b-interferon alone and nine in the group receiving recombinant alpha 2b-interferon with steroid priming (p = 0.0144 compared with controls). Side effects of the steroid were negligible; those of recombinant alpha 2b-interferon were transient and acceptable. We conclude that 6 weeks of prednisone followed by 16 weeks of recombinant alpha 2b-interferon is of use in inducing persistent loss of hepatitis B virus DNA (16.1 per cent) and e-seroconversion (12.9 per cent) in a proportion of Chinese HBsAg carrier children: the prednisone probably enhances the immunomodulatory effect of recombinant alpha 2b-interferon.
Beneficial effect of prednisolone withdrawal followed by human lymphoblastoid interferon on the treatment of chronic type B hepatitis in Asians: a randomized controlled trial.
To evaluate the effect of interferon and the benefit of prednisolone pretreatment in Oriental patients with chronic active hepatitis B, 120 male Chinese patients were randomly allocated to receive: 1) group A: a 4-week course of prednisolone followed by 2 weeks of no treatment and then a 12-week course of human lymphoblastoid interferon, 4 to 6 MU/m2 intramuscularly; 2) group B: as group A, but with placebo given instead of prednisolone; 3) group C: an 18-week course of placebo. Clearance of serum hepatitis B virus-DNA and HBeAg (complete response) was achieved in 21% of group A, 5% of group B and none of group C at the end of therapy (A vs B: p = 0.054; A vs C: p < 0.01). When assessed 12 months after the end of therapy, the complete response rate was 46% in group A, 24% in group B and 25% in group C (p < 0.05). Those with baseline alanine transaminase < or = 200 U/l showed a better response to interferon following prednisolone withdrawal (48%) than with interferon therapy alone (20%, p = 0.056) and no treatment (9%, p < 0.01). Those with a baseline serum hepatitis B virus-DNA < or = 1000 pg/ml also showed a higher complete response rate when pretreated with prednisolone (59%) than when treated with interferon alone (29%, p = 0.084) or untreated (22%, p < 0.03). The strongest independent predictor of a response to treatment was prednisolone withdrawal (p < 0.05). None of the responders lost hepatitis B surface antigen.(ABSTRACT TRUNCATED AT 250 WORDS)
Treatment of chronic type B hepatitis in Southeast Asia.
In Southeast Asia, 15 to 20 percent of the population are hepatitis B surface antigen carriers. The majority of these carriers have chronic hepatitis and would progress to cirrhosis or hepatocellular carcinoma at an annual incidence of 2 percent and 1 percent, respectively. Previous studies from Southeast Asia suggested that immunosuppressive therapy could be harmful, or at best of no value, and antiviral treatment with vidarabine, picibanil, or even interferon was also unsatisfactory. Currently, a randomized controlled trial of human lymphoblastoid interferon, with or without prednisolone pretreatment, versus placebo in patients with hepatitis B core antigen in the liver and hepatitis B e antigen in the serum is being conducted. Forty-five patients (29 receiving interferon, 16 receiving placebo) have been entered in the trial for at least two months. Actuarial analysis shows that the response to interferon therapy was better than that to placebo. Although flu-like symptoms, hair loss, and body weight loss were seen, no side effect requiring specific treatment has been encountered. These preliminary results suggest that human lymphoblastoid interferon is effective and safe in Oriental patients.
Olone modulates the therapeutic effect of interferon to eliminate preferentially the hepatitis B virus precore stop mutant.
BACKGROUND/AIMS: The aim of this study was to understand the changes in the proportion of hepatitis B virus precore stop mutant during the course of prednisolone primed interferon (IFN) therapy.
METHODS: Three groups of patients were included: patients receiving prednisolone-primed IFN treatment (Group I, n=31), IFN treatment only (Group II, n=29), and placebo (Group III, n=25). The proportion of precore stop mutant was measured by a quantitative amplification-created restriction site method.
RESULTS: Distinct patterns of the progression of the proportion of mutant were found among these three groups. A steady increase in the proportion of mutant was observed only in Group III patients. In Group II patients, the presence of a higher percentage of mutant (> 25%) immediately before IFN treatment was predictive for the subsequent clearance of hepatitis B e antigen (HBeAg) (p<0.01), but not for complete anti-viral response (p>0.05). Prednisolone pretreatment resulted in an increase in the proportion of mutant in patients with initially low percentages (< or = 25%) of mutant. During the period of IFN treatment, both the relative and absolute amount of the precore stop mutant decreased significantly in Group I patients who cleared HBeAg. The presence of such a decrease in this group of patients was predictive for both HBeAg clearance and complete anti-viral response.
CONCLUSIONS: Our data suggest that prednisolone serves as a modulator to enhance elimination of precore stop mutant by IFN, which advocates the benefit of corticosteroid pretreatment in an area where the precore mutants are prevalent.
A controlled trial of interferon with or without prednisone priming for chronic hepatitis B.
In a randomized, controlled trial of recombinant interferon alfa-2b with or without prednisone priming in Chinese adults with chronic hepatitis B virus infection, stratified randomization for pretreatment serum alanine aminotransferase levels was done. Partial or complete antiviral responses were achieved in 17 (21.5%) of 79 treated patients and 3 (8.3%) of 36 controls (P = 0.14). The response to interferon treatment was significantly better in those who had elevated pretreatment transaminase levels and comparable to that reported in white patients [15 (38.5%) of 39 patients compared with 2 (5%) of 40 who had normal pretreatment transaminase levels (P = 0.0005)]. The spontaneous seroconversion rate was also higher among the controls with elevated transaminase levels [3 (18.8%) of 16 compared with 0 of 20 with normal transaminase levels], but this difference was not statistically significant (P = 0.16). Among the interferon-treated patients, prednisone priming appeared to have a marginal benefit over treatment with interferon alone in patients with elevated transaminase levels (43% vs. 33%), but not in those with normal transaminase levels (0% vs. 9.5%). It was confirmed that Chinese patients with normal transaminase levels respond very poorly to interferon alfa therapy. However, the response was significantly better in patients with elevated transaminase levels.
A controlled trial of high dose interferon, alone and after prednisone withdrawal, in the treatment of chronic hepatitis B: long term follow up.
This study was designed to evaluate the safety and effectiveness of high dose interferon, with or without prednisone pretreatment, in patients with chronic hepatitis B. Patients were randomised to two treatment groups: group I (n = 26) received six weeks of prednisone followed by a two week, drug free period, and then 10 million units (MU) of interferon alfa-2b three times weekly subcutaneously for 16 weeks; group II (n = 24) were used as controls for 24 weeks and then treated with interferon. Loss of hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV)-DNA, with a return to normal alanine aminotransferase (ALT) activity, was seen in 16 of 26 group I patients (61.5%), in one group II patient (4.2%) during the control phase, and in 13 of 23 group II patients (56.5%) after interferon. Three of 26 (11.5%) in group I and one of 23 (4.3%) in group II eliminated the surface antigen (HBsAg). There were no statistically significant differences in response between groups I and II. Liver biopsies carried out in 20 patients showed that responders had a noticeable reduction in inflammation and disappearance of core antigen in liver tissue, changes not seen in non-responders. On long term follow up (four years), nine out of 28 responders (32.1%) eliminated HBsAg, and four initial non-responders had a late seroconversion.
Recombinant interferon alfa-2b following prednisone withdrawal in the treatment of chronic type B hepatitis.
The aim of the study was to evaluate the safety and effectiveness of interferon alfa-2b, alone and following prednisone withdrawal, in patients with chronic type B hepatitis. Thirty-five patients (27 men and eight women) were randomly allocated to two treatment groups. Group I (n = 17) received 6 weeks of prednisone followed by interferon alfa-2b (INTRON A, Schering-Plough Corporation) 10 million units subcutaneously, three times a week for 16 weeks. Group II (n = 18) was used as an untreated control group for 24 weeks, after which they received 16 weeks of treatment with the same dose of interferon as Group I. Both groups were followed up for 24 weeks after treatment. In Group I, 10/17 patients (58.8%) eliminated hepatitis B e antigen; 8/17 (47.1%) developed antibodies to hepatitis B e antigen; 9/17 (52.9%) became hepatitis B virus DNA negative and 1/17 (5.9%) was hepatitis B surface antigen negative at the end of follow up. In Group II, during the control phase, 1/18 (5.5%) became hepatitis B e antigen negative. When treated with interferon, 7/15 (46.7%) eliminated the e antigen, and 6/15 (40%) developed antibodies to hepatitis B e antigen and were hepatitis B virus DNA negative at the end of follow up. Serum alanine aminotransferase reached normal levels in all seroconverted patients. Liver biopsies showed a marked reduction of inflammation and disappearance of hepatitis B core antigen in liver cell nuclei in almost all cases.(ABSTRACT TRUNCATED AT 250 WORDS)
A randomized, controlled trial of interferon alfa-2b alone and after prednisone withdrawal for the treatment of chronic hepatitis B. The Hepatitis Interventional Therapy Group.
BACKGROUND AND METHODS: Chronic hepatitis B is a common and often progressive liver disorder for which there is no accepted therapy. To assess the efficacy of treatment with interferon, we randomly assigned patients with chronic hepatitis B to one of the following regimens: prednisone for 6 weeks followed by 5 million units of recombinant interferon alfa-2b daily for 16 weeks; placebo followed by 5 million units of interferon daily for 16 weeks; placebo followed by 1 million units of interferon daily for 16 weeks; or observation with no treatment.
RESULTS: Hepatitis B e antigen and hepatitis B viral DNA disappeared from serum significantly more often in the patients given prednisone plus interferon (16 of 44 patients, or 36 percent) or 5 million units of interferon alone (15 of 41; 37 percent) than in the untreated controls (3 of 43; 7 percent; P less than 0.001); the difference between those given 1 million units of interferon (7 of 41; 17 percent) and the controls was not significant. The strongest independent predictor of a response to treatment was the amount of hepatitis B viral DNA in serum at entry (P less than 0.0001). Of the 38 patients who responded to interferon, 33 (87 percent) had normal serum aminotransferase levels after therapy; 11 patients who responded (29 percent), but no controls, lost the hepatitis B surface antigen. Blinded histologic assessment revealed a significant improvement in periportal necrosis in the treated patients (P = 0.03).
CONCLUSIONS: In chronic hepatitis B, treatment with interferon alfa-2b (5 million units per day for 16 weeks) was effective in inducing a sustained loss of viral replication and achieving remission, assessed biochemically and histologically, in over a third of patients. Moreover, in about 10 percent of the patients treated with interferon, hepatitis B surface antigen disappeared from serum.
Efficacy of steroid withdrawal and low-dose interferon treatment in chronic active hepatitis B. Results of a randomized multicenter trial. Swiss Association for the Study of the Liver.
Fifty-six patients with biopsy-proven, chronic active hepatitis B were included in a multi-center, randomized trial comparing steroid withdrawal followed by 1.5 MU recombinant interferon alpha 2b (Intron) with placebo withdrawal followed by either 1.5 or 5 MU interferon. The patients were equally distributed between the treatment groups with respect to biochemical and histologic activity as well as with respect to DNA levels and quantitative liver function tests. One patient was lost to follow up. After 1 year of treatment, 10/18, 13/19 and 11/18 patients had lost hepatitis B virus DNA in the three groups, respectively (non-significant). Transaminase levels were normal in 27/34 of the responders but in only 4/21 of the non-responders (p < 0.0001). Both galactose elimination capacity and aminopyrine breath test improved significantly in responders, but either did not change (aminopyrine breath test) or deteriorated in non-responders (galactose elimination capacity). Biopsy score improved in both groups but this reached statistical significance only in responders. This effect was due to improvements in both inflammatory and fibrotic activity. Side effects included almost universally a flu-like syndrome, granulocytopenia (1), depression (3) and thyroid dysfunction (2). Two deaths occurred, one due to hepatocellular cancer, and the other to hepatorenal syndrome after spontaneous bacterial peritonitis. A severe cytolytic episode was observed in three patients in the steroid withdrawal group. We conclude that in patients with marked histologic activity, lower doses of interferon may be as effective as the standard dose of 5 MU.(ABSTRACT TRUNCATED AT 250 WORDS)
Prolonged and high dose recombinant interferon alpha-2b alone or after prednisone priming accelerates termination of active viral replication in children with chronic hepatitis B infection.
BACKGROUND: There is no generally accepted treatment for chronic hepatitis B (HB) infection in children.
OBJECTIVES: To evaluate the efficacy of a prolonged course of high dose interferon alone or after prednisone priming in children with chronic HB infection.
METHODS: The outcome of 31 children with HB e antigen (HBeAg)-positive chronic hepatitis who randomly received either no treatment (n = 9) or 10 million units of interferon alpha-2b/m2, alone (n = 13) or after prednisone priming (n = 9), three times weekly for 1 year was studied.
RESULTS: One patient withdrew from treatment. By the end of the first year treatment induced a loss of HB virus DNA and HBeAg from serum in 10 of 21 patients (48%), and a loss of HB surface antigen (HBsAg) in 4 (19%). Alanine aminotransferase values became normal in one patient (4.8%). Response rates in the two groups of treated patients were similar. In controls only one patient lost HBeAg and HBV DNA (11%; P = 0.05), and none lost HBsAg or showed alanine aminotransferase normalization (P = 0.21 and 0.70, respectively). After a posttreatment 2-year follow-up there were still no differences in the response rates of the two treatments; of the 21 pooled treated patients, 61% lost HBeAg and DNA and 67% normalized alanine aminotransferase (vs. 33 and 44% of controls, respectively; P = 0.32 and 0.40). Reversion to HBeAg and HBV DNA negativity in treated patients occurred significantly earlier (P = 0.02 and 0.006, respectively) than in controls. No further patient lost HBsAg, but one reacquired HBsAg. Treated patients had posttreatment histologic scores better than controls (P = 0.03).
CONCLUSIONS: Our medium term follow-up results indicate that a prolonged course of high dose interferon in children with chronic HB infection, regardless of prednisone priming, poorly affects response rates but significantly speeds termination of active viral replication.
Recombinant interferon-alpha-2A with or without steroid pretreatment in children with chronic hepatitis B.
Interferon is the most promising therapeutic agent for the treatment of chronic viral hepatitis. The results of studies suggest that corticosteroid pretreatment may improve the response rate. Twenty-nine children with chronic hepatitis B (CHB) were randomly assigned to receive recombinant interferon alpha (rIFN-alpha) alone (Group 1.5 million units/m2 body surface, 3 times a week for 24 weeks) or to receive oral prednisone (Group 2.2 mg/kg/day for 3 weeks, discontinued by tapering the dose within 1 week) followed by rIFN-alpha (same dose as above). Tests for liver function and hepatitis B virus (HBV) markers including HBV-DNA were done periodically. Overall, 10 patients (34.5%) cleared hepatitis Be antigen and 13 (44.8%) HBV-DNA. Anti-HBe seroconversion was observed in nine patients (31%). Only three patients (10.3%) cleared hepatitis B surface antigen and seroconverted to anti-HBs. No response was obtained in 11 patients (37.9%). There was no statistically significant difference between the two treatment groups regarding response rate. Baseline transaminases levels and HBV-DNA concentrations were predictive parameters for HBeAg clearance. It is concluded that prednisone pretreatment does not have a beneficial effect in children with CHB.
Options:
A: The combination significantly increased the loss of hepatitis B 'e' antigen and hepatitis B virus DNA.
B: The combination significantly improved seroconversion from hepatitis B 'e' antigen to antibodies to hepatitis B 'e' antigen.
C: The combination significantly improved liver histology and quality of life.
D: The combination significantly reduced mortality and adverse events. | A |
447 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What were the findings regarding the use of anti-cholinergic therapy in the treatment of wheezing infants under the age of two years? Please answer this question based on the information provided below:
Nebulised ipratropium bromide and sodium cromoglycate in the first two years of life.
In a double blind crossover trial, we compared sodium cromoglycate, ipratropium bromide, and water in 23 asthmatic children less than 2 years old (mean age 11.8 months). Each child received nebulised solutions containing 20 mg of sodium cromoglycate, 250 micrograms of ipratropium bromide, or 2 ml water three times a day for three two month periods. Daily symptom scores did not show significant differences between the treatments but parental preferences indicated that both sodium cromoglycate and ipratropium bromide were superior to placebo. Sodium cromoglycate was prophylactic and was more likely to help the older patients. Ipratropium bromide produced an immediate clinical benefit and the response was not age dependent. We were unable to pick responders from non-responders on the basis of lung function tests performed on a routine outpatient basis. Both ipratropium bromide and sodium cromoglycate help some but not all asthmatic children aged less than 2 years.
Bronchodilator effect of fenoterol and ipratropium bromide in infants with acute wheezing: use of MDI with a spacer device.
Twenty-eight infants admitted to Exequiel González Cortes Children's Hospital because of acute wheezing (AW) were randomly assigned to three study groups. Fenoterol (FNT), ipratropium bromide (IB), and placebo were administered respectively to children in the different groups by means of metered dose inhalers (MDI) with spacers, using doses of 3 puffs every hour, for 4 hours. The degree of bronchial obstruction was assessed clinically and scored with the single-blind method every hour prior to each treatment. The criterion of a bronchodilator effect was a significant decrease in the degree of bronchial obstruction at subsequent scorings. The scores of the three groups were compared using the Student's t test for matched samples. The same test was also applied to the independent samples for determining the superiority of one treatment, FNT or IB, over the other. The results indicated a significant decrease in the scores of the groups receiving FNT and IB (P less than 0.05); this did not occur in the group in which placebo was used. FNT produced a more rapid and sustained effect than IB (P less than 0.05). Significant bronchodilator effect was obtained in infants with AW when repeated doses of FNT or IB were administered with MDI and spacers. This effect was significantly greater in the group treated with FNT.
Use of nebulized bronchodilators in infants under 1 year of age: analysis of four forms of therapy.
The main purpose of this study was to evaluate four different forms of treatment in young infants admitted for acute wheezing (AW). Seventy-nine infants less than one year of age were randomly assigned to one of five groups. Group 1 received nebulized fenoterol plus ipratropium bromide, group 2 fenoterol, group 3 fenoterol plus steroids, and group 4 aminophylline, IV, plus steroids and oral fenoterol; the control group, or group 5, received nebulized normal saline solution. Clinical evaluation was done by means of a scoring system. The effectiveness of treatments was estimated by a score decrease in the first 24 hours, by the percentage of patients whose scores did not decrease during the same period, and by the number of days in the hospital. All infants had significantly decreased scores, except those in the control group; the aminophylline group included a greater percentage of patients who did not abate their scores, and they stayed in the hospital for more days than those in the other groups. The fenoterol group had the shortest hospital stay. All four treatments produced objective clinical improvement in bronchial obstruction. However, the nebulized bronchodilator treatments were more effective than aminophylline IV in decreasing scores on the first day, and they resulted in shorter hospitalization.
Treatment of acute wheezing and dyspnea attacks in children under 2 years old: inhalation of fenoterol plus ipratropium bromide versus fenoterol.
Two treatment regimens for the initial treatment of acute wheezing were evaluated in 61 wheezing infants. Thirty-one patients received fenoterol (F) (0.1 mg/kg) and placebo (P) and 30 patients received fenoterol (F) (0.1 mg/kg) plus a fixed dose of ipratropium bromide (IB) (50 micrograms). Both groups received the drugs by inhalation using an ultrasonic nebulizer and face mask. A clinical score system based on wheezing and rib cage retraction was established and evaluations were performed before and at 15, 30, and 45 minutes after treatment. After the last evaluation based on the clinical score, it was decided whether to repeat or not to repeat the treatment. Our results showed that a combination of a beta agonist and ipratropium bromide (FB) was more effective than a beta agonist alone (F) in reducing wheezing and dyspnea during an acute attack (63.4 versus 25.8%; p less than 0.05).
Efficacy of adding nebulized ipratropium bromide to nebulized albuterol therapy in acute bronchiolitis.
Nebulized ipratropium bromide is though to be synergistic with albuterol in therapy for acute childhood asthma. Because the efficacy of ipratropium in bronchiolitis is uncertain and some infants with bronchiolitis do not respond to nebulized albuterol alone, the following study was undertaken. In this double-blind, placebo-controlled trial, 69 infants between 6 weeks and 24 months of age who exhibited the first episode of acute bronchiolitis were randomly assigned to receive either nebulized albuterol (0.15 mg/kg per dose) and ipratropium bromide (250 micrograms per dose) (group A, n = 36) or nebulized albuterol and normal saline (placebo) (group B, n = 33) for two doses, 1 hour apart. The two groups were comparable at baseline. Both therapies resulted in clinically significant improvement. However, the addition of ipratropium resulted in no additional benefit with respect to decrease in the respiratory rate (mean decreases 10.6/min vs decreases 8.6/min, P = .86), accessory muscle score (range 0 through 3) (decreases 0.92 vs decreases 0.82, z = -0.44), wheeze score (range 0 through 3) (decreases 0.94 vs 0.85, z = -0.20), oxygen saturation (increases 0.25% vs increases -0.33%, P = .86), or hospitalization rate (17 vs 10). The number of "nonresponders" and "clear responders" was also very similar in both groups. No toxicity was noted. The increase in heart rate was mild and similar in both groups (increases 6.7 vs increases 11.1). The power of the study to detect a difference between the two treatment groups in the respiratory rate change > or = 8/min is greater than 90%.(ABSTRACT TRUNCATED AT 250 WORDS)
Bronchodilators for treatment of mild bronchiolitis: a factorial randomised trial.
A randomised double blind trial was conducted to determine the efficacy of inhaled bronchodilators, salbutamol and ipratropium bromide, compared with placebo in the treatment of bronchiolitis. Patients, who were 2 months to 2 years of age and without underlying cardiac or pulmonary disease, received drug 1 (salbutamol or saline placebo) followed one hour later by drug 2 (ipratropium bromide or placebo). Both agents were administered every four hours. The patients were allocated to one of four groups according to a factorial design. The four groups were similar in demographic characteristics, initial oxygenation, and clinical score. The change in oxygen saturation of recipients of both agents was significantly better than that of recipients of salbutamol alone or ipratropium bromide alone. This change, however, was not statistically different from that of the control group. No difference was observed in the clinical score or hospital duration. Inhaled bronchodilators did not improve the condition of hospitalised mild bronchiolitis.
Options:
A: Anti-cholinergic therapy significantly reduced the need for additional treatment and improved respiratory rate and oxygen saturation in the emergency department.
B: Anti-cholinergic therapy combined with beta2-agonist showed no significant difference in clinical outcomes compared to beta2-agonist alone.
C: Anti-cholinergic therapy combined with beta2-agonist showed significantly improved clinical scores at 24 hours compared to placebo, but no significant difference in length of hospital stay.
D: Anti-cholinergic therapy alone was found to be more effective than beta2-agonist in treating wheezing infants. | C |
448 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What were the main findings regarding the effectiveness and side effects of sertindole compared to placebo and haloperidol for treating schizophrenia? Please answer this question based on the information provided below:
Long-term efficacy and safety comparison of sertindole and haloperidol in the treatment of schizophrenia. The Sertindole Study Group.
Sertindole is an atypical antipsychotic that is efficacious in schizophrenia and is associated infrequently with extrapyramidal symptoms (EPS). This study assessed time to treatment failure with 24 mg/day sertindole or 10 mg/day haloperidol in 282 clinically stable neuroleptic-responsive outpatients with schizophrenia. During a 5-week transition period, patients were randomized to treatment with sertindole or haloperidol; other treatments were gradually discontinued. Patients then received treatment through Day 365. Time to treatment failure was numerically superior in sertindole-treated patients compared with haloperidol-treated patients, although this difference was not statistically significant. Sertindole-treated patients, however, remained free of hospitalization for exacerbation of schizophrenia and remained medically compliant significantly longer than did haloperidol-treated patients. In addition, there were significantly fewer reports of EPS in sertindole-treated patients and sertindole therapy was generally well tolerated. Patients transitioned well from other antipsychotic agents to sertindole. Sertindole appears to be an effective long-term treatment for schizophrenia.
Sertindole improves both the positive and negative symptoms of schizophrenia: Results of a phase III trial.
OBJECTS: This large multicentre, double-blind, randomized study was designed to evaluate four doses of sertindole and haloperidol 10 mg in the treatment of patients with DSM-III-R schizophrenia.
METHOD: 617 patients were randomized, of whom 595 were included in an intention-to-treat analysis. 375 patients completed the study. Patients were randomized to receive sertindole 8 mg/day, sertindole 16 mg/day, sertindole 20 mg/day, sertindole 24 mg/day or haloperidol 10 mg/day for 56days. Efficacy was assessed through the changes in score on the Positive and Negative Syndrome Scale (PANSS), and the Clinical Global Impressions (CGI) scale. Improvement in all end-points was observed for all treatment groups.
RESULTS: Sertindole 16 mg showed significantly greater efficacy against negative symptoms than haloperidol 10 mg. The optimal dose of sertindole was 16 mg/day. Sertindole 8 mg appeared to be suboptimal with respect to efficacy, and increasing the dose of sertindole above 20 mg did not appear to offer any additional benefit. Sertindole at all doses caused significantly fewer extrapyramidal symptoms than haloperidol.
CONCLUSION: Sertindole is effective against positive and negative symptoms of schizophrenia within the dose range 12-24 mg daily, with an optimal starting dose of 16 mg daily. Efficacy is comparable to 10 mg of haloperidol with no difference in the time course of treatment response. The dose response relationship for efficacy with sertindole seems to plateau at about 16 mg daily with no demonstrable difference in increasing doses above this point. (Int J Psych Clin Pract 2000; 4:55-62).
Sertindole is associated with a low level of extrapyramidal symptoms in schizophrenic patients: Results of a phase III trial.
OBJECT: The objective of this double-blind, multicentre study was to evaluate four doses of sertindole and haloperidol 10 mg.
METHOD: The 617 schizophrenic patients were randomized to receive sertindole 8, 16, 20 or 24 mg/day or haloperidol 10 mg/day. Patients were assessed for extrapyramidal symptoms (EPS) using the Simpson-Angus Scale (SAS) and Barnes Akathisia Scale (BAS), and for movement disorders using the Abnormal Involuntary Movement Scale (AIMS).
RESULTS: Patients receiving haloperidol experienced significantly more EPS than patients receiving sertindole, supporting observations made in previous studies. The incidence of adverse events was similar for all doses of sertindole. SAS and BAS scores were significantly worse in the haloperidol group than in the sertindole groups. There were significantly greater increases in mean QT c interval in the sertindole groups than in the haloperidol group. Sertindole did not cause sedation.
CONCLUSIONS: Sertindole is well tolerated and does not cause the debilitating EPS associated with traditional antipsychotic drugs. (Int J Psych Clin Pract 2000; 4:47-54).
A randomized, controlled, dose-ranging trial of sertindole in patients with schizophrenia.
Sertindole is a novel antipsychotic agent with high selectivity for the mesolimbic dopaminergic pathway and nanomolar affinities for dopamine D2, serotonin 5-HT2, and norepinephrine NE alpha 1 receptors. This 40-day randomized, placebo-controlled, dose-ranging multicenter study was designed to assess the effect of sertindole on previously neuroleptic-responsive, hospitalized schizophrenic patients (n = 205). Sertindole doses began at 4 mg/day and were increased to 8, 12, or 20 mg/day, depending on randomization. Efficacy measures included the Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impression (CGI). Extrapyramidal symptoms (EPS) were assessed by movement rating scales, EPS-related adverse events, and use of anti-EPS medications. A dose-related improvement was observed for PANSS, BPRS, and CGI, with statistically significant mean differences (P < 0.05) between placebo and 20-mg/day sertindole (decreases from baseline of -5.8 versus -16.9 for PANSS, -4.8 versus -10.4 for BPRS, respectively). The differences in CGI final improvement score between placebo and 20-mg/day sertindole were 3.8 versus 2.9, respectively. EPS-related events were comparable in the placebo and sertindole groups. In conclusion, sertindole 20 mg/day was effective, well tolerated, and not associated with significant motor system abnormalities.
Options:
A: Sertindole was more effective than placebo at 20mg/day, had fewer movement disorders and sedation issues than haloperidol, but was associated with more cardiac problems, weight gain, rhinitis, and sexual dysfunction.
B: Sertindole was less effective than placebo at all doses, had more movement disorders and sedation issues than haloperidol, but was associated with fewer cardiac problems, weight gain, rhinitis, and sexual dysfunction.
C: Sertindole was equally effective as placebo at all doses, had more movement disorders and sedation issues than haloperidol, but was associated with fewer cardiac problems, weight gain, rhinitis, and sexual dysfunction.
D: Sertindole was more effective than placebo at all doses, had fewer movement disorders and sedation issues than haloperidol, and was associated with fewer cardiac problems, weight gain, rhinitis, and sexual dysfunction. | A |
449 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What were the findings regarding the effectiveness and side effects of depot perphenazine decanoate and enanthate compared to other depot antipsychotics for people with schizophrenia? Please answer this question based on the information provided below:
Clopenthixol decanoate and perphenazine enanthate in schizophrenic patients. A double-blind Nordic multicentre trial.
The clinical properties of clopenthixol decanoate has been investigated versus perphenazine enanthate in a double-blind clinical multicentre trial including 14 psychiatric hospitals in Finland, Sweden, Norway, and Denmark. Test treatment was initiated in 172 chronic schizophrenic patients and the planned 6 months test period was completed by 57 patients receiving clopenthixol decanoate and 48 receiving perphenazine enanthate. The therapeutic effect was assessed by means of CGI, BPRS, and NOSIE-30 and was found significant with both test drugs. Significant differences in the effect were seen only in "Hostile-suspiciousness" (BPRS) and "Social interest" (NOSIE-30). For these items clopenthixol decanoate was found superior to perphenazine enanthate. The influence of side effects on the patients' functioning was found to be slightly, but not significantly more troublesome in the perphenazine enanthate patients.
[Double-blind comparison of 2 depot neuroleptics (perphenazine enanthate and flupentixol decanoate) in chronic schizophrenia (author's transl)].
Perphenazine decanoate vs. perphenazine enanthate: efficacy and side effects in a 6 week double-blind, comparative study of 50 drug monitored psychotic patients.
In a six-week randomized, double-blind study the efficacy and side effects of perphenazine decanoate (PD) and perphenazine enanthate (PE) were evaluated and compared in 26 and 24 acute psychotic patients respectively. Of either formulation 100 mg were administered intramuscularly every two weeks. Maximum and minimum plasma concentrations of perphenazine were measured for each injection period using gas liquid chromatography. There was no statistically significant difference between PD and PE in terms of overall antipsychotic efficacy, assessed by means of the Brief Psychiatric Rating Scale (BPRS). However, when an 'Amelioration Score' (AMS) of at least 50% of the totally obtainable scores was defined as individual response criterion it was revealed that the PD group only one patient (4%) did not meet this criterion, compared with six patients (25%) in the PE group. Extrapyramidal side effects were significantly more pronounced in the PE-treated patients, who also required significantly higher amounts of antiparkinson medication. The mean maximum concentration of perphenazine in plasma was 5.0 nmol/l in the PD, and 10.6 nmol/l in the PE-treated patients. The ratio of the mean maximum to the mean minimum concentration was 1.41 and 4.02 in the decanoate and enanthate groups respectively. In the patients treated with PD there were signs of accumulation indicating the possibility of prolonging dosage intervals. The present study yielded further support to previous findings demonstrating that intramuscular administration of PD dissolved in sesame oil, in contrast to PE, results in even and flat plasma perphenazine concentration curves, which not only provides a stable antipsychotic effect but also most likely carry the responsibility for the low incidence of extrapyramidal side effects observed.
[A comparative study of the longacting neuroleptics perphenazin-enanthate and fluspirilene (author's transl)].
The clinical profile and side-effects of perphenazin-enanthate and fluspirilene were compared in 45 female chronic schizophrenic patients. 100 mg perphenazin-enanthate fortnightly or 8 mg fluspirilene weekly were administered. During the four months' period the psychopathological and somatic symptoms were evaluated by means of the AMP-system and the self-evaluation scale PD-S (v. Zerssen). A covariance analysis was carried out covering 12 AMP syndromes and 6 PD-S factors. The antipsychotic effect of both drugs was similar concerning the paranoid, the hallucinatory-desintegrative and the catatonic syndromes. A significant difference with regard to perphenazin-enanthate was found in the AMP-syndromes of hostility, hypochondria, and autonomic symptoms. Neither drug induced any depression. In the self-rating scale, the factors anxiousness and depressivity were also significantly lower in the perphenazin-enanthate regime. The patients under perphenazin-enanthate required a smaller amount of antiparkinsonian drugs. The more pronounced sedative effect of perphenazin-enanthate can be recommended in hostile and restless schizophrenic patients, whereas fluspirilene should be given to inactive autistic patients.
Options:
A: Depot perphenazine decanoate and enanthate were significantly more effective than other depot antipsychotics in improving global state and reducing relapse rates.
B: Depot perphenazine decanoate and enanthate were significantly less effective than other depot antipsychotics in improving global state and reducing relapse rates.
C: Depot perphenazine decanoate and enanthate were not significantly different from other depot antipsychotics in terms of effectiveness, but had more adverse effects.
D: Depot perphenazine decanoate and enanthate were significantly more effective than oral antipsychotics in improving global state and reducing relapse rates. | C |
450 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What was the conclusion regarding the effectiveness of adrenergic agonists in the treatment of urinary incontinence in adults? Please answer this question based on the information provided below:
Effect of combined treatment with phenylpropanolamine and estriol, compared with estriol treatment alone, in postmenopausal women with stress urinary incontinence.
Twenty-nine postmenopausal women with slight to severe stress urinary incontinence and estrogen deficiency symptoms in the urogenital tract were treated with estriol, p.o. 4 mg once daily, and either phenylpropanolamine (PPA), p.o. 50 mg twice daily, or placebo for periods of 6 weeks according to a randomized double-blind crossover schedule. At urodynamic recordings the maximum urethral closure pressure increased by 22% with combined treatment (p less than 0.001) and an additional effect of PPA to estriol was shown (p = 0.022). The pressure transmission ratio increased, by about 15%, with both treatments (p less than 0.07). The number of leakage episodes was reduced by 28% with combined treatment (p = 0.007), but not with estriol alone (p = 0.08). Both combined treatment and estriol alone reduced significantly (p less than 0.01) the urinary incontinence complaints. Twelve women (43%) preferred combined treatment, while 7 (25%) preferred estriol alone. In women with initially slight to very severe urine loss, combined treatment reduced also (p = 0.02) the amount of urine loss, measured at a standardized physical stress test. Signs of estrogen deficiency in vulva, vagina and urethra were reduced, 75% (p less than 0.001) or 65% (p = 0.001) with estriol given in combination with PPA or alone. Maturation index of both urethral and vaginal epithelium displayed significant changes. It is concluded that the combined treatment, PPA + estriol, by affecting both the muscular and mucosal factor of the urethra, is more effective than estriol alone for treatment of female stress urinary incontinence in the postmenopausal ages.
Urethral sphincteric insufficiency in postmenopausal females: treatment with phenylpropanolamine and estriol separately and in combination. A urodynamic and clinical evaluation.
A randomized open comparative cross-over trial was carried out in 20 postmenopausal women, mean age 69 years, suffering from urinary incontinence due to urethral sphincteric insufficiency. They were treated with phenylpropanolamine (PPA) 50 mg p.o. twice daily or estriol vaginal suppositories 1 mg daily separately and in combination for periods of 4 weeks. Urodynamic investigations were carried out before and after each period of treatment. Both PPA and estriol increased the maximal urethral closure pressure and the continence area significantly compared to the initial values, but combined treatment was substantially more effective. The functional urethral length increased significantly while on estriol. No significant change was registered in the bladder pressure or in the pressure transmission ratio. PPA was clinically more effective than estriol, but not sufficient to obtain complete continence. With combined treatment 8 patients became completely continent, 9 were considerably improved and only 1 patient remained unchanged. 2 patients dropped out of the study because of side effects. Combined treatment with PPA and estriol represents a recommendable treatment to postmenopausal women with urinary incontinence due to urethral sphincteric insufficiency.
Phenylpropanolamine in treatment of female stress urinary incontinence. Double-blind placebo controlled study in 24 patients.
Twenty-four women with stress urinary incontinence of slight to moderate grade were treated with phenylpropanolamine (PPA), po 50 mg twice daily, and placebo for periods of two weeks according to randomized double-blind cross-over schedule. A significant increase in maximum urethral closure pressure (MUCP) was found after treatment with PPA compared to placebo, but functional urethral length was unchanged. Number of leakage episodes were significantly reduced during PPA treatment, but micturition frequency was unchanged. Fourteen women preferred PPA, 4 preferred placebo, and 6 considered PPA and placebo to be ineffective. The scored improvements obtained by PPA were highly significant when tested against the scored placebo effect. There was a significant correlation between subjective assessment and improvement in number of leakage episodes and increase of MUCP. Plasma-PPA levels showed no significant correlation with any of the effect variables. Adverse reactions were few and negligible.
The effects of long-term treatment with norephedrine on stress incontinence and urethral closure pressure profile.
Twenty-five women with stress incontinence of urine were given an alpha-adrenoceptor stimulating agent (norephedrine) and a placebo during respective 14-day periods according to a double-blind cross-over schedule. The results were classified as the patient's own assessment of therapeutic effect and as change in urethral closure pressure profile measured by a microtransducer catheter. Norephedrine had a significant therapeutic effect on the symptom stress incontinence and produced significant increase in maximum urethral pressure and maximum urethral closure pressure in the lithotomy and the erect position. Reduction of incontinence was associated with increase in maximum urethral closure pressure. The sum therapeutic effect was of moderate degree.
Effects of oestradiol and combined norephedrin and oestradiol treatment on female stress incontinence.
Thirteen postmenopausal stress incontinent women were treated with oestradiol for one month, and then with oestradiol in combination with norephedrine or placebo according to a double-blind, cross-over schedule. Therapeutic results were assessed by measuring changes in urethral closure pressure profile (UCPP) by means of micro transducer catheters, and by the patient's subjective assessment of the effects. Oestradiol had no effect on the symptom stress incontinence or on UCPP. Norephedrine in combination with oestradiol had a statistically significant therapeutic effect on the symptoms of the patients, and increased UCPP. However, the combination did not increase UCPP more than did norephedrine alone.
Stress incontinence in females: treatment with phenylpropanolamine. A urodynamic and pharmacological evaluation.
23 females, mean age 53 years, with genuine stress incontinence were treated with phenylpropanolamine (PPA), 50 mg twice daily, versus placebo. Simultaneous urethrocystometry with recording of the transmission of increased abdominal pressure to the bladder and the urethra was carried out, and serum concentration of PPA measured and related to subjective effect, effect on the maximal urethral closure pressure (MUCP) and on the pressure transmission ratio. 3 patients were excluded, 1 because of side effects, and 2 were dropouts. 12 patients reported improvement while on PPA, but none became continent. 3 patients improved on placebo. The remaining patients were unchanged. A plasma level of PPA of more than 150 ng/ml seemed necessary to obtain an effect; this level was reached after approximately 90 min after intake of 50 mg. Objectively a rise in MUCP was recorded, but there was no correlation between serum concentration and the increase in MUCP. An improvement of the pressure transmission ratio was also recorded.
[Conservative therapy of female stress incontinence. Double-blind study with the alpha-sympathomimetic midodrin].
Midodrine, an alpha-adrenergic agent, was tested in a double-blind randomized fashion in 50 female patients suffering from stress incontinence. 61,5% of the patients receiving midodrine became completely continent, 23,1% improved and 15,4% were considered failure. The results obtained, have been statistically significant.
Treatment of motor urge incontinence with clenbuterol and flavoxate hydrochloride.
A controlled double-blind trial is reported of the parasympatholytic drug, flavoxate hydrochloride, and the new sympathomimetic drug, clenbuterol, in the treatment of 39 women with motor urge incontinence. The clinical results and the urodynamic findings of urethro-cystomanometry after therapy showed clenbuterol to be very effective with few side effects.
Oral and intravaginal estrogens alone and in combination with alpha-adrenergic stimulation in genuine stress incontinence.
beta(2)-adrenergic agonists and pelvic floor exercises for female stress incontinence.
OBJECTIVE: We compared beta(2)-adrenergic agonist therapy with clenbuterol (DT) and physiological therapy (PT) in a randomized study to establish the first line therapy for stress incontinence (SI).
METHOD: The clinical efficacy of DT (group A), PT (group B), and a combination of DT and PT (group C) was investigated in 61 patients with SI by means of a 12-week randomized controlled study. The frequency and volume of SI and the patients' own impressions were used as the basis for the assessment of efficacy.
RESULTS: The SI improvement rates in groups A, B, and C were 76.9, 52.6, and 89. 5%, respectively (P=0.0361). A significant therapeutic effect on the frequency of SI was observed in group B and group C at 2 weeks after the start of treatment (both P<0.05), and in all groups at 6 weeks (all P<0.01). The efficacy rates based on the patients' own impressions in groups A, B, and C were 84.6, 31.6, and 68.4%, respectively (P=0.0064).
CONCLUSION: The beta(2)-adrenergic agonist appeared to be clinically useful as a drug of choice for SI.
Estrogens and phenylpropanolamine in combination for stress urinary incontinence in postmenopausal women.
Thirty-six postmenopausal women with objectively verified stress incontinence were treated with oral estriol (Triovex, 2 mg x 1) and phenylpropanolamine (Kontexin, 50 mg x 2) alone and in combination. After an initial four-week single-blind period with phenylpropanolamine (PPA), either estriol or estriol and PPA were given randomly in four-week periods, in a crossover design. PPA and estriol in combination as well as PPA alone, raised the intraurethral pressure and significantly reduced the urinary loss by 35 per cent in a standardized physical strain test. In women with an initial low urethral pressure estriol also induced pressure increase. The leakage episodes and the assessed leakage amounts were significantly reduced by both estriol and PPA given separately as single treatment (28%) or when given as combined therapy (40%). Most of the women preferred the combined treatment to either drug alone. Additive but no synergistic effects are indicated.
The effect of phenylpropanolamine on female stress urinary incontinence.
In a randomized double-blind manner, 43 women with grade I and II stress urinary incontinence were treated with either phenylpropanolamine p.o. 50 mg twice daily (Rinexin, 1 tablet b.i.d.) or placebo during two weeks. Urethral CO2 profilometry, with recording of maximum urethral closure pressure (MUCP) and functional urethral length (FUL), and subjective response were considered for effect evaluation. The subjective response of Rinexin was highly significant (p = 0.01) above that of placebo. Clinical improvement was reported by 15 of 21 women on Rinexin and by 8 of 22 women on placebo. A significant increase in MUCP, 14%, was registered in women on Rinexin treatment. This increase was more pronounced in the grade I than in the grade II incontinent women. No statistically significant correlations were obtained between subjective response and increase in MUCP. An increase in FUL was recorded in both two treatment groups, but no statistically significant difference between them was obtained. Adverse drug reactions were rare. No changes in blood pressure occurred. Based on the present study, Rinexin (1 tablet b.i.d.) is an effective and safe medication for female grade I and II stress incontinence and is also recommended as adjunctive therapy to physiotherapy before Teflon injection or operation.
Does medical therapy cure female stress incontinence?
Forty-four consecutive female patients, who were scheduled for operation for genuine stress incontinence but instead treated pharmacologically with an alpha-agonist or placebo for 3-4.5 months, were evaluated after a median observation period of 30 months. Ten patients (23%) underwent colposuspension. Fourteen patients (32%) claimed to be continent or so much improved that further treatment was considered unnecessary by the patients themselves. Of the remaining 20 patients who still claimed to have stress incontinence, 11 (25%) preferred to resume the pharmacological treatment whereas 9 patients (20%) had not decided whether they wanted further treatment. These results suggest that some operations for stress incontinence may be avoided by introduction of a standard trial of medical therapy prior to intended surgical intervention.
Norfenefrine in the treatment of female stress incontinence. A double-blind controlled trial.
Forty-four consecutive patients with genuine stress incontinence were treated with norfenefrine 15-30 mg t.i.d. in a 6-week, double-blind and parallel, placebo-controlled study. Subjectively, 52% were improved and 26% became continent during norfenefrine treatment. Objectively (stress test), 30% became continent and the maximum urethral closure pressure increased 10% which was statistically significant. These results, however, were not statistically different from those of placebo treatment. Simultaneously, subjective and objective improvement was seen more often in patients given norfenefrine compared to placebo (p less than 0.1). In patients with most severe incontinence according to urodynamic criteria the effect of norfenefrine was statistically significantly better than placebo. A low incidence of side effects was observed and no differences between norfenefrine and placebo were found. It is concluded that norfenefrine may be of value in the treatment of female stress incontinence.
A randomized crossover study to evaluate Ro 115-1240, a selective alpha1A/1L-adrenoceptor partial agonist in women with stress urinary incontinence.
OBJECTIVES: To investigate the potential therapeutic benefits of the selective alpha1A/1l-adrenoceptor partial agonist Ro 115-1240 in women with mild-to-moderate stress urinary incontinence (SUI).
PATIENTS AND METHODS: Thirty-seven women with mild-to-moderate SUI were enrolled in a randomized, placebo-controlled crossover study. Patients received 1.5 mg Ro 115-1240 twice daily or matching placebo for 2 or 4 weeks. Voiding diaries were used to record the number of SUI episodes, urge incontinence episodes and pads used. Sitting blood pressures and heart rate were recorded at each visit.
RESULTS: Ro 115-1240 was associated with a significantly lower mean weekly number of SUI episodes than placebo (8.4 vs 6.0; P= 0.0079), a 28% relative improvement over placebo. There was also a significantly lower mean number of pads used and wet pads changed/week with Ro 115-1240 than with placebo (P = 0.0055 and 0.0066, respectively). The most frequently reported treatment-emergent adverse events were scalp tingling, headache, chills, piloerection, and pruritus. Generally these events were transient and mild to moderate. There was a slightly lower mean sitting heart rate with Ro 115-1240 than with placebo, but no difference in mean systolic or diastolic blood pressure between treatments.
CONCLUSIONS: This study suggests that selective alpha1A/1l-adrenoceptor partial agonists have the potential to improve the symptoms of SUI with little or no cardiovascular effect. These results are encouraging and a randomized controlled trial of Ro 115-1240 in a larger population with SUI is warranted to substantiate these findings.
Randomized double-blind placebo-controlled multicenter evaluation of efficacy and dose finding of midodrine hydrochloride in women with mild to moderate stress urinary incontinence: a phase II study.
Midodrine is a potent and selective alpha1-receptor agonist and its potential to increase urethral closure pressure could be useful in the treatment of female stress incontinence. The aim of this randomized double-blind placebo-controlled multicenter study was to evaluate the efficacy and safety of midodrine for the treatment of stress urinary incontinence. The primary criterion of efficacy was the maximum urethral closure pressure at rest. Voiding diaries, symptom and incontinence questionnaires and patient/investigator global assessment were also used to evaluate its efficacy. After 4 weeks of treatment no significant changes in MUCP were found. The global assessment by the patient and investigator did indicate that patients on active treatment had a more positive assessment than the placebo group. In conclusion, midodrine did not cause significant improvements in urodynamic parameters, but there were subjective improvements in some of the patients in the treated groups. Furthermore midodrine was well tolerated.
Pelvic muscle exercise for stress urinary incontinence in elderly women.
PURPOSE: To compare pelvic muscle exercise to pharmacologic treatment of stress urinary incontinence, the most common cause of urine leakage reported by community-living elderly women.
SUBJECTS: Convenience sample of 157 community-living women, aged 55 to 90 years, after completion of a comprehensive diagnostic evaluation.
METHODS: Eighty-two subjects were randomly assigned to the exercise protocol (with a 34% attrition rate). Pelvic muscle exercises were taught and monitored for 6 months. Phenylpropanolamine hydrochloride was given to the other group in a dose of 50 mg a day, increasing to 50 mg twice a day.
MAIN RESULTS: Treatment outcomes (subjective improvement, self recorded frequency of wetting) were equally satisfactory in both groups. The response to exercises was as good in 5 months as in 6. It was also as good when the minimum recommended number of exercises per day was 80 as when it was 125.
CONCLUSIONS: Among those completing the protocol, pelvic exercises were beneficial in reducing stress incontinence, and the benefit was comparable to that produced by phenylpropanolamine.
Options:
A: Adrenergic agonists were found to be highly effective and had no significant side effects.
B: There was weak evidence suggesting adrenergic agonists were better than placebo, but not enough evidence to compare them with other treatments.
C: Adrenergic agonists were found to be ineffective and had significant side effects that limited their use.
D: Adrenergic agonists were found to be more effective than all other treatments and had no side effects. | B |
451 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What is the efficacy and safety of using oral anticoagulants (OACs) for the primary prevention of stroke in patients with chronic non-valvular atrial fibrillation and no history of transient ischemic attack (TIA) or stroke? Please answer this question based on the information provided below:
Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation. The Copenhagen AFASAK study.
From November, 1985, to June, 1988, 1007 outpatients with chronic non-rheumatic atrial fibrillation (AF) entered a randomised trial; 335 received anticoagulation with warfarin openly, and in a double-blind study 336 received aspirin 75 mg once daily and 336 placebo. Each patient was followed up for 2 years or until termination of the trial. The primary endpoint was a thromboembolic complication (stroke, transient cerebral ischaemic attack, or embolic complications to the viscera and extremities). The secondary endpoint was death. The incidence of thromboembolic complications and vascular mortality were significantly lower in the warfarin group than in the aspirin and placebo groups, which did not differ significantly. 5 patients on warfarin had thromboembolic complications compared with 20 patients on aspirin and 21 on placebo. 21 patients on warfarin were withdrawn because of non-fatal bleeding complications compared with 2 on aspirin and none on placebo. Thus, anticoagulation therapy with warfarin can be recommended to prevent thromboembolic complications in patients with chronic non-rheumatic AF.
The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation.
BACKGROUND: Nonrheumatic atrial fibrillation increases the risk of stroke, presumably from atrial thromboemboli. There is uncertainty about the efficacy and risks of long-term warfarin therapy to prevent stroke.
METHODS: We conducted an unblinded, randomized, controlled trial of long-term, low-dose warfarin therapy (target prothrombin-time ratio, 1.2 to 1.5) in patients with nonrheumatic atrial fibrillation. The control group was not given warfarin but could choose to take aspirin.
RESULTS: A total of 420 patients entered the trial (212 in the warfarin group and 208 in the control group) and were followed for an average of 2.2 years. Prothrombin times in the warfarin group were in the target range 83 percent of the time. Only 10 percent of the patients assigned to receive warfarin discontinued the drug permanently. There were 2 strokes in the warfarin group (incidence, 0.41 percent per year) as compared with 13 strokes in the control group (incidence, 2.98 percent per year), for a reduction of 86 percent in the risk of stroke (warfarin:control incidence ratio = 0.14; 95 percent confidence interval, 0.04 to 0.49; P = 0.0022). There were 37 deaths altogether. The death rate was markedly lower in the warfarin group than in the control group: 2.25 percent as compared with 5.97 percent per year, for an incidence ratio of 0.38 (95 percent confidence interval, 0.17 to 0.82; P = 0.005). There was one fatal hemorrhage in each group. The frequency of bleeding events that led to hospitalization or transfusion was essentially the same in both groups. The warfarin group had a higher rate of minor hemorrhage than the control group (38 vs. 21 patients).
CONCLUSIONS: Long-term low-dose warfarin therapy is highly effective in preventing stroke in patients with non-rheumatic atrial fibrillation, and can be quite safe with careful monitoring.
Canadian Atrial Fibrillation Anticoagulation (CAFA) Study.
The Canadian Atrial Fibrillation Anticoagulation Study was a randomized double-blind placebo-controlled trial to assess the potential of warfarin to reduce systemic thromboembolism and its inherent risk of hemorrhage. As a result of the publication of two other "positive" studies of similar design and objective, this study was stopped early before completion of its planned recruitment of 630 patients. There were 187 patients randomized to warfarin and 191 to placebo. Permanent discontinuation of study medication occurred in 26% of warfarin-treated and 23% of placebo-treated patients. The target range of the international normalized ratio was 2 to 3. For the warfarin-treated patients, the international normalized ratio was in the target range 43.7% of the study days, above it 16.6% of the study days and below it 39.6% of the study days. Fatal or major bleeding occurred at annual rates of 2.5% in warfarin-treated and 0.5% in placebo-treated patients. Minor bleeding occurred in 16% of patients receiving warfarin and 9% receiving placebo. The primary outcome event cluster was nonlacunar stroke, noncentral nervous systemic embolism and fatal or intracranial hemorrhage. Events were included in the primary analysis of efficacy if they occurred within 28 days of permanent discontinuation of the study medication. The annual rates of the primary outcome event cluster were 3.5% in warfarin-treated and 5.2% in placebo-treated patients, with a relative risk reduction of 37% (95% confidence limits, -63.5%, 75.5%, p = 0.17).(ABSTRACT TRUNCATED AT 250 WORDS)
Stroke Prevention in Atrial Fibrillation Study. Final results.
BACKGROUND: Atrial fibrillation in the absence of rheumatic valvular disease is associated with a fivefold to sevenfold increased risk of ischemic stroke.
METHODS AND MAIN RESULTS: The Stroke Prevention in Atrial Fibrillation Study, a multicenter, randomized trial, compared 325 mg/day aspirin (double-blind) or warfarin with placebo for prevention of ischemic stroke and systemic embolism (primary events), and included 1,330 inpatients and outpatients with constant or intermittent atrial fibrillation. During a mean follow-up of 1.3 years, the rate of primary events in patients assigned to placebo was 6.3% per year and was reduced by 42% in those assigned to aspirin (3.6% per year; p = 0.02; 95% confidence interval, 9-63%). In the subgroup of warfarin-eligible patients (most less than 76 years old), warfarin dose-adjusted to prolong prothrombin time to 1.3-fold to 1.8-fold that of control reduced the risk of primary events by 67% (warfarin versus placebo, 2.3% versus 7.4% per year; p = 0.01; 95% confidence interval, 27-85%). Primary events or death were reduced 58% (p = 0.01) by warfarin and 32% (p = 0.02) by aspirin. The risk of significant bleeding was 1.5%, 1.4%, and 1.6% per year in patients assigned to warfarin, aspirin, and placebo, respectively.
CONCLUSIONS: Aspirin and warfarin are both effective in reducing ischemic stroke and systemic embolism in patients with atrial fibrillation. Because warfarin-eligible patients composed a subset of all aspirin-eligible patients, the magnitude of reduction in events by warfarin versus aspirin cannot be compared. Too few events occurred in warfarin-eligible patients to directly assess the relative benefit of aspirin compared with warfarin, and the trial is continuing to address this issue. Patients with nonrheumatic atrial fibrillation who can safely take either aspirin or warfarin should receive prophylactic antithrombotic therapy to reduce the risk of stroke.
Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation. Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation Investigators.
BACKGROUND: Nonrheumatic atrial fibrillation is common among the elderly and is associated with an increased risk of stroke. We investigated whether anticoagulation with warfarin would reduce this risk.
METHODS: We conducted a randomized, double-blind, placebo-controlled study to evaluate low-intensity anticoagulation with warfarin (prothrombin-time ratio, 1.2 to 1.5) in 571 men with chronic nonrheumatic atrial fibrillation; 525 patients had not previously had a cerebral infarction, whereas 46 patients had previously had such an event. The primary end point was cerebral infarction; secondary end points were cerebral hemorrhage and death.
RESULTS: Among the patients with no history of stroke, cerebral infarction occurred in 19 of the 265 patients in the placebo group during an average follow-up of 1.7 years (4.3 percent per year) and in 4 of the 260 patients in the warfarin group during an average follow-up of 1.8 years (0.9 percent per year). The reduction in risk with warfarin therapy was 0.79 (95 percent confidence interval, 0.52 to 0.90; P = 0.001). The annual event rate among the 228 patients over 70 years of age was 4.8 percent in the placebo group and 0.9 percent in the warfarin group (risk reduction, 0.79; P = 0.02). The only cerebral hemorrhage occurred in a 73-year-old patient in the warfarin group. Other major hemorrhages, all gastrointestinal, occurred in 10 patients: 4 in the placebo group, for a rate of 0.9 percent per year, and 6 in the warfarin group, for a rate of 1.3 percent per year. There were 37 deaths that were not preceded by a cerebral end point--22 in the placebo group and 15 in the warfarin group (risk reduction, 0.31; P = 0.19). Cerebral infarction was more common among patients with a history of cerebral infarction (9.3 percent per year in the placebo group and 6.1 percent per year in the warfarin group) than among those without such a history.
CONCLUSIONS: Low-intensity anticoagulation with warfarin prevented cerebral infarction in patients with nonrheumatic atrial fibrillation without producing an excess risk of major hemorrhage. This benefit extended to patients over 70 years of age.
Options:
A: OACs significantly reduce the risk of all strokes, ischemic strokes, disabling or fatal strokes, and death without a significant increase in bleeding risks.
B: OACs do not significantly reduce the risk of strokes or death and are associated with a significant increase in bleeding risks.
C: OACs significantly reduce the risk of strokes but are associated with a significant increase in bleeding risks.
D: OACs do not significantly reduce the risk of strokes but do reduce the risk of death without increasing bleeding risks. | A |
452 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What are the potential benefits and drawbacks of using concomitant chemotherapy and radiation therapy compared to radiation therapy alone for treating locally advanced cervical cancer? Please answer this question based on the information provided below:
Pelvic irradiation with concurrent chemotherapy versus pelvic and para-aortic irradiation for high-risk cervical cancer: an update of radiation therapy oncology group trial (RTOG) 90-01.
PURPOSE: To report mature results of a randomized trial that compared extended-field radiotherapy (EFRT) versus pelvic radiotherapy with concomitant fluorouracil and cisplatin (CTRT) in women with locoregionally advanced carcinomas of the uterine cervix.
PATIENTS AND METHODS: Four hundred three women with cervical cancer were randomly assigned to receive either EFRT or CTRT. Patients were eligible if they had stage IIB to IVA disease, stage IB to IIA disease with a tumor diameter > or = 5 cm, or positive pelvic lymph nodes. Patients were stratified by stage and by method of lymph node evaluation.
RESULTS: The median follow-up time for 228 surviving patients was 6.6 years. The overall survival rate for patients treated with CTRT was significantly greater than that for patients treated with EFRT (67% v 41% at 8 years; P <.0001). There was an overall reduction in the risk of disease recurrence of 51% (95% CI, 36% to 66%) for patients who received CTRT. Patients with stage IB to IIB disease who received CTRT had better overall and disease-free survival than those treated with EFRT (P <.0001); 116 patients with stage III to IVA disease had better disease-free survival (P =.05) and a trend toward better overall survival (P =.07) if they were randomly assigned to CTRT. The rate of serious late complications of treatment was similar for the two treatment arms.
CONCLUSION: Mature analysis confirms that the addition of fluorouracil and cisplatin to radiotherapy significantly improved the survival rate of women with locally advanced cervical cancer without increasing the rate of late treatment-related side effects.
Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer.
BACKGROUND AND METHODS: We compared the effect of radiotherapy to a pelvic and para-aortic field with that of pelvic radiation and concurrent chemotherapy with fluorouracil and cisplatin in women with advanced cervical cancer. Between 1990 and 1997, 403 women with advanced cervical cancer confined to the pelvis (stages IIB through IVA or stage IB or IIa with a tumor diameter of at least 5 cm or involvement of pelvic lymph nodes) were randomly assigned to receive either 45 Gy of radiation to the pelvis and para-aortic lymph nodes or 45 Gy of radiation to the pelvis alone plus two cycles of fluorouracil and cisplatin (days 1 through 5 and days 22 through 26 of radiation). Patients were then to receive one or two applications of low-dose-rate intracavitary radiation, with a third cycle of chemotherapy planned for the second intracavitary procedure in the combined-therapy group.
RESULTS: Of the 403 eligible patients, 193 in each group could be evaluated. The median duration of follow-up was 43 months. Estimated cumulative rates of survival at five years were 73 percent among patients treated with radiotherapy and chemotherapy and 58 percent among patients treated with radiotherapy alone (P=0.004). Cumulative rates of disease-free survival at five years were 67 percent among patients in the combined-therapy group and 40 percent among patients in the radiotherapy group (P<0.001). The rates of both distant metastases (P<0.001) and locoregional recurrences (P<0.001) were significantly higher among patients treated with radiotherapy alone. The seriousness of side effects was similar in the two groups, with a higher rate of reversible hematologic effects in the combined-therapy group.
CONCLUSIONS: The addition of chemotherapy with fluorouracil and cisplatin to treatment with external-beam and intracavitary radiation significantly improved survival among women with locally advanced cervical cancer.
[Uterine cervix cancer. Clinical stage III. Combined radiotherapy and chemotherapy treatment].
55 patients with stage III carcinoma of the uterine cervix were entered into a prospective randomized study to evaluate the possible radiation-potentiating properties of bleomycin. Group A received classical radiation treatment with telecobalt-therapy 50 Gy/25 fractions plus 32 Gy/4 fractions (Cathetron). The other two groups received 15 mg of bleomycin by continue infusion two time of week during 5 week, groups B before, and group C after, irradiation. The morbidity was minimal. The initial response was complete in 49 cases and partial in 6 cases. At 2 years there were 26 recurrences, 22 (88.8%), locoregional recurrences and 4 distant metastasis, 3 in the group of bleomycin treatment. The probability of actuarial survival was 62.1%, 30.1% and 35.6% respectively to groups A, B and C. Addition of bleomycin to radiotherapy failed to increase the recurrence-free survival.
[Comparative parameters of myelotoxicity in patients treated with simultaneous chemotherapy and radiotherapy or only radiotherapy].
BACKGROUND: The Modern oncological treatment usually consists of the different kind of the therapies. Improvement of survival and local control of disease could be possible with combined treatments: surgery, radiotherapy, chemotherapy, etc. However if these treatments are given concomitantly one can expect higher toxicity.
AIM: Comparation of parameters of miclotoxicity: red blood cell count, white blood cell count, platelets and hemoglobin in patients with advanced cervical carcinoma treated with concomitant chemo-radiotherapy versus radiotherapy alone.
PATIENTS AND METHODS: From 1997-1999, we performed prospective, by randomised, study, and 80 patients were divided in two groups: Group A--40 patients treated with concomitant chemo-radiotherapy versus, Group B--40 patients treated with radiotherapy alone. Red blood cell count, white blood cell count, platelets and hemoglobin were evaluated before enrollement, during the theraphy, after 3 and 6 months, according to CTC toxicity criteria.
RESULTS: We perform statistical analysis using H2 test, and we found no significant difference in mild nad severe toxicity in red blood cell count, white blood cell count, platelets and hemoglobin among groups.
Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma.
BACKGROUND: Bulky stage IB cervical cancers have a poorer prognosis than smaller stage I cervical cancers. For the Gynecologic Oncology Group, we conducted a trial to determine whether weekly infusions of cisplatin during radiotherapy improve progression-free and overall survival among patients with bulky stage IB cervical cancer.
METHODS: Women with bulky stage IB cervical cancers (tumor, > or =4 cm in diameter) were randomly assigned to receive radiotherapy alone or in combination with cisplatin (40 mg per square meter of body-surface area once a week for up to six doses; maximal weekly dose, 70 mg), followed in all patients by adjuvant hysterectomy. Women with evidence of lymphadenopathy on computed tomographic scanning or lymphangiography were ineligible unless histologic analysis showed that there was no lymph-node involvement. The cumulative dose of external pelvic and intracavitary radiation was 75 Gy to point A (cervical parametrium) and 55 Gy to point B (pelvic wall). Cisplatin was given during external radiotherapy, and adjuvant hysterectomy was performed three to six weeks later.
RESULTS: The relative risks of progression of disease and death among the 183 women assigned to receive radiotherapy and chemotherapy with cisplatin, as compared with the 186 women assigned to receive radiotherapy alone, were 0.51 (95 percent confidence interval, 0.34 to 0.75) and 0.54 (95 percent confidence interval, 0.34 to 0.86), respectively. The rates of both progression-free survival (P<0.001) and overall survival (P=0.008) were significantly higher in the combined-therapy group at four years. In the combined-therapy group there were higher frequencies of transient grade 3 (moderate) and grade 4 (severe) adverse hematologic effects (21 percent, vs. 2 percent in the radiotherapy group) and adverse gastrointestinal effects (14 percent vs. 5 percent).
CONCLUSIONS: Adding weekly infusions of cisplatin to pelvic radiotherapy followed by hysterectomy significantly reduced the risk of disease recurrence and death in women with bulky stage IB cervical cancers.
Concurrent mitomycin C, 5-fluorouracil, and radiotherapy in the treatment of locally advanced carcinoma of the cervix: a randomized trial.
PURPOSE: This is a prospective, Phase III multicenter randomized trial to assess the effectiveness of concurrent intravenous mitomycin C, oral 5-fluorouracil (5-FU), and radiotherapy (RT) in locally advanced carcinoma of the cervix.
METHODS AND MATERIALS: Between January 1988 and November 1994, 926 patients with locally advanced carcinoma of the cervix, FIGO Stage IIB-IVA, were entered into this study. The patients were randomized into four arms, as follows: Arm 1: conventional RT; Arm 2: conventional RT and adjuvant chemotherapy; Arm 3: conventional RT plus concurrent chemotherapy; Arm 4: conventional RT plus concurrent chemotherapy and adjuvant chemotherapy. Concurrent chemotherapy consisting of intravenous mitomycin C at 10 mg/m(2) was given on Days 1 and 29, and oral 5-FU at 300 mg/day was administered on Days 1-14 and 29-42 during RT. Adjuvant chemotherapy of 5-FU orally at 200 mg/day was given for three courses of 4 weeks, with a 2-week rest every 6 weeks. Six centers participated in the trial.
RESULTS: The median follow-up time was 89 months. Acute side effects were generally higher in concurrent arms, but most of the patients tolerated the treatment well. Bone marrow toxicity was also higher in concurrent arms. The 5-year actuarial disease-free survival (DFS) was 48.2%, 54.1%, 64.5%, and 59.7% for arms 1, 2, 3, and 4, respectively. The pattern of failure revealed a significant increase in locoregional recurrence in the nonconcurrent chemoradiotherapy arm. The local recurrence was 25.5%, 20.6%, 14.3%, and 17.6% for arms 1, 2, 3, and 4, respectively. The metastatic rates were not significantly different in all four arms. At the time of analysis, there were no increases in late side effects, especially in gastrointestinal and genitourinary systems.
CONCLUSIONS: Concurrent chemotherapy, mitomycin C, and 5-FU together with conventional RT showed an improved DFS rate when compared with conventional RT alone in patients with locally advanced carcinoma of the cervix.
Induction chemotherapy and irradiation in advanced carcinoma of the cervix.
The survival rate of patients with locally advanced cervical cancer has not changed during the past several years. The purpose of the study is to evaluate the efficacy of concomitant Mitomycin and 5-FU with irradiation. Six hundred seventy-three patients were randomized into four arms. Arm one RT alone, no maintenance chemotherapy Arm two RT alone, with maintenance chemotherapy Arm three RT concomitant chemo, no maintenance Arm four RT concomitant chemo, with maintenance Concomitant chemotherapy used Mitomycin C 10 mg/m2 day 1, 30 and oral 5-FU 300 mg/day day 1-14 and 42-56. Maintenance chemotherapy was oral using 5-FU 200 mg/day for 4 weeks with 2 weeks rest every 6 weeks for 3 courses. Six centers participated in the trial. The side effects were higher in concomitant chemotherapy arms, especially hematologic toxicity. Median follow-up time was 25 months (range 15 to 59 months). The disease-free survival data from life table analysis suggested a better disease-free survival in arms 3 and 4 (concomitant arms) and arm 2 (maintenance oral 5-FU arm) than in control (RT alone arm). The pattern of failure showed a greater difference in loco-regional recurrence in stage IIB than IIIB patients. This interim analysis shows a trend favoring the arm with concomitant chemotherapy.
Effect of concurrent intra-arterial infusion of platinum drugs for patients with stage III or IV uterine cervical cancer treated with radical radiation therapy.
PURPOSE: The purpose of this study was to explore the effect of concurrent intra-arterial infusion of platinum drugs in patients with stage III or IV uterine cervical cancer treated with radical radiation therapy.
PATIENTS AND METHODS: Thirty-three patients with advanced (stage IIIA, 2; IIIB, 28; IVA, 3) uterine cervical squamous cell carcinoma were randomized into a concurrent intra-arterial infusion of platinum drugs with radiation therapy (IAPRT) group (18 patients) and a radiation therapy alone group (15 patients). After altering intrapelvic blood flow by embolization of the superior and inferior gluteal arteries under pelvic angiography, intra-arterial infusion of platinum drug through catheters inserted into both internal iliac arteries was performed concurrently with radiation therapy. One-shot infusion of cisplatin (100 mg/m2) twice with a 2- to 3-week interval was performed in eight patients, weekly infusion of carboplatin (100 mg/m2) via a reservoir five to six times was performed in four patients, and daily shot of cisplatin (10 mg/body) or 21 days via a reservoir was performed in six patients. Radiation therapy consisted of external-beam irradiation of 50 Gy/25 fractions/5 weeks for the whole pelvis with midline block after 30 Gy and intracavitary high-dose-rate brachytherapy using tandem and ovoids of 24 Gy/4 fractions/4 weeks to point A.
RESULTS: The local complete response rate of the IAPRT group was 94% and was significantly higher than that of the radiation therapy group (67%). There were no significant differences in local response in the three drug delivery methods. Two- and 5-year overall survival rates were 54.5% and 44.4% in the IAPRT group, and 74.5% and 50.0% in the radiation therapy group, respectively. There was no significant difference between the two groups. In the IAPRT group, grade 3 or 4 acute bowel complications were seen in 33% of patients, grade 3 or 4 late bowel complications were seen 44%, and grade 3 or 4 myelosuppression was seen in 33%, and these complications were seen more in the IAPRT group than in the radiation therapy group and caused death in some patients.
CONCLUSIONS: IAPRT had a better local response than radiation therapy but showed no proof of control over recurrence and had a poorer survival than radiation therapy. There were many local recurrences and distant metastases, contrary to the better first response of the IAPRT group over the radiation therapy group. Complications of the IAPRT group were very severe and made the patient's performance status and prognosis worse than in the radiation therapy group. We need to design some methods to decrease these complications to make use of the good local response acquired with IAPRT. Furthermore, we should re-examine the indication of IAPRT in patients with a large tumor because local recurrence and distant metastasis would be inevitable.
Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix.
PURPOSE: To test the hypothesis that cisplatin (CDDP) administered concurrently with standard radiotherapy (RT) would improve pelvic control and survival in patients with advanced squamous cell cancer of the cervix.
PATIENTS AND METHODS: A total of 259 patients with International Federation of Gynecology and Obstetrics stage IB to IVA squamous cell cervical cancer with central disease greater-than-or-equal 5 cm or histologically confirmed pelvic lymph node involvement were randomized to receive RT (external-beam RT plus brachytherapy) plus weekly CDDP chemotherapy (40 mg/m(2)) (arm 1) or the same RT without chemotherapy (arm 2).
RESULTS: A total of 253 patients were available for analysis. Median follow-up was 82 months. No significant difference was found in progression-free survival (P =.33). No significant difference in 3- and 5-year survival rates was found (69% v 66% and 62% v 58%, respectively; P =.42). The hazard ratio for survival (arm 2 to arm 1) was 1.10 (95% confidence interval, 0.75 to 1.62).
CONCLUSION: This study did not show a benefit to either pelvic control or survival by adding concurrent weekly CDDP chemotherapy in a dose of 40 mg/m(2) to radical RT as given in this trial. Careful attention to RT details is important for achieving optimum outcome for patients with this disease.
Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix.
PURPOSE: To determine whether the addition of cisplatin-based chemotherapy (CT) to pelvic radiation therapy (RT) will improve the survival of early-stage, high-risk patients with cervical carcinoma.
PATIENTS AND METHODS: Patients with clinical stage IA(2), IB, and IIA carcinoma of the cervix, initially treated with radical hysterectomy and pelvic lymphadenectomy, and who had positive pelvic lymph nodes and/or positive margins and/or microscopic involvement of the parametrium were eligible for this study. Patients were randomized to receive RT or RT + CT. Patients in each group received 49.3 GY RT in 29 fractions to a standard pelvic field. Chemotherapy consisted of bolus cisplatin 70 mg/m(2) and a 96-hour infusion of fluorouracil 1,000 mg/m(2)/d every 3 weeks for four cycles, with the first and second cycles given concurrent to RT.
RESULTS: Between 1991 and 1996, 268 patients were entered onto the study. Two hundred forty-three patients were assessable (127 RT + CT patients and 116 RT patients). Progression-free and overall survival are significantly improved in the patients receiving CT. The hazard ratios for progression-free survival and overall survival in the RT only arm versus the RT + CT arm are 2.01 (P =.003) and 1.96 (P =. 007), respectively. The projected progression-free survivals at 4 years is 63% with RT and 80% with RT + CT. The projected overall survival rate at 4 years is 71% with RT and 81% with RT + CT. Grades 3 and 4 hematologic and gastrointestinal toxicity were more frequent in the RT + CT group.
CONCLUSION: The addition of concurrent cisplatin-based CT to RT significantly improves progression-free and overall survival for high-risk, early-stage patients who undergo radical hysterectomy and pelvic lymphadenectomy for carcinoma of the cervix.
Interim results of a randomized trial of mitomycin C as an adjunct to radical radiotherapy in the treatment of locally advanced squamous-cell carcinoma of the cervix.
The purpose of this study was to determine the efficacy of mitomycin C as an adjunct to radiotherapy for the treatment of locally advanced cervix cancer. Patients with squamous-cell carcinoma of the cervix, stages IB2-IVA, were randomized to receive radiotherapy alone or radiotherapy with concomitant mitomycin C. An initial cohort of 160 patients, having a mean follow-up of 46 months, is analyzed. Intravenous mitomycin C, 15 mg/M(2), was given on the first and sixth week of radiotherapy. The 78 patients in the radiotherapy with mitomycin C group and 82 patients in the radiotherapy alone group have a comparable distribution by age and stage (mean age 47 years; stage IB 3%, IIA 11%, IIB 48%, IIIA 1%, IIIB 36%, IVA 3%). The four-year actuarial survival rates for radiotherapy with mitomycin C and radiotherapy alone were 72% and 56%, respectively (P = 0.13). The four-year actuarial disease-free survival rates for radiotherapy with mitomycin C and radiotherapy alone were 71% and 44%, respectively, a statistically significant difference (P = 0.01). The four-year actuarial local recurrence-free survival rates for patients receiving radiotherapy with mitomycin C and radiotherapy alone were 78% and 63%, respectively (P = 0.11). Differences in four-year distant recurrence-free survival between radiotherapy plus mitomycin C and radiotherapy alone were significantly different at 85% vs. 61% (P = 0.01); this analysis is not adjusted for local failure. On subgroup analysis, stage III-IVA patients had a four-year actuarial disease-free survival of 75% for radiotherapy plus mitomycin C compared with 35% for radiotherapy alone (P = 0.03). There were no treatment- related deaths. Mild hematologic toxicity was seen only in the group treated with mitomycin C. No excess in non-hematologic toxicity has been observed thus far with combined mitomycin C and radiotherapy. In this open phase III trial of mitomycin C as an adjunct to radical radiotherapy for squamous-cell carcinoma of the cervix, there were minimal hematologic effects and no increase in acute radiation reactions. A statistically significant difference in favor of patients receiving mitomycin C is shown for disease-free survival. Thus far, there are trends in favor of those patients receiving mitomycin C for survival and local control. Patients with more advanced stage disease, predominantly stage IIIB, appear to have the most benefit. These preliminary results support the hypothesis that targeting hypoxic cells may lead to a therapeutic enhancement in the radiotherapy of cervix cancer. This trial continues to accrue patients and follow-up data. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 206-223 (2000).
Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer.
BACKGROUND AND METHODS: On behalf of the Gynecologic Oncology Group, we performed a randomized trial of radiotherapy in combination with three concurrent chemotherapy regimens -- cisplatin alone; cisplatin, fluorouracil, and hydroxyurea; and hydroxyurea alone -- in patients with locally advanced cervical cancer. Women with primary untreated invasive squamous-cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix of stage IIB, III, or IVA, without involvement of the para-aortic lymph nodes, were enrolled. The patients had to have a leukocyte count of at least 3000 per cubic millimeter, a platelet count of at least 100,000 per cubic millimeter, a serum creatinine level no higher than 2 mg per deciliter (177 micromol per liter), and adequate hepatic function. All patients received external-beam radiotherapy according to a strict protocol. Patients were randomly assigned to receive one of three chemotherapy regimens: 40 mg of cisplatin per square meter of body-surface area per week for six weeks (group 1); 50 mg of cisplatin per square meter on days 1 and 29, followed by 4 g of fluorouracil per square meter given as a 96-hour infusion on days 1 and 29, and 2 g of oral hydroxyurea per square meter twice weekly for six weeks (group 2); or 3 g of oral hydroxyurea per square meter twice weekly for six weeks (group 3).
RESULTS: The analysis included 526 women. The median duration of follow-up was 35 months. Both groups that received cisplatin had a higher rate of progression-free survival than the group that received hydroxyurea alone (P<0.001 for both comparisons). The relative risks of progression of disease or death were 0.57 (95 percent confidence interval, 0.42 to 0.78) in group 1 and 0.55 (95 percent confidence interval, 0.40 to 0.75) in group 2, as compared with group 3. The overall survival rate was significantly higher in groups 1 and 2 than in group 3, with relative risks of death of 0.61 (95 percent confidence interval, 0.44 to 0.85) and 0.58 (95 percent confidence interval, 0.41 to 0.81), respectively.
CONCLUSIONS: Regimens of radiotherapy and chemotherapy that contain cisplatin improve the rates of survival and progression-free survival among women with locally advanced cervical cancer.
Chemotherapy-radiotherapy combination in the treatment of carcinoma of the cervix.
Three hundred eligible patients with carcinoma of the cervix out of a total of 560, registered between July 1981 and June 1983 were randomized into receiving either radiotherapy alone or radiotherapy plus weekly injection of bleomycin 15 mg and mitomycin C4 mg. To date (22 Feb. 1985) patients have been evaluated for response to therapy at 3 months and 1 year from completion of treatment. Although both at 3 months and 1 year the combined modality treatment appears to be marginally better (68% and 71% at 3 months, 56% and 63% at 1 year), the long term results remain uncertain at present. Treatment by the addition of chemotherapy to radiation was however well tolerated with a few complications.
Role of chemoradiation in advanced cervical cancer.
A prospective randomized study was conducted in our department of Radiotherapy, Regional Institute of Medical Sciences, Imphal to evaluating the role of chemoradiation in the management of advanced inoperable cervical cancer (stage IIB-IIIB) taking only radiation treatment as control spanning the period 1996-1999. Of the fifty patients accumulated in the study group, three patients did not complete treatment, one expired due to other causes and three were lost to follow up. Likewise, of the forty-six patients in the control group, one patient did not complete treatment and 4 were lost to follow up. Thus only 43 and 41 patients were available for the result analysis for the study and control groups respectively. The early treatment response as assessed after two months of treatment conclusion were 79.1%, 13.9%, 93.0% and 58.5%, 31.7%, 90.2% as complete response (CR), partial response (PR), and total response (TR) respectively for the study and control groups. Our patients included in this study had a median follow up of 35 months and 33 months for study and control groups respectively. For this follow up, the disease-free survival, survival with disease and overall survival were 67.4%, 7.0%, 74.4% and 43.9%, 12.2%, 56.1% for study and control groups respectively. There was an increase in early side-effects in the chemoradiation group but the difference was not significant. Because of the early side effects, treatment delays ensued in 7 patients (16.3%) and in 3 patients (7.3%) in the study and control groups respectively. There was no significant increase in the late treatment toxicities in both the groups.
A randomized trial of standard versus partially hyperfractionated radiation with or without concurrent 5-fluorouracil in locally advanced cervical cancer.
The objective of this study was to determine whether the addition of concurrent 5-fluorouracil (5-FU) and/or a change in radiation fractionation improves pelvic control and survival or decreases complications in advanced cervical cancer, FIGO stages IB/IIA (>=5 cm) to IVA inclusive. After stratification by pelvic disease extent, 234 of a planned 292 patients were randomized to receive one of four possible treatments: (a) standard external beam pelvic irradiation (RT) 5000 cGy in 25 fractions versus (b) RT as in arm (a) with infusional IV 5-FU 1g/m2 daily in the first and last 4 days of RT, (c) partially hyperfractionated RT, 5280 cGy in 33 fractions, two fractions per day on the first and last 4 days of RT, or (d) arm (c) with the same FU. All were followed with a linear source of intracavitary RT to deliver 40 Gy. The median duration of follow-up for the 221 evaluable patients was 59 months. The 5-year Kaplan-Meier disease-free survival (DFS) in arm (a), (c), (d), and (b), respectively, were 45, 53, 58, and 61%. The differences in survival and pelvic control were not statistically significant. An exploratory subset analysis was performed within stratum 1 and stratum 2 to generate hypotheses for future studies. Only for the 99 patients in stratum 1 (IB/IIA or medial parametrial IIB disease) was the 5-year DFS significantly better (long rank P = 0.05) for standard RT and 5-FU. The DFS was 39% for arm (a), 76% for arm (b), 58% for arm (c), and 65% for arm (d). A multivariate analysis of patient, tumor, and treatment related prognostic factors identified only the use of 5-FU to account for the observed difference. The crude serious late bowel or bladder complication rate was 5.9%. Overall concurrent infusional 5-FU was not beneficial when added to standard RT in this study. The possible benefit for patients in stratum 1 requires exploration in a further randomized trial with appropriate accrual.
A randomized trial of concurrent chemoradiotherapy versus radiotherapy in advanced carcinoma of the uterine cervix.
The purpose of our study was to determine whether the chemoradiation is better than radiotherapy alone with respect to survival and treatment toxicity in patients with advanced carcinoma of the cervix. From October 1990 to April 1995, a total of 122 patients with advanced cervical carcinoma were included in this study and randomly assigned to either radiotherapy or concurrent chemotherapy and radiotherapy. The patients in the concurrent group received cisplatin, vincristine, and bleomycin every 3 weeks for a total of four courses, in combination with radiotherapy concurrently. Sixty patients were randomized to the concurrent chemoradiotherapy, and 62 were randomized to the radiotherapy alone. A tumor response was observed in 88.3% of the patients in concurrent group and in 74.2% of the patients in radiotherapy group (P = 0.04). After a median follow-up of 46.8 months, the overall disease-free survival and actuarial survival rate at 3 years were 51.7 and 61.7% in the concurrent group, and 53.2 and 64.5% in the radiotherapy group, respectively. Treatment-related toxicity appears to be higher with the combination of radiotherapy and chemotherapy compared with radiotherapy alone (36.7% versus 17.7%, P = 0.02). However, analysis by Kaplan-Meier method showed that the actuarial survival was not statistically different between the chemoradiotherapy and radiotherapy groups (mean survival time: 38.1 months versus 41.5 months, P = 0.27). In conclusion, this study showed that concurrent multiagent chemoradiotherapy did not prove to be a superior definitive therapy over radiotherapy alone for patients with advanced cervical carcinoma.
Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study.
PURPOSE: In 1986, a protocol comparing primary radiation therapy (RT) plus hydroxyurea (HU) to irradiation plus fluorouracil (5-FU) and cisplatin (CF) was activated by the Gynecologic Oncology Group (GOG) for the treatment of patients with locally advanced cervical carcinoma. The goals were to determine the superior chemoradiation regimen and to quantitate the relative toxicities.
METHODS: All patients had biopsy-proven invasive squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix. Patients underwent standard clinical staging studies and their tumors were found to be International Federation of Gynaecology and Obstetrics stages IIB, III, or IVA. Negative cytologic washings and para-aortic lymph nodes were required for entry. Patients were randomized to receive either standard whole pelvic RT with concurrent 5-FU infusion and bolus CF or the same RT plus oral HU.
RESULTS: Of 388 randomized patients, 368 were eligible; 177 were randomized to CF and 191 to HU. Adverse effects were predominantly hematologic or gastrointestinal in both regimens. Severe or life-threatening leukopenia was more common in the HU group (24%) than in the CF group (4%). The difference in progression-free survival (PFS) was statistically significant in favor of the CF group (P = .033). The sites of progression in the two treatment groups were not substantially different. Survival was significantly better for the patients randomized to CF (P = .018).
CONCLUSION: This study demonstrates that for patients with locally advanced carcinoma of the cervix, the combination of 5-FU and CF with RT offers patients better PFS and overall survival than HU, and with manageable toxicity.
Potentiation of radiotherapy by cis-dichlorodiammine platinum (II) in advanced cervical carcinoma.
Forty-five patients with Stages II and III cervical carcinoma were randomized to receive either radiation or cis-dichlorodiammine platinum (II) (cis-DPP) with radiation. Cis-DPP was administered in bolus injections of 25 mg/m2 at weekly intervals until completion of radium application. Complete response was noted in 11/20 (55%) patients in the radiochemotherapy group compared to 5/25 (20%) patients in the radiation group (P less than 0.025). No enhanced toxicities were observed with the addition of cis-DPP to radiation. The combined use of cis-DPP and radiotherapy offers promising potential in improving local-regional control of advanced cervical carcinoma.
Long-term follow-up of potentiation of radiotherapy by cis-platinum in advanced cervical cancer.
Between January 1982 and January 1983 all patients with advanced cervical cancer were randomized into three groups: radiotherapy only (group I), radiotherapy plus weekly cis-platinum (group II), and radiation plus twice-weekly cis-platinum (group III). Better initial central control was observed in group III patients. Long-term survival was similar in the three groups. Potentiation of radiotherapy with cis-platinum failed to show any significant improvement in long-term survival.
Chemoradiation and adjuvant chemotherapy in cervical cancer.
PURPOSE: Radiotherapy is the standard treatment for locally advanced cervical cancer, but treatment results remain disappointing, particularly for women with bulky central disease. We investigated the role of concurrent chemoradiation and adjuvant chemotherapy in a randomized trial.
PATIENTS AND METHODS: Two hundred twenty patients with bulky stage I, II, and III cervical cancer were randomized to receive either standard pelvic radiotherapy or chemoradiation (epirubicin 60 mg/m(2)) followed by adjuvant chemotherapy with epirubicin 90 mg/m(2) administered at 4-week intervals for five additional cycles.
RESULTS: Fifty-nine patients have relapsed, with a median follow-up duration of 77 months. Patients who received epirubicin radiation therapy showed a significantly longer disease-free (P =.03) and cumulative survival (P =.04). Patients who received radiation alone had significantly more distant metastasis than those who received chemoradiation (P =.012). There was no difference in long-term local tumor control (P =.99).
CONCLUSION: Survival benefit has been demonstrated in patients treated with chemoradiation followed by adjuvant chemotherapy with epirubicin as compared with patients treated with standard pelvic radiotherapy alone.
Options:
A: Improved overall survival and progression-free survival, with increased acute toxicity but unclear long-term side effects.
B: No significant difference in overall survival and progression-free survival, with increased acute toxicity and well-documented long-term side effects.
C: Improved overall survival and progression-free survival, with no increase in acute toxicity and well-documented long-term side effects.
D: No significant difference in overall survival and progression-free survival, with no increase in acute toxicity and unclear long-term side effects. | A |
453 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What is the conclusion regarding the use of uterine muscle relaxant drugs for women with threatened miscarriage? Please answer this question based on the information provided below:
Buphenine and threatened abortion.
One hundred and seventy patients with threatened abortion have been studied in two groups. Group 1 of eighty-five patients were treated with the uterine muscle relaxant, buphenine hydrochloride. The second group of eighty-five patients were given placebo. Pregnancy continuation was 90.6% in group 1 and 62.3% in group 2. Only three of 22 patients with history of recurrent abortion using buphenine aborted.
Options:
A: Uterine muscle relaxant drugs significantly reduce the risk of miscarriage and should be widely used.
B: There is insufficient evidence to support the use of uterine muscle relaxant drugs for women with threatened miscarriage, and their use should be limited to randomised trials.
C: Uterine muscle relaxant drugs increase the risk of preterm birth and should be avoided.
D: Uterine muscle relaxant drugs have no effect on the risk of miscarriage or preterm birth. | B |
454 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What were the findings regarding the effectiveness of high dose chemotherapy with autologous bone marrow or stem cell transplantation compared to conventional chemotherapy for women with metastatic breast cancer? Please answer this question based on the information provided below:
Conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer. Philadelphia Bone Marrow Transplant Group.
BACKGROUND: We conducted a randomized trial in which we compared high-dose chemotherapy plus hematopoietic stem-cell rescue with a prolonged course of monthly conventional-dose chemotherapy in women with metastatic breast cancer.
METHODS: Women 18 to 60 years of age who had metastatic breast cancer received four to six cycles of standard combination chemotherapy. Patients who had a complete or partial response to induction chemotherapy were then randomly assigned to receive either a single course of high doses of carboplatin, thiotepa, and cyclophosphamide plus transplantation of autologous hematopoietic stem cells or up to 24 cycles of cyclophosphamide, methotrexate, and fluorouracil in conventional doses. The primary end point was survival.
RESULTS: The median follow-up was 37 months. Of 553 patients who enrolled in the study, 58 had a complete response to induction chemotherapy and 252 had a partial response. Of these, 110 patients were assigned to receive high-dose chemotherapy plus hematopoietic stem cells and 89 were assigned to receive conventional-dose chemotherapy. In an intention-to-treat analysis, we found no significant difference in survival overall at three years between the two treatment groups (32 percent in the transplantation group and 38 percent in the conventional-chemotherapy group). There was no significant difference between the two treatments in the median time to progression of the disease (9.6 months for high-dose chemotherapy plus hematopoietic stem cells and 9.0 months for conventional-dose chemotherapy).
CONCLUSIONS: As compared with maintenance chemotherapy in conventional doses, high-dose chemotherapy plus autologous stem-cell transplantation soon after the induction of a complete or partial remission with conventional-dose chemotherapy does not improve survival in women with metastatic breast cancer.
Randomized trial of high-dose chemotherapy with autologous peripheral-blood stem-cell support compared with standard-dose chemotherapy in women with metastatic breast cancer: NCIC MA.16.
PURPOSE: We conducted a multicenter, randomized trial to compare progression-free survival (PFS), overall survival (OS), and quality of life in women with metastatic breast cancer (MBC) receiving high-dose chemotherapy plus autologous stem-cell transplantation (ASCT; HDCT) compared with standard-dose therapy.
PATIENT AND METHODS: Between April 1997 and December 2000, 386 women with MBC and no prior chemotherapy for metastatic disease were registered. After initial response to anthracycline- or taxane-based induction chemotherapy, 224 patients were randomly assigned: 112 to high-dose cyclophosphamide, mitoxantrone, and carboplatin chemotherapy and ASCT (HDCT), and 112 to standard therapy (ST). Median age was 47 years (range, 25 to 67 years). Thirty two percent of women randomly assigned had estrogen and progesterone receptor-negative breast cancer, 42% had visceral metastases, and 58% had bone metastases. Complete remission rates before random assignment were 11% for those receiving HDCT and 12% for those receiving ST.
RESULTS: After a median follow-up of 48 months, 79 deaths were observed in the HDCT arm and 77 deaths were observed in the ST arm; seven patients (6%) in the HDCT arm died as a result of toxicity. The median OS was 24 months for the HDCT arm (95% CI, 21 to 35 months) and 28 months for ST (95% CI, 22 to 33 months; hazard ratio [HR], 0.9; 95% CI, 0.6 to 1.2; P = .43). PFS was 11 months for HDCT and 9 months for ST (HR, 0.6 in favor of HDCT; 95% CI, 0.5 to 0.9; P = .006).
CONCLUSION: HDCT did not improve OS in women with MBC when used as consolidation after response to induction chemotherapy.
Pegase 03: a prospective randomized phase III trial of FEC with or without high-dose thiotepa, cyclophosphamide and autologous stem cell transplantation in first-line treatment of metastatic breast cancer.
Pegase 03 is a multicenter prospective randomized phase III trial evaluating the impact of first-line high-dose chemotherapy (HDC) with stem cell support on overall survival (OS), disease-free survival (DFS) and response rate in 308 patients with histologically proven metastatic breast cancer responding to induction therapy. Eligible patients received four induction cycles with FEC 100 (5-fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2), cyclophosphamide 500 mg/m(2)). Patients with objective response (N=179) were randomized to one cycle of HDC (cyclophosphamide 6000 mg/m(2) and thiotepa 800 mg/m(2) (CHUT)) and stem cell support (N=88), or no further treatment (N=91). All patients were observed until disease progression or death. One toxic death occurred after CHUT. Other toxicities were manageable. The response rate at 3 months was higher in the intensification arm: 82.7% (25.3% complete response (CR)) versus 59.2% (14.1% CR) (P=0.0002). Median follow-up was 48 months. Median DFS was 11 and 6.6 months in the intensification and the observation arms, respectively (P=0.0001). There was no survival difference: 33.6 versus 27.3% OS at 3 years (P=0.8) and 22.9 versus 22.3 months median time to relapse in the intensification and observation arms, respectively. In this randomized trial, HDC with CHUT improved DFS but not OS, corroborating findings from earlier trials.
High-dose chemotherapy for breast cancer: the French PEGASE experience.
BACKGROUND: Early studies of high-dose chemotherapy (HDC) for breast cancer were limited by small numbers and the lack of adequate control groups. The French PEGASE Group was founded to perform larger and properly randomized comparative studies of this approach.
METHODS: The program was created to determine the effects of intensive chemotherapy for breast cancer. The seven PEGASE protocols addressed HDC as adjuvant therapy (01 and 06) and as treatment for inflammatory nonmetastatic disease (02, 05, and 07) and metastatic disease (03 and 04). Two of these protocols are ongoing.
RESULTS: The PEGASE 01 adjuvant therapy trial showed that 3-year disease-free survival was significantly better in the HDC arm but overall survival was unchanged. The ongoing phase III 06 trial is studying a higher dosage regimen. The HDC trials for metastatic and inflammatory nonmetastatic disease are encouraging.
CONCLUSIONS: Many clinicians no longer subscribe to the concept of HDC for breast cancer. Overall outcomes from management of poor-risk breast cancer remain poor, however, and it is possible that some selected subgroups of patients may benefit from such an approach.
[Intensive chemotherapy and autograft of hematopoietic stem cells in the treatment of metastatic cancer: results of the national protocol Pegase 04].
UNLABELLED: We report hereby the results of the french multicentric randomized PEGASE 04 protocol established to evaluate the impact on survival of high-dose chemotherapy over conventional chemotherapy for MBC patients.
PATIENTS AND METHODS: Inclusion criteria were: age < or = 60 year, PS < 2, adenocarcinoma initially metastatic or in first relapse, chemosensitive disease. Randomization was done after 4-6 courses of conventionnal chemotherapy between high-dose (Mitoxantrone, 45 mg/m2, Cyclophosphamide: 120 mg/kg, Melphalan: 140 mg/m2), and the pursuit of the same conventionnal chemotherapy. Between 09/92 and 12/96, 61 chemosensitive patients were enrolled: 29 were referred to standard chemotherapy, 32 to intensive therapy. At randomization, 13 pts (21.3%) were in complete response and 48 in partial response.
RESULTS: The median progression-free survivals were 20 and 35.3 months in the standard and intensive groups (p=0.06). The relapse rates were respectively 79.3% vs 50.8% at 3 years and 90.8% vs 90.7% at 5 years. The median overall survivals were 20 and 43.4 months, with an overall survival rate of 18.5% vs 29.8% at 5 years (p=0.12).
CONCLUSION: The CMA regimen could prolong the progression-free survival of MBC patients, however without any significant impact on overall survival.
High-dose chemotherapy with haematopoietic stem cell transplantation for metastatic breast cancer patients: final results of the French multicentric randomised CMA/PEGASE 04 protocol.
The aim of our study was to evaluate the impact on time to progression (TTP) and overall survival (OS) of high-dose chemotherapy (HD-CT) over conventional CT in metastatic breast cancer patients. Between 09/92 and 12/96, 61 patients with chemosensitive metastatic breast cancer were randomised between HD-CT using the CMA regimen (Mitoxantrone, Cyclophosphamide, Melphalan) applied as consolidation (32 patients) or maintenance CT (29 patients). At randomisation, 13 patients were in complete response, 47 in partial response and one had stable disease. The median TTPs from randomisation were 6 and 12 months in the standard and intensive groups, respectively (P < 0.0056), with a relapse rate of 86.2% vs. 62.5% at 2 years, and 100% vs. 81.3% at 5 years. The median OS times were 19.3 and 44.1 months, with an OS rate of 13.8% vs. 36.8% at 5 years (P < 0.0294). The CMA regimen could prolong the TTP of patients with chemosensitive metastatic breast cancer. Further studies are needed to determine if this translates into an effect on OS.
High-dose chemotherapy for breast cancer: the French PEGASE experience.
BACKGROUND: Early studies of high-dose chemotherapy (HDC) for breast cancer were limited by small numbers and the lack of adequate control groups. The French PEGASE Group was founded to perform larger and properly randomized comparative studies of this approach.
METHODS: The program was created to determine the effects of intensive chemotherapy for breast cancer. The seven PEGASE protocols addressed HDC as adjuvant therapy (01 and 06) and as treatment for inflammatory nonmetastatic disease (02, 05, and 07) and metastatic disease (03 and 04). Two of these protocols are ongoing.
RESULTS: The PEGASE 01 adjuvant therapy trial showed that 3-year disease-free survival was significantly better in the HDC arm but overall survival was unchanged. The ongoing phase III 06 trial is studying a higher dosage regimen. The HDC trials for metastatic and inflammatory nonmetastatic disease are encouraging.
CONCLUSIONS: Many clinicians no longer subscribe to the concept of HDC for breast cancer. Overall outcomes from management of poor-risk breast cancer remain poor, however, and it is possible that some selected subgroups of patients may benefit from such an approach.
Up-front tandem high-dose chemotherapy compared with standard chemotherapy with doxorubicin and paclitaxel in metastatic breast cancer: results of a randomized trial.
PURPOSE: The role of high-dose chemotherapy (HDCT) in metastatic breast cancer remains controversial. Trials with late intensification HDCT have failed to show an advantage in overall survival. This study was initiated to compare up-front tandem HDCT and standard combination therapy in patients with metastatic breast cancer.
PATIENTS AND METHODS: Patients without prior chemotherapy for metastatic disease were randomly assigned to standard combination therapy with doxorubicin and paclitaxel (AT) or double HDCT with cyclophosphamide, mitoxantrone, and etoposide followed by peripheral-blood stem-cell transplantation. HDCT was repeated after 6 weeks. Patients were stratified by menopausal and hormone-receptor status. The primary objective was to compare complete response (CR) rates.
RESULTS: A total of 93 patients were enrolled onto the trial. Intent-to-treat CR rates for patients randomized to HDCT and AT were 12.5% and 11.1%, respectively (P = .84). Objective response rates were 66.7% for patients in the high-dose group and 64.4% for patients in the AT arm (P = .82). In an intent-to-treat analysis, there were no significant differences between the two treatments in median time to progression (HDCT, 11.1 months; AT, 10.6 months; P = .67), duration of response (HDCT, 13.9 months; AT, 14.3 months; P = .98), and overall survival (HDCT, 26.9 months; AT, 23.4 months; P = .60). HDCT was associated with significantly more myelosuppression, infection, diarrhea, stomatitis, and nausea and vomiting, whereas patients treated with AT developed more neurotoxicity.
CONCLUSION: This trial failed to show a benefit for up-front tandem HDCT compared with standard combination therapy. HDCT was associated with more acute adverse effects.
Up-front tandem high-dose chemotherapy compared with standard chemotherapy with doxorubicin and paclitaxel in metastatic breast cancer: results of a randomized trial.
PURPOSE: The role of high-dose chemotherapy (HDCT) in metastatic breast cancer remains controversial. Trials with late intensification HDCT have failed to show an advantage in overall survival. This study was initiated to compare up-front tandem HDCT and standard combination therapy in patients with metastatic breast cancer.
PATIENTS AND METHODS: Patients without prior chemotherapy for metastatic disease were randomly assigned to standard combination therapy with doxorubicin and paclitaxel (AT) or double HDCT with cyclophosphamide, mitoxantrone, and etoposide followed by peripheral-blood stem-cell transplantation. HDCT was repeated after 6 weeks. Patients were stratified by menopausal and hormone-receptor status. The primary objective was to compare complete response (CR) rates.
RESULTS: A total of 93 patients were enrolled onto the trial. Intent-to-treat CR rates for patients randomized to HDCT and AT were 12.5% and 11.1%, respectively (P = .84). Objective response rates were 66.7% for patients in the high-dose group and 64.4% for patients in the AT arm (P = .82). In an intent-to-treat analysis, there were no significant differences between the two treatments in median time to progression (HDCT, 11.1 months; AT, 10.6 months; P = .67), duration of response (HDCT, 13.9 months; AT, 14.3 months; P = .98), and overall survival (HDCT, 26.9 months; AT, 23.4 months; P = .60). HDCT was associated with significantly more myelosuppression, infection, diarrhea, stomatitis, and nausea and vomiting, whereas patients treated with AT developed more neurotoxicity.
CONCLUSION: This trial failed to show a benefit for up-front tandem HDCT compared with standard combination therapy. HDCT was associated with more acute adverse effects.
Options:
A: High dose chemotherapy with autologous bone marrow or stem cell transplantation significantly improved overall survival compared to conventional chemotherapy.
B: High dose chemotherapy with autologous bone marrow or stem cell transplantation significantly improved event-free survival but did not significantly improve overall survival compared to conventional chemotherapy.
C: High dose chemotherapy with autologous bone marrow or stem cell transplantation significantly improved both overall survival and event-free survival compared to conventional chemotherapy.
D: High dose chemotherapy with autologous bone marrow or stem cell transplantation did not significantly improve either overall survival or event-free survival compared to conventional chemotherapy. | B |
455 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What were the findings regarding the efficacy and safety of continuous intravenous infusion compared to bolus intravenous administration of loop diuretics in patients with congestive heart failure Class III-IV? Please answer this question based on the information provided below:
Effect of bolus injection versus continuous infusion of furosemide on diuresis and neurohormonal activation in patients with severe congestive heart failure.
Previous studies have demonstrated that continuous infusion of furosemide results in increased diuresis and natriuresis compared with bolus administration of the drug in patients with severe heart failure. We reasoned that continuous infusion of furosemide caused less activation of neurohumoral mechanisms, since other studies have shown that bolus administration of furosemide may activate this system. We therefore tested the hypothesis that continuous administration of furosemide would increase water and sodium excretion due to less activation of neurohormones. Eight patients with severe heart failure were studied during continuous infusion over 24 h and bolus injections of furosemide twice daily in a randomized cross-over study. Bolus administration of furosemide increased diuresis and natriuresis significantly in the first 4 h after administration compared with continuous administration, but this was later reversed, resulting in similar 24 h total output. The neurohormones measured at baseline were all markedly elevated. Neither regimens of furosemide caused any further significant changes in neurohumoral response except that pro-ANF decreased more during the first 8 h after bolus administration compared to continuous infusion. This study has demonstrated that bolus administration of furosemide in conventional doses is equally effective as continuous intravenous infusion in patients with severe heart failure. This may be due to maximal neurohormonal activation in severe heart failure (NYHA III-IV) which could not be further activated by bolus administration.
Diuretic efficacy of high dose furosemide in severe heart failure: bolus injection versus continuous infusion.
OBJECTIVES: The efficacy of high dose furosemide as a continuous infusion was compared with a bolus injection of equal dose in patients with severe heart failure.
BACKGROUND: The delivery rate of furosemide into the nephron has been proved to be a determinant of diuretic efficacy in healthy volunteers.
METHODS: In a randomized crossover study we compared the efficacy of a continuous infusion of high dose furosemide (mean daily dosage 690 mg, range 250 to 2,000) versus a single bolus injection of an equal dose in 20 patients with severe heart failure. The patients received an equal dosage, either as a single intravenous bolus injection or as an 8-h continuous infusion preceded by a loading dose (20% of total dosage).
RESULTS: Mean (+/- SEM) daily urinary volume (infusion 2,860 +/- 240 ml, bolus 2,260 +/- 150 ml, p = 0.0005) and sodium excretion (infusion 210 +/- 40 mmol, bolus 150 +/- 20 mmol, p = 0.0045) were significantly higher after treatment with continuous infusion than with bolus injection, despite significantly lower urinary furosemide excretion (infusion 310 +/- 60 mg every 24 h, bolus 330 +/- 60 mg every 24 h, p = 0.0195). The maximal plasma furosemide concentration was significantly higher after bolus injection than during continuous infusion (infusion 24 +/- 5 micrograms/ml, bolus 95 +/- 20 micrograms/ml, p < 0.0001). Short-term, completely reversible hearing loss was reported only after bolus injection in 5 patients.
CONCLUSIONS: We conclude that in patients with severe heart failure, high dose furosemide administered as a continuous infusion is more efficacious than bolus injection and causes less ototoxic side effects.
Pharmacodynamics of torsemide administered as an intravenous injection and as a continuous infusion to patients with congestive heart failure.
The natriuretic and diuretic effects of a 100-mg dose of torsemide administered as a continuous infusion of torsemide and as a single bolus were compared in a group of patients with stable mild-to-moderate congestive heart failure (CHF). Patients received in random order 100 mg of torsemide as an intravenous bolus and as a 75-mg infusion over 24 hours started simultaneously with a 25-mg loading bolus. Administration of torsemide to patients with CHF as a continuous infusion was an effective dosing regimen, resulting in 24-hour diuresis and natriuresis that was numerically but not statistically greater than that observed with bolus administration. The response with continuous infusion occurred with less torsemide in the urine, resulting in a significantly greater efficiency of torsemide with this regimen. The effectiveness of torsemide as a continuous infusion does not mean that this mode of administration should be used in all patients. The response to 100 mg of torsemide in patients with mild-to-moderate CHF is the same whether administered as an intravenous bolus, a continuous intravenous infusion, or by mouth. This is consistent with the high bioavailability demonstrated in previous studies. The mode of therapy used should be dictated by each individual patient's needs. This study shows that continuous infusion is a viable option for administration of torsemide, and dosing guidelines for use of such a strategy are presented.
Intermittent administration of furosemide vs continuous infusion preceded by a loading dose for congestive heart failure.
Several reports have suggested that continuous intravenous administration of loop diuretics may be superior to intermittent administration. We performed a prospective randomized crossover study comparing intermittent intravenous administration (IA) of furosemide with continuous infusion following a single loading dose (LDCI) in nine patients with severe congestive heart failure. At the time of hospital admission, patients were randomly assigned to one of two treatment groups. One group (four patients) received an IV bolus injection of furosemide followed immediately by a continuous infusion for 48 h. The second group (five patients) was treated with three IV bolus injections a day for 48 h. Total doses of furosemide were equivalent in the two groups. After 48 h, each patient was crossed over to the other method and treated for an additional 48 h. LDCI produced significantly greater diuresis and natriuresis than IA (total urine output increased by 12 to 26 percent, total sodium excretion increased by 11 to 33 percent) (p less than 0.01). There were no significant differences in side effects between the two methods. These results indicate that LDCI may be a preferred method for administration of furosemide in patients with congestive heart failure.
Effects of high-dose furosemide and small-volume hypertonic saline solution infusion in comparison with a high dose of furosemide as bolus in refractory congestive heart failure: long-term effects.
BACKGROUND: Diuretics have been accepted as first-line treatment in refractory congestive heart failure (CHF), but a lack of response to them is a frequent event. A randomized, single-blind study was performed to evaluate the effects of the combination of high-dose furosemide and small-volume hypertonic saline solution (HSS) infusion in the treatment of refractory New York Heart Association (NYHA) class IV CHF and a normosodic diet during follow-up. Materials and Methods One hundred seven patients (39 women and 68 men, age range 65-90 years) with refractory CHF (NYHA class IV) of different etiologies, who were unresponsive to high oral doses of furosemide, angiotensin-converting enzyme inhibitors, digitalis, and nitrates, were enrolled. Inclusion criteria included an ejection fraction (EF) <35%, serum creatinine level <2 mg/dL, blood urea nitrogen level < or =60 mg/dL, reduced urinary volume, and low natriuresis. The patients were randomized in 2 groups (single-blind). Patients in group 1 (20 women and 33 men) received an intravenous (IV) infusion of furosemide (500-1000 mg) plus HSS (150 mL of 1.4%-4.6% NACl) twice a day in 30 minutes. Patients in group 2 (19 women and 35 men) received an IV bolus of furosemide (500-1000 mg) twice a day, without HSS, during a period lasting 6 to 12 days. Both groups received IV KCl (20-40 mEq) to prevent hypokalemia. At study entry, all patients underwent a physical examination and measurement of body weight (BW), blood pressure (BP), and heart rate (HR), an evaluation of signs of CHF, and measurement of control levels of serum Na, K, Cl, bicarbonate, albumin, uric acid, creatinine, urea, and glycemia daily during hospitalization, and measurements of the daily output of urine for Na, K, and Cl. A chest radiograph, electrocardiogram, and echocardiogram were obtained at study entry, during hospitalization, and at the time of discharge from the hospital. During the treatment and after discharge, the daily dietary Na intake was 120 mmol in group 1 versus 80 mmol in group 2, with a fluid intake of 1000 mL daily in both groups. An assessment of BW and 24-hour urinary volume, serum, and urinary laboratory parameters were performed daily until patients reached a compensated state, when IV furosemide was replaced with oral administration (250-500 mg/d). After discharge from the hospital, patients were observed as outpatients weekly for the first 3 months and, subsequently, once a month.
RESULTS: The groups were similar in age, sex, EF, risk factors, treatment, and etiology of CHF. All patients showed a clinical improvement. Ten patients in both groups had hyponatremia at entry. A significant increase in daily diuresis and natriuresis was observed in both groups, but it was more significant in the group receiving HSS (P <.05). The serum Na level increased in group 1 and decreased in group 2 (P <.05). The serum K level was decreased in both groups (P <.05). BW was reduced in both groups (P <.05). Group 2 had an increase in serum creatinine level. Serum uric acid levels increased in both groups. BP values decreased and HR was corrected to normal values in both groups. In the follow-up period (31 +/- 14 months), 25 patients from group 1 were readmitted to the hospital for heart failure. In group 2, 43 patients were readmitted to the hospital at a higher class than at discharge. Twenty-four patients in group 1 died during follow-up, versus 47 patients in group 2 (P <.001).
CONCLUSION: This treatment is effective and well tolerated, improves the quality of life through the relief of signs and symptoms of congestion, and may delay more aggressive treatments. The effects were also beneficial in a long period for mortality reduction (55% vs 13% survival rate) and for clinical improvement.
Effects of high-dose furosemide and small-volume hypertonic saline solution infusion in comparison with a high dose of furosemide as a bolus, in refractory congestive heart failure.
BACKGROUND: Diuretics, have been accepted as first-line treatment in refractory heart failure, but a lack of response is a frequent event. A randomised single blind study was performed to evaluate the effects of the combination of high-dose furosemide and small-volume hypertonic saline solution (HSS) infusion in the treatment of refractory NYHA class IV congestive heart failure (CHF).
MATERIALS AND METHODS: Sixty patients (21 F/39 M) with refractory CHF (NYHA class IV) of different etiologies, unresponsive to high oral doses of furosemide, ACE-inhibitors, digitalis, and nitrates, aged 65-90 years, were enrolled. They had to have an ejection fraction (EF) <35%, serum creatinine <2 mg/dl, BUN </=60 mg/dl, a reduced urinary volume and a low natriuresis. The patients were randomised in two groups (single blind): group 1 (11 F/19 M) received an i.v. infusion of furosemide (500-1000 mg) plus HSS (150 ml of 1.4-4.6% NaCl) b.i.d. in 30 min. Group 2 (10 F/20 M) received an i.v. bolus of furosemide (500-1000 mg) b.i.d., without HSS, during a period lasting 6-12 days. Both groups received KCl (20-40 mEq.) i.v. to prevent hypokalemia. All patients underwent at entry a physical examination, measurement of body weight (BW), blood pressure (BP), heart rate (HR), evaluation of signs of CHF, and controls of serum Na, K, Cl, bicarbonate, albumin, uric acid, creatinine, urea and glycemia and daily during hospitalization, as well as the daily output of urine for, Na, K and Cl measurements. Chest X-ray, ECG and echocardiogram were obtained at entry during and at the discharge. During the treatment and after discharge the daily dietary Na intake was 120 mmol with a drink fluid intake of 1000 ml daily. An assessment of BW and 24-h urinary volume, serum and urinary laboratory parameters, until reaching a compensated state, were performed daily, when i.v. furosemide was replaced with oral administration (250-500 mg/day). After discharge, patients were followed as outpatients weekly for the first 3 months and subsequently once per month.
RESULTS: The groups were similar for age, sex, EF, risk factors, treatment and etiology of CHF. All patients showed a clinical improvement. Six patients in both groups had hyponatremia (from 120 to 128 mEq./l) at entry. A significant increase in daily diuresis in both groups was observed (from 390+/-155 to 2100+/-626, and from 433+/-141 to 1650+/-537 ml/24 h, P<0.05). Natriuresis (from 49+/-15 to 198+/-28 mEq./24 h) was higher in group 1 vs. group 2 (from 53.83+/-12 to 129+/-39 mEq./24 h, P<0.05). Serum Na (from 135.9+/-6.8 to 142.2+/-3. 8 mEq./l, P<0.05) increased in the group 1 and decreased in the group 2 (from 134.7+/-7.9 to 130.1+/-4.3 mEq./l). Serum K was decreased (from 4.4+/-0.6 to 3.9+/-0.6, and 4.6+/-9 to 3.6+/-0.5 mEq. /l, P<0. 05) in both groups. BW was reduced (from 73.8+/-9.1 to 63. 8+/-8.8, and from 72.9+/-10.2 to 64.5+/-7.5 kg, P<0. 05) in both groups. Group 2 showed more patients in NYHA class III than group 1 (18 vs. 2 patients, P<0.05). Group 2 showed an increase of serum creatinine. Serum uric acid increased in both groups. BP values decreased, and HR was corrected to normal values in both groups. Group 2 showed a longer hospitalization time than group receiving HHS infusion (11.67+/-1.8 vs. 8.57+/-2.3 days, P<0.001). In the follow-up (6-12 months), none of the patients from group 1 were readmitted to the hospital and they maintained the NYHA class achieved at the discharge. Group 2 showed 12 patients readmitted to hospital and a higher class than at discharge.
CONCLUSION: Our data suggest that the combination of furosemide with HSS is feasible and it appears that this combination produces an improvement of hemodynamic and clinical parameters, reduces the hospitalization time and maintains the obtained results over time in comparison with those receiving high-dose furosemide as bolus.
Diuretic effects of furosemide infusion versus bolus injection in congestive heart failure.
In a randomized, single-blind, crossover clinical trial, the diuretic efficacy of the same total dose of furosemide (2 x 40 mg) administered in either conventional intravenous bolus injection or continuous infusion was studied in 20 patients (nine males and 11 females), aged 37-75 years, with congestive heart failure. Furosemide infusion, administered first, produced a significantly greater diuresis than the bolus when compared with baseline (86%: 29.6%; p = 0.029). This was followed by a similar increase in 24-h urinary sodium, potassium and chloride excretion, with no significant difference from the bolus effect. The following day, diuretic and saluretic effects of furosemide did not differ significantly between the study groups. Nevertheless, when continuous furosemide infusion was administered first, it produced a greater increase in urinary volume, 24-h urinary sodium, potassium and chloride than when bolus injection was applied the next day. Conversely, when furosemide bolus was administered first, followed by the infusions the next day, the effects were almost equal, regardless of the mode of administration. It is concluded that in the treatment of refractory edema in patients with congestive heart failure, continuous intravenous infusion of furosemide is superior to the conventional intermittent bolus injection, especially if it is administered at the very beginning of the hospital treatment, and presumably is even better with higher dosage and longer infusion time span.
Protocol-guided diuretic management: comparison of furosemide by continuous infusion and intermittent bolus.
OBJECTIVE: To evaluate the safety and relative effectiveness of two diuretic protocols in the intensive care unit (ICU).
DESIGN: Prospective, randomized comparative study.
PATIENTS: Thirty-three cardiac and medical ICU patients with pulmonary edema or fluid overload for which aggressive diuresis was intended.
INTERVENTIONS: Enrolled patients were randomized to fluid management strategies combining fluid restriction and individually adjusted diuretic therapy by either continuous or bolus infusions of furosemide, titrated to achieve negative hourly fluid balance.
MEASUREMENTS AND MAIN RESULTS: Cumulative intake minus output (primary endpoint); change in serum creatinine, and length of ICU and hospital stay (secondary endpoints). Diuresis by either protocol was feasible, safe, and effective. The main outcome measures were not significantly different for either group managed with a standardized protocol.
CONCLUSIONS: Protocol-guided diuretic management, with individualized titration of dosage to defined physiologic endpoints can be readily and safely implemented in the ICU. Both continuous and bolus diuretic regimens appear equally effective in achieving negative fluid balance. Larger studies with a randomized control arm are needed before these protocols can be recommended as routine practice.
Options:
A: Continuous infusion resulted in greater urine output, fewer adverse effects, and shorter hospital stays, but no significant difference in electrolyte disturbances or mortality.
B: Continuous infusion resulted in greater urine output, fewer adverse effects, shorter hospital stays, and significantly lower cardiac and all-cause mortality, with no significant difference in electrolyte disturbances.
C: Bolus administration resulted in greater urine output, fewer adverse effects, shorter hospital stays, and significantly lower cardiac and all-cause mortality, with no significant difference in electrolyte disturbances.
D: There was no significant difference between continuous infusion and bolus administration in terms of urine output, adverse effects, hospital stays, electrolyte disturbances, or mortality. | B |
456 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What was the conclusion regarding the comparison of functional treatment and immobilization for closed fifth metacarpal neck fractures in adults? Please answer this question based on the information provided below:
Functional taping of fractures of the 5th metacarpal results in a quicker recovery.
Fractures of the fifth metacarpal can be treated non-operatively by plaster immobilisation or functional taping. In order to evaluate the better treatment policy, the two methods were compared in a prospective randomised series. We treated 25 patients with an ulnar gutter plaster-cast splintage and 25 with functional tape. Functional recovery was evaluated after one week and four weeks, three months and six months. Mobility, power-grip, pulling- and torque strengths were measured. The change in fracture angulation was calculated at the one and four-week follow-up. Residual symptoms were evaluated after six months. The functional tape group showed significant earlier functional recovery. After six months, there were no significant differences between the groups with regard to functional and anatomical results or the number of patients with residual symptoms. In both groups, we noted a change in fracture angulation only in those fractures that had been reduced. We conclude that fractures of the 5th metacarpal are better treated by functional taping than by cast immobilisation.
The use of a moulded metacarpal brace versus neighbour strapping for fractures of the little finger metacarpal neck.
Seventy-three patients with fractures of the neck of the little finger metacarpal were randomized to treatment with a moulded metacarpal brace or neighbour strapping. Sixty-five of these attended for follow-up at 3 weeks. Both treatment modalities permitted a functional range of movement, but patients treated with the metacarpal brace had significantly less pain than those treated with neighbour strapping, and this facilitated an early return to work.
Treatment of subcapital fractures of the fifth metacarpal bone: a prospective randomised comparison between functional treatment and reposition and splinting.
We did a prospective study to compare the results of treatment of subcapital fractures of the fifth metacarpal bone by closed reduction and splinting or by functional treatment. Twenty-nine consecutive patients were randomly divided into the two treatment groups (functional n = 14, and reposition and splinting n = 15). The results of treatment were satisfactory in both groups. Functionally treated patients recovered their grip force and range of movement of the affected hand a little sooner. All fractures in both groups had united within three months. There were no complications. We conclude that subcapital fractures of the fifth metacarpal bone can successfully be treated without closed reduction and splinting.
Immediate mobilization gives good results in boxer's fractures with volar angulation up to 70 degrees: a prospective randomized trial comparing immediate mobilization with cast immobilization.
BACKGROUND: The management of the subcapital fracture of the fifth metacarpal bone, the boxer's fracture, is still a matter of debate. Besides the question of which rate of angulation is acceptable before a reduction becomes necessary, recommendations for further treatment of this fracture vary as well. Therefore, the aim of our study was to compare randomly and prospectively the results of an immobilization treatment for 3 weeks with cast with a functional treatment, all with accepted angulations up to 70 degrees.
PATIENTS AND METHODS: Between June 1997 and June 1998, 40 patients were randomly allocated either to treatment with an ulnar gutter plaster cast for a period of 3 weeks followed by mobilization, or a pressure bandage for 1 week and immediate mobilization within limits imposed by pain. All patients were monitored at the outpatient clinic 6 and 12 weeks after the fracture. Clinical outcome was measured by the range of motion (ROM) of the fifth metacarpal phalangeal (MCP) joint, and by interviewing the patients about their satisfaction, pain perception, return to work and hobby, and need for physiotherapy.
RESULTS: A total of 35 patients with a mean age of 29 years (range 15-84) completed the required follow-up program. The mean angulation of the fracture was 39 degrees (range 15-70 degrees ). Between the two groups, no statistical differences were scored with respect to ROM, satisfaction, pain perception, return to work and hobby, and need for physiotherapy. According to a sample size calculation (power 90%, alpha 0.05, to detect 5 degrees difference in ROM), 12 patients needed to be included in each group to reach significance.
CONCLUSIONS: A pressure bandage for 1 week, followed by immediate mobilization, is a sufficient alternative treatment for a boxer's fracture, if it is not angulated greater than 70 degrees and not rotated. This treatment resulted in satisfied patients who perceived no more pain and had a good ROM of the fifth MCP joint. Reduction of angulated fractures of less than 70 degrees seems not of value, with respect to ROM of the fifth MCP joint.
Options:
A: Functional treatment was found to be significantly superior to immobilization.
B: Immobilization was found to be significantly superior to functional treatment.
C: No single non-operative treatment regimen was found to be superior to another.
D: Both treatment methods were found to be equally effective and superior to no treatment. | C |
457 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What were the findings regarding the effectiveness and safety of breast stimulation for third trimester cervical ripening or induction of labour? Please answer this question based on the information provided below:
Cervical ripening and induction of labour by breast stimulation.
The value of gentle, unilateral breast stimulation in the ripening of cervix and induction of labour was studied. Three hundred patients with uncomplicated term pregnancies, (38-42 weeks) were recruited into the study, consisting of three separate randomised double blind prospective trials. The first trial was to evaluate the effectiveness of breast stimulation in ripening the cervices of 200 term primigravid patients. There was a mean change of 3.90 +/- 2.39 points in cervical score among the study group compared to 0.50 +/- 0.67 among the control group. Thirty-three per cent of the study group went into labour when compared with 4% among the control group. In a second study of cross-over trial involving 78 of the original 200 patients, the study (ex-control) group had a mean change in cervical score of 3.84 +/- 2.24 when compared with the control (ex-study) group, (1.43 +/- 1.08). In a third study involving 100 multiparous patients, a mean change in cervical score of 2.74 +/- 1.16 was observed in the study group when compared with the control group, 0.92 +/- 1.07. Forty-six per cent of the patients went into labour compared with 12% in the control group. All findings were highly significant and there were no maternal or fetal side-effects. The study confirmed the efficacy of breast stimulation in cervical ripening and induction of labour.
Cervical ripening and induction of labour by breast stimulation.
The value of gentle, unilateral breast stimulation in the ripening of cervix and induction of labour was studied. Three hundred patients with uncomplicated term pregnancies, (38-42 weeks) were recruited into the study, consisting of three separate randomised double blind prospective trials. The first trial was to evaluate the effectiveness of breast stimulation in ripening the cervices of 200 term primigravid patients. There was a mean change of 3.90 +/- 2.39 points in cervical score among the study group compared to 0.50 +/- 0.67 among the control group. Thirty-three per cent of the study group went into labour when compared with 4% among the control group. In a second study of cross-over trial involving 78 of the original 200 patients, the study (ex-control) group had a mean change in cervical score of 3.84 +/- 2.24 when compared with the control (ex-study) group, (1.43 +/- 1.08). In a third study involving 100 multiparous patients, a mean change in cervical score of 2.74 +/- 1.16 was observed in the study group when compared with the control group, 0.92 +/- 1.07. Forty-six per cent of the patients went into labour compared with 12% in the control group. All findings were highly significant and there were no maternal or fetal side-effects. The study confirmed the efficacy of breast stimulation in cervical ripening and induction of labour.
Induction of labor with an electric breast pump.
Nipple stimulation with an electric breast pump was compared with oxytocin infusion as a means of labor induction. The time from stimulation to the onset of regular uterine activity and to 200 Montevideo units of uterine activity and the time until entrance into the active phase of labor were significantly shorter in the nipple stimulation group. Once the women were in active labor, there was no difference between the groups in the length of labor or mode of delivery.
Evaluation of two methods employed for cervical ripening.
The study evaluates breast stimulation and oxytocin infusion as methods for cervical ripening in patients where an obstetric indication for induction of labour exists. Forty patients with a Bishop score of 5 or 6 were randomly selected for either breast stimulation or oxytocin infusion. In a similar group of 20 cases, no method was employed. The Bishop score improved in 41.2% of cases where breast stimulation was used as compared to 75% where an oxytocin infusion was given. Three foetal deaths in the breast stimulation group brought the study to a stop after 17 cases. Cervical ripening with an oxytocin infusion drip appears to be a better method since infusion dosage can be precisely controlled making the technique more predictable and reliable. Though breast stimulation is effective in ripening the cervix, it may be used only in cases of intrauterine foetal death as it may otherwise adversely affect foetal outcome.
The use of breast stimulation to prevent postdate pregnancy.
Postdate pregnancy is estimated to occur in 3% to 12% of all gestations. Morbidity and mortality rates associated with this common obstetric problem are higher than those with term gestation. The incidence of fetal distress, birth injury, meconium aspiration, congenital malformations, macrosomia, and oligohydramnios is also greater in postdate pregnancy. We prospectively evaluated breast self-stimulation to determine its effect on the incidence of postdate pregnancy. Two hundred low-risk patients at 39 weeks' gestation were randomly assigned to either a control group or a breast-stimulation group. Results showed that breast stimulation reduced the number of pregnancies managed as postdates from 17 per 100 (17%) to five per 100 (5%) (p less than 0.01), a 70% reduction. It is concluded that breast stimulation in postdates pregnancies can decrease significantly the number of patients that must be monitored by biochemical or biophysical means.
Cervical ripening by breast stimulation.
The effect of breast stimulation on cervical ripening was studied. One hundred patients who had completed 38 weeks' gestation and had uncomplicated antenatal courses were recruited and divided into two groups: treatment and control. In the treatment group, gentle breast stimulation of alternate breasts was performed first for 1.5 hours under monitoring in the hospital and then for three hours daily for three days at home. No uterine hypertonus was detected. It was found that there was a significant change in the Bishop score of 3.96 +/- 1.34 points in the stimulated group as compared with the control group 1.04 +/- 1.03 points. After three days, a cross-over trial was performed with the extreatment group becoming the control and the excontrol group undergoing breast stimulation for the same period of time and under the same conditions. Again, the excontrol group was found to have a better mean cervical score (3.11 +/- 1.42 points) than the extreatment group (0.76 +/- 0.97 points) during breast stimulation. It is stressed that no uterine hypertonus was detected with gentle, unilateral breast stimulation, and there were no maternal or fetal complications as a result of this modality of cervical ripening.
Options:
A: Breast stimulation significantly reduced the number of women not in labour at 72 hours and postpartum haemorrhage rates, but had no significant effect on caesarean section rates or meconium staining.
B: Breast stimulation significantly increased the number of women not in labour at 72 hours and postpartum haemorrhage rates, and had a significant effect on caesarean section rates and meconium staining.
C: Breast stimulation had no significant effect on the number of women not in labour at 72 hours, postpartum haemorrhage rates, caesarean section rates, or meconium staining.
D: Breast stimulation significantly reduced the number of women not in labour at 72 hours, but increased postpartum haemorrhage rates and had a significant effect on caesarean section rates and meconium staining. | A |
458 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What were the findings regarding the effectiveness of adjunctive vitamin A treatment in infants and children diagnosed with non-measles pneumonia? Please answer this question based on the information provided below:
Vitamin A supplementation and severity of pneumonia in children admitted to the hospital in Dar es Salaam, Tanzania.
Vitamin A deficiency and acute lower respiratory tract infections coexist as important public health problems in many developing countries. We carried out a randomized, double-blind, placebo-controlled trial to examine whether large doses of vitamin A given to Tanzanian children who are admitted to the hospital with nonmeasles pneumonia would reduce the severity of respiratory disease. Six hundred eighty-seven children were randomly assigned to receive either placebo or vitamin A [200 000 IU (60 mg retinol equivalents) for children > 1 y of age and 100000 IU (30 mg retinol equivalents) for infants] on the day of admission and another dose on the following day. Of the 346 children in the vitamin A group, 13 died in the hospital, compared with 8 of 341 children in the placebo group; the relative mortality was 1.63 (95% CI: 0.67, 3.97; P = 0.28). The mean number of days of hospitalization was the same in both groups (4.2 d). There were no differences between the vitamin A and placebo groups in the duration of hospital stay when examined within categories of children stratified by age, sex, breast-feeding status, nutritional status at baseline, or quartile of dietary vitamin A intake in the 4 mo before admission to the hospital. There were also no differences in the mean number of days of fever, rapid respiratory rate, or hypoxia, whether these endpoints were examined in the total number of subjects or in a subset with more severe clinical conditions at baseline. Large doses of vitamin A had no protective effect on the course of pneumonia in hospitalized Tanzanian children.
Randomised, double blind, placebo controlled clinical trial of efficacy of vitamin A treatment in non-measles childhood pneumonia.
OBJECTIVE: To evaluate the impact on clinical recovery and severity of the addition of large doses of vitamin A to the standard treatment for childhood pneumonia.
DESIGN: A randomised, double blind, placebo controlled trial.
SETTING: Study children were recruited at a public hospital in Recife, north east Brazil, an area of marginal vitamin A deficiency.
SUBJECTS: 472 children aged 6 to 59 months with clinical diagnosis of pneumonia.
INTERVENTIONS: 200,000 IU (infants) or 400,000 IU (1-4 year olds) of vitamin A in oil or similar capsules of placebo divided into two daily oral doses, in addition to the standard treatment.
MAIN OUTCOME MEASURES: Duration of the episode and incidence of adverse outcomes.
RESULTS: The groups were similar with respect to overall duration of pneumonia and incidence of adverse outcomes. Children who received vitamin A, however, were less likely to have fever by day 3 (P = 0.008) and were 29% less likely to fail to respond to the first line antibiotic (P = 0.054).
CONCLUSION: There was little evidence for an effect of vitamin A treatment on the immediate outcome of the pneumonia episode.
Effects of moderate doses of vitamin A as an adjunct to the treatment of pneumonia in underweight and normal-weight children: a randomized, double-blind, placebo-controlled trial.
BACKGROUND: Randomized controlled trials have shown inconsistent responses of childhood pneumonia to the use of vitamin A as an adjunct to the standard treatment of pneumonia.
OBJECTIVE: We evaluated the effect of a moderate dose of vitamin A as an adjunct to standard antimicrobial treatment on the duration of respiratory signs in children with pneumonia.
DESIGN: Children, aged 2-59 mo, with pneumonia and weight-for-age <50th percentile who had been admitted to the Baca Ortíz Children's Hospital in Quito, Ecuador, were randomly assigned to receive 50,000 IU (aged 2-12 mo) or 100,000 IU (aged >12-59 mo) vitamin A or a placebo.
RESULTS: Of the 287 children enrolled, 145 received vitamin A and 142 received placebo. No overall differences were observed between the 2 groups in the duration of signs of pneumonia. Multiple linear regression showed a significant interaction between basal serum retinol concentration and vitamin A group for the time (in h) to remission of respiratory signs (beta = -3.57, SE = 1.09, P = 0.001). Duration of clinical signs was less in children with basal serum retinol concentrations >200 microg/L who received vitamin A supplements than in children with similar concentrations who received placebo (69.9 +/- 49.9 h compared with 131.3 +/- 143.9 h; P = 0.049).
CONCLUSIONS: Overall, we found no effect of a moderate dose of vitamin A supplementation on the duration of uncomplicated pneumonia in underweight or normal-weight children aged <5 y. However, a beneficial effect was seen in children with high basal serum retinol concentrations.
Adverse effects of high-dose vitamin A supplements in children hospitalized with pneumonia.
OBJECTIVE: To test the hypothesis that high-dose vitamin A supplements will enhance recovery of children hospitalized for the treatment of community-acquired pneumonia.
DESIGN: We conducted a randomized, double-blind, placebo-controlled clinical trial of high-dose vitamin A supplements among children 3 months to 10 years of age (N = 95) admitted to hospital with community-acquired pneumonia in Lima, Peru. Children </=1 year of age received 100 000 IU of water-miscible vitamin A on admission to the hospital and an additional 50 000 IU the next day. Children >1 year of age received 200 000 IU on admission and 100 000 IU the next day.
RESULTS: Children receiving vitamin A (n = 48) had lower blood oxygen saturation (the mean difference on day 3 in hospital was 1.1%), higher prevalence rates of retractions (37% in the vitamin A group vs 15% in the placebo group on day 3), auscultatory evidence of consolidation (28% in the vitamin A group vs 17% in the placebo group on day 3), and were more likely to require supplemental oxygen (21% in the vitamin A group vs 8% in the placebo group on day 3) than children in the placebo group (n = 47). Adjustment for baseline severity of disease and nutritional status did not alter the association of vitamin A with increased clinical severity, although the difference in blood oxygen saturation was no longer statistically significant. No differences were seen in duration of hospitalization or in chest x-ray changes 14 days after admission. No deaths occurred, and toxicity of vitamin A was not seen.
CONCLUSIONS: This study indicates that high-dose vitamin A supplements cause modest adverse effects in children recovering from pneumonia and should not be used therapeutically in such patients unless there is clinical evidence of vitamin A deficiency or concurrent measles infection.
Options:
A: Vitamin A significantly reduced mortality and the duration of hospital stay in children with non-measles pneumonia.
B: Vitamin A significantly reduced the severity of pneumonia and the recurrence rate of bronchopneumonia in children with non-measles pneumonia.
C: Vitamin A did not significantly reduce mortality, measures of morbidity, or affect the clinical course of pneumonia in children with non-measles pneumonia.
D: Vitamin A significantly increased the risk of adverse effects such as vomiting, diarrhea, and irritability in children with non-measles pneumonia. | C |
459 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What were the findings regarding the effectiveness of different treatment modalities for childhood Crohn's disease in promoting normal growth and reversing growth failure? Please answer this question based on the information provided below:
A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn's disease.
BACKGROUND & AIMS: Clinical experience suggests that 6-mercaptopurine (6-MP) is effective therapy for children with active steroid-dependent Crohn's disease (CD). We report the results of a prospective, placebo-controlled, multicenter trial evaluating the combination of 6-MP and prednisone as therapy for children with newly diagnosed moderate-to-severe CD.
METHODS: Fifty-five children (age, 13+/-2 years) were randomized to treatment with 6-MP (1.5 mg x kg(-1) x day(-1)) or placebo within 8 weeks of initial diagnosis. Both groups also received prednisone (40 mg/day). Prednisone dosage adjustments were based on a defined schedule determined by the change in a subject's disease activity score, and steroid administration was discontinued as remission was achieved. Study treatment with 6-MP or placebo continued for 18 months.
RESULTS: Groups were comparable for age, sex, and site and activity of disease. In the 6-MP group, the duration of steroid use was shorter (P<0.001) and the cumulative steroid dose lower at 6, 12, and 18 months (P<0.01). Although remission was induced in 89% of both groups, only 9% of the remitters in the 6-MP group relapsed compared with 47% of controls (P = 0.007). Growth was comparable in both groups. No clinically significant adverse events occurred, although mild leukopenia and increases in aminotransferase activity were noted in the 6-MP group.
CONCLUSIONS: Addition of 6-MP to a regimen of corticosteroids significantly lessens the need for prednisone and improves maintenance of remission. 6-MP should be part of the initial treatment regimen for children with newly diagnosed moderate-to-severe CD.
Remission induced by an elemental diet in small bowel Crohn's disease.
Seventeen children with active Crohn's disease of the small intestine were entered into a randomised control trial comparing the efficacy of an elemental diet with that of a high dose steroid regimen. Eight children received an elemental diet (Flexical) through a nasogastric tube for six weeks, followed by reintroduction of food over six weeks during which the Flexical was stopped. Seven children were given intramuscular adrenocorticotrophic hormone followed by oral prednisolone with sulphasalazine. Two children were withdrawn from the trial. The elemental diet was equally effective in inducing an improvement in Lloyd-Still disease activity index, erythrocyte sedimentation rate, C reactive protein and albumin concentrations, and body weight as the high dose steroid regimen. Linear growth, assessed from height velocity over six months, was significantly greater in the children receiving an elemental diet.
Dietary intake and nutritional treatment in childhood Crohn's disease.
Dietary intake was assessed in 24 children with active Crohn's disease. Seventeen of the children were sex and height matched with healthy siblings of other patients. The mean energy intake was 1,764 KJ/day (420 kcal/day) lower in patients during relapse than controls (p < 0.05). All 24 children entered a randomised controlled trial of high-dose steroids compared to an elemental diet. The elemental diet was well tolerated orally in most cases; only one patient required nasogastric administration. There was a similar improvement in disease activity and duration of remission in both groups regardless of the site of disease. Subsequent growth velocity was significantly better in the group treated with the elemental diet despite a greater and more sustained increase in energy intake in the group treated with steroids. Reintroduction of specific foods in the elemental diet group initially caused symptoms in three children but were subsequently tolerated. During remission, there was no significant difference in energy intake, but vegetables were consumed significantly less frequently (p < 0.01) and confectionery significantly more frequently (p < 0.05) when patients were compared with their own siblings.
Options:
A: 6-mercaptopurine (6-MP) significantly improved linear growth compared to placebo.
B: Enteral feeding significantly increased height velocity standard deviation scores compared to corticosteroids.
C: Corticosteroids were found to be more effective than enteral feeding in promoting growth.
D: No treatment modality showed any significant impact on growth. | B |
460 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What was the conclusion regarding the use of herbal medicines for treating HIV infection and AIDS based on the assessment of randomized clinical trials? Please answer this question based on the information provided below:
Pilot randomized controlled trial of Chinese herbal treatment for HIV-associated symptoms.
We wished to determine the short-term safety and efficacy of a Chinese medicinal herb preparation in treating symptoms of human immunodeficiency virus (HIV) infection in a 12-week randomized, double-blind, placebo-controlled clinical trial in a University-affiliated acquired immunodeficiency syndrome (AIDS) clinic at a public general hospital. Thirty adults with symptomatic HIV infection, no previous AIDS-defining diagnosis, and CD4+ counts of 0.200-0.499 x 10(9)/L (200-499/mm3) received 28 tablets each day of either a standardized oral preparation of 31 Chinese herbs or a cellulose placebo. Primary outcome measures were changes in life satisfaction, perceived health, and number and severity of symptoms. Other outcomes included adherence, and changes in weight, CD4+ count, depression, anxiety, physical and social function, and mental health. Two placebo- and no herb-treated subjects had mild adverse events (AE). Subjects on both arms reported taking 94% of prescribed tablets. No differences between treatment groups reached the p < 0.05 level. Life satisfaction improved in herb-treated [+0.86, 95% confidence interval (CI): +0.29, +1.43] but not in placebo-treated subjects (+0.20, 95% CI -0.35, + 0.75). Number of symptoms was reduced in subjects receiving herbs (-2.2, 95% CI -4.1, -0.3) but not in those receiving placebo (-0.3, 95% CI -3.2, +2.7). There were trends toward greater improvements among herb-treated subjects on all symptom subscales except dermatologic. Believing that one was receiving herbs was strongly associated with reporting that the treatment had helped (p < 0.005), but not with changes in life satisfaction or symptoms. There were improvements in life satisfaction and symptoms among subjects receiving the herbal therapy. Whether Chinese herbs are effective in the management of symptomatic HIV infection can be adequately addressed only by larger trials of longer duration.
Efficacy and safety of Buxus sempervirens L. preparations (SPV(30)) in HIV-infected asymptomatic patients: a multicentre, randomized, double-blind, placebo-controlled trial.
The objective of the present study was to compare the efficacy and safety of two doses of SPV(30) in HIV asymptomatic patients. The study was designed as a randomized double-blind multicentre trial of two doses of SPV(30) (990 mg/d and 1980 mg/d) versus placebo. 145 previously untreated subjects with asymptomatic HIV infection (CDC group IV) and CD4 cell counts between 250 and 500 × 10(6)/1 were recruited. There was a statistically significant difference in therapeutic failures between groups in favor of SPV(30) 990 mg including decreases of CD4 cell count < 200 × 10(6)/1 and/or number of clinical aggravations (progression to AIDS or AIDS related complex). The treatment groups differed statistically in the rate of disease progression also in favor of SPV(30) 990 mg/d. Fewer patients receiving SPV(30) 990 mg/d had at the end an increase of viral load greater than 0.5 log (P = 0.029). No severe side-effects were reported in the 3 groups. From these results we conclude that SPV(30) 990 mg/d has beneficial effects in HIV asymptomatic patients and appears to delay the progression of HIV disease.
A double blind, randomized, placebo-controlled phase II study to assess the safety and efficacy of orally administered SP-303 for the symptomatic treatment of diarrhea in patients with AIDS.
OBJECTIVE: The aim of this study was to investigate the safety and effectiveness of orally administered SP-303 in patients with AIDS and diarrhea.
METHODS: This is a multicenter, phase II, randomized, double blind, placebo-controlled study. HIV-positive subjects with a history of a CD4 count <200 or an AIDS-defining illness were admitted to an inpatient study unit and screened for diarrhea defined as at least three abnormal (i.e., soft or watery) stools and >200 g of abnormal stool weight over a 24-h period. Subjects discontinued all antidiarrheal agents >24 h before enrollment. Stool samples were studied for routine pathogens. Subjects received 500 mg p.o. of SP-303 or placebo every 6 h for 96 h (4 days). Stool frequency and weights were recorded. Subjects were monitored for symptoms and side effects and were seen 1 wk later in follow-up.
RESULTS: A total of 26 subjects received SP-303, and 25 received placebo. There were no significant demographic differences between treatment arms. A total of 41 subjects (80%) were receiving antiretroviral therapy and 39 subjects (77%) were receiving at least one protease inhibitor. Stool studies revealed no pathogens in 48 of 51 patients (94%). There were no serious adverse events or laboratory abnormalities. The SP-303 treatment group demonstrated a mean reduction from baseline stool weight of 451 g/24 h versus 150 g/24 h with placebo on day 4 of treatment (p = 0.14), and a mean reduction in abnormal stool frequency of three abnormal stools in 24 h versus two in 24 h in the placebo group (p = 0.30). Daily measures analysis over 4 days of treatment demonstrated that SP-303 subjects had a significant reduction in stool weight (p = 0.008) and abnormal stool frequency (p = 0.04) when compared to placebo-treated subjects.
CONCLUSIONS: SP-303 is safe and well tolerated. These results suggest that SP-303 may be effective in reducing stool weight and frequency in patients with AIDS and diarrhea.
Topical capsaicin in the management of HIV-associated peripheral neuropathy.
Distal symmetrical peripheral neuropathy (DSPN) is a particularly distressing pain syndrome associated with human immunodeficiency virus (HIV) disease. Capsaicin has been found to be effective in relieving pain associated with other neuropathic pain syndromes, and is mentioned as a possible topical adjuvant analgesic for the relief of DSPN. This multicenter, controlled, randomized, double-masked clinical trial studied patients with HIV-associated DSPN and compared measures of pain intensity, pain relief, sensory perception, quality of life, mood, and function for patients who received topical capsaicin to the corresponding measures for patients who received the vehicle only. Twenty-six subjects were enrolled in the study. At the end of 1 week, subjects receiving capsaicin tended to report higher current pain scores than did subjects receiving the vehicle (Mann-Whitney test; P = 0.042). The dropout rate was higher for the capsaicin group (67%) than for the vehicle group (18%) (chi 2 test of association; P = 0.014). There were no other statistically significant differences between the capsaicin and vehicle groups with respect to current pain, worst pain, pain relief, sensory perception, quality of life, mood, or function at study entry or at any time during the 4-week trial. These results suggest capsaicin is ineffective in relieving pain associated with HIV-associated DSPN.
Randomized, placebo-controlled trial of Chinese herb therapy for HIV-1-infected individuals.
CONTEXT: Alternative medicine or complementary remedies that have not been scientifically tested are nonetheless widely used to treat chronic illnesses, particularly if curative options are limited.
OBJECTIVES: To assess the effectiveness of Chinese medicinal herbs in reducing symptoms and improving the quality of life of HIV-infected persons.
DESIGN: Prospective, placebo-controlled double-blind study.
SETTING: University-based HIV outpatient clinic.
PATIENTS: 68 HIV-infected adults with CD4 cell counts <0.5 x 10(9)/L.
INTERVENTION: Participants were randomized to receive four daily doses of seven pills containing a standardized preparation of 35 Chinese herbs or placebo for 6 months.
MAIN OUTCOME MEASURES: Symptoms, HIV disease progression, HIV-1 RNA plasma viral loads, CD4 and CD8 cell counts, and scores on standard questionnaires for quality of life, depression, anxiety, and coping.
RESULTS: Intervention and placebo groups were equivalent at baseline regarding, respectively, previous antiretroviral therapy (74% versus 79%), median CD4 cell counts (0.20 x 10(9)/L versus 0.25 x 10(9)/L), and median HIV-1 plasma viral loads (35,612 copies/ml versus 52,027 copies/ml). At enrollment, none of the study subjects was seriously ill or depressed, and average coping and quality of life scores were in the normal range. In all, 53 (78%) participants completed the study. Patients taking Chinese herbs reported significantly more gastrointestinal disturbances (79% versus 38%; p = .003) than those receiving placebo. No therapy-related toxicities were observed. At completion of the study, no significant differences between the intervention and placebo groups were found regarding plasma viral loads, CD4 cell counts, symptoms, and psychometric parameters. HIV-1 RNA level was unchanged at study end. Among participants who were not on concomitant antiretroviral therapy, median CD4 cell counts declined by 0.05 x 10(9)/L in both the intervention and placebo groups.
CONCLUSIONS: This standardized formulation of Chinese herbs for HIV-infected individuals did not improve quality of life, clinical manifestations, plasma virus loads, or CD4 cell counts. The data suggest that this formulation of Chinese herbs is not effective when administered in a Western medicine setting.
Options:
A: Herbal medicines showed significant improvement in CD4 cell counts and viral load in HIV-infected individuals.
B: Herbal medicines were found to be effective in reducing mortality and HIV disease progression.
C: There is insufficient evidence to support the use of herbal medicines in HIV-infected individuals and AIDS patients.
D: Herbal medicines were proven to be effective in improving psychological status and quality of life in AIDS patients. | C |
461 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What is the conclusion regarding the efficacy and safety of oral rutosides for the conservative management of symptomatic haemorrhoids during pregnancy and the puerperium? Please answer this question based on the information provided below:
A clinical trial of hydroxyethylrutosides in the treatment of haemorrhoids of pregnancy.
The safety and efficacy of 500 mg O-(beta-hydroxyethyl)rutosides given orally twice daily in the treatment of 97 patients with first-, second-, or third-degree haemorrhoids were investigated in a double-blind, randomized placebo-controlled trial. The rutosides produced a significant (P less than 0.001) improvement in patient-assessed subjective symptoms (pain, bleeding, exudation and pruritus) compared with placebo. There was also a significant (P less than 0.001) improvement in clinician-assessed subjective and objective signs (bleeding, inflammation and dilatation of the haemorrhoidal plexus) after 2 and 4 weeks' treatment compared with placebo. There were three mild, transient side-effects reported in the active treatment group and no drug-related problems in the pregnancy or delivery were observed. The results suggest that O-(beta-hydroxyethyl)rutosides provide a safe and effective treatment for women with haemorrhoids of pregnancy.
Trihydroxyethylrutosides in the treatment of hemorrhoids of pregnancy: a double-blind placebo-controlled trial.
The safety and efficacy of Trihydroxyethylrutosides (HR) in the treatment of 53 patients with 1st-2nd degree hemorrhoids of pregnancy (16th-34th week) was investigated in a double-blind randomised, placebo controlled trial. The dosage of Trihydroxyethylrutosides was 1 tablet of 300 milligrams twice daily for the first 2 weeks. If the treatment was successful, the treatment was stopped. If the clinical signs or symptoms still persisted, the treatment was continued for another two weeks using the same dosage and re-evaluated at the end of the fourth week after initial treatment. The parameters for efficacy were symptoms (pain, bleeding, exudation and pruritus) and the objective signs on proctoscopy (bleeding, inflammation and dilatation of the hemorrhoidal venous plexus). The study revealed improvement of symptoms in the study group which was better than in the control group after 2 weeks of treatment but the clinical signs were not different. After a further 2 weeks of treatment, the result showed improvement of both clinical signs and symptoms in this study. Only one mild transient side effect was reported in the HR group and there were no drug-related problems in the pregnancies, delivery or the babies.
Options:
A: Oral rutosides are effective and safe for symptom relief in haemorrhoids during pregnancy and the puerperium.
B: Oral rutosides are effective for symptom relief but their safety during pregnancy and the puerperium is not yet confirmed.
C: Oral rutosides are neither effective nor safe for symptom relief in haemorrhoids during pregnancy and the puerperium.
D: Oral rutosides are safe but not effective for symptom relief in haemorrhoids during pregnancy and the puerperium. | B |
462 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What are the comparative outcomes of using multiple lumen umbilical venous catheters (ML-UVCs) versus single lumen umbilical venous catheters (SL-UVCs) in newborn infants in terms of the need for additional peripheral intravenous lines and catheter-related complications? Please answer this question based on the information provided below:
Double lumen umbilical venous catheters in critically ill neonates: a randomized prospective study.
OBJECTIVES: To compare relative efficacies and complications associated with the use of double lumen vs. single lumen umbilical venous catheters in critically ill neonates.
DESIGN: Prospective randomized control trial.
SETTING: Neonatal ICU.
PATIENTS: Forty-three critically ill neonates.
INTERVENTIONS: Group 1 patients (n = 20) received single lumen umbilical venous catheters and group 2 patients (n = 23) received double lumen catheters. A record of the following information was kept: demographic data including diagnosis and indication for umbilical venous catheter insertion, catheter tip location, length of catheterization (days), number of additional iv catheters and complications (sepsis, hepatic necrosis, thrombosis, or mechanical complications).
MEASUREMENTS AND MAIN RESULTS: Double lumen umbilical venous catheters were well tolerated and were associated with no significant increased risk of mechanical complications when compared with single lumen umbilical venous catheters. The number of additional iv catheters required (0.8 +/- 0.1 [SD]) was significantly (p less than .05) less in the double lumen umbilical venous catheter group as compared with additional iv catheters required (2.3 +/- 0.8) in the single lumen umbilical venous catheter group.
CONCLUSION: Double lumen umbilical venous catheters are well tolerated for short-term use, decrease the need for additional venous catheters in critically ill neonates, and may not significantly increase the risk of mechanical complications when compared with single lumen umbilical venous catheters.
Intravenous access in newborn infants: impact of extended umbilical venous catheter use on requirement for peripheral venous lines.
Central venous lines are used to care for critically ill neonates in cases of limited peripheral venous access. This prospective, randomized study evaluated the risks and benefits of the use of single- and double-lumen umbilical venous catheters for up to 14 days. Patients were randomized to one of three treatment arms: (1) single-lumen umbilical catheter, (2) double-lumen umbilical catheter, or (3) no umbilical catheter; peripheral intravenous lines only. Infants in the groups treated with an umbilical venous catheter had significantly fewer venipunctures and peripheral intravenous lines placed during their first 2 weeks of life than those in the peripheral line only group. Less time and money were spent obtaining peripheral line placement in the umbilical venous catheter groups. The incidence rates of sepsis and complications were not higher in treated patients than in control patients. The double-lumen catheter further reduced peripheral venipunctures and lines. We conclude that an umbilical venous catheter used during the first 2 weeks of life is a relatively safe, less stressful, cost-effective means of providing intravenous therapy to neonates.
Options:
A: ML-UVCs reduce the need for additional peripheral intravenous lines in the first week of life but increase the risk of catheter malfunctions.
B: ML-UVCs increase the need for additional peripheral intravenous lines in the first week of life and have no effect on catheter malfunctions.
C: ML-UVCs have no effect on the need for additional peripheral intravenous lines in the first week of life and reduce the risk of catheter malfunctions.
D: ML-UVCs reduce the need for additional peripheral intravenous lines in the first four weeks of life and have no effect on catheter malfunctions. | A |
463 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What conclusion can be drawn about the effectiveness of different antibiotic regimens for the treatment of suspected late onset sepsis in newborn infants? Please answer this question based on the information provided below:
Ticarcillin plus clavulanic acid (Timentin) compared with standard antibiotic regimes in the treatment of early and late neonatal infections.
Options:
A: There is strong evidence favoring the use of beta-lactam therapy over a combination of beta-lactam plus aminoglycoside.
B: There is inadequate evidence from randomized trials to support any particular antibiotic regimen for the treatment of suspected late onset neonatal sepsis.
C: Beta-lactam therapy is significantly more effective than a combination of beta-lactam plus aminoglycoside in reducing mortality and treatment failure.
D: Antibiotic resistance is a significant issue in the treatment of late onset neonatal sepsis, with high rates observed in both beta-lactam and combination therapies. | B |
464 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What was the conclusion regarding the effectiveness of oral vitamin B12 compared to intramuscular vitamin B12 for treating vitamin B12 deficiency? Please answer this question based on the information provided below:
Oral versus intramuscular cobalamin treatment in megaloblastic anemia: a single-center, prospective, randomized, open-label study.
BACKGROUND: Cobalamin (vitamin B12) deficiency, the most common cause of megaloblastic anemia, is treated with intramuscular (IM) cobalamin. It has been suggested by some investigators that oral (p.o.) cobalamin treatment may be as effective in the treatment of this condition, with the advantages of ease of administration and lower cost.
OBJECTIVE: This study assessed the effects and cost of p.o. versus i.m. cobalamin treatment in patients with megaloblastic anemia due to cobalamin deficiency.
METHODS: This was a 90-day, prospective, randomized, open-label study conducted at the Division of Hematology, Department of Internal Medicine, Adnan Menderes University Research and Practice Hospital (Aydin, Turkey). Patients aged > or =16 years with megaloblastic anemia due to cobalamin deficiency were randomized to receive 1000-microg cobalamin p.o. once daily for 10 days (p.o. group) or 1000-microg cobalamin i.m. once daily for 10 days (i.m. group). After 10 days, both treatments were administered once a week for 4 weeks, and after that, once a month for life. Patients were assessed for the presence of reticulocytosis between treatment days 5 and 10 until it was detected. Therapeutic effectiveness was assessed by measuring hematologic parameters on days 0, 10, 30, and 90 and serum vitamin B12 concentration on days 0 and 90. The Mini-Mental State Examination was used before and after the B12 therapy for cognitive function assessment and 125-Hz diapozone was used for vibration threshold testing. Neurologic sensory assessment, including soft-touch and pinprick examinations, was used to identify neuropathy at baseline and study end. Tolerability was assessed using laboratory tests and patient interview. Cost was assessed using the cost of the study drug and of the injection.
RESULTS: Sixty patients completed the study 26 in the p.o. group (16 men, 10 women; mean [SD] age, 60 [15] years) and 34 in the i.m. group (17 men, 17 women; mean [SD] age, 64 [10] years). Reticulocytosis was observed in all patients. In the p.o. group, at days 30 and 90, all hematologic parameters changed significantly versus day 0 (mean hemoglobin levels increased [both P<0.001]; mean corpuscular volume decreased [both P<0.001]; mean white blood cell count increased [day 30, P<0.01; day 90, P<0.001]; and mean platelet count increased [both P<0.001]). The mean serum vitamin B12 concentration increased significantly from day 0 to 90 (P<0.001). These hematologic parameters and the recovery patterns were similar between the 2 groups. Neurologic findings included sensitive peripheral neuropathy in 9 patients (15.0%), alteration of cognitive function (loss of memory, impaired concentration) in 7 patients (11.7%), and loss of sense of vibration in 5 patients (8.3%). Neurologic improvement was detected in 7 of 9 patients (77.8%) in the p.o. group and 9 of 12 patients (75.0%) in the i.m. group at day 30.
CONCLUSIONS: In this study of patients with megaloblastic anemia due to cobalamin deficiency, p.o. cobalamin treatment was as effective as i.m. cobalamin treatment. P.o. treatment also was better tolerated and less expensive compared with IM treatment. However, because of the small sample size and the short term of this study, further long-term studies are needed to determine the efficacy of p.o. cobalamin treatment.
Effective treatment of cobalamin deficiency with oral cobalamin.
Because cobalamin deficiency is routinely treated with parenteral cobalamin, we investigated the efficacy of oral therapy. We randomly assigned 38 newly diagnosed cobalamin deficient patients to receive cyanocobalamin as either 1 mg intramuscularly on days 1, 3, 7, 10, 14, 21, 30, 60, and 90 or 2 mg orally on a daily basis for 120 days. Therapeutic effectiveness was evaluated by measuring hematologic and neurologic improvement and changes in serum levels of cobalamin (normal, 200 to 900 pg/mL) methylmalonic acid (normal, 73 to 271 nmol/L), and homocysteine (normal, 5.1 to 13.9 micromol/L). Five patients were subsequently found to have folate deficiency, which left 18 evaluable patients in the oral group and 15 in the parenteral group. Correction of hematologic and neurologic abnormalities was prompt and indistinguishable between the 2 groups. The mean pretreatment values for serum cobalamin, methylmalonic acid, and homocysteine were, respectively, 93 pg/mL, 3,850 nmol/L, and 37. 2 micromol/L in the oral group and 95 pg/mL, 3,630 nmol/L, and 40.0 micromol/L in the parenteral therapy group. After 4 months of therapy, the respective mean values were 1,005 pg/mL, 169 nmol/L, and 10.6 micromol/L in the oral group and 325 pg/mL, 265 nmol/L, and 12.2 micromol/L in the parenteral group. The higher serum cobalamin and lower serum methylmalonic acid levels at 4 months posttreatment in the oral group versus the parenteral group were significant, with P < .0005 and P < .05, respectively. In cobalamin deficiency, 2 mg of cyanocobalamin administered orally on a daily basis was as effective as 1 mg administered intramuscularly on a monthly basis and may be superior.
Options:
A: Oral vitamin B12 is less effective than intramuscular vitamin B12 in achieving haematological and neurological responses.
B: Oral vitamin B12 is more effective than intramuscular vitamin B12 in achieving haematological and neurological responses.
C: Oral vitamin B12 is as effective as intramuscular vitamin B12 in achieving haematological and neurological responses.
D: Oral vitamin B12 is only effective when combined with intramuscular vitamin B12. | C |
465 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What are the comparative outcomes of rubber band ligation (RBL) and excisional haemorrhoidectomy (EH) in the treatment of haemorrhoids, particularly in terms of symptom remission, re-treatment rates, postoperative pain, and complications? Please answer this question based on the information provided below:
The treatment of second degree haemorrhoids by injection, rubber band ligation, maximal anal dilatation, and haemorrhoidectomy: a prospective clinical trial.
One hundred and twenty patients with confirmed second degree haemorrhoids were randomly allocated to four treatment groups; injection, rubber band ligation, maximal anal dilatation, and haemorrhoidectomy. Each groups consisted of 30 patients. All patients were regularly followed up for at least one year. Assessment at one year showed that haemorrhoidectomy "cured" the haemorrhoids in 29 out of 30 patients. Rubber band ligation relieved 25 out of 30 and maximal anal dilatation 24 out of 30. Injection was the least effective treatment, and relieved 18 of the 30 patients, with a cure rate of 60% only. Haemorrhoidectomy caused pain in all cases, anal stenosis in two, postoperative haemorrhage in two, and the patients required an average hospital stay of 11.5 days and an average of a further 15.5 days off work. Rubber band ligation was painless in 26 patients out of 30, and maximal anal dilatation was painless in 25 our of 30. There were no postoperative complications in the latter two treatment groups. Haemorrhoidectomy is good in "curing" the disease, but the higher possibility of postoperative pain and complications and longer hospital stay would not justify its use in the treatment of second degree haemorrhoids. Both rubber band ligation and maximal anal dilatation are effective and relatively free from complications. Rubber band ligation has the additional advantage of not requiring hospital stay or anaesthesia and is therefore considered to be the most appropriate method of treatment for second degree haemorrhoids.
Trial of maximal anal dilatation, cryotherapy and elastic band ligation as alternatives to haemorrhoidectomy in the treatment of large prolapsing haemorroids.
A selected group of 112 patients with prolapsing haemorrhoids which had failed to respond to injections of phenol in oil or which required manual replacement after defecation, were randomly allocated treatment by haemorrhoidectomy, maximal anal dilation, elastic band ligation or cryotherapy. When results were assessed 5 weeks after treatment, haemorrhoidectomy and maximal anal dilatation were equally effective in reducing symptoms, although more physical signs remained after maximal anal dilatation; cryotherapy and elastic band ligation were less effective in both respects. When patients were followed up between 6 months and 5 years haemorrhoidectomy was found to be the most effective method. Patients in the other three groups developed recurrent symptoms requiring haemorrhoidectomy.
Comparison of rubber band ligation and haemorrhoidectomy for second- and third-degree haemorrhoids: a prospective clinical trial.
One hundred patients with second- or third-degree haemorrhoids were randomly allocated to haemorrhoidectomy (50) or rubber band ligation (50). Forty-two in each group presented with rectal bleeding; haemorrhoidectomy relieved 36 and rubber band ligation relieved 31 of this symptom. All patients had prolapsing haemorrhoids at presentation. One year after treatment 45 haemorrhoidectomy and 43 rubber band ligation patients were assessed. Haemorrhoidectomy relieved 44 of 45 patients and rubber band ligation relieved 34 of 43 (P < 0.05). Haemorrhoidectomy caused pain in all cases, lasting for more than 48 h in 35. Rubber band ligation was painless in 5 and produced pain for more than 48 h in 15. Mean time off work was 32 days for haemorrhoidectomy and 3 days for rubber band ligation (P < 0.001). Rubber band ligation as an outpatient procedure is an effective treatment for second- and third-degree haemorrhoids and should be considered before recourse to surgery.
Options:
A: RBL is more effective than EH in achieving complete remission of haemorrhoidal symptoms and has fewer complications.
B: EH is more effective than RBL in achieving complete remission of haemorrhoidal symptoms, especially for grade III haemorrhoids, but is associated with higher postoperative pain and complications.
C: RBL and EH have similar effectiveness in achieving complete remission of haemorrhoidal symptoms, with no significant differences in postoperative pain and complications.
D: EH is less effective than RBL in achieving complete remission of haemorrhoidal symptoms and has higher re-treatment rates. | B |
466 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What was the conclusion regarding the effectiveness of inhaled beta2-agonists, specifically salbutamol, in treating non-specific chronic cough in children over the age of 2 years? Please answer this question based on the information provided below:
A randomised, placebo controlled trial of inhaled salbutamol and beclomethasone for recurrent cough.
AIMS: To test the hypothesis that inhaled salbutamol or beclomethasone will reduce the frequency of cough in children with recurrent cough. A secondary aim was to determine if the presence of airway hyperresponsiveness (AHR) can predict the response.
DESIGN: Randomised, double blind, placebo controlled trial.
METHODS: During a coughing phase, 43 children (age 6-17 years) with recurrent cough were randomised to receive inhaled salbutamol or placebo (phase I) for 5-7 days and then beclomethasone or placebo (phase II) for 4-5 weeks, and in a subgroup of children for 8-9 weeks. The children used an ambulatory cough meter, kept cough diaries, and performed the capsaicin cough sensitivity, hypertonic saline bronchoprovocation, and skin prick tests.
RESULTS: Salbutamol or beclomethasone had no effect on cough frequency or score, irrespective of the presence of AHR.
CONCLUSIONS: Most children with recurrent cough without other evidence of airway obstruction, do not have asthma and neither inhaled salbutamol nor beclomethasone is beneficial.
Options:
A: Salbutamol significantly reduced the frequency of cough compared to placebo.
B: Salbutamol was no different from placebo in reducing the frequency of cough.
C: Salbutamol increased the frequency of cough compared to placebo.
D: Salbutamol was effective only in children under the age of 2 years. | B |
467 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What was the conclusion regarding the effectiveness of combining amodiaquine (AQ) or chloroquine (CQ) with sulfadoxine-pyrimethamine (SP) for treating uncomplicated falciparum malaria compared to using SP alone? Please answer this question based on the information provided below:
Therapeutic efficacy of sulfadoxine-pyrimethamine, amodiaquine and the sulfadoxine-pyrimethamine-amodiaquine combination against uncomplicated Plasmodium falciparum malaria in young children in Cameroon.
OBJECTIVE: To evaluate the therapeutic efficacy of sulfadoxine-pyrimethamine, amodiaquine, and the sulfadoxine-pyrimethamine-amodiaquine combination for the treatment of uncomplicated Plasmodium falciparum malaria in young children in Cameroon.
METHODS: In a randomized study we evaluated the effectiveness and tolerance of (i) sulfadoxine-pyrimethamine (SP) (25 mg/kg body weight of sulfadoxine and 1.25 mg/kg of pyrimethamine in a single oral dose), (ii) amodiaquine (AQ) (30 mg/kg body weight in three divided daily doses), and (iii) the sulfadoxine-pyrimethamine-amodiaquine combination (SP+AQ) (same doses as in the other two treatment groups, given simultaneously on day 0) in young children in southern Cameroon. The parasitological and clinical responses were studied until day 28 in accordance with the modified 1996 WHO protocol for the evaluation of the therapeutic efficacy of antimalarial drugs.
FINDINGS: Of 191 enrolled patients, 6 and 8 were excluded or lost to follow-up before day 14 and between day 14 and day 28, respectively. For the AQ-treated patients, parasitological and clinical evaluation on day 14 showed late treatment failure in 2 of 61 (3.3%) and adequate clinical response with parasitological failure in one (1.6%). There was an adequate clinical response in all patients treated with SP or SP+AQ. Therapeutic failure rates on day 28 were 13.6%, 10.2% and 0% in the SP, AQ, and SP+AQ groups, respectively. Anaemia improved in all three regimens. AQ produced faster fever clearance but was associated with more transient minor side-effects than SP. SP+AQ reduced the risk of recrudescence between day 14 and day 28 but increased the incidence of minor side-effects.
CONCLUSION: SP+AQ can be recommended as a temporary means of slowing the spread of multidrug resistance in Plasmodium falciparum in Africa while the introduction of other combinations, including artemisinin derivatives, is awaited.
A trial of Fansidar plus chloroquine or Fansidar alone for the treatment of uncomplicated malaria in Gambian children.
Chloroquine can no longer be recommended as the first-line treatment for uncomplicated malaria in several parts of Africa because of the increasing prevalence of chloroquine resistance. However, chloroquine was a highly effective treatment for malaria not only because of its ability to kill parasites quickly but also because it is an anti-inflammatory drug. Therefore, we have investigated whether Fansidar (pyrimethamine/sulfadoxine) plus chloroquine is a more effective treatment for uncomplicated malaria than Fansidar alone. Four hundred and five Gambian children with uncomplicated Plasmodium falciparum malaria were studied in a randomized controlled trial. Significantly more children treated with Fansidar alone, compared to those treated with Fansidar plus chloroquine (19/203 vs. 2/202; P < 0.001), returned to the clinic with persistent symptoms during the first 3 d after treatment. Three children who had received Fansidar alone had fits, but none of the children treated with Fansidar plus chloroquine did so. At the day 7 follow-up, the parasite failure rate in the Fansidar alone group was 3/198 (1.5%), whilst in the Fansidar plus chloroquine group it was 3/201 (1.5%). At the day 28 follow-up, there was still no significant difference between the parasite failure rate in the Fansidar alone group (15/150; 10.0%) and the Fansidar plus chloroquine group (7/141; 5.0%) and the mean packed cell volume (PCV) in the 2 groups was similar. Thus, a combination of Fansidar plus chloroquine was a more effective symptomatic treatment than Fansidar given alone, but neither the parasite cure rate nor the PCV was enhanced by use of the combination.
Sulfadoxine-pyrimethamine for the treatment of acute malaria in children in Papua New Guinea. I. Plasmodium falciparum.
Chloroquine-resistant Plasmodium falciparum malaria is increasing in prevelance in Papua New Guinea and alternative therapies for acute malaria are being sought. A trial of sulfadoxine-pyrimethamine for the treatment of acute falciparum malaria in children has been carried out in Madang, Papau New Guinea. Eighty-five children were treated with sulfadoxine-pyrimethamine, either alone or in combination with a single 10 mg/kg dose of chloroquine. Of 78 children completing 28-days follow-up, treatment failures occurred in 15 (19.2%) and of these, 8 (10.3%), are believed to be sulfadoxine-pyrimethamine resistant; the others remain equivocal. There was no advantage in this study in combining a single dose of chloroquine with sulfadoxine-pyrimethamine; indeed, this combination was associated with an increased incidence of vomiting. It is argued that sulfadoxine-pyrimethamine should not become the standard presumptive treatment for acute malaria in Papua New Guinea.
[Comparative study of sulfadoxine-pyrimethamine and amodiaquine + sulfadoxine-pyrimethamine for the treatment of malaria caused by chloroquine-resistant Plasmodium falciparum in Maputo, Mozambique].
To compare the efficacy and side-effects of two therapeutic regimens for chloroquine-resistant falciparum malaria, a randomized study was carried out in 69 patients in Maputo Central Hospital in 1986-1987. The two treatments were sulfadoxine 25 mg/kg + pyrimethamine 1.25 mg/kg as a single dose (S + P) and amodiaquine 10 + 10 + 5 mg/kg over three days with sulfadoxine + pyrimethamine on the third day (A + S + P). The cure rate was 25/29 (86%) with S + P and 27/30 (90%) with A + S + P. No serious side-effects were observed. The probably slightly higher cure rate with the triple combination is hardly of clinical importance in semi-immune patients, but may theoretically help retard the development of resistance to sulfadoxine-pyrimethamine. This point and the question of the incidence of side-effects with the two regimens should be made the object of an epidemiological study.
Sulfadoxine/pyrimethamine alone or with amodiaquine or artesunate for treatment of uncomplicated malaria: a longitudinal randomised trial.
BACKGROUND: New antimalarial treatments are urgently needed in sub-Saharan Africa. Improved therapies should decrease failure rates in the short term, but their effect on incidence of subsequent episodes of malaria is little studied. We aimed to compare the short-term and long-term effectiveness of three antimalarial regimens in children from Kampala, Uganda.
METHODS: We randomly allocated healthy children aged 6 months to 5 years to receive 25 mg/kg sulfadoxine and 1.25 mg/kg pyrimethamine plus either placebo, 25 mg/kg amodiaquine, or 12 mg/kg artesunate. Participants were followed up for 1 year and received the same preassigned treatment for every new episode of uncomplicated malaria diagnosed during follow-up. Recrudescent and new infections were distinguished by comparison of polymorphisms in merozoite surface protein 2 (MSP2). Our primary endpoint was the total number of treatments for malaria per time at risk. Analyses were done per protocol.
FINDINGS: 183 (61%) of 316 participants were diagnosed with at least one episode of uncomplicated malaria. A total of 577 episodes of uncomplicated Plasmodium falciparum malaria were treated with study drugs; all regimens were safe and well tolerated. Clinical treatment failure after 14 days was significantly more frequent in the sulfadoxine/pyrimethamine group (38 of 215, 18%) compared with either the sulfadoxine/pyrimethamine plus amodiaquine group (two of 164, 1%; p<0.0001) or sulfadoxine/pyrimethamine plus artesunate group (one of 198, 1%; p<0.0001). After 28 and 42 days, patients in the sulfadoxine/pyrimethamine plus amodiaquine group were significantly less likely to develop malaria than were those in the other groups. Overall, sulfadoxine/pyrimethamine plus amodiaquine reduced the rate of subsequent treatments for malaria by 54% (95% CI 36-66, p<0.0001) compared with sulfadoxine/ pyrimethamine alone and by 37% (12-54, p=0.007) compared with sulfadoxine/pyrimethamine plus artesunate.
INTERPRETATION: Sulfadoxine/pyrimethamine plus amodiaquine could be used as an inexpensive regimen to decrease the rate of subsequent episodes of malaria.
Prevention of increasing rates of treatment failure by combining sulfadoxine-pyrimethamine with artesunate or amodiaquine for the sequential treatment of malaria.
Combination antimalarial therapy may delay the spread of drug resistance, but clinical data supporting this notion are limited. For 1 year, we studied Ugandan children who were treated for uncomplicated malaria with sulfadoxine-pyrimethamine (SP), SP + amodiaquine (AQ), or SP + artesunate (AS). We compared treatment responses and the prevalence of resistance-conferring mutations of new infections with those of recrudescent infections due to parasites that survived prior treatment. Recrudescent infections were associated with the selection of SP resistance-conferring mutations in all treatment groups, but responses to repeat therapy differed. Compared with initial treatments, treatment of recrudescent infections was associated with a higher rate of treatment failure (hazard ratio [HR], 2.44; P=.01), for the SP group, but with a lower rate of treatment failure (HR, 0.40; P=.08), for the SP + AS group. Treatment failure in the SP + AQ group was uncommon, limiting the analysis of recrudescent parasites. Our results suggest that the use of combination antimalarial therapy in Africa may slow the spread of drug-resistant malaria and prolong the therapeutic life span of available treatment regimens.
Comparative efficacy of aminoquinoline-antifolate combinations for the treatment of uncomplicated falciparum malaria in Kampala, Uganda.
Resistance to chloroquine (CQ) requires its replacement as first-line therapy for uncomplicated malaria in much of Africa. Combination therapy may improve efficacy and delay the selection of resistant malaria parasites. Combinations of sulfadoxine-pyrimethamine (SP) with 4-aminoquinolines offer affordable and available alternatives to CQ. We conducted a randomized, single-blinded trial to compare the efficacy of SP monotherapy with combinations of SP and either CQ or amodiaquine (AQ) for the treatment of uncomplicated falciparum malaria in patients over 6 months of age in Kampala, Uganda. Of the 448 patients enrolled, 428 (95%) completed follow-up. Clinical treatment failure after 14 days occurred in 21/140 (15.0%, 95% CI 9.5-22.0%) SP-treated, 11/152 (7.2%, 95% CI 3.7-12.6%) SP/CQ-treated, and 0/136 (0%, 95% CI 0-2.7%) SP/AQ-treated patients. Combination therapies were safe and offered superior efficacy to SP monotherapy. SP/AQ was the most efficacious. This low-cost combination regimen may provide an optimal alternative to CQ for the treatment of uncomplicated malaria in Uganda.
Effectiveness of amodiaquine, sulfadoxine-pyrimethamine, and combinations of these drugs for treating chloroquine-resistant falciparum malaria in Hainan Island, China.
The study was carried out in 1985-86 in Hainan Island where Plasmodium falciparum is resistant to chloroquine. Fifty cases of falciparum malaria were treated with 1800 mg amodiaquine for 3 days: the cure rate was 65.3%, and the mean time to clear fever and asexual parasitaemia was 30.7 and 60.3 hours, respectively; 34.7% of cases showed RI or RII recrudescence, and one patient's temperature did not come down to normal within 7 days.Twenty-one cases were treated with sulfadoxine-pyrimethamine (1500 mg and 75 mg, respectively): 19 were cured, I showed RI and another had an S or RI response; the mean time for fever control was 56.1 hours.Fifty cases were treated with amodiaquine plus sulfadoxine and 49 received amodiaquine plus sulfadoxine-pyrimethamine: the cure rate was 97.9% and 100%, respectively; the mean time for fever clearance was 25.0 and 25.7 hours and for parasite clearance 57.1 and 52.8 hours, respectively. These drug combinations gave much better results for cure and for symptom control than amodiaquine or sulfadoxine-pyrimethamine alone, and may be considered for treatment of chloroquine-resistant falciparum malaria.
[Efficacy of amodiaquine, Fansidar and their combination in the treatment of chloroquine-resistant falciparum malaria].
The efficacy of chloroquine, sulfadoxine-pyrimethamine and a combination of both for the treatment of uncomplicated Plasmodium falciparum malaria in an area of low transmission in western Uganda.
We conducted an efficacy study of chloroquine (CQ), sulfadoxine-pyrimethamine (SP) and a combination of both (SP+CQ) for the treatment of uncomplicated malaria in an area of low transmission with low drug pressure. On day 3, fever clearance was 97.4% (95% CI, 86.8-99.9), 100% (95% CI, 87.2-100) and 96.6% (95% CI, 82.2-99.9) in the CQ, SP and SP+CQ groups, respectively, (P=0.65). On day 14, clinical success was 92.5% (95% CI, 79.6-98.4), 100% (95% CI, 87.2-100) and 100% (95% CI, 88.1-100) in the CQ, SP and CQ+SP groups, respectively. Clinical failure was seen in 7.5% with 5% (95% CI, 0.61-16.9) early treatment failure and 2.5% (95% CI, 0.06-13.2) late treatment failure of cases in the CQ group and 0% in the SP and SP+CQ groups. Parasitological resistance was observed at RI level in 10% (95% CI, 2.8-23.7), 18.5% (95% CI, 6.3-38.1) and 6.9% (95% CI, 0.85-22.8) for the CQ, SP and SP+CQ, respectively (P=0.37). There was no age-dependent difference in clinical failure or parasitological resistance in any of the treatment groups and prior CQ use within the last 2 weeks did not affect CQ treatment outcome. The findings of this study suggest that CQ is still effective for the treatment of uncomplicated malaria in this area of low transmission and SP. However, combination therapy of SP+CQ is recommended to delay the development SP resistance, and regular surveillance for emerging CQ and SP resistance is needed to plan for alternative antimalarial drug regimens.
Evaluation of four therapeutic regimens for falciparum malaria in Mozambique, 1986.
A randomized study on the effect of the following four treatment regimens on Plasmodium falciparum parasitaemia was carried out on 200 asymptomatic schoolchildren in Maputo, Mozambique: chloroquine (25 mg/kg body weight), amodiaquine (25 mg/kg), sulfadoxine-pyrimethamine (25 mg/kg and 1.25 mg/kg), or amodiaquine (25 mg/kg) + sulfadoxine-pyrimethamine (25 mg/kg and 1.25 mg/kg) administered on the third day of the study. The results of in vivo tests indicated that 94% of the infections were resistant to chloroquine, 76% to amodiaquine, and 16% to sulfadoxine-pyrimethamine. The cure rate with amodiaquine + sulfadoxine-pyrimethamine was 100%, which was not significantly different from that with sulfadoxine-pyrimethamine alone; the latter regimen was the most rapidly acting of the treatments studied. It is concluded that amodiaquine is not an appropriate substitute for chloroquine, but that the effect of the combination amodiaquine + sulfadoxine-pyrimethamine may be superior to that of sulfadoxine-pyrimethamine alone, although this requires further study.
The safety and efficacy of sulfadoxine-pyrimethamine, amodiaquine, and their combination in the treatment of uncomplicated Plasmodium falciparum malaria.
The safety and efficacy of amodiaquine (AQ), sulfadoxine-pyrimethamine (SP), and coadministered AQ+SP was assessed in 351 Tanzanian children (age range, 6-59 months) with uncomplicated Plasmodium falciparum malaria. This open, randomized study followed the 28-day World Health Organization (WHO) protocol and evaluated safety using clinical and laboratory parameters. Children receiving SP were more likely to vomit during follow-up (32% vs. 17%: P = 0.03), and SP alone resulted in prolonged fever clearance times. Although Day 7 and Day 14 clinical and parasitological cure rates were similar, by Day 28 45% of children treated with AQ demonstrated R1 resistance and 27.5% were clinical failures compared with 25% and 6.3%, respectively, for SP alone. Coadministered AQ+SP was safe, combined the greater clinical (96.2%) and parasitological (64.2%) efficacy of SP with the more rapid symptom resolution of AQ, and reduced the incidence of gametocytemia during follow-up (AQ+SP 12.6% vs. SP 29.9%; P = 0.001). The level of R1 resistance to SP may herald a rapid decline in its efficacy as SP drug pressure increases. Coadministration of AQ+SP may delay this.
Therapeutic efficacy of chloroquine plus sulphadoxine/ pyrimethamine compared with monotherapy with either chloroquine or sulphadoxine/pyrimethamine in uncomplicated Plasmodium falciparum malaria in Laos.
In a southern border province of Lao PDR, we compared the efficacy of antimalarial drug combinations in patients aged >or=1 year with uncomplicated Plasmodium falciparum malaria: monotherapy with either mefloquine (MQ), chloroquine (CQ), or sulphadoxine/pyrimethamine (SP) vs. the combination of both CQ and SP. Follow-up time was 14 days. Of 265 P. falciparum positive patients, 119 were enrolled in the drug trial. Significantly more patients treated with CQ than with SP developed early or late treatment failure [44.8%vs. 17.9%, relative risk (RR) = 2.51, 95% CI 1.03-6.12]. In the SP group, 82.1% were sensitive and 17.9% were treatment failures. The combination treatment CQ plus SP resulted in 83.3% sensitivity and 16.7% treatment failures. Combination treatment has no advantage over monotherapy with SP (RR = 1.01, 95% CI 0.8-1.3). All patients who received MQ for treatment (total dose 25 mg/kg) were cured within the 14 days of follow-up. The findings of this study suggest that use of CQ as first-line treatment of uncomplicated malaria in the Lao PDR has to be reconsidered. The combination of both CQ and SP has been discussed as a cost-effective alternative treatment, but in our patient population achieved no better results than single therapy with SP.
Amodiaquine, sulfadoxine/pyrimethamine, and combination therapy for treatment of uncomplicated falciparum malaria in Kampala, Uganda: a randomised trial.
BACKGROUND: Increasing Plasmodium falciparum resistance to chloroquine in sub-Saharan Africa necessitates use of alternative antimalarial agents. Affordable alternative treatments include sulfadoxine/pyrimethamine and amodiaquine. Combination of antimalarial agents can increase therapeutic efficacy and delay emergence of drug resistance. We compared the efficacy of sulfadoxine/pyrimethamine, amodiaquine, and an amodiaquine/sulfadoxine/pyrimethamine combination for treatment of uncomplicated malaria in a region of high chloroquine resistance.
METHODS: Patients with symptoms of uncomplicated falciparum malaria and confirmed disease in Kampala, Uganda, were randomly assigned to receive sulfadoxine/pyrimethamine (25 mg/kg sulfadoxine, and 1.25 mg/kg pyrimethamine) plus placebo; amodiaquine (25 mg/kg) plus placebo; or amodiaquine plus sulfadoxine/pyrimethamine. Patients were followed up for 14 days, and clinical and parasitological outcomes were assessed.
FINDINGS: 90% (400/445) of patients enrolled in the study successfully completed 14 days of follow-up. Treatment failure based on clinical criteria occurred in 13 of 131 (10%) patients on sulfadoxine/ pyrimethamine, nine of 131 (7%) on amodiaquine, and four of 138 (3%) on amodiaquine/sulfadoxine/pyrimethamine. Based on parasitological criteria, treatment failed in 26%, 16%, and 10% of these patients, respectively. Amodiaquine/sulfadoxine/pyrimethamine was significantly more effective than sulfadoxine/pyrimethamine alone in children aged younger than 5 years (clinical failure in 3.5% vs 13.9%, respectively, risk difference 10.4% [95% CI, 1.6-19.3] p=0.021; parasitological failure in 12.8% vs 26.4%, risk difference 13.6% [1.2-26.0] p=0.041).
INTERPRETATION: Sulfadoxine/pyrimethamine, amodiaquine, and amodiaquine/sulfadoxine/pyrimethamine were all effective for treatment of uncomplicated falciparum malaria in Uganda. The amodiaquine/sulfadoxine/pyrimethamine combination was the most effective, and could be the optimum low-cost alternative to chloroquine in Africa.
Options:
A: The combination of AQ plus SP significantly reduces both total and clinical failure at day 28 compared to SP alone, while CQ plus SP shows no advantage.
B: The combination of CQ plus SP significantly reduces both total and clinical failure at day 28 compared to SP alone, while AQ plus SP shows no advantage.
C: Both AQ plus SP and CQ plus SP significantly reduce total and clinical failure at day 28 compared to SP alone.
D: Neither AQ plus SP nor CQ plus SP show any significant reduction in total and clinical failure at day 28 compared to SP alone. | A |
468 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What were the findings regarding the effectiveness of vitamin A therapy in reducing mortality and secondary complications in children diagnosed with measles? Please answer this question based on the information provided below:
Vitamin A supplements and mortality related to measles: a randomised clinical trial.
One hundred and eighty children admitted with measles were randomly allocated to receive routine treatment alone or with additional large doses of vitamin A (200,000 IU orally immediately and again the next day). Baseline characteristics of the two groups were virtually identical for age, severity of measles, and vitamin A and general nutritional states. In 91% of the children serum vitamin A concentrations were less than 0.56 mumol/l. Of the 88 subjects given vitamin A supplements, six (7%) died; of the 92 controls, 12 (13%) died (p = 0.13). This difference in mortality was most obvious for children aged under 2 years (one death out of 46 children receiving supplements versus seven deaths out of 42 controls; p less than 0.05) and for cases complicated by croup or laryngotracheobronchitis. Mortality was several times higher in marasmic than in better nourished children, regardless of study allocation (p less than 0.01).
Vitamin A supplementation reduces measles morbidity in young African children: a randomized, placebo-controlled, double-blind trial.
The effects of vitamin A supplementation on measles morbidity are unclear. Sixty hospitalized children aged 4-24 mo with complicated measles received a World Health Organization--(WHO) recommended dose of vitamin A or placebo. The two groups were comparable in known covariants of measles severity: weight-for-age percentiles, overcrowding, rash, total lymphocytes, and serum concentrations of zinc, albumin, prealbumin, retinol-binding protein, and vitamins A and E. Ninety percent of the patients had hyporetinemia. Integrated morbidity scores, determined by severity of condition (eg, diarrhoea, herpes, and respiratory-tract infection) were assigned on day 8 and 6 wk and 6 mo; these were reduced by 82%, 61%, and 85%, respectively, in the supplemented group, which was mainly due to reduced respiratory-tract infection. There was one death in the placebo group. At 6 wk weight gain was significant in the supplemented group. Despite the selected sample, attention to multiple covariates enhances the validity of the data obtained and supports the current WHO recommendations for vitamin A supplementation during measles.
Micronutrient utilisation during measles treated with vitamin A or placebo.
Micronutrients (zinc, vitamins A and E) and related proteins (retinol binding protein (RBP), prealbumin, albumin) were measured in the serum of African children with measles, and the changes induced in these by vitamin A supplementation (offered in a randomised, double blind, placebo controlled trial) were studied. All these substances were significantly reduced early in the exanthem in measles patients as compared to controls; they attained control values by day 8 after the rash, except for serum albumin which became normal by day 42. Vitamin A and prealbumin levels on day 8 were significantly increased in the supplemented over the placebo group. Vitamin A levels in serum correlated with those of RBP, prealbumin and zinc. These findings strengthen the hypothesis that hyporetinemia during measles is the consequence of impaired mobilisation. Our results indicate that our patients did not have pre-existing low liver stores. Accordingly, the results obtained here provide rational support for the recommendation that vitamin A should be given to all children with severe measles, even in communities where vitamin A deficiency is not a recognised public health problem.
Vitamin A supplementation enhances specific IgG antibody levels and total lymphocyte numbers while improving morbidity in measles.
The effect of vitamin A supplementation on selected factors of immunity was tested in African children (ages 4 to 24 months with complicated measles) during a randomized double-blind intervention trial. Placebo (n = 31) and treated groups (n = 29) had similar baseline characteristics. The supplemented group had significant reductions in morbidity (expressed as integrated morbidity scores) during the acute (Day 8, P = 0.006) and chronic (Day 42, P = 0.02; 6 months; P = 0.002) phases. In the treated group there was an increase in total number of lymphocytes (Day 42, P = 0.05) and measles IgG antibody concentrations (Day 8, P = 0.02), both of which have consistently been previously shown to correlate more closely with outcome in measles than other immunologic, clinical and radiologic factors. Interleukin 2 and plasma complement values were unaffected by vitamin A supplementation. These findings reinforce results from animal studies that show that the pathways of vitamin A activity in decreasing morbidity and mortality are partly founded on selective immunopotentiation.
Measles incidence, case fatality, and delayed mortality in children with or without vitamin A supplementation in rural Ghana.
Data on measles incidence, acute case fatality, and delayed mortality were collected on 25,443 children aged 0-95 months during the course of a community-based, double-blind, placebo-controlled, randomized trial of vitamin A supplementation in rural, northern Ghana between 1989 and 1991. Measles vaccine coverage in these children was 48%. The overall estimated measles incidence rate was 24.3 per 1,000 child-years, and acute case fatality was 15.7%. There was not significantly increased mortality in survivors of the acute phase of measles compared with controls (rate ratio = 1.22, 95% confidence interval (CI) 0.65-2.30). Reported incidence rates and case fatality were higher in families with low paternal education, in the dry season, and in unvaccinated children, and case fatality was higher in malnourished children. There was no sex difference in incidence, but acute case fatality was somewhat higher in girls than boys (adjusted odds ratio = 1.3, 95% CI 0.9-2.1). Measles incidence was lower in vitamin A-supplemented groups (23.6 per 1,000 child-years) than in placebo groups (28.9 per 1,000 child-years), but this difference was not statistically significant (p = 0.33). Among 946 measles cases in clusters randomized to receive vitamin A or placebo, there was no marked difference in acute measles case fatality between vitamin A-supplemented and placebo groups (15.4% vs. 14.5%, respectively). The biologic effects of vitamin A supplemented on the subsequent clinical manifestations and severity of measles need further elucidation.
INTENSIVE VITAMIN THERAPY IN MEASLES.
A randomized, controlled trial of vitamin A in children with severe measles.
BACKGROUND: Measles kills about 2 million children annually, and there is no specific therapy for the disease. It has been suggested that vitamin A may be of benefit in the treatment of measles.
METHODS: We conducted a randomized, double-blind trial involving 189 children who were hospitalized at a regional center in South Africa because of measles complicated by pneumonia, diarrhea, or croup. The children (median age, 10 months) were assigned to receive either vitamin A (total dose, 400,000 IU of retinyl palmitate, given orally; n = 92) or placebo (n = 97), beginning within five days of the onset of the rash. At base line, the characteristics of the two groups were similar.
RESULTS: Although clinically apparent vitamin A deficiency is rare in this population, the children's serum retinol levels were markedly depressed (mean [+/- SEM], 0.405 +/- 0.021 mumols per liter [11.6 +/- 0.6 micrograms per deciliter]), and 92 percent of them had hyporetinemia (serum retinol level less than 0.7 mumols per liter [20 micrograms per deciliter]). Serum concentrations of retinol-binding protein (mean, 30.1 +/- 2.0 mg per liter) and albumin (mean, 33.4 +/- 0.5 g per liter) were also low. As compared with the placebo group, the children who received vitamin A recovered more rapidly from pneumonia (mean, 6.3 vs. 12.4 days, respectively; P less than 0.001) and diarrhea (mean, 5.6 vs. 8.5 days; P less than 0.001), had less croup (13 vs. 27 cases; P = 0.03), and spent fewer days in the hospital (mean, 10.6 vs. 14.8 days; P = 0.01). Of the 12 children who died, 10 were among those given placebo (P = 0.05). For the group treated with vitamin A, the risk of death or a major complication during the hospital stay was half that of the control group (relative risk, 0.51; 95 percent confidence interval, 0.35 to 0.74).
CONCLUSIONS: Treatment with vitamin A reduces morbidity and mortality in measles, and all children with severe measles should be given vitamin A supplements, whether or not they are thought to have a nutritional deficiency.
Routine high-dose vitamin A therapy for children hospitalized with measles.
Measles is without specific therapy and remains important globally as a cause of childhood death. In controlled studies, high-dose vitamin A therapy (Hi-VAT)--with 400,000 IU vitamin A--has been demonstrated to markedly reduce measles-associated morbidity and mortality. We performed a retrospective study of the hospital records of 1720 children < 15 years of age who were hospitalized for measles, to determine the extent to which these findings, in research settings, are applicable to the case management of measles under conditions of routine hospital practice. The outcomes were studied of children hospitalized during two non-consecutive 2 year periods (1985-6 and 1989-90). A policy of Hi-VAT for all children hospitalized with measles was started during the intervening period. As compared with the group of children on standard therapy (n = 1061), children receiving Hi-VAT (n = 651) had a shorter hospital stay (mean 10 versus 13 days; P < 0.001), a lower requirement for intensive care (4.3 versus 10.5 per cent; P < 0.001), and a lower death rate (1.6 versus 5 per cent; P < 0.001). No adverse effects of Hi-VAT therapy were observed. We conclude that a policy of high dose oral vitamin A (400,000 IU) supplementation in measles provides benefits which are equivalent to those previously observed only in controlled research trials, that it is highly cost effective, and that it should form part of the routine case management of all children hospitalized with measles.
[The efficacy of oral vitamin A supplementation for measles and respiratory syncytial virus (RSV) infection].
Recently, the efficacy of oral vitamin A supplementation for measles and respiratory syncytial (RSV) infection has been evaluated in developing countries. However, in developed countries where vitamin A deficiency is little worth consideration, few studies have been conducted on the effect of vitamin A supplementation. The effect of oral vitamin A (100,000 IU) supplementation was evaluated in 105 children with measles (age 5 months to 4 years) and in 96 children with RSV infection (ages a month to 2.5 years) in Fukushima, Japan. Comparisons were made of clinical signs, duration of hospitalization and complications between treated groups and non-treated groups. Treated group (measles n = 47, RSV n = 54) and non-treated groups (measles n = 58, RSV n = 42) had similar baseline characteristics. Patients with measles given a vitamin A supplementation had a shorter duration of cough (7.2 +/- 1.6 vs 9.2 +/- 1.8 days, p < 0.05) and patients with severe RSV infection given a vitamin A supplementation had a shorter duration of retraction (3.6 +/- 1.4 vs 5.3 +/- 0.8 days, p < 0.05) and wheezing (4.4 +/- 1.7 vs 6.3 +/- 1.5 days, p < 0.05). Toxicities, including excess vomiting and bulging fontanel were not observed. Our findings may suggest the efficacy of oral vitamin A supplementation for measles and severe RSV infection, in children who have no malnutrition.
Effect of vitamin A on diarrhoeal and respiratory complications of measles.
A randomized placebo-controlled trial of high dose vitamin A in acute measles was performed in Nairobi, Kenya to determine if it reduced the incidence or severity of diarrhoeal and respiratory complications. On enrollment laryngotracheobronchitis (LTB) pneumonia, diarrhoea and otitis media were each found in 45-80% of children in the treatment and placebo groups. While 4 of 119 cases of LTB in the placebo group progressed to grade III (loud stridor, markedly diminished air entry, chest indrawing, cyanosis), none of 116 in the vitamin A group did. Episodes of diarrhoea, but not pneumonia, resolved faster and were less severe in the vitamin A group. There were no differences in the incidences of pneumonia, LTB or diarrhoea during hospitalization, but children treated with vitamin A had a lower rate of developing otitis media. The overall case fatality rate was 2.7% and did not differ by group. These findings, along with those from three other trials in Africa, suggest that high dose vitamin A reduces the severity of complications during measles.
Efficacy of a single oral dose of 200,000 IU of oil-soluble vitamin A in measles-associated morbidity.
The authors assessed the efficacy of the World Health Organization (WHO) recommendation of 200,000 IU of vitamin A in oil to treat acute non-xerophthalmic measles patients. Acute measles patients who did not require hospitalization were enrolled in a randomized, double-masked, clinical trial of vitamin A (n=90) versus placebo (n=110) carried out in Ndola, Zambia, in 1991. Measles-associated morbidity was defined by the presence of signs and symptoms of acute respiratory infection. Daily evaluations for the first 3 days were followed by weekly visits for a month at urban health centers. Baseline demographic, clinical, and biochemical characteristics were similar in both groups. Cross-sectional analysis of morbidity status, by group, at each weekly evaluation showed no significant differences until week 4, when more placebo-treated patients had cough or pneumonia (p=0.005). However, longitudinal analysis, which looked at changes among individuals and controlled for initial health status, showed more equivocal results. The odds ratio for the development of pneumonia in patients with measles cough in vitamin A-treated subjects was 0.73 (95% confidence interval (Cl) 0.30-1.80). The odds ratio for the development of measles-associated cough or pneumonia in asymptomatic measles patients was 0.52 (95% Cl 0.24-1.13), in favor of vitamin A, but the odds ratio for failing to improve from pneumonia in vitamin A-treated subjects was 1.23 (95% Cl 0.68-2.3), a result in favor of placebo. These results suggest that the evidence for the efficacy of one dose of vitamin A in oil to prevent measles complications is not as strong as that previously shown for two 200,000 IU doses of water-miscible vitamin A, and that the WHO recommendation may need to be reexamined.
Options:
A: Vitamin A therapy significantly reduced overall mortality in children with measles.
B: Two doses of vitamin A significantly reduced mortality and pneumonia-specific mortality in children under the age of two years.
C: A single dose of vitamin A significantly reduced the incidence of pneumonia and diarrhea in children with measles.
D: Vitamin A therapy had no significant effect on the incidence of croup in children with measles. | B |
469 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What is the effect of long-term domiciliary oxygen therapy on survival in patients with chronic obstructive pulmonary disease (COPD) with varying levels of hypoxaemia? Please answer this question based on the information provided below:
A randomized trial of nocturnal oxygen therapy in chronic obstructive pulmonary disease patients.
The beneficial effects of nocturnal oxygen therapy (NOT) in chronic obstructive pulmonary disease (COPD) patients with mild-to-moderate daytime hypoxaemia (arterial oxygen tension (Pa,O2) in the range 7.4-9.2 kPa (56-69 mmHg)) and exhibiting sleep-related oxygen desaturation remains controversial. The effectiveness of NOT in that category of COPD patients was studied. The end points included pulmonary haemodynamic effects after 2 yrs of follow-up, survival and requirement for long-term oxygen therapy (LTOT). Seventy-six patients could be randomized, 41 were allocated to NOT and 35 to no NOT (control). The goal of NOT was to achieve an arterial oxygen saturation of >90% throughout the night. All these patients underwent polysomnography to exclude an associated obstructive sleep apnoea syndrome. The two groups exhibited an identical meansD daytime Pa,O2 of 8.4+/-0.4 kPa (63+/-3 mmHg) at baseline. Twenty-two patients (12 in the NOT group and 10 in the control group, p=0.98) required LTOT during the whole follow-up (35+/-14 months). Sixteen patients died, nine in the NOT group and seven in the control group (p=0.84). Forty-six patients were able to undergo pulmonary haemodynamic re-evaluation after 2 yrs, 24 in the NOT and 22 in the control group. In the control group, mean resting pulmonary artery pressure increased from 19.8+/-5.6 to 20.5+6.5 mmHg, which was not different from the change in mean pulmonary artery pressure in the NOT group, from 18.3+/-4.7 to 19.5+/-5.3 mmHg (p= 0.79). Nocturnal oxygen therapy did not modify the evolution of pulmonary haemodynamics and did not allow delay in the prescription of long-term oxygen therapy. No effect of NOT on survival was observed, but the small number of deaths precluded any firm conclusion. These results suggest that the prescription of nocturnal oxygen therapy in isolation is probably not justified in chronic obstructive pulmonary disease patients.
A double-blind trial of nocturnal supplemental oxygen for sleep desaturation in patients with chronic obstructive pulmonary disease and a daytime PaO2 above 60 mm Hg.
The efficacy of nasal oxygen during sleep was evaluated in patients with COPD, episodic rapid eye movement sleep desaturation, and a daytime PaO2 greater than 60 mm Hg. The double-blind, randomized 3-yr trial used nasal oxygen versus room air in two groups of nocturnal sleep desaturating subjects. The setting was the outpatient chest clinic of a Veterans Affairs Medical Center. There were 51 patients with moderate to severe COPD, daytime PaO2 greater than or equal to 60 mm Hg: 38 with proven REM sleep desaturation and 13 without desaturation. Nocturnal oxygen at 3 L/min was delivered by concentrator to 19 desaturating subjects, and room air at 3 L/min was delivered by defective concentrator to the remaining 19 desaturating subjects. There was no gas therapy for the 13 nondesaturating subjects. The nocturnal desaturator group who received supplemental oxygen during sleep over 36 months showed a significant downward trend in pulmonary artery pressure (-3.7 mm Hg) compared with desaturating patients treated with room air (+3.9 mm Hg). Nonvascular parameters of hypoxia, such as hemoglobin and red blood cell mass, did not differ between the sham- and oxygen-treated groups. Mortality was decidedly higher in the desaturating patients compared with non-desaturating subjects, but there was no significant difference between oxygen- and sham-treated desaturating subjects. We conclude that nasal supplemental oxygen used during sleep to reverse episodic desaturation in COPD patients whose daytime PaO2 is above 60 mm Hg has a beneficial effect in reducing pulmonary artery pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of long-term oxygen therapy on survival in patients with chronic obstructive pulmonary disease with moderate hypoxaemia.
BACKGROUND: To date only two controlled studies have been published on the effects of domiciliary oxygen treatment on survival in patients with chronic obstructive pulmonary disease (COPD) with advanced respiratory failure. The survival in such patients despite oxygen treatment remains poor. The prescription of long term oxygen therapy (LTOT) in less severe disease remains controversial. The aim of this study was to evaluate the rationale for prescribing oxygen to patients with COPD with moderate hypoxaemia.
METHODS: One hundred and thirty five patients with COPD, with PaO2 7.4-8.7 kPa (56-65 mmHg) and advanced airflow limitation (mean (SD) forced expiratory volume in one second (FEV1) 0.83 (0.28) 1), were randomly allocated to a control (n = 67) and LTOT (n = 68) group. The patients were followed every three months for at least three years or until death.
RESULTS: The cumulative survival rate was 88% at one year, 77% at two years, and 66% at three years. No significant differences were found in survival rates between patients treated with LTOT and controls, nor did longer oxygen use (over 15 hours per day) improve survival. Younger age, better spirometric values, and higher body mass index predicted better survival.
CONCLUSIONS: Domiciliary oxygen treatment does not prolong survival in patients with COPD with moderate hypoxaemia. Airway limitation seems to determine survival in this group of patients.
Long-term oxygen therapy stops the natural decline of endurance in COPD patients with reversible hypercapnia.
BACKGROUND: Respiratory muscle weakness is one of the most important causes of hypercapnia in patients with COPD. There is evidence that stable hypercapnic patients will benefit from long-term oxygen therapy (LTOT).
OBJECTIVES: The prognostic role of reversible hypercapnia in COPD is still unclear. Early implementation of LTOT in these patients may influence endurance time and mortality.
METHODS: In this pilot study, we investigated 28 patients (26 males, 49-74 years) with COPD, advanced airflow limitation [forced expiratory volume in 1 s (percentage of predicted value) 40.8 +/- 10.2] and mild hypoxaemia (pO(2) 66.5 +/- 6.3 mm Hg). All patients had developed a moderate reversible hypercapnia during an acute exacerbation or during exercise testing (peak pCO(2) 48.0 +/- 2.5 mm Hg). Patients were allocated randomly to a control group (n = 14) or an LTOT group (n = 14). The two groups were well matched in terms of physiological data. Lung function, endurance time (cycle ergometer), dyspnoea score, blood gases and LTOT compliance were measured at baseline and every 6 months over a period of 3 years.
RESULTS: Endurance time increased from 6.4 +/- 2.7 min at baseline to 7.1 +/- 2.7 min after 1 year in the LTOT group and decreased from 6.1 +/- 3.0 to 4.9 +/- 3.8 min in the controls (p < 0.05). After 1 year, the end-exercise dyspnoea score was significantly lower in the LTOT group (4.5 +/- 1.5) than in the controls (5.7 +/- 1.9).
CONCLUSION: COPD patients with reversible hypercapnia and mild hypoxaemia benefit from LTOT in terms of endurance time and a reduction of exertional dyspnoea after 1 year.
Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Report of the Medical Research Council Working Party.
A controlled trial of long term domiciliary oxygen therapy has been carried out in three centres in the U.K. The 87 patients, all under 70 years of age, who took part had chronic bronchitis or emphysema with irreversible airways obstruction, severe arterial hypoxaemia, carbon dioxide retention, and a history of congestive heart failure. The patients were randomised to oxygen therapy (treated) or no oxygen (controls). Oxygen was given by nasal prongs for at least 15 h daily, usually at 2 1/min. The two groups were well matched, both clinically and in terms of lung function and other laboratory findings. 19 of the 42 oxygen treated patients died in the five years of survival follow-up compared with 30 out of 45 controls: in the 66 men in this trial the survival advantage of oxygen did not emerge until 500 days had elapsed. Survival for the 12 female controls was surprisingly poor, 8 of them being dead at 3 years. Mortality was not easy to predict, though a summation of arterial carbon dioxide tension and red cell mass was helpful. Neither time spent in hospital because of exacerbations of respiratory failure nor work attendance were affected by oxygen therapy, but these patients were very ill at the start of the trial and many had already retired on grounds of age or ill-health. Physiological measurements suggested that oxygen did not slow the progress of respiratory failure in those who died early. However, in longer term survivors on oxygen, arterial oxygenation did seem to stop deterioration.
Neuropsychologic findings in hypoxemic chronic obstructive pulmonary disease.
As part of a six-center clinical trial of the effectiveness of continuous v nocturnal oxygen in the management of hypoxemic chronic obstructive pulmonary disease (COPD), we performed detailed neuropsychologic assessments of these patients prior to their beginning treatment. The 203 patients (age, 65 years; Pao2, 51 mm Hg; forced expiratory volume in 1 s, 0.74 L) performed significantly worse than controls on virtually all neuropsychologic tests. Moderate to severe test impairment suggestive of cerebral dysfunction was found in 42% of the patients, as compared with 14% of controls. Higher cognitive functions (abstracting ability, complex perceptual-motor integration) were most severely affected, although half the patients also showed decrements in motor speed, strength, and coordination. Low-order significant inverse correlations were found between neuropsychologic impairment and Pao2, resting arterial oxygen saturation and hemoglobin levels and maximum work. It is concluded that cerebral disturbance is common in hypoxemic COPD and may be related in part to decreased availability of oxygen to the brain.
Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Nocturnal Oxygen Therapy Trial Group.
At six centers, 203 patients with hypoxemic chronic obstructive lung disease were randomly allocated to either continuous oxygen (O2) therapy or 12-hour nocturnal O2 therapy and followed for at least 12 months (mean, 19.3 months). The two groups were initially well matched in terms of physiological and neuropsychological function. Compliance with each oxygen regimen was good. Overall mortality in the nocturnal O2 therapy group was 1.94 times that in the continuous O2 therapy group (P = 0.01). This trend was striking in patients with carbon dioxide retention and also present in patients with relatively poor lung function, low mean nocturnal oxygen saturation, more severe brain dysfunction, and prominent mood disturbances. Continuous O2 therapy also appeared to benefit patients with low mean pulmonary artery pressure and pulmonary vascular resistance and those with relatively well-preserved exercise capacity. We conclude that in hypoxemic chronic obstructive lung disease, continuous O2 therapy is associated with a lower mortality than is nocturnal O2 therapy. The reason for this difference is not clear.
Hemodynamic response to oxygen therapy in chronic obstructive pulmonary disease.
At six centers, 203 patients with stabilized hypoxemic chronic obstructive pulmonary disease were evaluated hemodynamically during a continuous or 12-hour oxygen therapy program. Neither oxygen therapy program resulted in correction or near-correction of the baseline hemodynamic abnormalities. The continuous oxygen therapy group did show improvement in pulmonary vascular resistance, pulmonary arterial pressure, and stroke volume index. The improvement in pulmonary vascular resistance was associated with improved cardiac function, as evidenced by an increase in baseline and exercise stroke volume index. The nocturnal oxygen therapy group showed stable hemodynamic variables. For both groups, changes in mean pulmonary artery pressure during the first 6 months were associated with subsequent survival after adjustment for association with the baseline mean pulmonary artery pressure. Continuous oxygen therapy can improve the hemodynamic abnormalities of patients with hypoxic chronic obstructive pulmonary disease. The hemodynamic response to this treatment is predictive of survival.
Options:
A: Improves survival in patients with severe hypoxaemia but not in those with mild to moderate hypoxaemia or nocturnal desaturation.
B: Improves survival in all patients with COPD regardless of the severity of hypoxaemia.
C: Does not improve survival in any patients with COPD.
D: Improves survival only in patients with nocturnal desaturation. | A |
470 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What was the conclusion regarding the effectiveness of preoperative radiotherapy in improving the survival of patients with potentially resectable esophageal carcinoma? Please answer this question based on the information provided below:
Low dose preoperative radiotherapy for carcinoma of the oesophagus: results of a randomized clinical trial.
One-hundred-and-seventy-six patients with potentially operable squamous cell carcinoma or adenocarcinoma of the middle or lower thirds of the oesophagus were randomly assigned to preoperative radiotherapy or surgery alone. Patients assigned to the radiotherapy arm received 20 Gy in 10 treatments over 2 weeks, using parallel opposed 4 MV beams. The preoperative radiotherapy was not associated with any significant acute morbidity or any increase in operative complications. The median survival of the overall group of 176 patients was 8 months, and the 5-year survival was 13%. There was no significant difference in the survival of the 90 patients who received preoperative radiotherapy and the 86 who were managed by surgery alone. Proportional hazards analysis identified lymph node involvement, high tumour grade and male sex as significant adverse prognostic features, but the treatment option assigned had no prognostic significance. It was concluded that low dose preoperative radiotherapy offered no advantage over surgery alone.
The value of preoperative radiotherapy in esophageal cancer: results of a study by the EORTC.
Preoperative radiotherapy for carcinoma of the esophagus.
From 21 March to 22 June 1976, 124 patients with squamous cell carcinoma of the esophagus were randomized for inclusion in a prospective trial of preoperative irradiation. Fifteen patients were excluded because of inoperability. Sixty-seven patients were randomly selected to receive 4,000 rads of cobalt radiation for eight days prior to operation; 57 patients were operated upon without receiving radiation therapy. No significant differences were noted between the two groups with regard to age, sex, tumor site, experience of the surgeon, method of approach or surgical technique. Eight esophageal resections were performed upon 47 of the 62 irradiated patients and 33 of the 47 nonirradiated patients. Of the 62 irradiated patients, 14 died during operation, compared with 11 of the 47 nonirradiated patients, the difference between the two groups not being statistically significant. Irradiation was associated with a higher mortality for lesions in the mid third part of the esophagus, 11 of 29 versus four of 19, but again, the difference was not significant. In the irradiated patients, the five year actuarial postoperative survival rate was 9.5 versus 11.5 per cent for the nonirradiated patients. In conclusion, preoperative radiation therapy does not produce a statistically significant short term or long term benefit in the management of squamous cell carcinoma of the esophagus.
Pre-operative radiotherapy prolongs survival in operable esophageal carcinoma: a randomized, multicenter study of pre-operative radiotherapy and chemotherapy. The second Scandinavian trial in esophageal cancer.
In a prospective multicenter study, 186 patients with squamous cell esophageal carcinoma, who after evaluation were considered suitable for surgery, were randomized to 4 treatment groups: Group 1, surgery alone; Group 2, pre-operative chemotherapy (cisplatin and bleomycin) and surgery; Group 3, pre-operative irradiation (35 Gy) and surgery; Group 4, pre-operative chemotherapy, radiotherapy, and surgery. Three-year survival was significantly higher in the pooled groups receiving radiotherapy as compared with the pooled groups not receiving radiotherapy. Comparison of the groups having pre-operative chemotherapy with those not having chemotherapy showed no significant difference in survival. Female patients had a significantly better survival than males. The results indicate that pre-operative irradiation had a beneficial effect on intermediate term survival, whereas the chemotherapy regime used did not influence survival.
Pre-operative radiotherapy prolongs survival in operable esophageal carcinoma: a randomized, multicenter study of pre-operative radiotherapy and chemotherapy. The second Scandinavian trial in esophageal cancer.
In a prospective multicenter study, 186 patients with squamous cell esophageal carcinoma, who after evaluation were considered suitable for surgery, were randomized to 4 treatment groups: Group 1, surgery alone; Group 2, pre-operative chemotherapy (cisplatin and bleomycin) and surgery; Group 3, pre-operative irradiation (35 Gy) and surgery; Group 4, pre-operative chemotherapy, radiotherapy, and surgery. Three-year survival was significantly higher in the pooled groups receiving radiotherapy as compared with the pooled groups not receiving radiotherapy. Comparison of the groups having pre-operative chemotherapy with those not having chemotherapy showed no significant difference in survival. Female patients had a significantly better survival than males. The results indicate that pre-operative irradiation had a beneficial effect on intermediate term survival, whereas the chemotherapy regime used did not influence survival.
Randomized clinical trial on the combination of preoperative irradiation and surgery in the treatment of esophageal carcinoma: report on 206 patients.
From June 1977 to May 1985, a prospective randomized clinical trial on pre-operative radiation for esophageal carcinoma was carried out in 206 patients. Lesions under 8 cm in length and patients younger than 65 years, at least on semi-liquid diet and not contra-indicated for surgery were randomized into a combined group (104 patients) or a surgery alone group (102 patients). Eight MV X ray units were used for the pre-operative radiation using A-P portals to deliver 4,000 cGy to the whole mediastinum and the left gastroepiploic lymphatic chain. Surgery was carried out after 2 to 4 week's rest. The immediate results of the combined group and the surgery alone group were: resection rate 93% and 85%, operative mortality 5% and 6%, intra-thoracic anastomotic leak 0% and 1%, positive pathology at the esophageal stump 0% and 2%, and lymph nodes metastasis 27% and 35% respectively. The 5-year survival rates of the combined group and the surgery alone group were 35% and 30%. We have noticed that those patients with lesions showing radiation reaction of grade III gave a 5-year survival of 50% (12/24). Because intra- and extra-thoracic lymphnode metastasis caused failures (41% and 34% of these two groups), increasing the preoperative tumor dose to 60 Gy or designing post-operative irradiation to cover the bilateral supraclavicular areas was necessary. The whole mediastinum and the left gastroepiploic lymphatics could further improve the results of surgery. Further studies are needed.
Options:
A: Preoperative radiotherapy significantly improves survival rates in patients with potentially resectable esophageal carcinoma.
B: Preoperative radiotherapy does not improve survival rates in patients with potentially resectable esophageal carcinoma.
C: Preoperative radiotherapy shows a modest improvement in survival rates, but the results are not statistically significant.
D: Preoperative radiotherapy significantly reduces the risk of death in patients with potentially resectable esophageal carcinoma. | C |
471 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What is the conclusion regarding the effectiveness of surgical interruption of pelvic nerve pathways for the treatment of primary and secondary dysmenorrhoea? Please answer this question based on the information provided below:
Presacral neurectomy for the treatment of pelvic pain associated with endometriosis: a controlled study.
OBJECTIVE: Our objective was to evaluate the efficacy of presacral neurectomy combined with conservative surgery for the treatment of pelvic pain associated with endometriosis.
STUDY DESIGN: In a randomized, controlled study performed in a tertiary institution 71 patients with moderate or severe endometriosis and midline dysmenorrhea were randomly assigned to conservative surgery alone (n = 36) or conservative surgery and presacral neurectomy (n = 35). Main outcome measures were relief of dysmenorrhea, pelvic pain, and deep dyspareunia after surgery according to a multidimensional and an analog pain scale.
RESULTS: Presacral neurectomy markedly reduced the midline component of menstrual pain, but no statistically significant differences were observed between the two groups in the frequency and severity of dysmenorrhea, pelvic pain, and dyspareunia in the long-term follow-up. After presacral neurectomy, constipation developed or worsened in 13 patients and urinary urgency occurred in three and a painless first stage of labor in two.
CONCLUSION: Presacral neurectomy should be combined with conservative surgery for endometriosis only in selected cases.
Comparison of laparoscopic presacral neurectomy and laparoscopic uterine nerve ablation for primary dysmenorrhea.
OBJECTIVE: To compare laparoscopic presacral neurectomy and laparoscopic uterine nerve ablation for primary dysmenorrhea.
STUDY DESIGN: Sixty-eight patients with primary dysmenorrhea and a poor response to medical treatment were randomized into two groups. One group (33 patients) had laparoscopic presacral neurectomy (LPSN) and the other group (35 patients), laparoscopic uterine nerve ablation (LUNA).
RESULTS: There were no complications, and all the patients left the hospital within 24 hours after surgery. The efficacy of both surgical methods was almost equal (87.9% vs. 82.9%) at the 3-month postoperative follow-up visit, but the efficacy of LPSN was significantly better than that of LUNA (81.8% vs 51.4%) at the 12-month visit.
CONCLUSION: LPSN is a valid option for treating primary dysmenorrhea.
A double-blind randomised controlled trial of laparoscopic uterine nerve ablation for women with chronic pelvic pain.
OBJECTIVE: To determine the effectiveness of laparoscopic uterine nerve ablation (LUNA) for chronic pelvic pain in women with endometriosis and women with no laparoscopic evidence of endometriosis.
DESIGN: A prospective double-blind randomised controlled trial (RCT).
SETTING: Single-centre, secondary-level gynaecology outpatient service and tertiary-level pelvic pain and endometriosis outpatient service in Auckland, New Zealand.
POPULATION: One hundred and twenty-three women undergoing laparoscopy for investigation and management of chronic pelvic pain, 56 with no laparoscopic evidence of endometriosis and 67 with endometriosis.
METHODS: Women were randomised from the two populations, firstly those with no evidence of endometriosis and secondly those undergoing laparoscopic surgical treatment for endometriosis, to receive LUNA or no LUNA. Participant and assessor blinding was employed. Follow up for pain outcomes was undertaken at 24 hours, 3 months and 12 months.
MAIN OUTCOME MEASURES: Changes in non-menstrual pelvic pain, dysmenorrhoea, deep dyspareunia and dyschezia were assessed primarily by whether there was a decrease in visual analogue score for these types of pain of 50% or more from baseline and additionally whether there was a significantly different change in median visual analogue score. The numbers requiring further surgery or starting a new medical treatment for pelvic pain and complications were also measured.
RESULTS: There was a significant reduction in dysmenorrhoea at 12 month follow up in women with chronic pelvic pain in the absence of endometriosis who underwent LUNA (median change in visual analogue scale (VAS) from baseline -4.8 versus-0.8 (P= 0.039), 42.1%versus 14.3% experiencing a successful treatment defined as a 50% or greater reduction in visual analogue pain scale for dysmenorrhoea (P= 0.045). There was no significant difference in non-menstrual pelvic pain, deep dyspareunia or dyschezia in women with no endometriosis undergoing LUNA versus no LUNA. The addition of LUNA to laparoscopic surgical treatment of endometriosis was not associated with a significant difference in any pain outcomes.
CONCLUSIONS: LUNA is effective for dysmenorrhoea in the absence of endometriosis, although there is no evidence of effectiveness of LUNA for non-dysmenorrhoeic chronic pelvic pain or for any type of chronic pelvic pain related to endometriosis.
Surgical treatment of primary dysmenorrhea with laparoscopic uterine nerve ablation.
With approximately 25% of dysmenorrheic patients reporting no improvement with nonsteroidal anti-inflammatory drugs, a study was devised to evaluate the effectiveness of a laparoscopic technique for the interruption of the uterosacral nerves. In a double-blind study of 21 patients with primary dysmenorrhea, 81% (9 of 11) reported significant relief from menstrual pain after the surgery. Performed as an outpatient procedure, laparoscopic uterine nerve ablation may alleviate dysmenorrheic complaints when other modalities have failed. Half the treated women reported continued relief of menstrual pain at 12 months. These results suggest that uterosacral nerve interruption may prove an effective alternative treatment for this menstrual disorder.
The efficacy of presacral neurectomy for the relief of midline dysmenorrhea.
The present study was undertaken to evaluate prospectively the efficacy of presacral neurectomy for the treatment of midline dysmenorrhea. All patients had moderate to severe dysmenorrhea and stage III-IV endometriosis. Of the patients undergoing presacral neurectomy (N = 17), only two had a recurrence of pain. The remainder of the patients undergoing presacral neurectomy remain pain-free at 42 months of follow-up. Of the patients undergoing resection of endometriosis but not presacral neurectomy (N = 9), none received relief of midline pain. Relief of lateral pain, back pain, and dyspareunia was variable in both groups. Our findings corroborate previous retrospective studies showing that presacral neurectomy is highly effective in the treatment of dysmenorrhea. We speculate that the most common reasons for failure of presacral neurectomy are inappropriate selection of patients and incomplete resection of the presacral nerve plexus.
Laparoscopic uterosacral ligament resection for dysmenorrhea associated with endometriosis: results of a randomized, controlled trial.
OBJECTIVE: To evaluate the efficacy of laparoscopic resection of the uterosacral ligaments in women with endometriosis and predominantly midline dysmenorrhea.
DESIGN: Randomized controlled trial.
SETTING: Two academic departments. One hundred eighty patients undergoing operative laparoscopy as first-line therapy for stage I to IV symptomatic endometriosis.
INTERVENTION(S): Operative laparoscopy including uterosacral ligament resection or conservative surgery alone.
MAIN OUTCOME MEASURE(S): Proportion of women with recurrence of moderate or severe dysmenorrhea 1 year after surgery.
RESULT(S): No complications occurred. Among the patients who were evaluable 1 year after operative laparoscopy, 23 of 78 (29%) women who had uterosacral ligament resection and 21 of 78 (27%) women who had conservative surgery only reported recurrent dysmenorrhea. The corresponding numbers of patients at 3 years were 21 of 59 (36%) women and 18 of 57 (32%) women, respectively. Time to recurrence was similar in the two groups. Pain was substantially reduced, and patients in both groups experienced similar and significant improvements in health-related quality of life, psychiatric profile, and sexual satisfaction. Overall, 68 of 90 (75%) patients in the uterosacral ligament resection group and 67 of 90 (74%) patients in the conservative surgery group were satisfied at 1 year.
CONCLUSION(S): Addition of uterosacral ligament resection to conservative laparoscopic surgery for endometriosis did not reduce the medium- or long-term frequency and severity of recurrence of dysmenorrhea.
Comparison of a levonorgestrel-releasing intrauterine device versus expectant management after conservative surgery for symptomatic endometriosis: a pilot study.
OBJECTIVE: To determine whether the frequency and severity of dysmenorrhea are reduced in women with symptomatic endometriosis in whom a levonorgestrel-releasing intrauterine device (Lng-IUD) is inserted after operative laparoscopy compared with those treated with surgery only.
DESIGN: Open-label, parallel-group, randomized, controlled trial.
SETTING: A tertiary care and referral center for patients with endometriosis.
PATIENTS(S): Parous women with moderate or severe dysmenorrhea undergoing first-line operative laparoscopy for symptomatic endometriosis.
INTERVENTION(S): Randomization to immediate Lng-IUD insertion or expectant management after laparoscopic treatment of endometriotic lesions. Proportions of women with recurrence of moderate or severe dysmenorrhea in the two study groups 1 year after surgery and overall degree of satisfaction with treatment. Moderate or severe dysmenorrhea recurred in 2 of 20 (10%) subjects in the postoperative Lng-IUD group and 9/20 (45%) in the surgery-only group. Thus, a medicated device inserted postoperatively will prevent the recurrence of moderate or severe dysmenorrhea in one out of three patients 1 year after surgery. A total of 15/20 (75%) women in the Lng-IUD group and 10/20 (50%) in the expectant management group were satisfied or very satisfied with the treatment received.
CONCLUSION(S): Insertion of an Lng-IUD after laparoscopic surgery for symptomatic endometriosis significantly reduced the medium-term risk of recurrence of moderate or severe dysmenorrhea.
Addition of laparoscopic uterine nerve ablation to laparoscopic bipolar coagulation of uterine vessels for women with uterine myomas and dysmenorrhea.
STUDY OBJECTIVE: To assess the effectiveness of laparoscopic uterine nerve ablation (LUNA) in women with dysmenorrhea caused by uterine myomas treated by laparoscopic bipolar coagulation of uterine vessels (LBCUV).
DESIGN: Prospective, randomized, longitudinal study (Canadian Task Force classification II-1).
SETTING: Private practice, university-affiliated hospital.
PATIENTS: Eighty-five women with uterine leiomyomas and associated dysmenorrhea.
INTERVENTION: Laparoscopic bipolar coagulation of uterine vessels with or without LUNA.
MEASUREMENTS AND MAIN RESULTS: Of 85 patients who entered the study, 41 were assigned to undergo LBCUV-LUNA (group A), which was successful in 40 (97.6%). In 44 women assigned to have LBCUV only (group B), 43 (97.7%) underwent successful surgery. Eighty women completed 1-, 3-, and 6-month follow-up (38 group A, 42 group B). The groups did not differ significantly in age, history of abdominopelvic surgery, intraperitoneal adhesions, endometriosis, concomitant surgery, and operating time. Seven (18.4%) of 38 women in group A and 12 (28.6%) of 42 in group B experienced lower abdominal pain postoperatively. Acceptable pain was defined as a score of zero or 1: 31 and 30 women in groups A and B reported scores of zero; 3 and 2 reported scores of 1; 4 and 8 reported scores of 2; zero and 2 reported scores of 3; and no patients reported scores of 4. The frequency and severity of postoperative pain were less in group A than in group B (both p <0.05). The efficacy of both methods was almost equal in shrinking the uterus and dominant myoma, and in improving menorrhagia and bulk-related symptoms. Dysmenorrhea improvement was 84.2% and 61.9% in groups A and B at 3 months and 92.1% and 73.8% at 6 months, respectively. This was more significant in group A than in group B (p <0.05).
CONCLUSION: Our results suggest that LUNA may decrease postoperative ischemic pain and improve dysmenorrhea associated with uterine myomas treated by LBCUV.
Effectiveness of presacral neurectomy in women with severe dysmenorrhea caused by endometriosis who were treated with laparoscopic conservative surgery: a 1-year prospective randomized double-blind controlled trial.
OBJECTIVE: The purpose of this study was to assess the effectiveness of presacral neurectomy in women with severe dysmenorrhea caused by endometriosis that was treated with conservative surgical intervention.
STUDY DESIGN: One hundred forty-one sexually active women of fertile age with chronic severe dysmenorrhea caused by endometriosis were treated with conservative laparoscopic surgery. Patients were assigned randomly to not receive (group A) or receive (group B) presacral neurectomy. At 6 and 12 months after the surgical procedures, the cure rate was evaluated in each patient. The frequency and severity of dysmenorrhea, dyspareunia, and chronic pelvic pain were also evaluated at the same time intervals.
RESULTS: The cure rate was significantly higher in group B compared with group A at a follow-up examination at 6 months (87.3% vs 60.3%) and 12 months (85.7% vs 57.1%). At follow-up visits, the frequency and severity of dysmenorrhea, dyspareunia, and chronic pelvic pain were significantly lower in both groups compared with baseline values; in particular, significantly lower values were observed in group B versus group A for the severity.
CONCLUSION: Presacral neurectomy improves the cure rate in women who are treated with conservative laparoscopic surgery for severe dysmenorrhea caused by endometriosis.
Options:
A: Laparoscopic uterine nerve ablation (LUNA) is significantly more effective than laparoscopic presacral neurectomy (LPSN) for long-term pain relief in primary dysmenorrhoea.
B: There is sufficient evidence to recommend the use of nerve interruption in the management of dysmenorrhoea.
C: LUNA combined with surgical treatment of endometrial implants significantly aids pain relief in secondary dysmenorrhoea.
D: There is insufficient evidence to recommend the use of nerve interruption in the management of dysmenorrhoea, regardless of cause. | D |
472 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What is the effect of carotid endarterectomy (CEA) on patients with asymptomatic carotid stenosis in terms of stroke prevention and perioperative risks? Please answer this question based on the information provided below:
Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study.
OBJECTIVE: To determine whether the addition of carotid endarterectomy to aggressive medical management can reduce the incidence of cerebral infarction in patients with asymptomatic carotid artery stenosis.
DESIGN: Prospective, randomized, multicenter trial.
SETTING: Thirty-nine clinical sites across the United States and Canada.
PATIENTS: Between December 1987 and December 1993, a total of 1662 patients with asymptomatic carotid artery stenosis of 60% or greater reduction in diameter were randomized; follow-up data are available on 1659. At baseline, recognized risk factors for stroke were similar between the two treatment groups.
INTERVENTION: Daily aspirin administration and medical risk factor management for all patients; carotid endarterectomy for patients randomized to receive surgery.
MAIN OUTCOME MEASURES: Initially, transient ischemic attack or cerebral infarction occurring in the distribution of the study artery and any transient ischemic attack, stroke, or death occurring in the perioperative period. In March 1993, the primary outcome measures were changed to cerebral infarction occurring in the distribution of the study artery or any stroke or death occurring in the perioperative period.
RESULTS: After a median follow-up of 2.7 years, with 4657 patient-years of observation, the aggregate risk over 5 years for ipsilateral stroke and any perioperative stroke or death was estimated to be 5.1% for surgical patients and 11.0% for patients treated medically (aggregate risk reduction of 53% [95% confidence interval, 22% to 72%]).
CONCLUSION: Patients with asymptomatic carotid artery stenosis of 60% or greater reduction in diameter and whose general health makes them good candidates for elective surgery will have a reduced 5-year risk of ipsilateral stroke if carotid endarterectomy performed with less than 3% perioperative morbidity and mortality is added to aggressive management of modifiable risk factors.
Study design for randomized prospective trial of carotid endarterectomy for asymptomatic atherosclerosis. The Asymptomatic Carotid Atherosclerosis Study Group.
This report summarizes the study design and organization of a multicenter, randomized trial of carotid endarterectomy for the treatment of asymptomatic carotid stenosis. The Asymptomatic Carotid Atherosclerosis Study will determine whether the addition of carotid endarterectomy to aspirin plus risk factor modifications affects the incidence of ipsilateral transient ischemic attack, amaurosis fugax, and retinal and cerebral infarction in patients with asymptomatic hemodynamically significant carotid stenosis in at least one artery. Power calculations are based on assumptions of alpha = 0.05 (two-sided test) with annual event rate 3% transient ischemic attack and 1% cerebral infarction per year. The study has 90% power for detection of a 25% difference in events in a 5-year study. Two continuous validation programs are in use: a Doppler/angiogram correlation study for each Doppler instrument used in screening potential candidates and a transient ischemic attack/stroke questionnaire/validation study for verification of end points. Quality assurance is a major component in study design.
The Asymptomatic Carotid Surgery Trial (ACST). Rationale and design. Steering Committee.
Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial.
BACKGROUND: Among patients with substantial carotid artery narrowing but no recent neurological symptom (stroke or transient ischaemia), the balance of surgical risks and long-term benefits from carotid endarterectomy (CEA) was unclear.
METHODS: During 1993-2003, 3120 asymptomatic patients with substantial carotid narrowing were randomised equally between immediate CEA (half got CEA by 1 month, 88% by 1 year) and indefinite deferral of any CEA (only 4% per year got CEA) and were followed for up to 5 years (mean 3.4 years). Kaplan-Meier analyses of 5-year risks are by allocated treatment.
FINDINGS: The risk of stroke or death within 30 days of CEA was 3.1% (95% CI 2.3-4.1). Comparing all patients allocated immediate CEA versus all allocated deferral, but excluding such perioperative events, the 5-year stroke risks were 3.8% versus 11% (gain 7.2% [95% CI 5.0-9.4], p<0.0001). This gain chiefly involved carotid territory ischaemic strokes (2.7% vs 9.5%; gain 6.8% [4.8-8.8], p<0.0001), of which half were disabling or fatal (1.6% vs 5.3%; gain 3.7% [2.1-5.2], p<0.0001), as were half the perioperative strokes. Combining the perioperative events and the non-perioperative strokes, net 5-year risks were 6.4% versus 11.8% for all strokes (net gain 5.4% [3.0-7.8], p<0.0001), 3.5% versus 6.1% for fatal or disabling strokes (net gain 2.5% [0.8-4.3], p=0.004), and 2.1% versus 4.2% just for fatal strokes (net gain 2.1% [0.6-3.6], p=0.006). Subgroup-specific analyses found no significant heterogeneity in the perioperative hazards or (apart from the importance of cholesterol) in the long-term postoperative benefits. These benefits were separately significant for males and females; for those with about 70%, 80%, and 90% carotid artery narrowing on ultrasound; and for those younger than 65 and 65-74 years of age (though not for older patients, half of whom die within 5 years from unrelated causes). Full compliance with allocation to immediate CEA or deferral would, in expectation, have produced slightly bigger differences in the numbers operated on, and hence in the net 5-year benefits. The 10-year benefits are not yet known.
INTERPRETATION: In asymptomatic patients younger than 75 years of age with carotid diameter reduction about 70% or more on ultrasound (many of whom were on aspirin, antihypertensive, and, in recent years, statin therapy), immediate CEA halved the net 5-year stroke risk from about 12% to about 6% (including the 3% perioperative hazard). Half this 5-year benefit involved disabling or fatal strokes. But, outside trials, inappropriate selection of patients or poor surgery could obviate such benefits.
Role of carotid endarterectomy in asymptomatic carotid stenosis. A Veterans Administration Cooperative Study.
A multi-centered cooperative study is being undertaken to determine the role of carotid endarterectomy in the treatment of asymptomatic carotid stenosis. The primary objective is to compare the incidence of transient ischemic attacks, stroke, and death in previously asymptomatic patients with arteriographically confirmed internal carotid stenoses (greater than or equal to 50%) randomly allocated to carotid endarterectomy and aspirin therapy versus aspirin therapy alone. Ten Veterans Administration Medical Centers (VAMC) in the United States are participating. The study will be conducted over a period of eight years. The first three years will be devoted to acquiring and randomizing patients, after which all patients will be followed clinically for a minimum of five years. It is anticipated that approximately 500 patients will be recruited into the study.
Efficacy of carotid endarterectomy for asymptomatic carotid stenosis. The Veterans Affairs Cooperative Study Group.
BACKGROUND: The efficacy of carotid endarterectomy in patients with asymptomatic carotid stenosis has not been confirmed in randomized clinical trials, despite the widespread use of operative intervention in such patients.
METHODS: We conducted a multicenter clinical trial at 11 Veterans Affairs medical centers to determine the effect of carotid endarterectomy on the combined incidence of transient ischemic attack, transient monocular blindness, and stroke. We studied 444 men with asymptomatic carotid stenosis shown arteriographically to reduce the diameter of the arterial lumen by 50 percent or more. The patients were randomly assigned to optimal medical treatment including antiplatelet medication (aspirin) plus carotid endarterectomy (the surgical group; 211 patients) or optimal medical treatment alone (the medical group; 233 patients). All the patients at each center were followed independently by a vascular surgeon and a neurologist for a mean of 47.9 months.
RESULTS: The combined incidence of ipsilateral neurologic events was 8.0 percent in the surgical group and 20.6 percent in the medical group (P < 0.001), giving a relative risk (for the surgical group vs. the medical group) of 0.38 (95 percent confidence interval, 0.22 to 0.67). The incidence of ipsilateral stroke alone was 4.7 percent in the surgical group and 9.4 percent in the medical group. An analysis of stroke and death combined within the first 30 postoperative days showed no significant differences. Nor were there significant differences between groups in an analysis of all strokes and deaths (surgical, 41.2 percent; medical, 44.2 percent; relative risk, 0.92; 95 percent confidence interval, 0.69 to 1.22). Overall mortality, including postoperative deaths, was primarily due to coronary atherosclerosis.
CONCLUSIONS: Carotid endarterectomy reduced the overall incidence of ipsilateral neurologic events in a selected group of male patients with asymptomatic carotid stenosis. We did not find a significant influence of carotid endarterectomy on the combined incidence of stroke and death, but because of the size of our sample, a modest effect could not be excluded.
Options:
A: CEA significantly increases the risk of perioperative stroke or death without providing any long-term benefits in stroke prevention.
B: CEA reduces the risk of ipsilateral stroke and any stroke by approximately 30% over three years, despite a 3% perioperative stroke or death rate.
C: CEA has no significant impact on the risk of stroke or death compared to medical treatment alone.
D: CEA is only beneficial for older patients and does not provide any significant benefits for younger patients. | B |
473 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What were the main findings regarding the effectiveness of Low Level Laser Therapy (LLLT) in the treatment of rheumatoid arthritis (RA) in terms of pain relief, morning stiffness, and flexibility? Please answer this question based on the information provided below:
Soft-laser therapy of rheumatoid arthritis.
The effect of soft-laser therapy on rheumatoid arthritis was evaluated in 17 patients with symmetrical involvement of the metacarpophalangeal joint of the index. Nine treatments with a He-Ne laser, 6 J/cm2, were given on the one hand with a sham irradiation of the other. The study was double-blind. The laser therapy gave some pain relief, but no difference in morning stiffness or joint performance was obtained. It is concluded that the laser therapy is of limited value in rheumatoid arthritis.
Low level laser therapy is ineffective in the management of rheumatoid arthritic finger joints.
Low level laser therapy (LLLT) is a relatively new and increasingly popular form of electrotherapy. It is used by physiotherapists in the treatment of a wide variety of conditions including RA despite the lack of scientific evidence to support its efficacy. A randomized, double-blind and placebo-controlled study was conducted to evaluate the efficacy of LLLT. The patient sample consisted of chronic RA patients with active finger joint synovitis. Forty RA patients with involvement of some or all of MCP or PIP joints were recruited. Following random allocation they received either active or placebo laser three times a week for 4 weeks. Measurements were taken prior to entry, after the treatment, 1 month and 3 months at follow-up. The groups were well matched in terms of age, sex, disease duration and severity. Few significant differences were noted in grip strength, duration of morning stiffness, joint tenderness, temperature of inflamed joints, range of movement or pain either within or between groups. Using these irradiation parameters the efficacy of LLLT is ineffective.
Low energy laser therapy in rheumatoid arthritis.
Low energy laser (LEL) is a widely used treatment for a variety of musculoskeletal disorders although convincing documentation of the effect is missing. We have examined the LEL effect on Rheumatoid Arthritis (RA) in a double blind placebo controlled study. Twenty-two patients completed the study (10 receiving LEL treatment) according to the protocol. A significant effect on pain score was found due to LEL treatment, but when data were corrected for disease variation the effect disappeared. No effect of LEL could be demonstrated on the other assessed variables: grip strength, morning stiffness, flexibility, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP). In conclusion, we did not find that LEL had any clinically relevant effects on RA.
Options:
A: LLLT significantly reduced pain, decreased morning stiffness duration, and increased flexibility compared to placebo.
B: LLLT had no significant effect on pain, morning stiffness duration, or flexibility compared to placebo.
C: LLLT significantly reduced pain and morning stiffness duration, but had no effect on flexibility compared to placebo.
D: LLLT significantly increased flexibility, but had no effect on pain or morning stiffness duration compared to placebo. | A |
474 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What is the impact of routinely administered case finding/screening questionnaires for depression on the detection, management, and outcome of depression in non-specialist settings? Please answer this question based on the information provided below:
Primary care physicians' medical decision making for late-life depression.
OBJECTIVE: To describe primary care physicians' clinical decision making regarding late-life depression.
DESIGN: Longitudinal collection of data regarding physicians' clinical assessments and the volume and content of patients' ambulatory visits as part of a randomized clinical trial of a physician-targeted intervention to improve the treatment of late-life depression.
SETTING: Academic primary care group practice.
PATIENTS/PARTICIPANTS: One-hundred and eleven primary care physicians who completed a structured questionnaire to describe their clinical assessments immediately following their evaluations of 222 elderly patients who had reported symptoms of depression on screening questionnaires.
INTERVENTIONS: Intervention physicians were provided with their patient's score on the Hamilton Depression rating scale (HAM-D) and patient-specific treatment recommendations prior to completing the questionnaire regarding their clinical assessment.
MAIN RESULTS: Those physicians not provided HAM-D scores were just as likely to rate their patients as depressed, as determined by specific query of these physicians regarding their clinical assessments. A physician's clinical rating of likely depression did not consistently result in the formulation of treatment intentions or actions. Treatment intentions and actions were facilitated by provision of treatment algorithms, but treatment was received by fewer than half of the patients whom physicians intended to treat. Barriers to treatment appear to include both physician and patient doubts about treatment benefits.
CONCLUSIONS: Lack of recognition of depressive symptoms did not appear to be the primary barrier to treatment. Recognition of symptoms and access to treatment algorithms did not consistently result in progression to subsequent stages in treatment decision making. More research is needed to determine how patients and physicians weigh the potential risks and benefits of treatment and how accurately they make these judgments.
Improving treatment of late life depression in primary care: a randomized clinical trial.
OBJECTIVE: Facilitate primary care physicians' compliance with recommended standards of care for late life depression by reducing barriers to recognition and treatment.
DESIGN: Randomized controlled clinical trial of physician-targeted interventions.
SETTING: Academic primary care group practice caring for an urban, medically indigent patient population.
PATIENTS/PARTICIPANTS: Patients aged 60 and older who exceeded the threshold on the Centers for Epidemiologic Studies Depression Scale (CES-D) and the Hamilton Depression Rating Scale (HAM-D) and their primary care physicians.
INTERVENTION: Physicians of intervention patients were provided with patient-specific treatment recommendations during 3 special visits scheduled specifically to address the patient's symptoms of depression. In general, physicians were encouraged to establish a diagnosis of depression and educate their patient about the diagnosis, discontinue medications that can cause or exacerbate depressive symptoms, initiate antidepressants when appropriate, and consider referral to psychiatry. Guidelines for prescribing antidepressants were provided. Control physicians received no intervention, and control patients received usual care.
MAIN OUTCOME MEASURES: Frequency of recording a depression diagnosis, stopping medications associated with depression, initiating antidepressant medication, and psychiatry referral; mean changes in HAM-D and Sickness Impact Profile (SIP) scores.
RESULTS: One hundred three physicians and 175 patients were involved in the clinical trial. Physicians of intervention patients were more likely to diagnose depression and prescribe antidepressants (P < 0.01). There were no differences between the groups in the frequency of stopping medications associated with depression or referrals to psychiatry. Medications with the strongest cause and effect relationship to depression were infrequently used in this cohort of patients. Although both groups showed improvement in HAM-D and SIP scores, we were unable to demonstrate significant differences in HAM-D or SIP scores between the 2 groups.
CONCLUSIONS: Intensive screening and feedback of patient-specific treatment recommendations increased the recognition and treatment of late life depression by primary care physicians. However, we were unable to demonstrate significant improvement in depression or disability severity among intervention patients despite the informational support provided to their physicians. Efforts to improve the functional status of these patients may require more integrated interventions and more aggressive attempts to target psychosocial stressors traditionally outside the purview of primary care.
Does testing for depression influence diagnosis or management by general practitioners?
This study set out to assess the effects on diagnosis and management of providing general practitioners with feedback of patients' scores on a depression screening instrument. One hundred and sixteen general practice attenders aged 16-64 with undetected depression were identified using the Beck Depression Inventory (BDI). The BDI scores of a random 45% were disclosed to the general practitioners. Subjects and medical casenotes were reviewed over 12 months. Thirty-one (27%) of subjects were later diagnosed as depressed. Rates of diagnosis were higher in the disclosed group, but only after six months. Rates of intention to treat were low, but were marginally higher for the disclosed group; they were much higher for patients diagnosed by the doctors themselves. Feedback of screening questionnaire results appears to be of limited value in enhancing general practitioners' detection or management of depression.
Twelve month outcome of depression in general practice: does detection or disclosure make a difference?
OBJECTIVES: To assess the extent to which the outcome of depression among primary care attenders may be affected by medical diagnosis or by feedback of questionnaire results in unrecognised cases.
DESIGN: Prospective 12 month study including a randomised controlled trial of the effects of disclosure, with data on depression status and clinical management collected by questionnaire and interview.
SETTING: Two group practices in north Liverpool.
SUBJECTS: 1099/1444 (76%) consecutive adult attenders completed the Beck depression inventory, of whom 179 with scores of at least 14 were followed up.
INTERVENTIONS: Disclosure of a random 45% (52/116) of depression scores to general practitioners for subjects whose depression was undetected.
MAIN OUTCOME MEASURES: Depression status estimated by depression score at start of study and at six and 12 months, with subsample validation against ICD-10 criteria.
RESULTS: Questionnaire response rates were 76% (136/179) at six months and 68% (122/179) at 12 months and were higher for women than men. The median depression score was 19 (interquartile range 15 to 22) initially, decreasing to 16 (11 to 23) at 12 months. The median depression score decreased significantly (two sided test, P = 0.019) in subjects whose depression was unrecognised at the index consultation but increased in those whose depression had been detected by their general practitioners. Disclosure of cases of unrecognised depression to general practitioners had no effect on outcome. Intention to treat was associated with a worse prognosis, although only a minority of subjects received adequate treatment.
CONCLUSIONS: Disclosure of undetected depression did not improve prognosis. A diagnosis of depression in general practice should be considered simply as a marker of its severity.
Detection and management of mental health problems of older patients by primary care providers.
Evidence is accruing that older individuals receive little attention for mental health problems and that any attention that is given is most often within the primary care setting. A randomized clinical trial was carried out at a primary care clinic of The Johns Hopkins University, Baltimore, testing the ability of feedback of the results of a screening instrument (the General Health Questionnaire) to increase awareness in clinicians of the emotional and psychological problems of their patients. This report contrasts those aged 65 years and older with younger patients. Detection and management of mental morbidity were lower for older individuals, but the feedback intervention increased the likelihood of attention to these problems. This was not true for younger patients. Detection was significantly higher for older patients when screening data were made available, as was management, although the latter difference was not statistically significant. There was evidence as well that the intervention moved clinicians to greater congruence with their older patients in the perception that current mental health problems existed. These findings have important implications for primary care.
An experiment to change detection and management of mental morbidity in primary care.
A randomized clinical trial was conducted in a group practice for the primary care of adult patients to address the effect of feedback to providers of information from a psychiatric screening questionnaire, the General Health Questionnaire (GHQ). The practice is staffed by faculty, residents, and health care extenders of The Johns Hopkins University School of Medicine's Division of Internal Medicine. The patient population was drawn mainly from the inner city community in Baltimore that surrounds the hospital, where the practice is physically based. The GHQ was administered at the time of a regular visit to the practice and results made available to the clinicians for randomly allocated subsamples of their patients. The study results showed that feedback of GHQ information led to only marginal effects on overall detection of mental health problems among the patients in general. However, marked increases in detection occurred among the elderly, blacks, and men, subgroups that ordinarily have relatively low rates of detection of mental morbidity by primary care practitioners. Feedback of GHQ information did not affect management.
The usefulness of screening for mental illness.
The study assessed the effect of screening for mental disorder by means of the General Health Questionnaire (GHQ) on the rate of detection of mental disorder by fourteen physicians in a primary-care clinic. After completing the GHQ, patients were randomised into control (722 patients) and experimental (730 patients) groups. GHQ results of the experimental group were made available to the physicians; those of the control group were not. Sociodemographic factors influenced the physicians' rate of diagnosis of mental disorders (rates were lower for men, students, and patients with at least a partial college education than in subjects who had a low income, less than 7 years of school, or were widowed) but there was no difference between control and experimental groups (16.8% vs 16.0%). Among patients with a prior diagnosis of a mental disorder, twice as many were found to have mental disorders by the physicians as by the GHQ (70% vs 33%).
Computerized assessment of common mental disorders in primary care: effect on clinical outcome.
OBJECTIVE: A randomized controlled trial was conducted to examine the clinical effectiveness of providing general practitioners (GPs) with the results of a self-administered computerized assessment of common mental disorders.
METHOD: Attenders at a general practice in a deprived inner city area of South London were identified using case finding questionnaires. Six hundred and eighty-one subjects were randomly allocated to three groups which differed in the information provided to the GP: 1) no additional information was given to the GP; 2) the results of the 12 item General Health Questionnaire (GHQ) were given to the GP (the GHQ is a paper and pencil questionnaire that assesses common mental disorders); 3) the results of a self-administered computerized assessment (PROQSY) of common mental disorders were provided for the GP.
RESULTS: Clinical outcome was assessed using the 12-item GHQ. Consultations with the GP, prescriptions and referrals within and outside the practice were also recorded. The group in whom the GP received the results of the computerized assessment showed a modest clinical improvement, relative to the other two groups after 6 weeks. There was no difference in clinical outcome between the groups at 6 months. There appeared to be no increase in consultations or prescriptions in the computerized assessment group.
CONCLUSIONS: Self-administered computerized assessments for psychiatric disorder have potential as a means of improving the clinical outcome of patients in primary care. It is likely that the effectiveness of the approach would be greatly increased by linking the results of computerized assessments to clinical practice guidelines, tailored to the individual patient by means of computerized technology.
Screening of depression in relationship to subsequent patient and physician behavior.
When internal medicine clinic patients were prescreened for depression and this information was fed back to their physicians, significant effects could be noted on the medical records. On the initial visit, prescreening and previsit feedback about depression increased its notation in the medical record by three times, and among depressed patients, resulted in significantly fewer laboratory tests being orders (X = 2.85 vs. 8.12 for depressed patients with feedback after). During the following year, record notations about depression were more likely to be made for those depressed patients that initially were in the "feedback before" group. These patients also saw twice as many providers, made three times as many visits, had three times as any tests ordered, and twice as many medications prescribed as those depressed patients in the "feedback after" group. These findings demonstrate that simple prescreening and feedback techniques may have significant and persistent influences on several dimensions of patient and physician behavior.
The effect of screening, sensitization, and feedback on notation of depression.
Medical records of 150 medical ambulatory care patients randomly assigned to groups in which screening for depression, physician sensitization about depression, and informational feedback to physicians were systemically varied were reviewed for physician notations about depression and its treatment. Forty-two percent of the 100 patients screened with the Zung self-rating depression scale had scores outside the normal range. Chart notation about depression was effectively and appropriately increased by feedback and sensitization from 8 to 25 percent, but these procedures were less effective in increasing treatment interventions, which were noted for 12 percent of the entire sample. Physicians responded to patient information about depression presented to them in the format of a laboratory test, and such previsit screening devices may increase physician attention to psychological problems in general medical settings.
Improving physicians' recognition and treatment of depression in general medical care. Results from a randomized clinical trial.
A randomized clinical trial was performed to assess whether the results of a depression screening instrument, when provided to physicians, could influence their recognition and treatment of depression in a primary care setting. The intervention consisted of randomly informing or not informing physicians of the depression status of 100 patients who screened positively for depression on both the Zung Self-rating Depression Scale (SDS) and a DSM-III screen. For 12 months patients were followed to assess depression status, and medical records were audited to assess depression recognition and treatment. Results show that feedback to physicians of SDS scores of previously unrecognized depressed patients makes a significant difference in greater recognition (56.2% vs. 34.6%) and treatment (56.2% vs. 42.3%) of depression over the 12-month study period. This was especially true for patients with high somatic (P less than 0.05) or low psychologic symptoms of depression (P less than 0.05). These results suggest that routine use of a depression screening instrument can improve physician recognition of depression, with increased initiation of treatment.
Recognition of depression by family medicine residents: the impact of screening.
Psychiatric problems are often encountered in general medical settings, yet physicians frequently fail to identify such problems. Validated questionnaires assessing psychiatric symptoms have been shown to be more sensitive than physicians in detecting cases of psychiatric morbidity. This study deals with depression, the psychiatric problem most frequently seen in primary care settings. A self-administered depression questionnaire was used to alert residents to possible cases of depression. Relay of information from the questionnaire significantly increased resident recognition of depression.
A randomized controlled trial of the Geriatric Depression Scale in an inpatient ward for older adults.
OBJECTIVES: To measure the prevalence of high scores on the Geriatric Depression Scale in an inpatient unit for older people and assess whether administration of this instrument increased the use of antidepressant medication.
DESIGN: Randomized controlled trial.
SETTING: Inpatient unit for assessment, treatment and rehabilitation of older adults in a district hospital.
SUBJECTS: Consecutive admissions to the inpatient unit were approached. Of 198 people, 100 gave consent and were randomized to receive the intervention.
INTERVENTIONS: The Geriatric Depression Scale and the Folstein Mini-mental State Examination were administered to the intervention group. The Nottingham Instrumental Activities of Daily Living questionnaire and the Folstein Mini-mental State Examination were administered to the placebo group. The scores of these instruments and a copy of the completed instrument were placed in the subject's case notes. For those subjects randomized to receive the Geriatric Depression Scale an interpretation of the score was written in the case notes.
MAIN OUTCOME MEASURES: The primary outcome measure was whether antidepressant medication was listed on the discharge summary for the admission. Other outcome measures were death, readmission and use of antidepressant medication three months after administration of the instruments.
RESULTS: There was a prevalence of Geriatric Depression Scale scores greater than 10 of 52% in the 50 people administered this instrument. Six out of 46 people administered the Geriatric Depression Scale, who were discharged in the study period, were on antidepressant medication at discharge. Three out of 47 people administered the placebo instrument were on antidepressant medication at discharge. The absolute difference in proportions was 6.7%, 95% confidence interval 19 to -5.3%.
CONCLUSIONS: A high proportion of patients admitted to an inpatient unit for assessment, treatment and rehabilitation scored in the depressed range on the Geriatric Depression Scale; however, use of the Geriatric Depression Scale in this clinical setting did not increase the use of antidepressant medication. This may be because the instrument is too nonspecific.
Randomized trial of case-finding for depression in elderly primary care patients.
OBJECTIVE: To determine the effect of case-finding for depression on frequency of depression diagnoses, prescriptions for antidepressant medications, prevalence of depression, and health care utilization during 2 years of follow-up in elderly primary care patients.
DESIGN: Randomized controlled trial.
SETTING: Thirteen primary care medical clinics at the Kaiser Permanente Medical Center, an HMO in Oakland, Calif, were randomly assigned to intervention conditions (7 clinics) or control conditions (6 clinics).
PARTICIPANTS: A total of 2,346 patients aged 65 years or older who were attending appointments at these clinics and completed the 15-item Geriatric Depression Scale (GDS). GDS scores of 6 or more were considered suggestive of depression.
INTERVENTIONS: Primary care physicians in the intervention clinics were notified of their patients' GDS scores. We suggested that participants with severe depressive symptoms (GDS score >/= 11) be referred to the Psychiatry Department and participants with mild to moderate depressive symptoms (GDS score of 6 -10) be evaluated and treated by the primary care physician. Intervention group participants with GDS scores suggestive of depression were also offered a series of organized educational group sessions on coping with depression led by a psychiatric nurse. Primary care physicians in the control clinics were not notified of their patients' GDS scores or advised of the availability of the patient education program (usual care). Participants were followed for 2 years.
MEASUREMENTS AND MAIN RESULTS: Physician diagnosis of depression, prescriptions for antidepressant medications, prevalence of depression as measured by the GDS at 2-year follow-up, and health care utilization were determined. A total of 331 participants (14%) had GDS scores suggestive of depression (GDS >/= 6) at baseline, including 162 in the intervention group and 169 in the control group. During the 2-year follow-up period, 56 (35%) of the intervention participants and 58 (34%) of the control participants received a physician diagnosis of depression (odds ratio [OR], 1.0; 95% confidence interval [CI], 0.6 to 1.6; P =.96). Prescriptions for antidepressants were received by 59 (36%) of the intervention participants and 72 (43%) of the control participants (OR, 0.8; 95% CI, 0.5 to 1.2; P =.3). Two-year follow-up GDS scores were available for 206 participants (69% of survivors): at that time, 41 (42%) of the 97 intervention participants and 54 (50%) of the 109 control participants had GDS scores suggestive of depression (OR, 0.7; 95% CI, 0.4 to 1.3; P =.3). Comparing participants in the intervention and control groups, there were no significant differences in mean GDS change scores (-2.4 +/- SD 3.7 vs -2.1 SD +/- 3.6; P =.5) at the 2-year follow-up, nor were there significant differences in mean number of clinic visits (1.8 +/- SD 3.1 vs 1.6 +/- SD 2.8; P =.5) or mean number of hospitalizations (1.1 +/- SD 1.6 vs 1.0 +/- SD 1.4; P =.8) during the 2-year period. In participants with initial GDS scores > 11, there was a mean change in GDS score of -5.6 +/- SD 3.9 for intervention participants (n = 13) and -3.4 +/- SD 4.5 for control participants (n = 21). Adjusting for differences in baseline characteristics between groups did not affect results.
CONCLUSIONS: We were unable to demonstrate any benefit from case-finding for depression during 2 years of follow-up in elderly primary care patients. Studies are needed to determine whether case-finding combined with more intensive patient education and follow-up will improve outcomes of primary care patients with depression.
Case-finding for depression in primary care: a randomized trial.
PURPOSE: Depression is a highly prevalent, morbid, and costly illness that is often unrecognized and inadequately treated. Because depression questionnaires have the potential to improve recognition, we evaluated the accuracy and effects on primary care of two case-finding instruments compared to usual care.
SUBJECTS AND METHODS: The study was conducted at three university-affiliated and one community-based medical clinics. Consecutive patients were randomly assigned to be asked a single question about mood, to fill out the 20-item Center for Epidemiologic Studies Depression Screen, or to usual care. Within 72 hours, patients were assessed for Diagnostic and Statistical Manual of Mental Disorders Third Revised Edition (DSM-III-R) disorders by an assessor blinded to the screening results. Process of care was assessed using chart audit and administrative databases; patient and physician satisfaction was assessed using Likert scales. At 3 months, depressed patients and a random sample of nondepressed patients were re-assessed for DSM-III-R disorders and symptom counts.
RESULTS: We approached 1,083 patients, of whom 969 consented to screening and were assigned to the single question (n = 330), 20-item questionnaire (n = 323), or usual care (n = 316). The interview for DSM-III-R diagnosis was completed in 863 (89%) patients; major depression, dysthymia, or minor depression was present in 13%. Both instruments were sensitive, but the 20-item questionnaire was more specific than the single question (75% vs 66%, P = 0.03). The 20-item questionnaire was less likely to be self-administered (54% vs 90%) and took significantly more time to complete (15 vs 248 seconds). Case-finding with the 20-item questionnaire or single question modestly increased depression recognition, 30/77 (39%) compared with 11/38 (29%) in usual care (P = 0.31) but did not affect treatment (45% vs 43%, P = 0.88). Effects on DSM-III-R symptoms were mixed. Recovery from depression was more likely in the case-finding than usual care groups, 32/67 (48%) versus 8/30 (27%, P = 0.03), but the mean improvement in depression symptoms did not differ significantly (1.6 vs 1.5 symptoms, P = 0.21).
CONCLUSIONS: A simple question about depression has similar performance characteristics as a longer 20-item questionnaire and is more feasible because of its brevity. Case-finding leads to a modest increase in recognition rates, but does not have consistently positive effects on patient outcomes.
Recognition and treatment of depression in a family medicine practice.
To test the hypothesis that depression is significantly underdiagnosed in general medical settings, the Zung Self-Rating Depression Scale was administered to 1,086 family medicine outpatients seen during a 12-month period before their initial medical examination. The effects of such screening on clinical recognition and treatment of depression were examined. Of the 1,086 patients, 143 (13.2%) were symptomatically depressed. These patients were randomized into two groups: 102 were identified as clinically depressed to their physician, and the remaining 41 were not (control group). Physicians diagnosed depression in 15% of the control group and in 68% of the identified group. At 4-week follow-up, 64% of the identified patients who were treated with maprotiline (16 of 25) showed improvement; only 28% of the identified patients who were electively not treated improved. Improvement occurred in only 18% of the control group. It appears that the diagnosis of depression is not ordinarily made in family medicine outpatient settings and that self-rating depression scales are useful diagnostic aids, whose regular use is indicated by the high prevalence of depression in general medical populations.
Options:
A: They significantly improve the detection, management, and outcome of depression.
B: They have minimal impact on the detection, management, or outcome of depression.
C: They significantly improve the detection of depression but have no impact on management or outcome.
D: They significantly improve the management and outcome of depression but have no impact on detection. | B |
475 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What is the effectiveness of intrauterine insemination (IUI) with or without ovarian stimulation in women with cervical hostility who have failed to conceive? Please answer this question based on the information provided below:
Higher pregnancy rates following treatment of cervical factor with intrauterine insemination without superovulation versus intercourse: the importance of a well-timed postcoital test for infertility.
A randomized study comparing the efficacy of timed intrauterine insemination (IUI) without hyperstimulation to sexual intercourse was performed in women with cervical factor infertility. Among the strict requirements for inclusion in the study were a normal semen analysis in the male partner, as well as the failure to demonstrate any sperm with progressive forward motion in a postcoital test performed 8-12 h after intercourse at the time of a mature follicle. All other infertility factors were negative. The data demonstrated a statistically significant fecundity rate at 1 month when IUI was compared to intercourse (21.2 vs. 3.9%). These data suggest that carefully timed IUI in nonhyperstimulated cycles is an effective treatment for cervical factor infertility.
The value of artificial insemination with husband's semen in infertility due to failure of postcoital sperm-mucus penetration--controlled trial of treatment.
Artificial insemination with husband's semen into the cervical canal and uterine cavity (high AIH) was assessed by a randomized controlled prospective study in 46 couples whose infertility was due to failure of sperm mucus penetration, as defined by negative postcoital tests, after excluding all interfering female factors and men with sperm density less than 1 x 10(6)/ml. Seminal analysis was abnormal in 18 of the 46 men and sperm antibodies in semen were detected in 19 of the remaining 28 with normal seminal analysis. Overall, the cumulative conception rate after 6 months with AIH was 4.7 (SE 3.8)% and without treatment was 6.6 (SE 3.9)%. The results were unaffected by the findings on seminal analysis or by the presence or absence of sperm antibodies in semen. AIH appeared to be of no benefit.
A prospective trial of intrauterine insemination of motile spermatozoa versus timed intercourse.
STUDY OBJECTIVE: The efficacy of intrauterine insemination (IUI) of selected motile sperm.
DESIGN: Prospective randomized sequential alternating cycle trial comparing IUI with luteinizing hormone (LH)-timed intercourse.
SETTING: Clinical infertility service.
PATIENTS: Couples selected included unexplained infertility (n = 73), cervical mucus hostility (n = 24), moderate semen defect (n = 110), and severe semen defect (n = 78). Two hundred eighty-five couples undertook 600 IUI cycles and 505 LH-timed intercourse.
RESULTS: Overall, IUI was slightly more effective than LH-timed intercourse with a pregnancy rate of 6.2% versus 3.4% per cycle. When individual categories were considered only, IUI for severe semen defect was significantly better (5.6% versus 1.3%, P less than 0.05). The first IUI cycle was more effective when compared with both subsequent IUI cycles and the initial LH-timed cycle. Overall, 74% (27/37) of IUI pregnancies occurred in the first cycle.
CONCLUSIONS: Compared with LH-timed intercourse, IUI provided little or no improved expectation of pregnancy but was beneficial in couples with severe semen defect. The occurrence of pregnancy was limited per cycle and confined essentially to the initial cycle of treatment. Continued IUI is considered to be unrewarding.
Intrauterine insemination does and clomiphene citrate does not improve fecundity in couples with infertility due to male or idiopathic factors: a prospective, randomized, controlled study.
In the present prospective study we compared, in terms of pregnancy rates, the differences between intrauterine insemination (IUI) of in vitro capacitated husband's semen and timed natural intercourse in spontaneous or clomiphene citrate (CC) stimulated cycles. A rapid urinary luteinizing hormone peak detection test was used for timing of ovulation. Forty patients suffering from longstanding infertility of male (n = 17), cervical (n = 2), and idiopathic (n = 21) origin were randomly assigned into four distinct treatment modalities during 4 consecutive cycles. A total of 132 cycles were analyzed. In 35 cycles treated with CC plus IUI, five conceptions were achieved, whereas three pregnancies occurred in 32 inseminated spontaneous cycles. Only 1 patient conceived after timed intercourse in 31 CC stimulated cycles, and no pregnancy resulted from 34 spontaneous cycles combined with timed intercourse. There was a statistically significant higher conception rate in cycles in which IUI was performed, whereas the use of CC does not seem to improve the pregnancy rate. Analysis of results for other modifying factors did not substantially affect the relative risk (odds ratio) of pregnancy.
Effectiveness of intrauterine insemination in subfertile couples with an isolated cervical factor: a randomized clinical trial.
After randomization of subfertile couples with an isolated cervical factor to intrauterine insemination for 6 months or expectant management for 6 months, 26 women (51%) vs. 16 women (33%) conceived, respectively. Of these pregnancies, 22 (43%) vs. 13 (27%) were ongoing (relative risk, 1.6; 95% confidence interval, 0.91 to 2.8). There was one multiple pregnancy in the group that was allocated to intrauterine insemination. This trial suggests a beneficial effect of IUI in couples with an isolated cervical factor.
Intrauterine insemination of washed husband's spermatozoa: a controlled study.
We performed intrauterine insemination with washed husband's spermatozoa in 27 couples with clear evidence of impaired sperm mucus interaction due to cervical hostility or immunologic male subfertility and in 30 couples with subnormal semen, but optimal cervical mucus qualities. In each couple insemination cycles were alternated with cycles during which normal intercourse took place. Both types of cycles were monitored for LH. When a clear rise of LH levels could be detected, either IUI was scheduled or intercourse advised for the following day. In the male subfertility group no difference between the pregnancy rates of insemination and intercourse cycles was present. In the group with impairment of sperm-mucus interaction, the pregnancy rate of the insemination cycles was 16%, whereas no pregnancies occurred during intercourse cycles.
Options:
A: IUI significantly increases pregnancy rates in women with cervical hostility.
B: IUI is an effective treatment for cervical hostility, leading to higher pregnancy rates compared to timed intercourse.
C: There is no evidence that IUI is an effective treatment for cervical hostility.
D: IUI leads to a higher incidence of spontaneous abortion, multiple pregnancies, and ovarian hyperstimulation syndrome. | C |
476 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What are the effects of using intraoperative mitomycin C (MMC) compared to placebo in trabeculectomy surgery for glaucoma? Please answer this question based on the information provided below:
Clinical evaluation of the effect of mitomycin-C in re-operation for primary open angle glaucoma.
The aim of the study was to evaluate the effect of mitomycin-C (MMC) in a second antiglaucoma operation after failure of the first operation. We assessed 46 patients (26 male, 20 female, mean age 64.2 years) with high intraocular pressure (IOP) (mean 32.4 +/- 5.2 mmHg) despite previous trabeculectomy (Tr-Ec) one to three years earlier and topical or systemic medical treatment. All patients underwent a second Tr-Ec and were randomly divided into two groups: group A, 24 patients, underwent a second Tr-Ec with MMC and group B, 22 patients, also underwent a second Tr-Ec but without MMC. Postoperative complications included: shallow anterior chamber (duration > 1 week), group A 29.2%, group B 13.6%; chroidal effusion, group A 8.3%, group B 0%; cystic degeneration of conjunctiva, group A 16.6%, group B 4.5%; transient maculopathy, group A 12.5%, group B 0%. IOP control (< or = 20 mmHg after 18 months) was: group A 20 patients (83.3%) with mean 12.5 +/- 3.2 mmHg and group B 13 patients (63.6%) with mean 19.6 +/- 6.1 mmHg. In conclusion, the use of MMC in re-operation for primary open-angle glaucoma is associated with a higher rate of and more severe postoperative complications than Tr-Ec alone. However, it achieves significantly lower IOP in a larger number of patients.
A randomized study of mitomycin augmentation in combined phacoemulsification and trabeculectomy.
PURPOSE: The purpose of the study is to determine whether the intraoperative application of subconjunctival mitomycin C (MMC), during combined phacoemulsification and trabeculectomy, is an effective means of improving filtration, defined as overall lower intraocular pressure (IOP) and less antiglaucoma medication use.
METHODS: Twenty-nine patients with a visually significant cataract and glaucoma were randomized, in a double-masked fashion, to receive intraoperative MMC (0.5 mg/ml) or placebo.
RESULTS: Follow-up ranged from 6 to 30 months (mean, 20 months). Postoperative visual acuity at 1 year was 20/40 or better in 14 of 15 eyes operated on in the placebo group and 13 of 14 eyes operated on in the MMC group. Intraocular pressure at 8 months averaged 15.2 +/- 1.5 mmHg in the placebo-treated eyes versus 12.3 +/- 1.6 mmHg in the MMC-treated eyes. At 12 months, IOPs averaged 16.2 +/- 1.5 mmHg in the placebo-treated eyes versus 12.6 +/- 1.0 mmHg in the MMC-treated eyes. On average, the MMC group had postoperative IOP levels 3.0 mmHg lower than did the placebo group (P = 0.04) throughout the study. In the placebo group, laser suture lysis was required in a greater number of patients (80% versus 43%) and to a greater extent (mean = 2.0 versus 0.7 suture lysed) (P < 0.05). At 12 months, 5 of the 15 patients in the placebo group required an average of 1.8 medications for IOP control, whereas 0 of the 14 patients in the MMC group needed IOP-lowering medications. A late endophthalmitis developed through an intact bleb in one patient in the MMC group; otherwise, complications were minimal in each group.
CONCLUSION: These results suggest that intraoperative MMC application, during combined phacoemulsification and trabeculectomy surgery, does improve early filtration as shown by overall lower IOPs and less antiglaucoma medication use.
A placebo-controlled, double-masked evaluation of mitomycin C in combined glaucoma and cataract procedures.
PURPOSE: This study was performed to determine if adjunctive use of mitomycin C (MMC) would increase the success of combined phacoemulsification, intraocular lens implantation, and trabeculectomy surgery with releasable sutures.
METHODS: Seventy-two eyes with cataract and glaucoma, requiring surgery for decreased vision, uncontrolled intraocular pressure, or to obtain a better view of the optic nerve, were randomized to receive a 2.5-minute subconjunctival exposure to either MMC (0.5 mg/ml) or placebo balanced salt solution. Postoperative evaluations at 3, 6, and 12 months were performed by a masked observer who recorded visual acuity, intraocular pressure, glaucoma medications, presence of filtering blebs, and complications. Endothelial cell counts were measured before and 3 months after surgery.
RESULTS: The MMC group had significantly greater reduction in mean intraocular pressure through the first 12 months of follow-up (7.05-7.65 mmHg versus 2.62-3.84 mmHg; P = 0.001-0.028). In addition, through the first 6 months of follow-up, the MMC group required significantly fewer medications (0.4-0.5 versus 1.1-1.2; P = 0.002-0.004). Requirements for additional glaucoma surgery were less in the MMC group (4/ 36) than in the placebo group (7/35) (P = 0.301). Filtering blebs were significantly larger at 6 and 12 months (P = 0.002 and P = 0.001, respectively), and would leaks were more common (P = 0.101) in the MMC group. The mean decrease in endothelial cell count at month 3 was slightly, although not significantly, greater in the MMC treatment group (206.9 versus 91.3 cells/mm2* P = 0.377).
CONCLUSION: The increased success of the glaucoma procedure in the MMC group together with relatively minor toxicity, suggests its use is beneficial in combined glaucoma-cataract surgery.
Low-dose mitomycin C trabeculectomy in patients with advanced glaucoma.
PURPOSE: The purpose of this study was to analyze the efficacy and safety of low-dose (0.2 mg/ml) intraoperative mitomycin C in primary trabeculectomy.
METHODS: Twenty-eight eyes of 28 patients with advanced primary open-angle glaucoma undergoing primary trabeculectomy were randomized to either mitomycin C (0.2 mg/ml) or saline solution intraoperatively for 3 min. Intraocular pressure was measured at 1 day; 1 week; 1, 3, and 6 months postoperatively; and at the final visit.
RESULTS: Mean follow-up was 17.0 +/- 5.6 months for the mitomycin C group and 15.7 +/- 5.1 months for the control group. Mean intraocular pressures were significantly lower in the treated group on the first postoperative day (p = 0.021), at the 6-month interval (p = 0.001), and at the final visit (p = 0.001). At the last follow-up examination, intraocular pressure was < or = 15 mm Hg in 12 (85.7%) of the mitomycin C-treated eyes and in four (28.6%) of the control eyes (p = 0.002). Life table analysis showed a significantly higher probability of intraocular pressure control in the mitomycin C group than in the control group (p = 0.0065). Choroidal effusion was observed in five (35.7%) treated eyes and two (14.3%) control eyes, whereas shallow anterior chamber were present in five (35.7%) treated eyes and one control eye (7.1%).
CONCLUSION: Despite inducing a higher short-term complication rate, low-dose mitomycin C may be an alternative in the treatment of eyes with advanced glaucomatous damage requiring low final intraocular pressures.
Low-dosage mitomycin C as an adjunct to trabeculectomy. A prospective controlled study.
PURPOSE: To assess the advantages and adverse effects of intraoperative low-dose Mitomycin C in filtering glaucoma surgery.
METHODS: Sixty eyes of 48 patients undergoing surgery for uncontrolled glaucoma were randomized to two groups: one underwent standard trabeculectomy, the other had trabeculectomy with intraoperative application of 0.1 mg/ml mitomycin C. Follow-up was at least one year.
RESULTS: The success rate (IOP < 18 mmHg) was 96.6% in the mitomycin C group and 73.3% in the control group. Mean IOP at one year of successful cases was 11.1 +/- 3.1 mmHg in the mitomycin C group and 16.4 +/- 6.1 mmHg in controls (p < 0.0001). Two patients in the mitomycin C group (6.6%) and six (20%) in the control group needed antiglaucomatous drugs to keep IOP below 18 mmHg.
CONCLUSIONS: Mitomycin C is a useful adjunct to glaucoma surgery. Adverse effects at the dosage used are mainly due to hypotony and are preventable with two-layer suture. Low-dose mitomycin C may be useful in standard primary trabeculectomy.
A long-term dose-response study of mitomycin in glaucoma filtration surgery.
OBJECTIVE: To establish the long-term, dose-response relationship between the concentration of and duration of exposure to mitomycin to a decrease in intraocular pressure (IOP) and fewer complications.
METHODS: We performed a prospective double-masked, placebo-controlled, 1-year study evaluating the decrease in IOP and fewer complications of fornix-based trabeculectomy surgery in 300 eyes equally divided among therapy with placebo; mitomycin, 0.2 mg/ mL, applied for 2 minutes; mitomycin, 0.4 mg/mL, applied for 4 minutes; or mitomycin, 0.4 mg/mL, applied for 2 minutes. All of the eyes had vertical and horizontal cup-disc ratios greater than 0.7.
RESULTS: We observed significant treatment-related differences in IOP, with a decrease in IOP in all 3 mitomycin-treated groups for all of the times beyond 1 month. The number of eyes achieving strict IOP control and the development of cataract suggest a possible dose-response effect for concentration and time of exposure. Progressive lens opacification was the most frequent complication in 54 eyes (18.1%). The incidence of progressive lens changes markedly increased in subjects receiving 4 minutes of mitomycin therapy. Cataract formation was unrelated to IOP. Other complications were rare. Macular folds developed in 6 patients, with visual acuity returning to better than 20/40 in all but 1 patient.
CONCLUSIONS: A possible dose-response relationship seemed to exist between the concentration of and duration of exposure to mitomycin. Length of exposure seems to be more important than concentration. The benefits of additional decreases in IOP must be weighed against the potential for increases in the risk of complications.
Adjunctive subconjunctival mitomycin C in glaucoma triple procedure.
PURPOSE: To evaluate the potential benefit of adjunctive subconjunctival mitomycin in patients with primary open-angle glaucoma undergoing primary trabeculectomy combined with phacoemulsification and intraocular lens implantation.
METHODS: Seventy-eight eyes of 78 patients with primary open-angle glaucoma with visually symptomatic cataracts and no previous incisional surgery were randomized to receive either no mitomycin C or a subconjunctival application of 1-, 3-, or 5-minute mitomycin C (0.5 mg/ml).
RESULTS: Follow-up (mean +/- standard deviation) was 21.0 +/- 7.7 months. The mean postoperative intraocular pressures were significantly lower with significantly less medications than the preoperative values at each follow-up time (1, 3, 6, 9, 12, 15 months, and last follow-up) for all groups (P < 0.05 for each). However, there was no significant difference at each follow-up time in intraocular pressure, medications, or best-corrected visual acuity among the four groups or between the control and the total mitomycin C group.
CONCLUSION: Adjunctive subconjunctival mitomycin C did not further improve the final intraocular pressure outcome of the primary trabeculectomy combined with phacoemulsification and intraocular lens implantation in patients with primary open-angle glaucoma. Future studies will determine the appropriate role, if any, for adjunctive mitomycin C in selected primary glaucoma triple procedures.
The role of adjunctive mitomycin C in secondary glaucoma triple procedure as compared to primary glaucoma triple procedure.
OBJECTIVE: This study aimed to investigate whether previously failed glaucoma filtration surgery is a risk factor for filtration failure of subsequent trabeculectomy combined with cataract surgery and to determine the role of adjunctive mitomycin C (MMC) in the secondary glaucoma triple procedure (SGTP) as compared to primary glaucoma triple procedure (PGTP).
DESIGN: A prospective, controlled study that was randomized with respect to assignment to adjunctive MMC and a case-control design with respect to comparisons between SGTP and PGTP was studied.
PARTICIPANTS: The SGTP group consisted of 49 eyes of 49 consecutive patients with primary open-angle glaucoma with a history of glaucoma filtration surgery requiring glaucoma medical therapy and in need of cataract surgery, randomized to adjunctive MMC (SGTP MMC subgroup of 21 eyes) and no adjunctive MMC (SGTP control subgroup of 28 eyes). The PGTP group consisted of 49 PGTP cases closely matched to the SGTP cases with respect to age, race, gender, MMC use, C:D ratio, and systemic diseases.
INTERVENTION: Trabeculectomy combined with phacoemulsification and a small incision (5 x 6 mm), all polymethylmethacrylate posterior chamber intraocular lens implantation with or without adjunctive MMC (0.5 mg/ml for 1 minute), was performed.
MAIN OUTCOME MEASURES: Surgery failure was defined as the need of an additional intraocular procedure or the need of more than one medication to achieve intraocular pressure control to the target level. Intragroup and intergroup comparisons were made with respect to filtration outcome among the SGTP and PGTP patients.
RESULTS: Without adjunctive MMC, filtration success was significantly less in SGTP than in PGTP (P = 0.03). Adjunctive MMC significantly increased the success rate of SGTP (P = 0.02) but not that of PGTP (P = 0.89) over the average follow-up period of 2 years.
CONCLUSIONS: Previously failed glaucoma filtration surgery is a significant risk factor for the filtration failure of combined surgery. Intraoperative use of adjunctive MMC significantly improves the filtration success rate of SGTP.
A fluorophotometric study of corneal endothelium after trabeculectomy using different concentrations of Mitomycin-C.
The aim of the study was to determine the corneal endothelial permeability coefficient (Pac) in subjects after trabeculectomies using different concentrations of Mitomycin-C (MMC). MMC, a highly toxic drug, is not without drawbacks and complications such as corneal damage. To ascertain a possible relationship between a level of endothelial permeability (Pac) and concentrations of MMC used, we performed, in a prospective study, trabeculectomies in cases of primary open-angle glaucoma (POAG), younger than 50 years, with either concentrations of 0.5 mg/ml of MMC (group 1: 11 eyes) or 0.2 mg/ml of MMC (group 2: 10 eyes). Group 3 consisted of 8 patients after a typical trabeculectomy without MMC and served as a control group (8 eyes). In all groups, before surgery and again 1, 3 and 6 months after surgery, corneal endothelial permeability (Pac) was determined by using anterior segment fluorophotometry (Fluorotron Master). The thickness of the cornea (CT) was measured with a DGH Technology ultrasonic pachymeter. One month after surgery the mean values of Pac were statistically significantly higher in groups 1 and 2 (group 1: 4.78 x 10(-4) cm/min, group 2: 4.67 x 10(-4) cm/min) in comparison with the control group (group 3: 3.37 x 10(-4) cm/min), but the differences between groups 1 and 2 were not statistically significant (p = 0.05). Six months after operation the mean values of Pac in all groups were normalized. In eyes that underwent trabeculectomy with MMC, higher concentrations of MMC were likely to have a transient adverse effect on corneal endothelial permeability. In light of the resulting toxic intraocular effect of MMC, the damage in the function of the corneal endothelial barrier is greater with greater concentrations of MMC.
A comparative clinical trial of mitomycin C and cyclosporin A in trabeculectomy.
This prospective, randomized clinical trial assessed the effects of mitomycin C and cyclosporin A used as antimetabolites in trabeculectomy on the post-operative IOP and success rate. Eighty-six consecutive patients were randomly allocated to three treatment groups. There were 30 patients in the mitomycin C group, 28 in the cyclosporin A group and 28 in the control group. The follow-up periods were different for the three groups and ranged from 6 to 30 months. The treatment groups consisted of primary open-angle glaucoma, closed-angle glaucoma, various secondary glaucomas and prior failed trabeculectomy. There were no significant differences pre-operatively with respect to IOP and number of medications used (p > 0.05). Postoperative IOP was considered to be successfully reduced when it was reduced by more than 25% from baseline or when it was lower than 20 mmHg. According to these criteria, IOP was under control in 90% of the mitomycin C treated eyes, 85.7% of cyclosporin A treated eyes and 71.4% of the control eyes. Postoperatively there was a significant decrease in IOP (p < 0.01) and in the number of medications need to control IOP (p < 0.01) in the mitomycin C and cyclosporin A groups. Post-operative IOP and number of medications in the mitomycin C and cyclosporin A group were similar. Complications encountered in the three groups were similar. There were no serious complications like hypotonus maculopathy. Our study highlights the utility of mitomycin C as an adjunct in glaucoma filtering surgery and indicated that cyclosporin A may also be used as an antimetabolite.
[The effect of mitomycin C on filtration surgery of glaucoma with poor prognosis].
OBJECTIVE: To determine the anticicatrization effect of mytomycin C (MMC).
METHODS: We randomly divided 30 cases (40 eyes) into two groups: 21 eyes in MMC group and 19 eyes in control group. Intra-operatively, 0.4 mg/ml MMC was used in the trabeculectomy in MMC group, and no MMC was used in the control group. The post-operative follow-up periods ranged from 6 to 25 months (mean, 10.0 months).
RESULTS: The successful rate of the operation of MMC group was 90.4% and that of the control group, 26.3% (P < 0.0001). The rate of eyes with functional filtering blebs was 17/21 and that of the control group, 4/19 (P = 0.002). Macular edema occurred in 3 eyes of MMC group and none in the eyes in the control group. There were no corneal complication and leakage of the wound.
CONCLUSION: The results show that MMC can promote the formation of functional filtering bleb and elevate the successful rate of filtration surgery.
Options:
A: MMC reduces the risk of surgical failure in eyes with no previous surgery and those at high risk of failure, and reduces mean intraocular pressure (IOP) at 12 months in all groups.
B: MMC increases the risk of surgical failure in eyes with no previous surgery and those at high risk of failure, and increases mean intraocular pressure (IOP) at 12 months in all groups.
C: MMC has no significant effect on the risk of surgical failure or mean intraocular pressure (IOP) at 12 months in any group.
D: MMC reduces the risk of surgical failure in eyes with no previous surgery and those at high risk of failure, but has no effect on mean intraocular pressure (IOP) at 12 months. | A |
477 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What were the findings regarding the efficacy of acyclovir in treating chickenpox in otherwise healthy children and adolescents? Please answer this question based on the information provided below:
Acyclovir treatment of varicella in otherwise healthy children.
STUDY OBJECTIVE: To determine whether acyclovir administered orally affects the duration and severity of varicella in otherwise normal children.
DESIGN: Randomized, placebo-controlled, double-blind trial.
SETTING: Patients' residence and university hospital clinic.
PATIENTS: One hundred five children between 5 and 16 years of age with laboratory-confirmed varicella entered the study. Of the 102 who were included in the final analysis, 50 received acyclovir and 52 received placebo.
INTERVENTION: Placebo or acyclovir was given orally four times daily, for 5 to 7 days. The acyclovir dose was adjusted as follows: 5 to 7 years of age, 20 mg/kg; 7 to 12 years, 15 mg/kg; and 12 to 16 years, 10 mg/kg.
MEASUREMENTS AND MAIN RESULTS: Acyclovir recipients, compared with the placebo group, defervesced sooner (median, 1 day vs 2 days; p = 0.001), experienced onset of cutaneous healing sooner, as reflected by a decrease in number of lesions (median, 3 days vs 2 days; p = 0.002), and had fewer skin lesions (median, 500 vs 336; p = 0.02). Acyclovir did not significantly change the rate of complications of varicella (10% in the acyclovir group vs 13.5% among placebo subjects). Adverse drug effects were not observed. Acyclovir recipients had lower geometric mean serum antibody titers to varicella-zoster virus than their placebo counterparts 4 weeks after the onset of illness, but antibody titers in both groups were similar 1 year later.
CONCLUSIONS: These results provide evidence that acyclovir is useful and well tolerated for treatment of varicella in otherwise healthy children.
Acyclovir treatment of varicella in otherwise healthy adolescents. The Collaborative Acyclovir Varicella Study Group.
STUDY OBJECTIVE: To determine whether orally administered acyclovir is of therapeutic benefit for varicella in otherwise healthy adolescents, and to compare the severity of the disease in adolescents with that in younger children.
DESIGN: Multicenter, randomized, placebo-controlled, double-blind trial.
SETTING: Patients' homes and university hospital clinics.
PATIENTS: Sixty-eight adolescents between 13 and 18 years of age with varicella entered the study. Of the 62 adolescents with laboratory-confirmed varicella who were included in the final analysis, 31 received acyclovir and 31 received placebo.
INTERVENTIONS: Placebo or an 800 mg acyclovir tablet was given orally four times daily for 5 days, beginning within 24 hours of onset of rash.
MEASUREMENTS AND MAIN RESULTS: Acyclovir recipients had significant reductions in times to cessation of new lesion formation (p less than 0.001), maximum number of lesions (p = 0.019), and defervescence (p = 0.045). Mean constitutional illness score was significantly reduced on day 4 (0.5 vs 1.5, p = 0.05), as was the mean number of residual hypopigmented lesions present on 28-day follow-up examination (22.7 vs 92.7, p = 0.018). Two complications, both bacterial superinfections, occurred in placebo recipients. Adverse experiences and varicella-zoster virus antibody titers measured 28 days after enrollment were similar in both treatment groups. Comparison of placebo recipients with children 2 to 12 years of age participating in a companion study indicated that varicella is more severe in adolescents: mean maximum total lesions (421 vs 347, p = 0.003), mean maximum constitutional illness score (3.1 vs 2.2, p = 0.032), and mean number of residual lesions (92.7 vs 33.2, p = 0.01) were all greater in the adolescent population.
CONCLUSIONS: Oral acyclovir therapy is safe and effective for treatment of varicella in otherwise healthy adolescents; this may be an appropriate subgroup for treatment with antiviral drugs because the disease is more severe in them than in younger children.
A controlled trial of acyclovir for chickenpox in normal children.
BACKGROUND: Chickenpox, the primary infection caused by the varicella-zoster virus, affects more than 3 million children a year in the United States. Although usually self-limited, chickenpox can cause prolonged discomfort and is associated with infrequent but serious complications.
METHODS: To evaluate the effectiveness of acyclovir for the treatment of chickenpox, we conducted a multicenter, double-blind, placebo-controlled study involving 815 healthy children 2 to 12 years old who contracted chickenpox. Treatment with acyclovir was begun within the first 24 hours of rash and was administered by the oral route in a dose of 20 mg per kilogram of body weight four times daily for five days.
RESULTS: The children treated with acyclovir had fewer varicella lesions than those given placebo (mean number, 294 vs 347; P less than 0.001), and a smaller proportion of them had more than 500 lesions (21 percent, as compared with 38 percent with placebo; P less than 0.001). In over 95 percent of the recipients of acyclovir no new lesions formed after day 3, whereas new lesions were forming in 20 percent of the placebo recipients on day 6 or later. The recipients of acyclovir also had accelerated progression to the crusted and healed stages, less itching, and fewer residual lesions after 28 days. In the children treated with acyclovir the duration of fever and constitutional symptoms was limited to three to four days, whereas in 20 percent of the children given placebo illness lasted more than four days. There was no significant difference between groups in the distribution of 11 disease complications (10 bacterial skin infections and 1 case of transient cerebellar ataxia). Acyclovir was well tolerated, and there was no significant difference between groups in the titers of antibodies against varicella-zoster virus.
CONCLUSIONS: Acyclovir is a safe treatment that reduces the duration and severity of chickenpox in normal children when therapy is initiated during the first 24 hours of rash. Whether treatment with acyclovir can reduce the rare, serious complications of chickenpox remains uncertain.
Options:
A: Acyclovir significantly reduced the number of days with fever and the maximum number of lesions, but had less impact on the number of days to no new lesions and relief of itching.
B: Acyclovir had no significant effect on the number of days with fever, the maximum number of lesions, the number of days to no new lesions, or the relief of itching.
C: Acyclovir significantly reduced the number of days with fever, the maximum number of lesions, the number of days to no new lesions, and the relief of itching.
D: Acyclovir significantly increased the number of days with fever and the maximum number of lesions, but had no impact on the number of days to no new lesions and relief of itching. | A |
478 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What was the conclusion regarding the efficacy of psychological interventions in improving health and behavioural outcomes for children with asthma? Please answer this question based on the information provided below:
The immediate effects of systematic relaxation training on peak expiratory flow rates in asthmatic children.
Learning to cope with asthma: a behavioural self-management program for children.
An educational training program for children with asthma, aged between 8 and 13 years, was evaluated in an 18-month randomized, controlled experiment, including three follow-up evaluations. The objective of the program is to improve coping with asthma in daily life. The program, ten 1-hour sessions, is a combination of self-management training and cognitive behaviour therapy in a group, using games and learning materials specifically designed for this age group. From 195 asthmatic children, 112 with inadequate self-management abilities were selected; these children were randomly divided into an experimental group and two control groups. The results indicated highly significant differences in favor of the experimental group on the psychological and medical variables. There were no drop-outs during the program. The conclusion is that this multi-faceted program is an effective method of teaching children how to cope with their asthma and helping them to achieve a less anxious and more realistic attitude towards their illness.
Effects of a behavioral treatment program on children with asthma.
Twenty children with severe asthma using continual oral beta 2 agonists were randomized equally into either a behavioral intervention group or a control group. The behavioral intervention consisted of: symptom discrimination of asthma signals, self-management techniques of breathlessness, and contingency management of asthma-related behavior. The purpose of the study was to evaluate the effects of the behavioral treatment when superimposed on a regular medical treatment. The design consisted of a four-week baseline period, a four-week intervention period, and a four-week follow-up period. Results showed that the group receiving the behavioral intervention significantly reduced their use of beta 2 agonist spray doses and days of school absenteeism without increasing the number of asthma symptoms compared with the control group. It was concluded that children with severe asthma may benefit substantially from a behavioral program in addition to their regular medical treatment.
Medico-psychological interventions in male asthmatic children: an evaluation of physiological change.
The purpose of this study was systematically to evaluate the effectiveness of several modes of psychological intervention used with male asthmatic children being treated in the Allergy Outpatient Clinic. Therapeutic effectiveness was measured by large airway changes in respiratory function, and the number of recurrent asthmatic attacks. The psychotherapeutic modes used were Relaxation Training, Assertive Training, and combined Relaxation plus Assertive Training. All patients were administered medication by the responsible physician. The group psychotherapy experiences were controlled by using patients who received medication alone and by patients who received medication and met in a leaderless group. The effectiveness of the therapeutic interventions was determined by comparisons between pretreatment measures and measurements taken during and after the eight-week treatment program. Both Relaxation Training by itself and combined Relaxation plus Assertive Training increased respiratory functioning and reduced the number of attacks. Assertive Training alone failed to improve respiratory function and had a tendency to increase the frequency of asthmatic attacks. It was concluded that the most effective management in male asthmatic children was achieved by the combination of medical and psychological treatments.
Role of counter-conditioning in the treatment of asthma.
Effectiveness of biofeedback and counter-conditioning in the treatment of bronchial asthma.
Long-term effects of biofeedback-induced facial relaxation on measures of asthma severity in children.
We studied the effects of electromyographic biofeedback on measures of asthma severity in children. Fifteen children received biofeedback training to reduce facial tension, and 14 children, who served as controls, received biofeedback training to maintain facial tension at a stable level. Assignment to experimental condition was random. As a result of training, electromyographic levels decreased in children trained in facial relaxation and remained fairly constant in children trained in facial tension stability. Biofeedback training was augmented for children in both groups by having them practice their facial exercises at home. Each child's condition was followed for a five-month period subsequent to biofeedback training. Throughout the experiment, the following measures of asthma severity were monitored: lung function, self-rated asthma severity, medication usage, and frequency of asthma attacks. In addition, standardized measures of attitudes toward asthma, self-concept, and chronic anxiety were recorded at regular intervals. As compared to the facial stability subjects, the facial relaxation subjects exhibited higher pulmonary scores, more positive attitudes toward asthma, and lower chronic anxiety during the follow-up period. Subjects in the two groups, however, did not differ on self-rated asthma severity, medication usage, frequency of asthma attacks, or self-concept. Based on the improvements we observed in pulmonary, attitude, and anxiety measures, we concluded that biofeedback training for facial relaxation contributes to the self-control of asthma and would be a valuable addition to asthma self-management programs.
Effects of a self-management educational program for the control of childhood asthma.
The objective of the present study was to evaluate the effects of a self-management educational program on 29 children between 6 and 14 years old and their parents implemented in an office setting in Venezuela. Children were randomly assigned to experimental and control group. Children's asthma knowledge, self-management abilities, index morbidity, parents' asthma knowledge and management abilities were measured. The program consisted of six sessions of information giving and cognitive-behavioral strategies for the children, and two talks and an informative brochure for the parents. Results of t tests indicate that the experimental group experienced a statistical significant effects on children's asthma knowledge (P < 0.001) and practice of self-management abilities (P < 0.000) and in parents' knowledge (P < 0.008) compared to the control group. The educational Self-management program had a significant impact on the Morbidity Index of the study group at post-test (P < 0.05). Younger children benefited more from the program compared to older ones (P < 0.09). Children's age is highlighted as a critical variable in designing asthma educational programs. Results suggest the effectiveness on these programs independently of the cultural context.
Improving the psychological status of children with asthma: a randomized controlled trial.
Children with asthma are at special risk for problems in psychological functioning, as are children with other chronic illnesses. We conducted a controlled trial of a combined education and stress management program among children ages 6 to 14 years with asthma. Eighty-one children were randomly assigned to an intervention or a control group; 56 children completed data collection, 29 intervention and 27 control. Psychological status was assessed by the Child Behavior Checklist (CBCL) before and after the intervention, as were children's knowledge of asthma, stress (as measured by children's life events), and functional status (as indicated by such activities as school attendance, time playing with friends, and daily chore performance). Children in the intervention group had a significant improvement in the total Behavior Problems score (p less than .04) and Internalizing scale (p less than .01) on the CBCL and a significant increase in daily chores (p less than .04) compared with the control group. Before intervention, the two groups had statistically significant positive relationships between negative life events and behavior problems scores. After intervention, children in the control group still demonstrated a significant relationship between negative life events and total and Internalizing Behavior Problem scores, although participation in the intervention group negated that relationship. Children in the intervention group whose knowledge of asthma increased were more likely to report an increase in daily chores (p less than .02). We conclude that the intervention had a beneficial effect on psychological status and on children's daily activities. The effect may have occurred in part by decreasing the likelihood that perceived stress from negative life events led to poorer adjustment.
A pilot study of the multidisciplinary management of childhood asthma in a family practice.
A small, controlled trial of joint treatment of childhood asthma by a doctor, a physiotherapist, a psychologist, and a social worker, working together in the family setting, demonstrated an improvement in ventilatory capacity. The limited scope of this trial does not permit more general conclusions as to the effect of such treatment on the severity and frequency of attacks, but the observation that some measurable physiological improvement occurred suggests that the place of multidisciplinary nonpharmaceutical management of childhood asthma should be investigated in more detail.
Options:
A: Psychological interventions were found to significantly improve health and behavioural outcomes for children with asthma.
B: The review found no evidence to support the efficacy of psychological interventions in improving health and behavioural outcomes for children with asthma.
C: The review concluded that there is insufficient evidence to draw firm conclusions about the efficacy of psychological interventions for children with asthma.
D: Psychological interventions were found to worsen health and behavioural outcomes for children with asthma. | C |
479 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What were the findings regarding the effectiveness of Chinese herbal medicine for people with schizophrenia when used alone or in combination with antipsychotic drugs? Please answer this question based on the information provided below:
[Therapeutic effect of shuxuening combining neuroleptics for the treatment of chronic schizophrenia--a double blind study].
OBJECTIVE: To assess the therapeutic effect of Shuxuening (SXN), the extractum of Ginkgo biloba761 (EGb761) in treating chronic schizophrenia.
METHODS: A double-blind, placebo-controlled multi-center research on the treatment of chronic schizophrenics with SXN was used. Five hundred and forty-five patients were randomly divided into either SXN group or the control group. Patients in the former group received SXN 120 mg three times daily. Patients in both groups received their maintenance neuroleptics throughout the 16-week research treatment.
RESULTS: The patients' rating scores of brief psychiatric rating scale (BPRS) and Scale for the Assessment of Negative Symptoms reduced much greater in SXN group than those in the control group from the sixth week of treatment (P < 0.01). The effect of SXN for BPRS factors of retardation and thought disturbance was better than that of the control. SXN presented a better therapeutic effect for chronic schizophrenics than the control when rated with traditional global rating method as well, in which 44.98% marked improvement was obtained in SXN group compared to 20.98% in the control group.
CONCLUSION: SXN combining neuroleptics, was an effective medicine for chronic schizophrenics. Moreover, it appeared few side-effects within the recommended dose range.
Comparative study of schizophrenia treatment with electroacupuncture, herbs and chlorpromazine.
A double-blind, placebo-controlled trial of extract of Ginkgo biloba added to haloperidol in treatment-resistant patients with schizophrenia.
BACKGROUND: Many studies have indicated that excess free radical formation may be involved in the pathogenesis of patients with schizophrenia. Some investigators suggested that the use of free radical scavengers might provide improvement in schizophrenia. The aim of this study was to determine the effectiveness and to evaluate the side effects of extract of Ginkgo biloba (EGb) plus haloperidol in chronic, treatment-resistant inpatients with schizophrenia.
METHOD: One hundred nine patients meeting DSM-III-R criteria for schizophrenia completed a double-blind, placebo-controlled, parallel-group study of EGb plus haloperidol. Fifty-six of the patients were randomly assigned to receive a fixed dose of 360 mg/day of EGb plus a stable dose of haloperidol, 0.25 mg/kg/day, and 53 were assigned to receive placebo plus the same dose of haloperidol for 12 weeks. Patients were assessed using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), and the Scale for the Assessment of Positive Symptoms (SAPS) at baseline, week 6, and week 12 and the Treatment Emergent Symptom Scale (TESS) for side effects at week 12.
RESULTS: There was a significant reduction in both groups in BPRS total score after 12 weeks of treatment (p < .05). However, a significant reduction in total SAPS and SANS scores was noted in the EGb group (p < .05), but not in the placebo group. There was a lower SAPS total score in the EGb group than in the placebo group at the end of 12 weeks of treatment (p < .05). Of those treated with EGb plus haloperidol, 57.1% were rated as responders as compared with only 37.7% of those receiving placebo plus haloperidol when assessed by the SAPS (chi2 = 4. 111, p = .043). After 12 weeks of treatment, TESS subscore 1 (behavioral toxicity) and subscore 3 (symptoms of nerve system) were significantly decreased in the EGb group compared with the placebo group (p < .05).
CONCLUSION: EGb treatment may enhance the effectiveness of antipsychotic drugs and reduce their extrapyramidal side effects.
The effect of extract of ginkgo biloba added to haloperidol on superoxide dismutase in inpatients with chronic schizophrenia.
The purpose of the study was to evaluate the effect of the classic antipsychotic haloperidol plus extract of ginkgo biloba (EGb) on treatment-resistant chronic schizophrenia and on blood superoxide dismutase (SOD) levels. Eighty-two patients with chronic refractory schizophrenia were studied. Forty-three patients were treated with haloperidol plus extract of ginkgo biloba (group 1), and 39 received haloperidol plus placebo (group 2). SOD levels of these patients were measured before and after treatment and were compared with SOD levels of 30 healthy volunteers. Therapeutic efficiency was equated with a change in clinical rating scores assessed by standardized measurement tools that included the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms (SANS) over this period. Patients in group 1 improved significantly as demonstrated by scores from these two assessment instruments; those in group 2 improved significantly only as shown by scores on SANS. SOD levels before treatment in all patients were significantly higher than those in healthy controls; after treatment, the SOD level decreased significantly in group 1 but not in group 2. These results suggest that EGb may enhance the efficiency of the classic antipsychotic haloperidol in patients with schizophrenia, especially on their positive symptoms, and that EGb may work through an antioxidant effect that is involved in the therapeutic mechanism in patients with chronic refractory schizophrenia.
Extract of Ginkgo biloba added to haloperidol was effective for positive symptoms in refractory schizophrenia.
A double-blind, placebo-controlled trial of extract of Ginkgo biloba added to haloperidol in treatment-resistant patients with schizophrenia.
BACKGROUND: Many studies have indicated that excess free radical formation may be involved in the pathogenesis of patients with schizophrenia. Some investigators suggested that the use of free radical scavengers might provide improvement in schizophrenia. The aim of this study was to determine the effectiveness and to evaluate the side effects of extract of Ginkgo biloba (EGb) plus haloperidol in chronic, treatment-resistant inpatients with schizophrenia.
METHOD: One hundred nine patients meeting DSM-III-R criteria for schizophrenia completed a double-blind, placebo-controlled, parallel-group study of EGb plus haloperidol. Fifty-six of the patients were randomly assigned to receive a fixed dose of 360 mg/day of EGb plus a stable dose of haloperidol, 0.25 mg/kg/day, and 53 were assigned to receive placebo plus the same dose of haloperidol for 12 weeks. Patients were assessed using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), and the Scale for the Assessment of Positive Symptoms (SAPS) at baseline, week 6, and week 12 and the Treatment Emergent Symptom Scale (TESS) for side effects at week 12.
RESULTS: There was a significant reduction in both groups in BPRS total score after 12 weeks of treatment (p < .05). However, a significant reduction in total SAPS and SANS scores was noted in the EGb group (p < .05), but not in the placebo group. There was a lower SAPS total score in the EGb group than in the placebo group at the end of 12 weeks of treatment (p < .05). Of those treated with EGb plus haloperidol, 57.1% were rated as responders as compared with only 37.7% of those receiving placebo plus haloperidol when assessed by the SAPS (chi2 = 4. 111, p = .043). After 12 weeks of treatment, TESS subscore 1 (behavioral toxicity) and subscore 3 (symptoms of nerve system) were significantly decreased in the EGb group compared with the placebo group (p < .05).
CONCLUSION: EGb treatment may enhance the effectiveness of antipsychotic drugs and reduce their extrapyramidal side effects.
The effects of classic antipsychotic haloperidol plus the extract of ginkgo biloba on superoxide dismutase in patients with chronic refractory schizophrenia.
OBJECTIVES: To explore the association between schizophrenic symptoms and superoxide dismutase (SOD), and to investigate the effect of classic antipsychotic haloperidol plus the extract of Ginkgo biloba (EGb) on SOD.
METHODS: In 54 patients with chronic refractory schizophrenia, 27 were treated with haloperidol plus EGb (group 1), and the rest received haloperidol plus placebo (group 2). Superoxide dismutase (SOD) levels of these patients were measured before and after treatment and compared with the levels of 25 healthy volunteers. Therapeutic efficacy was equated with a change in clinical rating scores assessed by standardized measurement tools including the Scale for Assessment of Positive Symptoms (SAPS) and the Scale for Assessment of Negative Symptoms (SANS).
RESULTS: Patients in group 1 improved significantly as demonstrated by scores from both SAPS and SANS, while those in group 2 only by scores from SANS. Assessed by SAPS, the response of patients receiving haloperidol plus EGb was more significant than those receiving haloperidol only. SOD levels before treatment in all patients were significantly higher than those in normal controls. After treatment, SOD levels decreased significantly in group 1 but not in group 2. In addition, before treatment, SOD levels in all patients correlated significantly with SAPS score. The levels of SOD measured before treatment were also correlated with the improvement of patients as measured by SAPS and SANS after 12 weeks.
CONCLUSIONS: EGb may enhance the efficacy of classic antipsychotic haloperidol on schizophrenia, especially on positive symptoms. It may work through an antioxidant efficacy that is involved in the therapeutic mechanism.
[Clinical study of shuizhi-dahuang mixture in treating schizophrenics with blood stasis syndrome].
A clinical study of 67 female schizophrenics was conducted. Thirty two patients of them treated with the Shuizhi (leech)-Dahuang (rhubarb) mixture mainly with low dosage of antipsychotic drugs (combined therapy group), while other 35 cases were treated with antipsychotic drugs only (control group). The result showed that their overall therapeutic effects were similar and the combined therapy group could reduce the dosages of antipsychotic drugs and its side effects, and tended to normalize the hemorheologic indices.
Options:
A: Chinese herbal medicine alone was more effective than antipsychotic drugs in improving the global state of patients with schizophrenia.
B: Chinese herbal medicine combined with antipsychotic drugs showed no significant difference compared to antipsychotic drugs alone in improving the global state of patients with schizophrenia.
C: Chinese herbal medicine combined with antipsychotic drugs was more effective than antipsychotic drugs alone in improving the global state of patients with schizophrenia.
D: Chinese herbal medicine alone showed no significant difference compared to placebo in improving the global state of patients with schizophrenia. | C |
480 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What conclusion can be drawn about the efficacy of vitamin B6 and magnesium (B6-Mg) for treating social, communication, and behavioural responses in individuals with autism based on the available studies? Please answer this question based on the information provided below:
High-dose pyridoxine and magnesium administration in children with autistic disorder: an absence of salutary effects in a double-blind, placebo-controlled study.
Several reports have described salutary effects such as decreased physical aggression and improved social responsiveness being associated with the administration of high doses of pyridoxine and magnesium (HDPM) in open-labeled and controlled studies of patients with autism. Despite this fact, this intervention remains controversial. A 10-week double-blind, placebo-controlled trial was undertaken to examine both the efficacy and safety of HDPM in autism. Twelve patients were enrolled, and 10 patients (mean age 6 years 3 months) were able to complete the study. HDPM at an average dose of 638.9 mg of pyridoxine and 216.3 mg of magnesium oxide was ineffective in ameliorating autistic behaviors as assessed by the Children's Psychiatric Rating Scale (CPRS), the Clinical Global Impression Scale, and the NIMH Global Obsessive Compulsive Scale. Furthermore, no clinically significant side effects were noted during HDPM administration. A trend for a transient change on the CPRS was found that was possibly due to a placebo response. This study raises doubts about the clinical effectiveness of HDPM in autistic disorder.
Pyridoxine treatment in a subgroup of children with pervasive developmental disorders.
Brief report: lack of response in an autistic population to a low dose clinical trial of pyridoxine plus magnesium.
Options:
A: Vitamin B6 and magnesium (B6-Mg) significantly improve social, communication, and behavioural responses in individuals with autism.
B: There is insufficient evidence to recommend vitamin B6 and magnesium (B6-Mg) as a treatment for autism due to the small number of studies and their methodological limitations.
C: Vitamin B6 and magnesium (B6-Mg) have been proven to be ineffective in treating autism.
D: Vitamin B6 and magnesium (B6-Mg) are harmful and should not be used in treating autism. | B |
481 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What is the current evidence regarding the effectiveness of bed rest for women with hypertension during pregnancy in terms of maternal and fetal outcomes? Please answer this question based on the information provided below:
Does admission to hospital for bed rest prevent disease progression or improve fetal outcome in pregnancy complicated by non-proteinuric hypertension?
OBJECTIVE: To test whether a policy of admission to hospital for rest is of value in the management of women with non-proteinuric hypertension during pregnancy.
DESIGN: A randomized controlled trial.
SETTING: Harare Maternity Hospital, Zimbabwe.
SUBJECTS: 218 (28 first pregnancies) women with non-proteinuric hypertension and a singleton pregnancy at between 28 and 38 weeks gestation allocated to rest in hospital or routine outpatient care.
INTERVENTION: Admission to hospital for rest. Encouraged to rest in bed although voluntary ambulation around the ward was allowed. The women in the control group were encouraged to continue normal activity at home, to check urine each day for proteinuria. All the women were reviewed weekly.
MAIN OUTCOME MEASURES: Disease progression was assessed by the development of severe hypertension (greater than or equal to 160/110 mmHg), development of proteinuria, need for induction of labour and number of infants born preterm (less than 37 weeks). Fetal outcome was assessed by birthweight, number of infants small-for-gestational age (SGA), and the number of infants requiring admission to the neonatal unit and their length of stay.
RESULTS: The hospital rest group had a decreased risk of developing severe hypertension (blood pressure greater than or equal to 160/110 mmHg [odds ratio 0.47, 95% CI 0.26-0.83]). No differences were found in fetal growth or neonatal morbidity. The mean antenatal stay in hospital was 22.2 (SD 16.5), and 6.5 (SD 7.9) days in the rest and control groups, respectively.
CONCLUSIONS: Hospital admission for bed rest decreased the risk of developing severe hypertension but no improvement in fetal growth or neonatal morbidity was observed. Fetal monitoring at home and continued outpatient antenatal care provided a safe, alternative policy to hospital admission.
Is in-patient management of diastolic blood pressure between 90 and 100 mm Hg during pregnancy necessary?
A randomised controlled trial was performed at the Queen Elizabeth Hospital to compare the effects and acceptance of routine in-patient versus out-patient management of diastolic blood pressure between 90 and 100 mm Hg in pregnant women. There were no significant differences in the establishment of the diagnosis of hypertension, development of severe hypertension or proteinuric hypertension, the number of women requiring obstetric interventions, or the neonatal outcome between the two groups. Antenatal hospital stay for the in-patient group, however, was more than twice as long as for the out-patient group (difference in mean stay, 3.7 days; 95% confidence interval, 1.3-6.2). The number of hospitalisations in the in-patient group was almost four times greater than that in the out-patient group (difference in mean number of hospitalisations, 1.7; 95% confidence interval, 1.2-2.2). The two groups did not differ in their levels of satisfaction of the overall management of blood pressure. Nevertheless, a greater proportion of women preferred to choose the same type of care among the out-patient group than among the in-patient group if they had hypertension in a future pregnancy (83.7% versus 51.2%; P<0.001). More women were dissatisfied about the number of admissions than on the frequency of out-patient care (40.5% versus 16.3%; P<0.001). We conclude that in-patient care, day care, or home monitoring should be individualised.
A randomized controlled trial of complete bed rest versus ambulation in the management of proteinuric hypertension during pregnancy.
Forty patients participated in a randomized controlled trial of complete bed rest versus ambulation as desired in the management of proteinuric hypertension during pregnancy. Daily increases in serum human placental lactogen and oestriol concentrations were greater in the rested group. An especially 'at risk' group of 10 patients with both hyperuricaemia and severe fetal growth retardation was identified. Strict confinement to bed in these cases seemed to encourage the development of the premonitory symptoms of eclampsia, but was associated with a better prognosis for the fetus.
The effect of rest and ambulation on plasma urea and urate levels in pregnant women with proteinuric hypertension.
Plasma urea and urate concentrations were determined daily for up to seven days in 40 pregnant women who had been admitted to hospital because of proteinuric hypertension and who were then allocated at random to either complete rest in bed or to being allowed to move freely in the ward. Neither management was superior to the other in improving renal function. The prognostic significance of plasma urea and urate concentrations to maternal and fetal outcome was confirmed.
Options:
A: Bed rest significantly improves maternal and fetal outcomes and should be recommended routinely.
B: Bed rest shows some potential benefits but there is insufficient evidence to recommend it routinely.
C: Bed rest has no impact on maternal and fetal outcomes and should not be recommended.
D: Bed rest significantly worsens maternal and fetal outcomes and should be avoided. | B |
482 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What is the effectiveness and safety of extracorporeal shock wave therapy (ESWT) for treating lateral elbow pain? Please answer this question based on the information provided below:
Effectiveness of extracorporeal shock wave therapy in the treatment of previously untreated lateral epicondylitis: a randomized controlled trial.
BACKGROUND: Extracorporeal shock wave therapy is a relatively new therapy used in the treatment of chronic tendon-related pain. Few randomized controlled trials have been performed on it, and no studies have examined the effectiveness of extracorporeal shock wave therapy as a frontline therapy for tendon-related pain.
HYPOTHESIS: Subjects treated with active extracorporeal shock wave therapy will have higher rates of treatment success than subjects treated with sham extracorporeal shock wave therapy.
DESIGN: Double-blind randomized controlled trial.
METHODS: Sixty subjects who had previously untreated lateral epicondylitis for less than 1 year and more than 3 weeks were included in this study. Subjects were randomly allocated to receive 1 session per week for 3 weeks of either sham or active extra-corporeal shock wave therapy. Subjects in the active therapy group received 2000 pulses (energy flux density, 0.03-0.17 mJ/mm(2)). All subjects were provided with a forearm-stretching program. After 8 weeks of therapy, subjects were classified as either treatment successes or treatment failures according to fulfillment of all 3 criteria: (1) at least a 50% reduction in the overall pain visual analog scale score, (2) a maximum allowable overall pain visual analog scale score of 4.0 cm, and (3) no use of pain medication for elbow pain for 2 weeks before the 8 week follow-up. Visual analog scale scores were also collected for pain at rest, during sleep, during activity, at its worst, and at its least, as well as for quality of life (using the EuroQoL questionnaire) and grip strength.
RESULTS: Success rates in the sham and active therapy groups were 31% and 39%, respectively. No significant difference was detected between groups (chi(2)(1)= 0.3880, P = .533). Mean change in quality of life over 8 weeks was an increase of 1.3 and 3.3 for sham and active therapy groups, respectively, and mean change in grip strength over 8 weeks was an increase of 7.4 kg and 6.8 kg for sham and active therapy groups, respectively.
CONCLUSIONS: Despite improvement in pain scores and pain-free maximum grip strength within groups, there does not appear to be a meaningful difference between treating lateral epicondylitis with extracorporeal shock wave therapy combined with forearm-stretching program and treating with forearm-stretching program alone, with respect to resolving pain within an 8-week period of commencing treatment.
A prospective, randomised study to compare extracorporeal shock-wave therapy and injection of steroid for the treatment of tennis elbow.
We undertook a prospective, randomised study to compare the analgesic effect of injection of steroid and of extracorporeal shock-wave therapy (ESWT) for the treatment of tennis elbow. Group 1 received a single injection of 20 mg of triamcinolone with lignocaine while group 2 received 2000 shock waves in three sessions at weekly intervals. After six weeks there was a significant difference between the groups with the mean pain score for the injection group falling from 66 to 21 compared with a decrease from 61 to 35 in the shock-wave group (p = 0.05). After three months, 84% of patients in group 1 were considered to have had successful treatment compared with 60% in group 2. In the medium term local injection of steroid is more successful and 100 times less expensive than ESWT in the treatment of tennis elbow.
Side-effects of extracorporeal shock wave therapy (ESWT) in the treatment of tennis elbow.
Apart from a few observational reports, there are no studies on the side-effects of extracorporeal shock wave therapy (ESWT) in the treatment of insertion tendopathies. Within the framework of a randomised, placebo-controlled, single-blind, multicentre study to test the effectiveness of ESWT in the case of lateral epicondylitis (LE), side-effects were systematically recorded. A total of 272 patients from 15 centres was allocated at random to active ESWT (3 x 2000 pulses, energy flux density ED(+) 0.04 to 0.22 mJ/mm(2) under local anaesthesia) or placebo ESWT. In all, 399 ESWT and 402 placebo treatments were analysed. More side-effects were documented in the ESWT group (OR = 4.3, CI = [2.9; 6.3]) than in the placebo group. Most frequently, transitory reddening of the skin (21.1%), pain (4.8%) and small haematomas (3.0%) were found. Migraine was registered in four and syncopes in three instances after ESWT. ESWT for LE with an energy flux density of ED(+) 0.04 to 0.22 mJ/mm(2) is a treatment method which has very few side-effects. The possibility of migraine being triggered by ESWT and the risk of a syncope should be taken into account in the future. No physical shock wave parameters could be definitely identified as the cause of the side-effects observed.
Extracorporeal shock wave therapy in the treatment of lateral epicondylitis : a randomized multicenter trial.
BACKGROUND: On the basis of observational trials, numerous investigators have recommended extracorporeal shock wave therapy as an alternative treatment for chronic lateral epicondylitis of the elbow. However, there has been no evidence of its efficacy from well-designed randomized clinical trials. The objective of this study was to find out whether extracorporeal shock wave therapy in combination with local anesthesia was superior to placebo therapy in combination with local anesthesia.
METHODS: A randomized multicenter trial with a parallel-group design was conducted. Following administration of local anesthesia, either extracorporeal shock wave therapy with three treatments of 2000 pulses each and a positive energy flux density (ED+) of 0.07 to 0.09 mJ/mm (2) or placebo therapy was applied on an outpatient basis. Treatment allocation was blinded for patients and for observers. The primary end point was based on the rate of success, as determined with the Roles and Maudsley score and whether additional treatment was required, twelve weeks after the intervention. Crossover was possible after assessment of the primary end point. Secondary end points were the Roles and Maudsley score, subjective pain rating, and grip strength after six and twelve weeks and after twelve months. The planned number of 272 patients was included in the study.
RESULTS: The primary end point could be assessed for 90.8% of the patients. The success rate was 25.8% in the group treated with extracorporeal shock wave therapy and 25.4% in the placebo group, a difference of 0.4% with a 95% confidence interval of -10.5% to 11.3%. Similarly, there was no relevant difference between groups with regard to the secondary end points. Improvement was observed in two-thirds of the patients from both groups twelve months after the intervention. Few side effects were reported.
CONCLUSIONS: Extracorporeal shock wave therapy as applied in the present study was ineffective in the treatment of lateral epicondylitis. The previously reported success of this therapy appears to be attributable to inappropriate study designs. Different application protocols might improve clinical outcome. We recommend that extracorporeal shock wave therapy be applied only in high-quality clinical trials until it is proved to be effective.
The use of a mobile lithotripter in the treatment of tennis elbow and plantar fasciitis.
OBJECTIVE: To evaluate the use of the mobile lithotripter in the treatment of tennis elbow and plantar fasciitis.
METHOD: A prospective single blind randomised trial was performed on 24 patients with tennis elbow and 23 patients with plantar fasciitis, with a mean duration of symptoms of 11 months. All patients had failed one or more method of treatment--conservative, topical non-steriodal anti-inflammatory drugs (NSAID), steroid injection and/or surgery. The patients were divided into treatment and placebo groups. The placebo group received treatment with a clasp on the elbow/heel to stop penetration of shock waves. A baseline pain score was obtained using the Million Visual Analogue scale (0-10). The affected area was infiltrated with 3-5mls of 1% lignocaine. The treatment consisted of 2000 shock waves at 2.5 bars of air pressure with a frequency of 8-10Hz. A total of three treatments were given at an interval of two weeks, each lasting for three to four minutes.
RESULTS: In the treatment groups, a final pain score at six months post treatment showed significant improvement (three or more points) in 78% of patients with tennis elbow and 93% of patients with plantar fasciitis. In the placebo groups, significant improvement was seen in one patient (9%) with tennis elbow. The other patients in the placebo groups did not show significant improvement. This was statistically significant (chi square test) for both conditions.
CONCLUSION: The mobile lithotripter is an effective way of treating tennis elbow and plantar fasciitis but warrants further larger studies.
Extracorporeal shock-wave treatment for tennis elbow. A randomised double-blind study.
The efficacy of extracorporeal shock-wave therapy for tennis elbow was investigated using a single fractionated dosage in a randomised, double-blind study. Outcomes were assessed using the Disabilities of Arm, Shoulder and Hand questionnaire, measurements of grip strength, levels of pain, analgesic usage and the rate of progression to surgery. Informed consent was obtained before patients were randomised to either the treatment or placebo group. In the final assessment, 74 patients (31 men and 43 women) with a mean age of 43.4 years (35 to 71), were included. None of the outcome measures showed a statistically significant difference between the treatment and control groups (p > 0.05). All patients improved significantly over time, regardless of treatment. Our study showed no evidence that extracorporeal shock-wave therapy for tennis elbow is better than placebo.
Extracorporeal shock wave therapy without local anesthesia for chronic lateral epicondylitis.
BACKGROUND: The use of extracorporeal shock wave therapy for the treatment of lateral epicondylitis is controversial. The purpose of this study was to evaluate the use of extracorporeal shock wave therapy without local anesthesia to treat chronic lateral epicondylitis.
METHODS: One hundred and fourteen patients with a minimum six-month history of lateral epicondylitis that was unresponsive to conventional therapy were randomized into double-blind active treatment and placebo groups. The protocol consisted of three weekly treatments of either low-dose shock wave therapy without anesthetic or a sham treatment. Patients had a physical examination, including provocation testing and dynamometry, at one, four, eight, and twelve weeks and at six and twelve months after treatment. Radiographs, laboratory studies, and electrocardiograms were also evaluated prior to participation and at twelve weeks. A visual analog scale was used to evaluate pain, and an upper extremity functional scale was used to assess function. Crossover to active treatment was initiated for nonresponsive patients who had received the placebo and met the inclusion criteria after twelve weeks.
RESULTS: A total of 108 of the 114 randomized patients completed all treatments and the twelve weeks of follow-up required by the protocol. Sixty-one patients completed one year of follow-up, whereas thirty-four patients crossed over to receive active treatment. A significant difference (p = 0.001) in pain reduction was observed at twelve weeks in the intent-to-treat cohort, with an improvement in the pain score of at least 50% seen in 61% (thirty-four) of the fifty-six patients in the active treatment group who were treated according to protocol compared with 29% (seventeen) of the fifty-eight subjects in the placebo group. This improvement persisted in those followed to one year. Functional activity scores, activity-specific evaluation, and the overall impression of the disease state all showed significant improvement as well (p < 0.05). Crossover patients also showed significant improvement after twelve weeks of active treatment, with 56% (nineteen of thirty-four) achieving an improvement in the pain score of at least 50% (p < 0.0001).
CONCLUSIONS: These results demonstrate that low-dose shock wave therapy without anesthetic is a safe and effective treatment for chronic lateral epicondylitis.
Low-energy extracorporal shock wave therapy for persistent tennis elbow.
Fifty patients who suffered from persistent tennis elbow for more than 12 months, and were referred for surgical treatment, were assigned at random to 2 groups of low-energy extracorporal shock wave therapy. Group I received a total of 3000 impulses of 0.08 mJ/mm2; group II (controls) 30 impulses of 0.08 mJ/mm2. Follow up was after 3 and 12 weeks. We found no significant differences between the 2 groups before treatment, there was but significant relief of pain and improvement of function in group I with good or excellent outcome in 56% at the last evaluation.
Analgesic effect of extracorporeal shock-wave therapy on chronic tennis elbow.
We report a controlled, prospective study to investigate the effect of treatment by low-energy extracorporeal shock waves on pain in tennis elbow. We assigned at random 100 patients who had had symptoms for more than 12 months to two groups to receive low-energy shock-wave therapy. Group I received a total of 3000 impulses of 0.08 mJ/mm2 and group II, the control group, 30 impulses. The patients were reviewed after 3, 6 and 24 weeks. There was significant alleviation of pain and improvement of function after treatment in group I in which there was a good or excellent outcome in 48% and an acceptable result in 42% at the final review, compared with 6% and 24%, respectively, in group II.
[Extracorporeal shock-wave therapy. Experimental basis, clinical application].
The purpose of our studies was to investigate experimentally the dose-dependent effects of extracorporeal shock waves on tendon and bone and to unveil therapeutic possibilities in tendinopathies and pseudarthroses. In animal experiments, both positive and negative influences were exerted by shock waves, depending on the initial situation and on the power of the applied shock waves. In prospective clinical trials positive effects were found in the treatment of persistent tennis elbow, plantar fasciitis, calcifying tendinitis, and pseudarthrosis. Our data show that extracorporeal shock waves may provide analgesic, resorptive and osteo-inductive reactions with nearly no side effects. However, the high cost of apparatus and staff prevents a routine application. Extracorporeal shock waves thus remain a last alternative before the indication is made for an operative procedure.
Repetitive low-energy shock wave treatment for chronic lateral epicondylitis in tennis players.
BACKGROUND: There is conflicting evidence regarding extracorporeal shock wave treatment for chronic tennis elbow.
HYPOTHESIS: Treatment with repetitive low-energy extracorporeal shock wave treatment is superior to repetitive placebo extra-corporeal shock wave treatment.
METHODS: Seventy-eight patients enrolled in a placebo-controlled trial. All patients were tennis players with recalcitrant MRI-confirmed tennis elbow of at least 12 months' duration. Patients were randomly assigned to receive either active low-energy extracorporeal shock wave treatment given weekly for 3 weeks (treatment group 1) or an identical placebo extracorporeal shock wave treatment (sham group 2). Main outcome measure was pain during resisted wrist extension at 3 months; secondary measures were >50% reduction of pain and the Upper Extremity Function Scale.
RESULTS: At 3 months, there was a significantly higher improvement in pain during resisted wrist extension in group 1 than in group 2 (mean [SD] improvement, 3.5 [2.0] and 2.0 [1.9]; P =.001 for between-group difference of improvement) and in the Upper Extremity Function Scale (mean [SD] improvement, 23.4 [14.8] and 10.9 [14.9]; P <.001 for between-group difference of improvement). In the treatment group, 65% of patients achieved at least a 50% reduction of pain, compared with 28% of patients in the sham group (P =.001 for between-group difference).
CONCLUSION: Low-energy extracorporeal shock wave treatment as applied is superior to sham treatment for tennis elbow.
Extracorporeal shock wave therapy for lateral epicondylitis--a double blind randomised controlled trial.
UNLABELLED: Extracorporeal shock wave therapy (ESWT) is an increasingly popular therapeutic approach to the treatment of a number of soft tissue complaints. Whilst benefit has been demonstrated in calcific tendinitis, evidence is lacking for benefit in the management of non-calcific rotator cuff disorders.
AIMS: To perform a double-blind placebo controlled trial of moderate dose ESWT in chronic lateral epicondylitis.
METHODS: Adults with lateral epicondylitis were randomised to receive either active treatment (1500 pulses ESWT at 0.12 mJ/ mm2) or sham therapy, monthly for three months. All were assessed before each treatment and one month after completion of therapy. Outcome measures consisted of visual analogue scores for pain in the day and at night.
RESULTS: Seventy-five subjects participated and there were no significant differences between the two groups at baseline. The mean duration of symptoms was 15.9 and 12 months in the ESWT and sham groups, respectively. Both groups showed significant improvements from two months. No significant difference existed between the groups with respect to the degrees of change in pain scores over the study period. In the ESWT group the mean (SD, range) pain score was 73.4 (14.5, 38-99) at baseline and 47.9 (31.4, 3-100) at three months. In the sham group the mean (SD, range) pain score was 67.2 (21.7, 12-100) at baseline and 51.5 (32.5, 3-100) at three months. At three months, 50% improvement from baseline was noted in 35% of the ESWT group and 34% of the sham group with respect to pain.
CONCLUSIONS: There appears to be a significant placebo effect of moderate dose ESWT in subjects with lateral epicondylitis but there is no evidence of added benefit of treatment when compared to sham therapy.
Options:
A: ESWT provides significant benefit in terms of pain and function compared to placebo.
B: ESWT provides little or no benefit in terms of pain and function compared to placebo.
C: ESWT is less effective than placebo in terms of pain and function.
D: ESWT is more effective than steroid injection in terms of pain reduction. | B |
483 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What was the conclusion regarding the use of Ginkgo biloba extract for improving functional outcomes in patients with acute ischaemic stroke? Please answer this question based on the information provided below:
A double blind placebo controlled trial of ginkgo biloba extract in acute cerebral ischaemia.
A double blind placebo controlled trial was conducted in 55 patients of acute ischaemic stroke. Twenty one and twenty six patients were randomly allotted in group A and group B respectively. In group A, the patients received 40 mg Ginkgo biloba extract at 6 hourly intervals along with routine management. The placebo tablets were dispensed in the tablet form of same size, shape and colour and were given in the same way. After the patients were subjected to computerized tomographic (CT) scan to confirm acute ischaemic infarction, they were assessed on Mathew's scale and reassessed, at 2 weeks and 4 weeks of drug/placebo administration. Both groups showed significant improvement in Mathew's scale score after 2 weeks and 4 weeks. The difference in degree of change was negligible (p > 0.05) in either group. Estimation of relative changes of neurological deficit based on baseline values also showed negligible (p > 0.05) difference. A trial of Ginkgo biloba extract within 6 hours of stroke in a larger dose and in larger sample could be beneficial clinically in patients of cerebral ischaemic infarct, and needs further study. The usefulness of the plant extract has been demonstrated clinically and experimentally in more than 40 trials of chronic cerebral ischaemia, done elsewhere. This was not evident in our study as our study group was different (more than 48 hours after stroke). There appears to be no contraindication or adverse effect of this medication (Ginkgo biloba) in acute ischaemic stroke.
Options:
A: Ginkgo biloba extract significantly improved functional outcomes and quality of life in patients with acute ischaemic stroke.
B: There was no convincing evidence to support the routine use of Ginkgo biloba extract for recovery after acute ischaemic stroke.
C: Ginkgo biloba extract was associated with a significant increase in adverse events in patients with acute ischaemic stroke.
D: Ginkgo biloba extract showed significant improvement in neurological outcomes in high-quality trials. | B |
484 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What were the findings regarding the effectiveness of acupuncture and electroacupuncture in the treatment of rheumatoid arthritis in terms of pain relief and disease activity measures? Please answer this question based on the information provided below:
The effect of acupuncture on patients with rheumatoid arthritis: a randomized, placebo-controlled cross-over study.
OBJECTIVE: Acupuncture is commonly used by patients with chronic painful musculoskeletal disorders. There are, however, few well-designed studies of its efficacy. This paper describes a randomized placebo-controlled cross-over design to evaluate acupuncture as a useful treatment adjunct in the management of patients with rheumatoid arthritis (RA).
METHODS: Sixty-four patients were centrally randomized from a hospital-based rheumatology out-patient clinic. Fifty-six patients were suitable for study, all were on second-line therapy and aged 18-75 yr. There had been no change in therapy for the preceding 3 months. Patients who had previous acupuncture, anticoagulation, fear of needles or infection were excluded. Single-point (Liver 3) acupuncture or placebo was given with an intervening 6 week wash-out period. The acupuncturist, patient and statistician were blinded as far as possible. The outcome measures included the inflammatory markers (erythrocyte sedimentation rate and C-reactive protein), visual analogue scale of pain, global patient assessment, 28 swollen and tender joint count, and a general health questionnaire.
RESULTS: The results demonstrated no significant effect of treatment or period and no significant interaction between treatment and period for any outcome variable. No adverse effects were reported.
CONCLUSION: Acupuncture of this type cannot be considered as a useful adjunct to therapy in patients with RA. Possible reasons why this is the case are discussed.
Preliminary clinical study of acupuncture in rheumatoid arthritis.
Options:
A: Acupuncture significantly reduced pain and improved disease activity measures such as ESR, CRP, and the number of swollen and tender joints.
B: Electroacupuncture significantly reduced knee pain both 24 hours and 4 months post-treatment, but acupuncture showed no significant effect on pain or disease activity measures.
C: Both acupuncture and electroacupuncture significantly reduced pain and improved disease activity measures in patients with rheumatoid arthritis.
D: Neither acupuncture nor electroacupuncture showed any significant effect on pain relief or disease activity measures in patients with rheumatoid arthritis. | B |
485 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What are the conclusions regarding the efficacy of surgical interventions for thumb-in-palm deformity in patients with spastic cerebral palsy? Please answer this question based on the information provided below:
Surgery of the spastic hand in cerebral palsy. Improvement in stereognosis and hand function after surgery.
Thirty-six patients with hemiplegic cerebral palsy had surgical treatment for the upper limb and were followed up for 18 months postoperatively. Various operations were done. A striking finding was a significant improvement of stereognosis (ability to describe and recognize objects without vision). Most patients had improvement in different functional grasps following surgical reconstruction. Range of movement in the forearm and wrist also increased in most patients. The thumb-in-palm deformity was completely corrected in 31 of the patients and improved in the other five. Most patients had some or all of their expectations of the procedure fulfilled.
Capsulodesis of the metacarpophalangeal joint of the thumb in children with cerebral palsy.
A deformity of hyperextension of the metacarpophalangeal joint of the thumb occurring in thirteen children with spastic cerebral palsy was corrected by capsulodesis of the joint. The technique involves shifting the metacarpal attachment of the volar plate more proximally in the metacarpal. When combined with selective release of the involved intrinsic muscles and selective transfer of the extrinsic motors, when indicated, the thumb is brough away from the palm and its function and appearance are improved. Moreover, there is not risk to growth of the thumb such as might follow arthrodesis in a growing child. Results were satisfactory except in two athetoid patients, in whom some of the intial correction was lost, but even their thumbs did not revert into hyperextension. In five patients, for reasons not entirely clear, the previously flexed interphalangeal joint had better extension postoperatively. This improved the function of the thumb, because the broad pulp of the thumb could then be used firmly against the side of the index finger.
A dynamic approach to the thumb-in palm deformity in cerebral palsy.
One hundred and sixty-five different surgical procedures were performed for the correction of thumb deformities in fifty-six patients with spastic cerebral palsy at Gillette Children's Hospital, St. Paul, Minnesota, between 1967 and 1975. The quality of voluntary muscle control and sensibility were the most important factors in predicting the success of operation. In the past, thumb deformities were classified on the basis of the static position of the thumb, but rational treatment decisions can be made only by a careful assessment of the patient's hand and thumb function. Using various combinations of releases, tendon transfers, and joint stabilizations, measurable and predictable improvement in function was achieved in all fifty-six patients whose records were analyzed.
Surgical correction of thumb deformities in spastic paralysis.
The brachioradialis for restoration of abduction and extension of spastic thumb in children.
The surgical technique is described for transfer of the brachioradialis for restoration of abduction and extension of the thumb in spastic children's hands. Long-term followup studies (average: 6.5 years) for 14 children demonstrate satisfactory functional and cosmetic results for patients carefully selected on the basis of Goldner's criteria.
4.5 year follow-up after surgical correction of upper extremity deformities in spastic cerebral palsy.
Reconstructive surgery was carried out on 27 upper extremities in 24 children with deformities due to spastic cerebral palsy. Functional evaluation of the affected extremities was made preoperatively, at 6 months and at a mean of 4.5 years postoperatively using a score added to the assessment system described by the Committee on Spastic Hand Evaluation. According to the score, dysfunction of the arm was significantly reduced 6 months after the reconstructive surgery and the improvements remained essentially unchanged at the later follow-up. The addition of a score to the original assessment system facilitated the overall assessment of postoperative results.
Treatment of spastic thumb-in-palm deformity: a modified extensor pollicis longus tendon rerouting.
Fourteen patients (15 hands) with spastic thumb-in-palm deformities were treated with a modified technique of extensor pollicis longus tendon rerouting. Twelve patients obtained satisfactory correction of their deformities. Although functional improvement was not always anticipated, it was achieved to some degree in 12 patients. Extensor pollicis longus tendon rerouting can provide satisfactory correction of severe thumb-in-palm deformity especially when combined with other procedures such as metacarpophalangeal joint arthrodesis and thumb intrinsic muscle release. The modified rerouting technique can be done with a single incision and allows easy adjustment of tension.
Functional outcome of upper limb tendon transfers performed in children with spastic hemiplegia.
Children with spastic hemiplegia often present with upper limb muscle imbalance. The purpose of this paper was to determine whether reconstructive surgery improved their functional ability. 17 children under the age of 16 years with spastic hemiplegia underwent reconstruction that included tendon transfers, tendon lengthenings and thumb metacarpophalangeal fusion. They were assessed pre-operatively and at an average follow-up period of 2.6 years. Children's abilities were classified according to House's functional rating scale. Tendon transfers improved functional grading by two grades, from good passive assist to fair active assist. Improvement in the arc of wrist motion and forearm rotation was also seen. Parental satisfaction was high. Reconstructive surgery improved the functional abilities in this group of children with spastic hemiplegia.
Surgery for cerebral palsy part 3: classification and operative procedures for thumb deformity.
Spastic thumb deformity is the result of imbalance between intrinsic and extrinsic forces acting across unstable joints. This paper presents a classification of spastic thumb deformity based on the accurate assessment of the deforming forces, outlines methods for their correction and reviews the results of our surgery. Thumb reconstruction procedures were performed in 32 patients with 33 spastic thumb deformities. All patients were assessed pre- and postoperatively using the same functional assessment system which was performed by the same team. The thumb was maintained out of the palm in 29 patients and lateral pinch was established in 26 patients.
Options:
A: Surgical interventions are highly effective and there is a clear consensus on the best procedures to use.
B: The methodological quality of the studies is poor, making it impossible to provide a reliable judgement on the role of surgery, though surgical reconstruction appears to improve hand function, hygiene, appearance, and quality of life.
C: There is strong evidence that surgical interventions do not improve outcomes for patients with thumb-in-palm deformity.
D: Surgical interventions are only effective for patients under the age of 10. | B |
486 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What was the conclusion regarding the efficacy of inhaled corticosteroids in treating non-specific chronic cough in children over the age of two years? Please answer this question based on the information provided below:
A randomised, placebo controlled trial of inhaled salbutamol and beclomethasone for recurrent cough.
AIMS: To test the hypothesis that inhaled salbutamol or beclomethasone will reduce the frequency of cough in children with recurrent cough. A secondary aim was to determine if the presence of airway hyperresponsiveness (AHR) can predict the response.
DESIGN: Randomised, double blind, placebo controlled trial.
METHODS: During a coughing phase, 43 children (age 6-17 years) with recurrent cough were randomised to receive inhaled salbutamol or placebo (phase I) for 5-7 days and then beclomethasone or placebo (phase II) for 4-5 weeks, and in a subgroup of children for 8-9 weeks. The children used an ambulatory cough meter, kept cough diaries, and performed the capsaicin cough sensitivity, hypertonic saline bronchoprovocation, and skin prick tests.
RESULTS: Salbutamol or beclomethasone had no effect on cough frequency or score, irrespective of the presence of AHR.
CONCLUSIONS: Most children with recurrent cough without other evidence of airway obstruction, do not have asthma and neither inhaled salbutamol nor beclomethasone is beneficial.
Persistent nocturnal cough: randomised controlled trial of high dose inhaled corticosteroid.
OBJECTIVE: To investigate the effect of a short course of inhaled corticosteroid in the treatment of isolated and persistent nocturnal cough in children.
DESIGN: Randomised double blind placebo controlled study.
SETTING: Subjects' homes in east London, England.
SUBJECTS: Consecutively referred children, 1-10 years old, with persistent nocturnal cough.
INTERVENTIONS: Placebo or fluticasone propionate 1 mg twice daily for three nights and 500 microg twice daily for 11 nights. Videotaping of children at night: two nights' baseline, nights 3 and 4 after three days of inhaled corticosteroid, and nights 15 and 16.
MAIN OUTCOME MEASURE: A fall in 75% of coughs from baseline.
RESULTS: 50 subjects were recruited. The median number of coughs in the baseline period for the inhaled corticosteroid group and placebo group were 92 and 71, respectively (p = 0.43) and, on nights 15 and 16, 8 and 36, respectively (p < 0. 01). Compared to baseline, both groups of subjects improved significantly by nights 15 and 16 (p < 0.01; p < 0.01). Comparing the inhaled corticosteroid and placebo groups, coughs fell to a median of 22% and 57% of baseline totals on nights 3 and 4, respectively (p = 0.38), and 8% and 35% on nights 15 and 16, respectively (p = 0.02). 17 of 24 subjects on inhaled corticosteroid who completed the study and 8 of 23 on placebo improved by 75% after two weeks (p = 0.03).
CONCLUSIONS: Children with persistent nocturnal cough improve in two weeks after referral on placebo. There is a modest benefit from a two week course of high dose inhaled corticosteroid.
Options:
A: Inhaled corticosteroids significantly reduce the frequency of non-specific chronic cough in children.
B: Inhaled corticosteroids at a lower dose are no different from placebo in reducing the frequency of non-specific chronic cough in children.
C: Inhaled corticosteroids at any dose are highly effective in treating non-specific chronic cough in children.
D: Inhaled corticosteroids at a higher dose show a significant improvement in cough frequency, but the clinical impact is minimal. | B |
487 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What were the findings regarding the effectiveness of topical vitamin A in treating and preventing napkin dermatitis in infants? Please answer this question based on the information provided below:
Diaper dermatitis. Value of vitamin A topically applied.
The role of vitamin A in preventing diaper dermatitis was evaluated in a double-blind, randomized, prospective study in which 114 newborns were enrolled over an 11-month period. Patients in Group A (58 infants) were treated with a cream that contained 1,000 IU/g of vitamin A, whereas patients in Group B (56 infants) were treated with a cream that had the same composition, but it did not contain vitamin A. Each participant returned once every 15 days for six follow-up visits.
Options:
A: Topical vitamin A was found to be highly effective in both treating and preventing napkin dermatitis.
B: Topical vitamin A showed significant effectiveness in preventing napkin dermatitis but not in treating it.
C: There was no evidence to support or refute the effectiveness of topical vitamin A in treating napkin dermatitis, and it did not significantly alter the development of napkin dermatitis for prevention.
D: Topical vitamin A was found to be ineffective in both treating and preventing napkin dermatitis. | C |
488 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What was the conclusion regarding the effectiveness of atovaquone-proguanil compared to other antimalarial drugs in treating uncomplicated Plasmodium falciparum malaria? Please answer this question based on the information provided below:
Combination atovaquone and proguanil hydrochloride vs. halofantrine for treatment of acute Plasmodium falciparum malaria in children.
BACKGROUND: Malaria is a major cause of pediatric mortality in sub-Saharan Africa. Worldwide estimates of mortality among children with Plasmodium falciparum malaria range from 1 to 2 million deaths per year. Management of malaria is increasingly difficult because of the global spread of drug-resistant strains of P. falciparum. There is an urgent need for safe and effective new therapies to treat multidrug-resistant malaria.
METHODS: This open label, randomized trial compared atovaquone and proguanil hydrochloride with halofantrine for treatment of acute, uncomplicated P. falciparum malaria in children age 3 to 12 years (84 patients per group). Study drug dosages were adjusted by weight (approximately 20 and 8 mg/kg daily for three doses for atovaquone and proguanil hydrochloride and 8 mg/kg every 6 h for three doses for halofantrine). Patients were monitored by serial clinical and laboratory assessments for 28 days after starting treatment.
RESULTS: Both regimens were effective (cure rate, 93.8% for atovaquone and proguanil hydrochloride and 90.4% for halofantrine) and produced prompt defervescence. Mean parasite clearance times were 50.2 h for halofantrine and 64.9 h for atovaquone and proguanil hydrochloride. More adverse experiences were reported in children treated with halofantrine (119) than with atovaquone and proguanil hydrochloride (73).
CONCLUSIONS: In Kenyan children the combination of atovaquone and proguanil hydrochloride has efficacy comparable with that of halofantrine for treatment of acute uncomplicated multidrug-resistant falciparum malaria and is associated with a lower rate of adverse events.
Atovaquone and proguanil versus amodiaquine for the treatment of Plasmodium falciparum malaria in African infants and young children.
Malaria-related morbidity and mortality are greatest among young children in areas with high malaria transmission intensity. An open-label, randomized study was done to evaluate the efficacy and safety of the combination of atovaquone and proguanil formulated as pediatric-strength tablets (20 and 8 mg/kg of body weight, respectively, administered once daily for 3 days), compared with amodiaquine (10 mg/kg of body weight, once daily for 3 days), among children weighing > or =5 and <11 kg in Gabon. Two hundred patients aged 3-43 months were recruited. Use of atovaquone/proguanil resulted in a cure rate on day 28 of 95% (87 of 92 children), compared with 53% (41 of 78 children) for amodiaquine (difference, 42%; 95% CI, 30%-54%; P<.001). The incidence of adverse events was similar in both groups, and no serious adverse events were attributed to the use of atovaquone/proguanil. Atovaquone/proguanil was found to be highly effective and safe for the treatment of Plasmodium falciparum malaria in infants and young children weighing 5-10 kg in Africa.
Atovaquone plus proguanil versus halofantrine for the treatment of imported acute uncomplicated Plasmodium falciparum malaria in non-immune adults: a randomized comparative trial.
In endemic zones, the atovaquone-proguanil (AP) combination is well tolerated and effective in treating acute, uncomplicated malaria. Trials involving non-immune patients are lacking, however. We conducted a randomized, multicenter open-label trial to determine the efficacy and tolerability of the AP combination (1,000 mg + 400 mg once daily for 3 days) in comparison with halofantrine (HF) (1,500 mg in 3 doses) in non-immune adults with imported uncomplicated Plasmodium falciparum malaria. Follow-up visits were programmed on Days 7, 14, 21, 28, and 35 after hospital discharge. Out of 48 patients enrolled in the study, 41 were assessable for the cure rate (21 in the AP group and 20 in the HF group). All the patients were cured. The mean parasite clearance time was longer (63+/-23 hours) in the AP group than in the HF group (48+/-15 hours) (P = 0.02). The frequency of gastrointestinal adverse events was higher in the AP group. No noteworthy electrocardiographic changes were observed, particularly in the QTc interval. The AP combination appears to be a valuable alternative treatment in non-immune adults.
Atovaquone and proguanil for the treatment of malaria in Brazil.
The purpose of this study was to compare an experimental regimen of atovaquone plus proguanil with the standard regimen of quinine plus tetracycline for the treatment of uncomplicated falciparum malaria. The study was designed as an open, randomized study of men presenting with symptoms of uncomplicated malaria and thick-smear slide confirmation of parasitemia (1000-100,000 ring forms/microL). Subjects were hospitalized for 28 days to insure medication compliance and to rule out the possibility of reinfections. With 77 patients in each group, the cure rates were 98.7% and 100% for atovaquone plus proguanil and quinine plus tetracycline, respectively. The parasite clearance times (mean, 56 h) and fever clearance times (mean, 19 h) were significantly shorter in the atovaquone plus proguanil group, and there were significantly fewer side effects in the atovaquone plus proguanil group. Atovaquone plus proguanil is an efficacious, easily administered, safe regimen for the treatment of uncomplicated, multidrug-resistant falciparum malaria in Brazil.
CV8, a new combination of dihydroartemisinin, piperaquine, trimethoprim and primaquine, compared with atovaquone-proguanil against falciparum malaria in Vietnam.
OBJECTIVES: To study a new combination, based on dihydroartemisinin and piperaquine (CV8) and atovaquone/proguanil (Malarone) for treatment of uncomplicated falciparum malaria in Vietnam.
METHODS: Vietnamese adults with falciparum malaria were allocated randomly to treatment with dihydroartemisinin/piperaquine/trimethoprim/primaquine 256/2560/720/40 mg (CV8, n = 84) or Malarone 3000/1200 mg (n = 81), both over 3 days. Patients were followed-up for 28 days.
RESULTS: All patients recovered rapidly. The mean (95% CI) parasite elimination half-life of CV8 was 6.8 h (6.2-7.4) and of Malarone 6.5 h (6.1-6.9) (P = 0.4). Complete parasite clearance time was 35 (31-39) and 34 h (31-38) (P = 0.9). The 28-day cure rate was 94% and 95%, respectively (odds ratio 0.84, 95% CI 0.18-3.81). No significant side-effects were found.
CONCLUSION: CV8 and Malarone are effective combinations against multi-drug resistant falciparum malaria. CV8 has the advantage of a low price.
Atovaquone and proguani hydrochloride compared with chloroquine or pyrimethamine/sulfodaxine for treatment of acute Plasmodium falciparum malaria in Peru.
The efficacy and safety of a fixed-dose combination of atovaquone and proguanil hydrochloride (Malarone) were compared with chloroquine or pyrimethamine/sulfadoxine in patients with acute falciparum malaria in northern Peru. Patients were initially randomized to receive 1,000 mg atovaquone and 400 mg proguanil hydrochloride daily for 3 days (n=15) or 1,500 mg chloroquine (base) over a 3 day period (n=14) (phase 1). The cure rate with chloroquine was lower than expected and patients were subsequently randomized to receive a single dose of 75 mg pyrimethamine and 1,500 mg sulfadoxine (n=9) or atovaquone/proguanil as before (n=5) (phase 2). In phase 1, atovaquone/proguanil was significantly more effective than chloroquine (cure rate 100% [14/14] vs. 8% [1/13], P<0.0001). In phase 2, atovaquone/proguanil and pyrimethamine/sulfadoxine were both highly effective (cure rates 100% [5/5] and 100% [7/7]). There were no significant differences between treatment groups in parasite or fever clearance times. Adverse events were typical of malarial symptoms and did not differ significantly between groups. Overall efficacy of atovaquone/proguanil was 100% for treatment of acute falciparum malaria in a region with a high prevalence of chloroquine resistance.
Efficacy and safety of atovaquone/proguanil compared with mefloquine for treatment of acute Plasmodium falciparum malaria in Thailand.
The increasing frequency of therapeutic failures in falciparum malaria underscores the need for novel, rapidly effective antimalarial drugs or drug combinations. Atovaquone and proguanil are blood schizonticides that demonstrate synergistic activity against multi-drug-resistant Plasmodium falciparum in vitro. In an open-label, randomized, controlled clinical trial conducted in Thailand, adult patients with acute P. falciparum malaria were randomly assigned to treatment with atovaquone and proguanil/hydrochloride (1,000 mg and 400 mg, respectively, administered orally at 24-hr intervals for three doses) or mefloquine (750 mg administered orally, followed 6 hr later by an additional 500-mg dose). Efficacy was assessed by cure rate (the percentage of patients in whom parasitemia was eliminated and did not recur during 28 days of follow-up), parasite clearance time (PCT), and fever clearance time (FCT). Safety was assessed by sequential clinical and laboratory assessments for 28 days. Atovaquone/proguanil was significantly more effective than mefloquine (cure rate 100% [79 of 79] vs. 86% [68 of 79]; P < 0.002). The atovaquone/proguanil and mefloquine treatments did not differ with respect to PCT (mean = 65 hr versus 74 hr) or FCT (mean = 59 hr versus 51 hr). Adverse events were generally typical of malaria symptoms and each occurred in < 10% of the patients in either group, with the exception of increased vomiting found in the atovaquone/proguanil group. Transient elevations of liver enzyme levels occurred more frequently in patients treated with atovaquone/proguanil than with mefloquine, but the differences were not significant and values returned to normal by day 28 in most patients. The combination of atovaquone and proguanil was well tolerated and more effective than mefloquine in the treatment of acute uncomplicated multidrug-resistant falciparum malaria in Thailand.
Atovaquone and proguanil versus pyrimethamine/sulfadoxine for the treatment of acute falciparum malaria in Zambia.
Atovaquone and proguanil hydrochloride are blood schizonticides that demonstrate in vitro synergy against drug-resistant strains of Plasmodium falciparum. When coadministered, they may therefore be effective for the treatment of malaria in regions where there is known or suspected drug resistance. In an open-label, randomized, parallel-group, clinical trial conducted in Zambia, 163 patients (age range, 14 to 54 years) with acute P falciparum malaria were randomly assigned to receive treatment with atovaquone and proguanil hydrochloride (1000 and 400 mg, respectively, administered orally at 24-hour intervals for 3 doses; n = 82) or pyrimethamine/sulfadoxine (75/1500 mg administered orally as a single dose; n = 81). Efficacy was assessed by cure rate (the percentage of patients in whom parasitemia was eliminated and did not recur during 28 days of follow-up), parasite clearance time (PCT), and fever clearance time (FCT). Safety was determined by sequential clinical and laboratory assessments over 28 days. Cure rates did not differ significantly between patients treated with atovaquone and proguanil (100%) and those treated with pyrimethamine/sulfadoxine (98.8%). Patients in the atovaquone and proguanil group had a significantly shorter FCT than patients in the pyrimethamine/sulfadoxine group (mean, 30.4 vs 44.9 hours; P < 0.05) but a longer PCT (mean, 64.0 vs 51.4 hours; P < 0.05). Both treatments were well tolerated; adverse events and laboratory abnormalities were typical of those normally observed in patients with malaria. In this study, the combination of atovaquone and proguanil was equally effective and as well tolerated as pyrimethamine/sulfadoxine for the treatment of acute, uncomplicated, drug-resistant falciparum malaria in Zambia.
Atovaquone and proguanil for Plasmodium falciparum malaria.
BACKGROUND: The increasing spread of multidrug-resistant Plasmodium falciparum malaria emphasises the urgent need for alternative treatment regimens. The objective of the study was to establish the efficacy of a novel drug combination. We compared a combination of atovaquone and proguanil with amodiaquine in the treatment of acute uncomplicated P falciparum malaria in Lambaréné, Gabon.
METHODS: 142 adults were randomly allocated either a combination treatment of atovaquone 1000 mg daily and proguanil 400 mg daily for 3 days or treatment with amodiaquine 600 mg on admission, 600 mg 24 h later, and 300 mg after a further 24 h. Symptoms and clinical signs were recorded and giemsa-stained thick blood smears were done every 12 h until patients had been symptom-free and aparasitaemic for 24 h. 126 patients were followed up for 28 days or until recrudescence.
FINDINGS: In the atovaquone plus proguanil group 62 (87%) of 71 patients were cured and only one had recrudescent infection. By contrast, the cure rate was significantly lower (p=0.022) with amodiaquine (51 [72%] of 71; there were 12 recrudescences in the amodiaquine group). Eight patients in each group were lost to follow-up. Patients treated with atovaquone plus proguanil complained of nausea (33%) and vomiting (29%), and the most commonly reported adverse effects of amodiaquine were pruritus (43%) and insomnia (27%).
INTERPRETATION: Atovaquone and proguanil was a highly effective and safe drug combination in patients with acute uncomplicated P falciparum malaria in Gabon.
Treatment of uncomplicated multidrug-resistant falciparum malaria with artesunate-atovaquone-proguanil.
In an open-label trial carried out on the northwest border of Thailand, 1596 patients with uncomplicated multidrug-resistant falciparum malaria were randomly assigned to receive atovaquone-proguanil, atovaquone-proguanil-artesunate, or artesunate-mefloquine and were followed up for 42 days. All 3 regimens were highly effective and well tolerated. Fever duration and parasite clearance times were significantly shorter among patients who received artesunate (P<.001). Polymerase chain reaction genotyping confirmed that recrudescence occurred in 13 patients who received artesunate-mefloquine (2.4%), 5 who received atovaquone-proguanil-artesunate (0.9%), and 15 who received atovaquone-proguanil (2.8%). Adding artesunate to atovaquone-proguanil reduced the risk of failure 3-fold (95% confidence interval [CI], 1.1-8.2) and subsequent gametocyte carriage 21-fold (95% CI, 14-30). Gastrointestinal complaints in the first 48 h after initiation of treatment were more common among artesunate recipients, but after day 2, dizziness, sleep disturbance, nausea, vomiting, and anorexia were more common among mefloquine recipients (P< or =.014). Artesunate-atovaquone-proguanil is a highly effective and well-tolerated treatment for multidrug-resistant falciparum malaria.
Options:
A: Atovaquone-proguanil is more effective than chloroquine, amodiaquine, and mefloquine, but there is insufficient data to compare it with other antimalarial drugs.
B: Atovaquone-proguanil is less effective than chloroquine, amodiaquine, and mefloquine, but there is sufficient data to compare it with other antimalarial drugs.
C: Atovaquone-proguanil is equally effective as chloroquine, amodiaquine, and mefloquine, and there is sufficient data to compare it with other antimalarial drugs.
D: Atovaquone-proguanil is more effective than all other antimalarial drugs tested, with sufficient data to support this conclusion. | A |
489 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What was the conclusion regarding the effectiveness of artesunate plus mefloquine compared to mefloquine alone for treating uncomplicated Plasmodium falciparum malaria in areas with low malaria transmission? Please answer this question based on the information provided below:
Pharmacokinetics of mefloquine alone or in combination with artesunate.
A randomized comparative trial of the pharmacokinetics and pharmacodynamics of oral doses of mefloquine and of mefloquine in combination with artesunate was carried out on 20 Thai male patients with acute, uncomplicated falciparum malaria. The patients were randomized to receive either mefloquine alone (8 patients; 1250 mg of mefloquine--initial dose, 750 mg; followed 6 hours later by 500 mg), or in combination with oral artesunate (12 patients--initial dose, 200 mg of artesunate; followed by 750 mg and 500 mg of mefloquine 6 hours and 12 hours later, respectively). The patients who received mefloquine alone all showed initially good responses to the treatment, with mean +/- SD values for the fever clearance time (FCT) and parasite clearance time (PCT) of 44.7 +/- 43.1 hours and 82.3 +/- 52.3 hours, respectively. Two patients had recrudescences on day 20 and day 31 (RI response). The cure rate was 75%, and one patient had Plasmodium vivax in his peripheral blood on day 52. The patients who received the combination treatment were clinically markedly improved, with a relatively shorter FCT (31.2 +/- 12.4 hours) and significantly shorter PCT (47.5 +/- 19.6 hours). Four had recrudescences on days 12, 18, 26 and 33; the cure rate was 66%. Artesunate caused three significant changes in mefloquine pharmacokinetics: a decrease in the maximum concentration (Cmax: 1623 ng.ml-1 versus 2212 ng.ml-1); an increase in the clearance rate (Cl/f:2.9 ml.min-1.kg-1 versus 1.1 ml.min-1.kg-1); and an expansion of the volume of distribution (Vdz/f: 31.8 l.kg-1 versus 25.0 l.kg-1).
Randomised trial of artesunate and mefloquine alone and in sequence for acute uncomplicated falciparum malaria.
The increasing frequency of therapeutic failures in falciparum malaria in Thailand shows an urgent need for effective drugs or drug combinations. Artesunate, a qinghaosu derivative, is effective in clearing parasitaemia rapidly, but the recrudescence rate can be as high as 50%. We have compared artesunate followed by mefloquine with each drug alone in acute, uncomplicated falciparum malaria. 127 patients were randomly assigned treatment with artesunate (600 mg over 5 days), mefloquine (750 mg then 500 mg 6 h later), or artesunate followed by mefloquine. All patients were admitted to hospital for 28 days to exclude reinfection. Cure was defined as no recrudescence during the 28 days' follow-up. The cure rates for mefloquine and artesunate alone were 81% (30/37 patients) and 88% (35/40); the combination was effective in all of 39 patients. Fever and parasite clearance times were significantly shorter in the groups that received artesunate than in the mefloquine-only group. The frequency of nausea and vomiting was slightly, but not significantly, higher among patients who received both drugs than in the other groups. The combination of artesunate followed by mefloquine is highly effective and well tolerated in patients with acute, uncomplicated falciparum malaria in Thailand.
Efficacy of mefloquine and a mefloquine-artesunate combination therapy for the treatment of uncomplicated Plasmodium falciparum malaria in the Amazon Basin of Peru.
In the Amazon Basin of Peru, more than 50% of patients with uncomplicated Plasmodium falciparum malaria fail to respond to treatment with chloroquine or sulfadoxine-pyrimethamine. To assist the National Malaria Control Program in identifying an alternative first-line therapy for this region, we conducted a trial of the safety and efficacy of mefloquine (MQ) compared with mefloquine-artesunate (MQ-AS) combination therapy. Patients with uncomplicated P. falciparum infections between the ages of 5 and 50 years were randomly assigned to be treated with either MQ (15 mg/kg in a single oral dose) or MQ (15 mg/kg) plus AS (4 mg/kg/day for three days). A total of 98 patients were enrolled and followed for 28 days. None of the 47 patients who received MQ alone or the 51 patients who received MQ-AS combination therapy had recurrences of parasitemia during the 28-day follow-up period. Asexual parasite densities decreased significantly more rapidly and the proportion of patients with gametocytes was significantly lower on days 3-21 in the MQ-AS group than in patients treated with MQ alone. All patients tolerated the medication well. Based on the results of this study and with the objective of slowing the development of resistance, the Peruvian Ministry of Health has decided to revise its malaria treatment policy and recommend combination therapy with MO-AS as the new first-line treatment of uncomplicated P. falciparum malaria in the Amazon region.
Lack of prediction of mefloquine and mefloquine-artesunate treatment outcome by mutations in the Plasmodium falciparum multidrug resistance 1 (pfmdr1) gene for P. falciparum malaria in Peru.
We assessed whether mutations in the Plasmodium falciparum multidrug-resistance gene 1 (pfmdr1) (C1034S, D1042N, and Y1246D) would predict treatment outcome during a 28-day in vivo treatment trial in the Peruvian Amazon. Mefloquine (MQ) was compared with mefloquine-artesunate (MQ-AS) in a randomized, multi-clinic protocol for the first time in the Americas. Of 115 patients enrolled in the in vivo arm, 97 patients were eligible for molecular analysis. All 97 patients remained parasite-free during 28 days of follow-up (MQ, n = 46; MQ-AS, n = 51), indicating 100% clinical efficacy of the MQ and MQ-AS treatment regimens. The reported MQ-sensitive alleles (C1034, D1042, and Y1246) were present in 48.5% (n = 47) of the cases, whereas 49 isolates (50.5%) contained the D1246 mutation reported to confer MQ resistance in vitro. However, neither this mutation nor a double mutation (S1034, D1246; n = 16) was predictive of MQ treatment outcome.
Treatment of multidrug-resistant Plasmodium falciparum malaria with 3-day artesunate-mefloquine combination.
Studies of 652 adults and children with acute uncomplicated falciparum malaria were done to determine the optimum treatment of multidrug-resistant Plasmodium falciparum malaria on the Thai-Burmese border. Single-dose artesunate (4 mg/kg) plus mefloquine (25 mg of base/kg) gave more rapid symptomatic and parasitologic responses than high-dose mefloquine alone but did not improve cure rates. Three days of artesunate (total dose, 10 mg/kg) plus mefloquine was 98% effective compared with a 28-day failure rate of 31% with high-dose mefloquine alone (relative risk [RR], 0.06; 95% confidence interval [CI], 0.02-0.2; P < .0001). By day 63, the reinfection adjusted failure rates were 2% and 44%, respectively (P < .0001). Artesunate also prevented high-grade failures. Both drugs were well tolerated. No adverse effects were attributable to artesunate. Vomiting was reduced significantly by giving mefloquine on day 2 of treatment (RR, 0.40; 95% CI, 0.20-0.79; P = .009. Artesunate (10 mg/kg over 3 days) plus mefloquine (25 mg/kg) is currently the most effective treatment for falciparum malaria in this area of increasing mefloquine resistance.
Treatment of multidrug-resistant Plasmodium falciparum malaria with 3-day artesunate-mefloquine combination.
Studies of 652 adults and children with acute uncomplicated falciparum malaria were done to determine the optimum treatment of multidrug-resistant Plasmodium falciparum malaria on the Thai-Burmese border. Single-dose artesunate (4 mg/kg) plus mefloquine (25 mg of base/kg) gave more rapid symptomatic and parasitologic responses than high-dose mefloquine alone but did not improve cure rates. Three days of artesunate (total dose, 10 mg/kg) plus mefloquine was 98% effective compared with a 28-day failure rate of 31% with high-dose mefloquine alone (relative risk [RR], 0.06; 95% confidence interval [CI], 0.02-0.2; P < .0001). By day 63, the reinfection adjusted failure rates were 2% and 44%, respectively (P < .0001). Artesunate also prevented high-grade failures. Both drugs were well tolerated. No adverse effects were attributable to artesunate. Vomiting was reduced significantly by giving mefloquine on day 2 of treatment (RR, 0.40; 95% CI, 0.20-0.79; P = .009. Artesunate (10 mg/kg over 3 days) plus mefloquine (25 mg/kg) is currently the most effective treatment for falciparum malaria in this area of increasing mefloquine resistance.
Artesunate versus artemether in combination with mefloquine for the treatment of multidrug-resistant falciparum malaria.
To compare the therapeutic efficacy of oral artesunate and artemether in combination with mefloquine for the treatment of multidrug resistant malaria, a trial was conducted in 540 adults and children on the Thai-Myanmar border. Three regimens were compared: artesunate (4 mg/kg/d for 3 d), artemether (4 mg/kg/d for 3 d), both in combination with mefloquine (25 mg/kg), and a single dose of mefloquine (25 mg/kg). The artesunate and artemether regimens gave very similar clinical and parasitological responses, and were both very well tolerated. There was no significant adverse effect attributable to the artemisinin derivatives. Fever and parasite clearance times with mefloquine alone were significantly longer (P < 0.001). After adjusting for reinfections the failure rates were 13.9% for the artesunate combination, 12.3% for the artemether combination and 49.2% for mefloquine alone (P < 0.0001; relative risk 3.8 [95% confidence interval 2.6-5.4]). Mefloquine should no longer be used alone for the treatment of multidrug resistant falciparum malaria in this area. Three-day combination regimens with artesunate or artemether are well tolerated and more effective.
Comparison of chloroquine, sulfadoxine/pyrimethamine, mefloquine and mefloquine-artesunate for the treatment of falciparum malaria in Kachin State, North Myanmar.
Multi-drug resistant falciparum malaria is widespread in Asia. In Thailand, Cambodia and Vietnam the national protocols have changed largely to artesunate combined treatment regimens but elsewhere in East and South Asia chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) are still widely recommended by national malaria control programmes. In Kachin State, northern Myanmar, an area of low seasonal malaria transmission, the efficacy of CQ (25 mg base/kg) and SP (1.25/25 mg/kg), the nationally recommended treatments at the time, were compared with mefloquine alone (M; 15 mg base/kg) and mefloquine combined with artesunate (MA; 15:4 mg/kg). An open randomized controlled trial enrolled 316 patients with uncomplicated Plasmodium falciparum malaria, stratified prospectively into three age-groups. Early treatment failures (ETF) occurred in 41% (32/78) of CQ treated patients and in 24% of patients treated with SP (18/75). In young children the ETF rates were 87% after CQ and 35% after SP. Four children (two CQ, two SP) developed symptoms of cerebral malaria within 3 days after treatment. By day 42, failure rates (uncorrected for reinfections) had increased to 79% for CQ and 81% for SP. ETF rates were 2.5% after treatment with M and 3.9% after treatment with MA (P > 0.2). Overall uncorrected treatment failure rates at day 42 following M and MA were 23% and 21%, respectively. Chloroquine and SP are completely ineffective for the treatment of falciparum malaria in northern Myanmar. Mefloquine treatment is much more effective, but three day combination regimens with artesunate will be needed for optimum efficacy and protection against resistance.
A comparative study of artesunate and artemether in combination with mefloquine on multidrug resistant falciparum malaria in eastern Thailand.
Plasmodium falciparum in Thailand is highly resistant to chloroquine, sulfadoxine-pyrimethamine and there is increasing resistance to quinine and mefloquine. The use of qinghaosu derivatives alone or in combination with mefloquine has been shown successfully effective against multidrug resistant P. falciparum in many clinical trials. However their applications with ambulatory treatment should be assessed. 394 uncomplicated falciparum malaria cases studied at Trat and Chanthaburi malaria clinics, eastern Thailand, were allocated at random to receive either one of the seven following regimens: A) artesunate 600 mg over 2 days and mefloquine 1,250 mg in divided doses. B) artemether 640 mg over 2 days and mefloquine 1,250 mg in divided doses. C) artesunate alone 700 mg over 5 days period. D) artemether alone 800 mg over 5 days period. E) quinine plus tetracycline for 7 days. F) mefloquine 1,250 mg in divided doses and G) artesunate 600 mg over 2 days period and mefloquine 750 mg. The follow-up was on Days 1, 2, 7, 14, 21 and 28. Patients tolerated all regimens very well and there was no serious side effects. The adverse effects did not differ among the seven regimens. The cure rates were 98.7, 97.1, 97.9, 96.7, 92.3, 100 and 95.2%, respectively. There was no significant difference of cure rates among various regimens. A total of 16 P. vivax and 1 P. malariae reinfections were reported among the study groups during the second half of the follow-up period, 14 of which were from the groups administered short action drugs (artesunate, artemether or quinine). The results suggested that either artesunate 600 mg or artemether 640 mg in combination with mefloquine 1,250 mg over a period of two days should be considered as alternative regimens for treating uncomplicated multi-drug resistant falciparum malaria.
Options:
A: Artesunate plus mefloquine is less effective than mefloquine alone.
B: Artesunate plus mefloquine is equally effective as mefloquine alone.
C: Artesunate plus mefloquine is more effective than mefloquine alone.
D: Artesunate plus mefloquine has significantly more adverse events than mefloquine alone. | C |
490 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What were the findings regarding the effectiveness of topical quinolone antibiotics compared to no drug treatment or topical antiseptics for treating chronically discharging ears with underlying eardrum perforations? Please answer this question based on the information provided below:
Controlled trial of medical treatment of active chronic otitis media.
A double-blind, randomized, prospective trial of a topical antiseptic versus a topical antibiotic in the treatment of otorrhoea.
The clinical efficacy was assessed of a topical antiseptic (aluminium acetate) and a topical antibiotic (gentamicin sulphate) for the initial treatment of otorrhoea. Evidence of resistant organisms developing to either treatments after 9 and 21 days was also examined. 139 affected ears were entered into the trial and of these, 102 (74%) completed the study. Improvement in the otorrhoea occurred in 68% of ears treated with gentamicin and 67% of ears treated with aluminium acetate, with no significant difference between the two treatments. No resistant organisms to aluminium acetate were encountered. Twelve gentamicin-treated ears had gentamicin-resistant organisms at presentation and one patient developed a gentamicin-resistant Pseudomonas during treatment. We therefore recommend a topical antiseptic such as aluminium acetate rather than a topical antibiotic in the initial treatment of otorrhoea on the grounds of cost, avoidance of resistance and toxicity.
Chronic otitis media treated topically with ciprofloxacin or tobramycin.
OBJECTIVE: To evaluate the efficacy of ciprofloxacin compared with tobramycin and placebo ear drops in the treatment of chronic suppurative otitis media without cholesteatoma.
DESIGN: Sixty ears (in 51 patients) were randomly divided into 3 treatment groups: ciprofloxacin hydrochloride, tobramycin, and placebo interventions.
SETTING: The otolaryngology department of a university teaching hospital.
INTERVENTION: All ears were treated topically for 3 weeks.
MAIN OUTCOME MEASURES: Each patient received a small, numbered bottle and was instructed to instill 5 drops 3 times daily for 3 weeks. The final clinical and bacteriologic assessment was made after 3 weeks.
RESULTS: The organism most commonly isolated from the ear discharge was Pseudomonas aeruginosa. Its sensitivity to ciprofloxacin and tobramycin was 94.2% and 70.6%, respectively. The clinical response was 78.9%, 72.2%, and 41.2% in the ciprofloxacin, tobramycin, and placebo groups, respectively. The bacteriologic response rate was 66.7% for the ciprofloxacin and tobramycin groups and 20% for the placebo group. Treatment with ciprofloxacin ear drops seemed to be as effective as treatment with tobramycin.
CONCLUSION: While the lack of ototoxicity of ciprofloxacin was not tested in our study, this treatment may be considered as a potential topical therapy for cases of chronic suppurative otitis media.
[Local treatment of purulent chronic otitis media with ciprofloxacin].
We evaluated the efficacy of ciprofloxacin eardrops compared to tobramycin and to a placebo in the treatment of chronic suppurative otitis media. 60 ears were randomly assigned to treatment for 3 weeks with ciprofloxacin, tobramycin or placebo eardrops. The organism most commonly isolated from the ear discharge was Pseudomonas aeruginosa. The clinical responses were 78.9% and 72.2%, respectively, in the ciprofloxacin and tobramycin groups, while it was only 41.2% in the placebo group. Treatment with ciprofloxacin eardrops seemed to be at least as efficient as treatment with tobramycin. Considering the lack of ototoxicity of ciprofloxacin, this treatment may be best for chronic otitis media.
[Double-blind comparative study of trimethroprim-sulphacetamide-polymyxin b and gentamicin in the treatment of otorrhoea (author's transl)].
A double-blind comparative study of the use of Garamycine (gentamicin) ear drops and TSP (trimethroprim-sulphacetamide-polomyxin B) ear drops in the treatment of 100 cases of otorrhoea due to external otitis, a recurrent otitis media accompanied by perforation of the drum, an infection of the mastoid cavity or a postoperative infection, provided evidence of the effectiveness of both medications. TSP ear drops gave positive results in 42 out of 50 cases treated, whilst for gentamicin aural solution results were positive for 46 out of 50 cases. Gentamicin gave a successful result in 5 of the 8 failures with TSP, whilst TSP cured the four original failures with gentamicin. There were no signs of ototoxicity, of excessive fungal proliferation nor of any local sensitivity to the ear drops. It would seem that these aural preparations are complementary, capable of resulting in the disappearance of the majority of bacterial agents responsible for pathogenic otorrhoea.
A double-blind comparative study of trimethoprim-polymyxin B versus trimethoprim-sulfacetamide-polymyxin B otic solutions in the treatment of otorrhea.
This was a double-blind randomized study to compare the safety and efficacy of trimethoprim-polymyxin B (TP) and trimethoprim-sulfacetamide-polymyxin B (TSP) drops in the treatment of otorrhea. The 68 cases treated suffered from external otitis, recurrent otitis media with tympanic membrane perforation, or infected mastoid cavities and post-operative tympanoplasties. The TP ototopical solution was successful in 60.6 per cent of cases compared to 88.6 per cent of cases with TSP. These rates were statistically different using the Chi Square with Yates' correction method. There were no signs of ototoxicity, fungal infection overgrowth or local sensitivity to either of the solutions. The study has shown that both drugs are equally safe and that TSP is significantly more effective in the treatment of otorrhea.
[Double-blind comparative trial of trimethoprim-polymyxin B and trimethoprim-sulphacetamide-polymyxin B ear drops in the treatment of otorrhoea (author's transl)].
The purpose of his double-blind, randomized trial was to compare ear drops containing either trimethoprim and polymyxin B (TP) or trimethoprim, sulphacetamide and polymyxin B (TSP) from the points of view of effectiveness and safety. The 68 patients treated had otitis externa or recurrent otitis media with perforated ear-drum, or mastoid cavity with post-tympanoplasty infection. Satisfactory results were obtained in 60.6% of the cases with TP and in 88.6% with TSP. When evaluated by the Chi-square method with Yates' correction, the difference was statistically significant. There was no evidence of ototoxicity, fungal infection or local hypersensitivity with either preparation. The trial demonstrated that both ear drops were active and that TSP was much more effective than TP in the treatment of otorrhea.
Evaluation of topical povidone-iodine in chronic suppurative otitis media.
OBJECTIVES: To evaluate if povidone-iodine (PVP-I) can be used topically in the treatment of chronic suppurative otitis media-tubotympanic disease and to compare it with ciprofloxacin hydrochloride ear drops.
DESIGN: Prospective double-blind randomized study.
SETTING: Academic tertiary medical center.
PATIENTS: Forty patients with chronic suppurative otitis media were randomized into 2 groups.
INTERVENTION: One group (19 patients) received 5% PVP-I ear drops, while the other group (21 patients) received 0.3% ciprofloxacin ear drops. Both were administered topically, 3 drops 3 times daily for 10 days. These patients were followed up at weekly intervals for up to 4 weeks after commencing therapy.
RESULTS: Clinical improvement at the end of study was 88% in the PVP-I group and 90% in the ciprofloxacin group. The most commonly isolated organism was Pseudomonas aeruginosa. In vitro resistance to ciprofloxacin was seen in 17% of organisms, while no resistance was seen for PVP-I.
CONCLUSIONS: To our knowledge, this is the first study to evaluate the efficacy of PVP-I as a topical agent in the treatment of chronic suppurative otitis media. The results show that clinically, topical PVP-I is as effective as topical ciprofloxacin, with a superior advantage of having no in vitro drug resistance. Also, there is an added benefit of reduced cost of therapy.
A double blind, prospective trial of topical ciprofloxacin versus normal saline solution in the treatment of otorrhoea.
The clinical and bacteriological efficacy of topical ciprofloxacin in saline solution and a saline solution without antibiotics, for the treatment of otorrhoea, was assessed. Fifty affected ears which had an acute exacerbation of chronic otitis media with tympanic membrane perforation were included in this study. Only 35 ears completed the study. Both medications were randomly given to patients. Therapeutic efficacy was evaluated on the seventh day of treatment. A favourable clinical response was observed in 89.5% of the ciprofloxacin-treated group and in 43.8% of the saline-treated group, respectively (P < 0.005). Bacteriological eradication was also observed to be higher in the ciprofloxacin-treated group (P < 0.005). From these preliminary results, topical ciprofloxacin appears to be effective in curing the acute phase of chronic otitis media.
[Efficacy of topical ciprofloxacin and tobramycin in combination with dexamethasone in the treatment of chronic suppurative otitis media].
OBJECTIVES: To evaluate the efficacy of topical ciprofloxacin and tobramycin with and without topical dexamethasone in the treatment of chronic suppurative otitis media without cholesteatoma.
PATIENTS AND METHODS: The study included 103 ears of 80 patients (49 males, 31 females; mean age 31 years; range 18 to 60 years) with chronic suppurative otitis media without cholesteatoma. The patients were randomly divided into four groups to receive topical applications of either ciprofloxacin and tobramycin alone, or in combination with dexamethasone. Cultures were obtained from the ears preoperatively and 24 hours after treatment.
RESULTS: Aerobic bacteria were isolated in 94.1% of patients before the treatment, the most common being Pseudomonas aeruginosa (38.9%). With dexamethasone, the clinical response for ciprofloxacin and tobramycin increased from 80% to 90% and from 70% to 75%, respectively, but this improvement was not significant (p > 0.03). Addition of dexamethasone to ciprofloxacin decreased the recovery period from 14 days to seven days, whereas no change (7 days) was observed with tobramycin.
CONCLUSION: The efficacy of ciprofloxacin and tobramycin were similar in the treatment of chronic suppurative otitis media. Addition of dexamethasone to ciprofloxacin decreased the treatment period.
[Multicenter study comparing the efficacy and tolerance of topical ciprofloxacin (0.3%) versus topical gentamicin (0.3%) in the treatment of simple, non-cholesteatomaous chronic otitis media in the suppurative phase].
A multicentre double-blind randomized study was carried out to compare topical ciprofloxacin and topical gentamicin in the treatment of simple non-cholesteatomatous purulent chronic otitis media. Three hundred and eight patients were included in the study, 159 treated with ciprofloxacin and 149 treated with gentamicin. The percentage of clinical success (elimination of otorrhoea) was 95% with ciprofloxacin and 94% with gentamicin (ns). Likewise, the percentage of bacteriological erradication was 96% with ciprofloxacin and 93% with gentamicin. Both drugs were well tolerated, without changes in the audiometric values. In these patients, topical ciprofloxacin shows the same efficacy as topical gentamicin without any potential ototoxic effect.
[Prospective double-blind randomized study of the efficacy and tolerance of topical ciprofloxacin vs topical gentamicin in the treatment of simple chronic otitis media and diffuse external otitis].
A prospective, randomized double-blind study was made of topical ciprofloxacillin (0.5%) compared with topical gentamicin (0.3%) in the treatment of simple chronic otitis media (COM) and diffuse external otitis (DEO). The study included 47 patients with COM and 54 patients with DEO. Success rates in the COM subgroup were 95% for ciprofloxacillin and 96% for gentamicin (p = 0.082), and in the DEO subgroup, 87% for ciprofloxacillin and 79% for gentamicin (p = 0.19). Both drugs were well tolerated and there was no significant change in audiometric measurements with either medication in either group. Therefore, ciprofloxacillin is at least as effective as gentamicin in such ear infections and has no potential ototoxic effect.
Topical quinolone vs. antiseptic for treating chronic suppurative otitis media: a randomized controlled trial.
OBJECTIVE: To compare a topical quinolone antibiotic (ciprofloxacin) with a cheaper topical antiseptic (boric acid) for treating chronic suppurative otitis media in children.
DESIGN: Randomized controlled trial.
SETTING AND PARTICIPANTS: A total of 427 children with chronic suppurative otitis media enrolled from 141 schools following screening of 39 841 schoolchildren in Kenya. Intervention Topical ciprofloxacin (n = 216) or boric acid in alcohol (n = 211); child-to-child treatment twice daily for 2 weeks.
MAIN OUTCOME MEASURES: Resolution of discharge (at 2 weeks for primary outcome), healing of the tympanic membrane, and change in hearing threshold from baseline, all at 2 and 4 weeks.
RESULTS: At 2 weeks, discharge was resolved in 123 of 207 (59%) children given ciprofloxacin, and in 65 of 204 (32%) given boric acid (relative risk 1.86; 95% CI 1.48-2.35; P < 0.0001). This effect was also significant at 4 weeks, and ciprofloxacin was associated with better hearing at both visits. No difference with respect to tympanic membrane healing was detected. There were significantly fewer adverse events of ear pain, irritation, and bleeding on mopping with ciprofloxacin than boric acid.
CONCLUSIONS: Ciprofloxacin performed better than boric acid and alcohol for treating chronic suppurative otitis media in children in Kenya.
Effects of topical otic preparations on hearing in chronic otitis media.
Most of the topical otic preparations have been shown to cause ototoxicity. In this study ciprofloxacin hydrochloride, a relatively new topical agent, and gentamicin sulfate were studied in two groups of 20 patients with chronic otitis media. Patients were randomly selected to receive either ciprofloxacin (200 microg/ml) or gentamicin sulfate (5 mg/ml) locally, five drops three times a day for 10 days. Clinical response was seen in 20 of 20 patients in the ciprofloxacin group compared with 6 of 20 patients in the gentamicin group. Audiometric evaluation revealed no significant ototoxic effect in either group. In fact, hearing thresholds were slightly better than pretreatment levels in both groups.
Treatment of chronic ear disease. Topical ciprofloxacin vs topical gentamicin.
OBJECTIVE: To determine and compare the therapeutic efficiency of ciprofloxacin hydrochloride and gentamicin sulfate in the treatment of chronic ear disease.
DESIGN: Prospective randomized study.
SETTING: Academic tertiary medical center.
PATIENTS: Consecutive referred sample of 44 patients with chronic suppurative otitis media randomized into two groups.
INTERVENTIONS: Ciprofloxacin hydrochloride (200 mg/mL) was administered to the first group (composed of 24 patients), while the second group (composed of 20 patients) received gentamicin sulfate (5 mg/mL) locally, five drops three times a day for 10 days.
RESULTS: In the ciprofloxacin group, 21 (88%) of the 24 patients with suppurative chronic otitis media were cured. On the other hand, only six (30%) of the patients in the gentamicin group were cured. The rest of the patients showed no clinical or bacteriological improvement.
CONCLUSIONS: To our knowledge, this is the first study to compare the efficiency of two topical otic preparations in the treatment of chronic ear disease. The results show that topical ciprofloxacin preparation is more efficacious and efficient than topical gentamicin for the treatment of chronic otitis media in the acute stage.
Treatment of chronic suppurative otitis media with ofloxacin in hydroxypropyl methylcellulose ear drops: a clinical/bacteriological study in a rural area of Malawi.
Chronic suppurative otitis media in young children is a major problem in Africa, with socio-economic consequences at a later age. Common treatment regimens with antibiotics are expensive and often not practically feasible. Therefore, a project was started to develop a low-cost and effective treatment in a rural area of Malawi by studying the clinical efficacy of an inexpensive application regimen of ofloxacin (0.075%) in hydroxypropyl methylcellulose (1.5%) ear drops. In earlier studies with this treatment regimen, it was possible to cure approximately 70% of ears. The aim of this study was to find out whether the bacteriological spectrum cultured from wet ears before and after treatment, and patterns of resistance to antibiotics, played a role in the percentage of cures. Patients with long-standing chronic suppurative otitis media were clinically assessed and treated with suction cleaning and instillation of ear drops on days 1, 3, 7 and 10. Bacterial swabs were taken for culture and sensitivity tests for ofloxacin were on days 1 and 10 from the ears that were still discharging. After 21 weeks, the ears were assessed again clinically. Clinical cure was considered to be complete cessation of otorrhea. Ninety of 104 tested patients (124 ears) completed the study. About 73% of the ears had become dry by day 10. This dropped to 42% after 21 weeks. Before treatment, most ears (91%) harbored fecal bacteria, Proteus mirabilis (74%) and enterococci (60%) being the most frequently isolated microbes. The second group of frequently cultured bacteria were water bacteria e.g. Pseudomonas species and other non-fermenters (69%), whereas the classical otitis media pathogens were detected only in 15% of ears. Before treatment, 9.7% of strains were resistant to ofloxacin, most (30/35) of which were cultured from ears that were eventually cured. After treatment, fecal and water bacteria were still the most frequently found, with 36% new strains and an overall sensitivity to ofloxacin of 58%. Bacterial resistance did not appear to play an important role in the outcome of treatment. These data rather suggest a very high risk of infection due to poor hygiene conditions. Medical treatment can only have a longer-lasting effect if accompanied by community-based programs that focus on improvement of hygiene. A public health approach is necessary alongside a medical approach for the management of CSOM.
Treatment of chronic suppurative otitis media with ofloxacin in hydroxypropyl methylcellulose ear drops: a clinical/bacteriological study in a rural area of Malawi.
Chronic suppurative otitis media in young children is a major problem in Africa, with socio-economic consequences at a later age. Common treatment regimens with antibiotics are expensive and often not practically feasible. Therefore, a project was started to develop a low-cost and effective treatment in a rural area of Malawi by studying the clinical efficacy of an inexpensive application regimen of ofloxacin (0.075%) in hydroxypropyl methylcellulose (1.5%) ear drops. In earlier studies with this treatment regimen, it was possible to cure approximately 70% of ears. The aim of this study was to find out whether the bacteriological spectrum cultured from wet ears before and after treatment, and patterns of resistance to antibiotics, played a role in the percentage of cures. Patients with long-standing chronic suppurative otitis media were clinically assessed and treated with suction cleaning and instillation of ear drops on days 1, 3, 7 and 10. Bacterial swabs were taken for culture and sensitivity tests for ofloxacin were on days 1 and 10 from the ears that were still discharging. After 21 weeks, the ears were assessed again clinically. Clinical cure was considered to be complete cessation of otorrhea. Ninety of 104 tested patients (124 ears) completed the study. About 73% of the ears had become dry by day 10. This dropped to 42% after 21 weeks. Before treatment, most ears (91%) harbored fecal bacteria, Proteus mirabilis (74%) and enterococci (60%) being the most frequently isolated microbes. The second group of frequently cultured bacteria were water bacteria e.g. Pseudomonas species and other non-fermenters (69%), whereas the classical otitis media pathogens were detected only in 15% of ears. Before treatment, 9.7% of strains were resistant to ofloxacin, most (30/35) of which were cultured from ears that were eventually cured. After treatment, fecal and water bacteria were still the most frequently found, with 36% new strains and an overall sensitivity to ofloxacin of 58%. Bacterial resistance did not appear to play an important role in the outcome of treatment. These data rather suggest a very high risk of infection due to poor hygiene conditions. Medical treatment can only have a longer-lasting effect if accompanied by community-based programs that focus on improvement of hygiene. A public health approach is necessary alongside a medical approach for the management of CSOM.
Treatment of chronic suppurative otitis media with ofloxacin in hydroxypropyl methylcellulose ear drops: a clinical/bacteriological study in a rural area of Malawi.
Chronic suppurative otitis media in young children is a major problem in Africa, with socio-economic consequences at a later age. Common treatment regimens with antibiotics are expensive and often not practically feasible. Therefore, a project was started to develop a low-cost and effective treatment in a rural area of Malawi by studying the clinical efficacy of an inexpensive application regimen of ofloxacin (0.075%) in hydroxypropyl methylcellulose (1.5%) ear drops. In earlier studies with this treatment regimen, it was possible to cure approximately 70% of ears. The aim of this study was to find out whether the bacteriological spectrum cultured from wet ears before and after treatment, and patterns of resistance to antibiotics, played a role in the percentage of cures. Patients with long-standing chronic suppurative otitis media were clinically assessed and treated with suction cleaning and instillation of ear drops on days 1, 3, 7 and 10. Bacterial swabs were taken for culture and sensitivity tests for ofloxacin were on days 1 and 10 from the ears that were still discharging. After 21 weeks, the ears were assessed again clinically. Clinical cure was considered to be complete cessation of otorrhea. Ninety of 104 tested patients (124 ears) completed the study. About 73% of the ears had become dry by day 10. This dropped to 42% after 21 weeks. Before treatment, most ears (91%) harbored fecal bacteria, Proteus mirabilis (74%) and enterococci (60%) being the most frequently isolated microbes. The second group of frequently cultured bacteria were water bacteria e.g. Pseudomonas species and other non-fermenters (69%), whereas the classical otitis media pathogens were detected only in 15% of ears. Before treatment, 9.7% of strains were resistant to ofloxacin, most (30/35) of which were cultured from ears that were eventually cured. After treatment, fecal and water bacteria were still the most frequently found, with 36% new strains and an overall sensitivity to ofloxacin of 58%. Bacterial resistance did not appear to play an important role in the outcome of treatment. These data rather suggest a very high risk of infection due to poor hygiene conditions. Medical treatment can only have a longer-lasting effect if accompanied by community-based programs that focus on improvement of hygiene. A public health approach is necessary alongside a medical approach for the management of CSOM.
Options:
A: Topical quinolone antibiotics were less effective than no drug treatment at clearing ear discharge.
B: Topical quinolone antibiotics were more effective than no drug treatment at clearing ear discharge.
C: Topical quinolone antibiotics were equally effective as no drug treatment at clearing ear discharge.
D: Topical quinolone antibiotics were less effective than topical antiseptics at clearing ear discharge. | B |
491 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What is the impact of using fiber as a laxative on the symptoms of symptomatic hemorrhoids? Please answer this question based on the information provided below:
Evaluation of a bulk-forming evacuant in the management of haemorrhoids.
Fybogel in haemorrhoid treatment.
Maintenance bran therapy for prevention of symptoms after rubber band ligation of third-degree haemorrhoids.
Proctoscopically diagnosed third-degree haemorrhoids were treated with rubber band ligation (RBL) in 92 patients, who were randomly assigned to management with or without twice-daily intake of unprocessed bran for 18 months. RBL was performed maximally five times at 2-week intervals. Patients who were symptom-free 10 weeks after first banding were considered cured and were enrolled in a follow-up study. The two treatment groups did not differ in regard to clinical or proctoscopic characteristics. The number of RBL required for cure was lower in the bran-treated group (p less than 0.01). The intergroup difference in cure rate 10 weeks after the first treatment was not significant (85% v. 91%). During the follow-up period symptoms recurred in 45% of the RBL group, but in only 15% of the RBL + bran group (p less than 0.01). A high-fiber diet thus increased the long-term cure rate among patients with third-degree haemorrhoids initially cured by RBL.
High-fiber diet reduces bleeding and pain in patients with hemorrhoids: a double-blind trial of Vi-Siblin.
Effect of fiber supplements on internal bleeding hemorrhoids.
BACKGROUND/AIMS: The aim of this study is to assess prospectively the effect of fiber additions on internal bleeding hemorrhoids.
MATERIALS AND METHODS: Fifty patients with bleeding internal hemorrhoids are studied and randomized in two groups. Patients in the study group were treated with a commercially available preparation of Plantago Ovata and those in the control group were treated with a placebo. Endoscopy was performed on every patient before and after treatment to establish: a) the degree of hemorrhoidal prolapse, b) the number of congested hemorrhoidal cushions and c) contact bleeding hemorrhoids.
RESULTS: During the 15 days of treatment, the average number of bleeding episodes was 4.8 +/- 3.8 for the study group versus 6.4 +/- 3 for the control group (n.s.). During the following 15 days, it decreased to 3.1 +/- 2.7 in the study group versus 5.5 +/- 3.2 (p < 0.05) in the control group and in the last 10 days of treatment a further reduction to 1.1 +/- 1.4 was found in the study group versus 5.5 +/- 2.9 (p < 0.001). The number of congested hemorrhoidal cushions diminished from 2.6 +/- 1 to 1.6 +/- 2.2 after fiber treatment (p < 0.01) and no differences were found in the control group. In the fiber group, hemorrhoids bled on contact in 5 out of 22 patients before treatment and in none after treatment; no differences were found in the control group. No modification of the degree of prolapse was observed after treatment.
CONCLUSION: Addition of dietary fiber may improve internal bleeding hemorrhoids although with no immediate effect. Fiber addition should be ensured in patients who refuse invasive treatment, waiting for a more defined form of treatment, or with contraindications.
The use of bulk evacuant in patients with haemorrhoids.
Fifty-three patients with symptomatic haemorrhoids have been studied in a double-blind cross-over trial of a bulk forming agent (ispaghula husk) against a placebo. Although only 11 per cent of patients ocmplained of constipation, a significant benefit in symptoms and improved bowel habit was demonstrated.
Options:
A: Fiber has no significant effect on the symptoms of symptomatic hemorrhoids.
B: Fiber increases the risk of persistent symptoms and does not improve hemorrhoids.
C: Fiber significantly reduces the risk of persistent symptoms and improves overall symptoms and bleeding.
D: Fiber only improves the symptoms of pain and itching but has no effect on bleeding. | C |
492 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What were the findings regarding the effectiveness of hyperbaric oxygen therapy (HBOT) for treating delayed onset muscle soreness (DOMS) and closed soft tissue injuries? Please answer this question based on the information provided below:
Effects of intermittent exposure to hyperbaric oxygen for the treatment of an acute soft tissue injury.
OBJECTIVE: To assess the hypothesis that subjects exposed to intermittent hyperbaric oxygen treatments would recover from signs and symptoms indicative of delayed-onset muscle soreness faster than subjects exposed to normoxic air.
DESIGN: Randomized, double-blinded study with a 4-day treatment protocol.
SETTING: University-based sports medicine clinic.
PARTICIPANTS: Sixteen sedentary female university students.
INTERVENTIONS: All subjects performed 300 maximal voluntary eccentric contractions (30 sets of 10 repetitions per minute) of their nondominant leg (110 to 35 degrees of knee flexion) at a slow speed (30 degrees per second) on a dynamometer to elicit muscle damage and injury. Hyperbaric oxygen treatments consisted of 100% oxygen for 60 minutes at 2.0 atmospheres absolute (ATA), while the control group received 21% oxygen at 1.2 ATA for the same amount of time. Both groups received treatment immediately after the induction of delayed-onset muscle soreness and each day thereafter for a period of 4 days (day 1 postexercise through day 4 postexercise).
MAIN OUTCOME MEASURES: Dependent variables (perceived muscle soreness, isokinetic strength, quadriceps circumference, creatine kinase, and malondialdehyde) were assessed at baseline (preexercise, day 0), 4 hours postexercise (day 1), 24 hours postexercise (day 2), 48 hours postexercise (day 3), and 72 hours postexercise (day 4). Magnetic resonance images (T2 relaxation time/short tip inversion recovery) were assessed at baseline (day 0), 24 hours postexercise (day 3), and 72 hours postexercise (day 5).
RESULTS: Repeated-measures analysis of variance was performed on all of the dependent variables to assess differences between treatment and control groups. Analyses revealed no significant differences between groups for treatment effects for any of the dependent variables (pain, strength, quadriceps circumference, creatine kinase, malondialdehyde, or magnetic resonance images).
CONCLUSIONS: The findings of this study suggest that hyperbaric oxygen therapy is not effective in the treatment of exercise-induced muscle injury as indicated by the markers evaluated.
Hyperbaric oxygen therapy to enhance recovery from delayed onset muscle soreness.
Effects of intermittent exposure to hyperbaric oxygen for the treatment of an acute soft tissue injury.
OBJECTIVE: To assess the hypothesis that subjects exposed to intermittent hyperbaric oxygen treatments would recover from signs and symptoms indicative of delayed-onset muscle soreness faster than subjects exposed to normoxic air.
DESIGN: Randomized, double-blinded study with a 4-day treatment protocol.
SETTING: University-based sports medicine clinic.
PARTICIPANTS: Sixteen sedentary female university students.
INTERVENTIONS: All subjects performed 300 maximal voluntary eccentric contractions (30 sets of 10 repetitions per minute) of their nondominant leg (110 to 35 degrees of knee flexion) at a slow speed (30 degrees per second) on a dynamometer to elicit muscle damage and injury. Hyperbaric oxygen treatments consisted of 100% oxygen for 60 minutes at 2.0 atmospheres absolute (ATA), while the control group received 21% oxygen at 1.2 ATA for the same amount of time. Both groups received treatment immediately after the induction of delayed-onset muscle soreness and each day thereafter for a period of 4 days (day 1 postexercise through day 4 postexercise).
MAIN OUTCOME MEASURES: Dependent variables (perceived muscle soreness, isokinetic strength, quadriceps circumference, creatine kinase, and malondialdehyde) were assessed at baseline (preexercise, day 0), 4 hours postexercise (day 1), 24 hours postexercise (day 2), 48 hours postexercise (day 3), and 72 hours postexercise (day 4). Magnetic resonance images (T2 relaxation time/short tip inversion recovery) were assessed at baseline (day 0), 24 hours postexercise (day 3), and 72 hours postexercise (day 5).
RESULTS: Repeated-measures analysis of variance was performed on all of the dependent variables to assess differences between treatment and control groups. Analyses revealed no significant differences between groups for treatment effects for any of the dependent variables (pain, strength, quadriceps circumference, creatine kinase, malondialdehyde, or magnetic resonance images).
CONCLUSIONS: The findings of this study suggest that hyperbaric oxygen therapy is not effective in the treatment of exercise-induced muscle injury as indicated by the markers evaluated.
Hyperbaric oxygen therapy for acute ankle sprains.
We conducted a randomized double-blind study of 32 subject with acute ankle sprains to compare treatment with hyperbaric oxygen at 2 atmospheres absolute pressure (N = 16) (treatment group) with treatment with air at 1.1 atmosphere absolute pressure (N = 16) (control group) in a hyperbaric chamber. Each group received three treatments at their respective pressures: one for 90 minutes and two for 60 minutes each. Mean age, severity grade, and time to treatment (treatment group, 34.3 +/- 6.3 hours; control group, 32.6 +/- 4.6 hours) were similar in both groups. Joint function measured by a functional index improved from 0.40 +/- 0.2 to 6.3 +/- 0.4 with hyperbaric oxygen and from 0.8 +/- 0.3 to 5.3 +/- 0.6 with air. The change from initial to final evaluation was significantly greater in the treatment group. Foot and ankle volume by water displacement decreased from 1451 +/- 57 ml to 1425 +/- 63 ml with hyperbaric oxygen and from 1403 +/- 50 ml of 1371 +/- 45 ml with air (no difference was noted between hyperbaric oxygen treatment and air treatment using a two-day analysis of variance). Subjective pain index fell from 3.3 +/- 0.5 to 0.8 +/- 0.3 with hyperbaric oxygen and from 2.6 +/- 0.3 to 0.3 +/- 0.2 with air. No differences were noted in passive or active range of motion when comparing hyperbaric oxygen treatment with air treatment. Time to recovery was the same in both groups (treatment, 16.0 +/- 6.3 days; control, 15.4 +/- 2.8 days). Regression analysis to determine the influence of time to treatment, initial severity of injury, hyperbaric oxygen, and age showed no effect of hyperbaric oxygen treatment on time to recovery.
Effect of hyperbaric oxygen therapy on exercise-induced muscle soreness.
The purpose of this study was to examine the effects of HBO2 therapy on exercise-induced muscle soreness. Subjects (n = 6 male and 10 female university student volunteers) were randomly divided into an experimental group that received HBO2 therapy and a control group that did not receive any treatments. HBO2 treatments consisted of 5 sessions of breathing 95% oxygen at 2.5 atm abs for 100 min. Temporary muscle soreness was created using a single-leg eccentric exercise task involving the quadriceps femoris. Over the next 14 days, measurements were obtained on muscle soreness, leg circumference, quadriceps peak torque, quadriceps average power, fatigue and plasma creatine kinase. After eccentric exercise, plasma creatine kinase (CK) levels and perceived muscle soreness were elevated but were not different between HBO2 and control groups. HBO2 therapy did not alter leg circumference, quadriceps peak torque, average power or fatigue compared to the control group. Faster recovery was observed in the HBO2 group on day 3 following the exercise protocol with perceived muscle soreness still elevated for the control group but not different from baseline for the HBO2 group. The data indicated that five HBO2 treatments did not speed recovery following eccentric exercise that induced temporary muscle soreness.
Treatment of exercise-induced muscle injury via hyperbaric oxygen therapy.
PURPOSE: This study examined the role of hyperbaric oxygen therapy (HBO) in the treatment of exercise-induced muscle injury.
METHODS: 21 college-aged male volunteers were assigned to three groups: control, immediate HBO (iHBO), and delayed HBO (dHBO). All subjects performed 6 sets (10 repetitions per set) of eccentric repetitions with a load equivalent to 120% of their concentric maximum. HBO treatments consisted of 100-min exposure to 2.5 ATA and 100% oxygen with intermittent breathing of ambient air (30 min at 100% O2, 5 min at 20.93% O2). HBO treatments began either 2 (iHBO) or 24 h (dHBO) postexercise and were administered daily through day 4 postexercise. Forearm flexor cross-sectional area (CSA) and T2 relaxation time via magnetic resonance imaging (MRI) were assessed at baseline, 2, 7, and 15 d postinjury. Isometric strength and rating of perceived soreness of the forearm flexors were assessed at baseline, 1, 2, 3, 4, 7, and 15 d postinjury. Serum creatine kinase (CK) was assessed on day 0 and on days 1, 2, 7, and 15 postinjury.
RESULTS: Mean baseline CSA values were: 2016.3, 1888.5, and 1972.2 mm2 for control, iHBO, and dHBO, respectively. All groups showed significant increases in CSA in response to injury (21% at 2 d, 18% at 7 d) (P < 0.0001), but there were no significant differences between groups (P = 0.438). Mean baseline T2 relaxation times were: 26.18, 26.28, and 27.43 msec for control, iHBO, and dHBO, respectively. Significant increases in T2 relaxation time were observed for all groups (64% at 2 d, 66% at 7 d, and 28% at 15 d) (P < 0.0001), but there were no significant differences between groups (P = 0.692). Isometric strength (P < 0.0001), serum CK levels (P = 0.0007), and rating of perceived soreness (P < 0.0001) also indicated significant muscle injury for all groups, but there were no differences between groups (P = 0.459, P = 0.943, and P = 0.448, respectively).
CONCLUSION: These results suggest that hyperbaric oxygen therapy was not effective in the treatment of exercise-induced muscle injury as indicated by the markers evaluated.
Hyperbaric oxygen therapy does not affect recovery from delayed onset muscle soreness.
PURPOSE: This study investigated whether hyperbaric oxygen therapy (HBOT) improves recovery after exercise-induced muscle injury.
METHODS: Healthy male subjects (N = 24) were randomly assigned to either a placebo group or a HBOT group. Subjects were tested for maximal isometric strength (preexercise) of their right elbow flexors. Each subject then completed a high-force eccentric workout of the elbow flexor muscle group to induce delayed onset muscle soreness (DOMS). On the seven successive days after this workout, the subjects were exposed to a hyperbaric environment of 2.5 ATA for 60 min, inspiring either a normoxic mixture (P(I)O2 = 0.2 ATA; placebo group) or a hyperoxic gas mixture (P(I)O2 = 2.5 ATA; HBOT group). Before the eccentric workout and daily for the next 10 d, measurements were obtained regarding: maximal isometric muscle strength of the elbow flexor muscles, right upper arm circumferences, and rating of the perceived muscle soreness.
RESULTS: Isometric strength decreased significantly from preexercise levels of 25.1 +/- 3.8 kp to postexercise levels of 12.0 +/- 4.6 kp, for the HBOT group, and from 24.6 +/- 3.4 kp to 12.5 +/- 3.7 kp, respectively, for the placebo group. Over the 10-d recovery period, there was no difference in the rate of recovery of muscle strength between the two groups. Perceived soreness peaked at about 48 h after exercise with no difference between groups. Also, the exercise-induced increases in arm circumference were similar in the two groups.
CONCLUSIONS: These results indicate that HBOT is not an effective therapy for the treatment of DOMS.
Effects of hyperbaric oxygen on a human model of injury.
To determine whether intermittent exposures to hyperbaric oxygen enhance recovery from delayed-onset muscle soreness of the quadriceps, we conducted a randomized, controlled, double-blinded, prospective study using 66 untrained men between the ages of 18 and 35 years. After the induction of muscle soreness, these subjects were treated in a hyperbaric chamber over a 5-day period in two phases, with four groups (control, hyperbaric oxygen treatment, delayed treatment, and sham treatment) in the first phase; and three groups (3 days of treatment, 5 days of treatment, and sham treatment) in the second phase. The hyperbaric exposures involved 100% oxygen for 1 hour per day at 2.0 atm. The sham treatments involved 21% oxygen for 1 hour per day at 1.2 atm. We monitored recovery using a leg dynamometer to test eccentric torque of the nondominant quadriceps muscle before and immediately after exercise and at 48 and 96 hours after exercise. Pain was tested daily using visual analog pain scales. In phase 1 a significant difference in recovery of eccentric torque was noted in the treatment group compared with the other groups. In phase 2, the recovery of eccentric torque for the 5-day treatment group was significantly greater than for the sham group from immediately after exercise to 96 hours after exercise. The pain data did not differ significantly in any comparison in either phase. The results suggest that treatment with hyperbaric oxygen may enhance recovery of eccentric torque of the quadriceps muscle from delayed-onset muscle soreness.
Effects of hyperbaric oxygen on a human model of injury.
To determine whether intermittent exposures to hyperbaric oxygen enhance recovery from delayed-onset muscle soreness of the quadriceps, we conducted a randomized, controlled, double-blinded, prospective study using 66 untrained men between the ages of 18 and 35 years. After the induction of muscle soreness, these subjects were treated in a hyperbaric chamber over a 5-day period in two phases, with four groups (control, hyperbaric oxygen treatment, delayed treatment, and sham treatment) in the first phase; and three groups (3 days of treatment, 5 days of treatment, and sham treatment) in the second phase. The hyperbaric exposures involved 100% oxygen for 1 hour per day at 2.0 atm. The sham treatments involved 21% oxygen for 1 hour per day at 1.2 atm. We monitored recovery using a leg dynamometer to test eccentric torque of the nondominant quadriceps muscle before and immediately after exercise and at 48 and 96 hours after exercise. Pain was tested daily using visual analog pain scales. In phase 1 a significant difference in recovery of eccentric torque was noted in the treatment group compared with the other groups. In phase 2, the recovery of eccentric torque for the 5-day treatment group was significantly greater than for the sham group from immediately after exercise to 96 hours after exercise. The pain data did not differ significantly in any comparison in either phase. The results suggest that treatment with hyperbaric oxygen may enhance recovery of eccentric torque of the quadriceps muscle from delayed-onset muscle soreness.
Effects of hyperbaric oxygen on recovery from exercise-induced muscle damage in humans.
OBJECTIVE: To determine whether hyperbaric oxygen (HBO) therapy could accelerate recovery from exercise-induced muscle damage in humans.
DESIGN: Pretest-posttest design with random assignment to either a treatment (HBO) or placebo control (sham) group.
SETTING: University of Alberta and Misericordia Hospital, Edmonton.
PARTICIPANTS: 12 healthy male students (24.2 +/- 3.2 years) who were unaccustomed to strenuous eccentric exercise of the calf muscles.
INTERVENTIONS: All subjects performed a strenuous eccentric exercise protocol designed to elicit muscle damage within the right gastrocnemius muscle. Subjects subsequently received either HBO (100% oxygen at 253 kPa [2.5 ATA] for 60 min; n = 6) or sham (atmospheric air at 132 kPa [1.3 ATA] for 60 min; n = 6) treatment conditions. The first treatment was administered 3-4 hours after damage, with a second and third at 24 and 48 hours after the first, respectively.
MAIN OUTCOME MEASURES: Dependent variables included peak torque at 0.52 radians/s, peak isometric torque, and muscular endurance using isokinetic dynamometry; muscle cross-sectional area using magnetic resonance imaging; inorganic phosphate levels and T2 relaxation time using 31P and 1H magnetic resonance spectroscopy; pain sensation and unpleasantness using the Descriptor Differential Scale. These variables were assessed at baseline and until day 5 postdamage.
RESULTS: There was little evidence of a difference in recovery rate between the HBO and sham groups. Faster recovery was observed in the HBO group only for isometric peak torque and pain sensation and unpleasantness.
CONCLUSIONS: HBO cannot be recommended as an effective method of treatment of this form of muscle injury.
Options:
A: HBOT significantly reduced pain and swelling in both acute closed soft tissue injuries and DOMS.
B: HBOT showed no significant differences in recovery time, functional outcomes, pain, or swelling for acute closed soft tissue injuries, and it may increase interim pain in DOMS.
C: HBOT significantly improved knee function scores and reduced pain in DOMS.
D: HBOT was found to be highly effective in reducing long-term pain and improving muscle strength in DOMS. | B |
493 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What is the effect of adding a long-acting beta2-agonist (LABA) to inhaled corticosteroid (ICS) therapy in adults with chronic asthma? Please answer this question based on the information provided below:
Fluticasone alone or in combination with salmeterol vs triamcinolone in asthma.
OBJECTIVES: To compare the efficacies of medium-dose fluticasone propionate (FP), medium-dose triamcinolone acetonide (TAA), and combined low-dose FP plus salmeterol (SL).
DESIGN: Randomized, double-blind, triple-dummy, multicenter, 12-week clinical trial.
SETTING: Allergy/respiratory care clinics.
PATIENTS: Six hundred eighty patients with asthma previously uncontrolled with low-dose inhaled corticosteroids.
INTERVENTIONS: FP, 220 microg bid; TAA, 600 microg bid; or FP, 88 microg plus SL, 42 microg bid.
MEASUREMENTS AND RESULTS: Outcome measures included FEV1, peak expiratory flow (PEF), supplemental albuterol use, nighttime awakenings, asthma symptoms, and physician global assessment. Compared with TAA, 600 microg bid, treatment with FP 220, microg bid, significantly increased FEV1, morning and evening PEF, and percent symptom-free days, and significantly reduced rescue albuterol use, number of nighttime awakenings, and overall asthma symptom scores (p < or = 0.035). Improvements with low-dose FP, 88 microg, plus SL, 42 microg bid, were significantly (p < or = 0.004) greater than TAA, 600 microg bid, in all the aforementioned efficacy measures as well as percent of rescue-free days. Combined low-dose FP, 88 microg, plus SL, 42 microg bid, also significantly increased FEV1 and percent of rescue-free days, and significantly reduced albuterol use compared with medium-dose FP, 220 microg bid (p < or = 0.018). At endpoint, both FP, 220 microg bid, and FP, 88 microg, plus SL, 42 microg bid, significantly increased FEV1 by 0.48 L and 0.58 L, respectively, compared with 0.34 L with TAA, 600 microg bid.
CONCLUSION: In patients who are symptomatic while taking low-dose inhaled corticosteroids, medium-dose FP (440 microg/d) and combination treatment with low-dose FP (176 microg/d) plus SL (84 microg/d) are both more effective than medium-dose TAA (1200 microg/d) in improving pulmonary function and asthma symptom control.
Steroid-sparing effects of fluticasone propionate 100 microg and salmeterol 50 microg administered twice daily in a single product in patients previously controlled with fluticasone propionate 250 microg administered twice daily.
BACKGROUND: Concurrent use of an inhaled corticosteroid (ICS) and an inhaled long-acting beta2-agonist provides better overall asthma control than the use of higher doses of ICS alone.
OBJECTIVE: The purpose of this investigation was to determine whether fluticasone propionate (FP) combined with salmeterol in the Diskus device can be used to reduce the dose of ICS in patients currently stable on medium-dose ICS while maintaining asthma control.
METHODS: This was a randomized, double-blind, parallel-group, 12- to 24-week trial consisting of a 3-part run-in period. The run-in period was designed to first establish FP 250 microg administered twice a day (bid) via Diskus as the minimum effective dose. During run-in period 1, patients received FP 220 microg bid or the equivalent for 10 to 14 days. Controlled patients moved to run-in period 2 (5-28 days), which assessed asthma stability on FP 100 microg bid administered via Diskus. Only patients who became unstable on FP 100 microg bid were eligible to enter run-in period 3 (26-30 days), during which they were placed on FP 250 microg bid and those regaining asthma control were eligible for randomization. The primary efficacy endpoint was the proportion of patients who remained in the study with no evidence of worsening asthma. Secondary efficacy measures included FEV1, morning peak expiratory flow, percent of symptom-free days, and daily albuterol use.
RESULTS: Only 5% of patients treated with FP100/salmeterol withdrew because of worsening asthma in the first 12 weeks; this compared with 7% in the FP250 group. All patients from a subset of sites continued in the study for an additional 12 weeks; only an additional 1% of patients treated with either FP100/salmeterol or FP250 withdrew because of worsening asthma. Secondary efficacy measures confirmed primary efficacy results.
CONCLUSION: In patients requiring FP250 bid for asthma stability, FP100/salmeterol bid was steroid-sparing, allowing a 60% reduction in the FP dose while maintaining overall asthma control.
A long-term study of the antiinflammatory effect of low-dose budesonide plus formoterol versus high-dose budesonide in asthma.
Adding inhaled long-acting beta(2)-agonists to a low dose of inhaled corticosteroids (ICS), results in better clinical asthma control than increasing the dose of ICS. However, this approach may mask underlying airway inflammation. In a double-blind parallel-group study, we evaluated the effect of adding formoterol to a low dose of budesonide, compared with a higher dose of budesonide, on the composition of induced sputum. After a 4-wk run-in period of treatment with budesonide (800 microg, twice daily), 60 patients with moderate asthma were randomly assigned to a 1-yr treatment with 400 microg of budesonide plus placebo, twice daily (BUD800), or 100 microg of budesonide plus 12 microg of formoterol, twice daily (BUD200+F). All drugs were administered via Turbuhaler. Budesonide (800 microg, twice daily) during run-in significantly reduced median sputum eosinophils from 4.5 to 0.68%. No significant changes in the proportion of eosinophils, EG2(+) cells, other inflammatory cells, or ECP levels in sputum were observed over the ensuing 1-yr treatment with BUD200+F or BUD800. Clinical asthma control was not significantly different between both groups. In conclusion, no significant differences in sputum markers of airway inflammation were observed during a 1-yr treatment with a low dose of inhaled budesonide plus formoterol compared with a higher dose of budesonide.
A long-term study of the antiinflammatory effect of low-dose budesonide plus formoterol versus high-dose budesonide in asthma.
Adding inhaled long-acting beta(2)-agonists to a low dose of inhaled corticosteroids (ICS), results in better clinical asthma control than increasing the dose of ICS. However, this approach may mask underlying airway inflammation. In a double-blind parallel-group study, we evaluated the effect of adding formoterol to a low dose of budesonide, compared with a higher dose of budesonide, on the composition of induced sputum. After a 4-wk run-in period of treatment with budesonide (800 microg, twice daily), 60 patients with moderate asthma were randomly assigned to a 1-yr treatment with 400 microg of budesonide plus placebo, twice daily (BUD800), or 100 microg of budesonide plus 12 microg of formoterol, twice daily (BUD200+F). All drugs were administered via Turbuhaler. Budesonide (800 microg, twice daily) during run-in significantly reduced median sputum eosinophils from 4.5 to 0.68%. No significant changes in the proportion of eosinophils, EG2(+) cells, other inflammatory cells, or ECP levels in sputum were observed over the ensuing 1-yr treatment with BUD200+F or BUD800. Clinical asthma control was not significantly different between both groups. In conclusion, no significant differences in sputum markers of airway inflammation were observed during a 1-yr treatment with a low dose of inhaled budesonide plus formoterol compared with a higher dose of budesonide.
Inhaled corticosteroid reduction and elimination in patients with persistent asthma receiving salmeterol: a randomized controlled trial.
CONTEXT: Inhaled long-acting beta(2)-agonists improve asthma control when added to inhaled corticosteroid (ICS) therapy.
OBJECTIVE: To determine whether ICS therapy can be reduced or eliminated in patients with persistent asthma after adding a long-acting beta(2)-agonist to their treatment regimen.
DESIGN AND SETTING: A 24-week randomized, controlled, blinded, double-dummy, parallel-group trial conducted at 6 National Institutes of Health-sponsored, university-based ambulatory care centers from February 1997 through January 1999.
PARTICIPANTS: One hundred seventy-five patients aged 12 through 65 years with persistent asthma that was suboptimally controlled during a 6-week run-in period of treatment with inhaled triamcinolone acetonide (400 microg twice per day).
INTERVENTION: Patients continued triamcinolone therapy and were randomly assigned to receive add-on therapy with either placebo (placebo-minus group, n = 21) or salmeterol xinafoate, 42 microg twice per day (n = 154) for 2 weeks. The entire placebo-minus group was assigned and half of the salmeterol group (salmeterol-minus group) was randomly assigned to reduce by 50% (for 8 weeks) then eliminate (for 8 weeks) triamcinolone treatment. The other half of the salmeterol group (salmeterol-plus group) was randomly assigned to continue both salmeterol and triamcinolone for the remaining 16 weeks (active control group).
MAIN OUTCOME MEASURE: Time to asthma treatment failure in patients receiving salmeterol.
RESULTS: Treatment failure occurred in 8.3% (95% confidence interval [CI], 2%-15%) of the salmeterol-minus group 8 weeks after triamcinolone treatment was reduced compared with 2.8% (95% CI, 0%-7%) of the salmeterol-plus group during the same period. Treatment failure occurred in 46.3% (95% CI, 34%-59%) of the salmeterol-minus group 8 weeks after triamcinolone therapy was eliminated compared with 13.7% (95% CI, 5%-22%) of the salmeterol-plus group. The relative risk (95% CI) of treatment failure at the end of the triamcinolone elimination phase in the salmeterol-minus group was 4.3 (2.0-9.2) compared with the salmeterol-plus group (P<.001).
CONCLUSIONS: Our results indicate that in patients with persistent asthma suboptimally controlled by triamcinolone therapy alone but whose asthma symptoms improve after addition of salmeterol, a substantial reduction (50%) in triamcinolone dose can occur without a significant loss of asthma control. However, total elimination of triamcinolone therapy results in a significant deterioration in asthma control and, therefore, cannot be recommended.
Salmeterol reduces the need for inhaled corticosteroid in steroid-dependent asthmatics.
Previous results have demonstrated addition of long-acting beta2-adrenergic agonists to be beneficial in asthma patients already receiving inhaled corticosteroid. The purpose of this study was to determine, qualitatively as well as quantitatively, the steroid-sparing properties of salmeterol in stable asthma patients receiving maintenance inhaled corticosteroids (800-1600 microg day(-1)). In these patients, the daily dose of beclomethasone dipropionate was reduced by 200 microg each week until asthma deteriorated, with the minimal acceptable dose (MAD) being defined as the dose one step above deterioration (sensitivity period). Following this, patients received three times the MAD for 2 weeks. Patients were randomized to receive either salmeterol 50 microg twice daily or placebo and the MAD was again determined (treatment period). Forced expiratory volume in 1 sec (FEV1) was measured each week. Morning and evening peak expiratory flow (PEF), symptom score and use of bronchodilator were recorded each day. Fifteen patients received salmeterol and 19 placebo. The MAD was significantly lower in the salmeterol group compared with placebo during the treatment period (P<0.01). A 50% reduction of the MAD was achieved by more patients treated with salmeterol than placebo (P = 0.001). Salmeterol caused a significantly greater reduction in daytime symptom score and use of as-needed beta2-agoinist therapy between sensitivity and treatment periods compared with placebo (P<0.05 for both). The results demonstrate, that the addition of salmeterol to corticosteroid treatment offers a clinically relevant potential for reduction of inhaled corticosteroid dose in steroid sensitive asthmatics.
Asthma quality of life during 1 year of treatment with budesonide with or without formoterol.
The Formoterol and Corticosteroids Establishing Therapy (FACET) study has provided the first opportunity to examine the long-term effects of inhaled steroids and long-acting beta2-agonists on asthma-specific quality of life. The objectives of the present study were to: evaluate the effects of long-term (1 yr) formoterol and increasing doses of budesonide on asthma quality of life; 2) to determine whether initial improvements in quality of life are sustained when improvements in clinical indices persist; and 3) to evaluate the long-term relationship between changes in clinical indices and changes in quality of life. Of the 852 asthmatic adults enrolled, 470 from five countries participated in this quality of life evaluation. After a 4-week run-in on 1,600 microg budesonide, patients were randomized to either 200 microg (Bud200) or 800 microg budesonide (Bud800) in combination with either 24 microg formoterol (F) or placebo daily for 1 yr. The Asthma Quality of Life Questionnaire (AQLQ) was completed and conventional clinical indices measured at enrolment and randomization and on seven occasions during the following 12 months. During the run-in, there was an improvement in AQLQ score (changes (delta) in overall score approximately 0.50; p<0.0001). After randomization, there was a further improvement in the Bud800+F group (delta=0.21; p=0.028). One month post-randomization, improvements in all groups stabilized and were sustained throughout the 12 months in a pattern very similar to that observed for the conventional clinical indices. The correlation of individual patient changes in clinical indices and changes in AQLQ score during the 12-month randomized period were weak to moderate (maximum r=0.51). Improvements in quality of life, which were greatest in the 800 microg budesonide plus 24 microg formoterol group, were sustained throughout the 12 months in a similar manner to the clinical indices. Long-term changes in conventional clinical indices cannot be used to predict the effect of treatment on individual patient experience.
Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group.
BACKGROUND: The role of long-acting, inhaled beta2-agonists in treating asthma is uncertain. In a double-blind study, we evaluated the effects of adding inhaled formoterol to both lower and higher doses of the inhaled glucocorticoid budesonide.
METHODS: After a four-week run-in period of treatment with budesonide (800 microg twice daily), 852 patients being treated with glucocorticoids were randomly assigned to one of four treatments given twice daily by means of a dry-powder inhaler (Turbuhaler): 100 microg of budesonide plus placebo, 100 microg of budesonide plus 12 microg of formoterol, 400 microg of budesonide plus placebo, or 400 microg of budesonide plus 12 microg of formoterol. Terbutaline was permitted as needed. Treatment continued for one year; we compared the frequency of exacerbations of asthma, symptoms, and lung function in the four groups. A severe exacerbation was defined by the need for oral glucocorticoids or a decrease in the peak flow to more than 30 percent below the base-line value on two consecutive days.
RESULTS: The rates of severe and mild exacerbations were reduced by 26 percent and 40 percent, respectively, when formoterol was added to the lower dose of budesonide. The higher dose of budesonide alone reduced the rates of severe and mild exacerbations by 49 percent and 37 percent, respectively. Patients treated with formoterol and the higher dose of budesonide had the greatest reductions -- 63 percent and 62 percent, respectively. Symptoms of asthma and lung function improved with both formoterol and the higher dose of budesonide, but the improvements with formoterol were greater.
CONCLUSIONS: In patients who have persistent symptoms of asthma despite treatment with inhaled glucocorticoids, the addition of formoterol to budesonide therapy or the use of a higher dose of budesonide may be beneficial. The addition of formoterol to budesonide therapy improves symptoms and lung function without lessening the control of asthma.
Exacerbations of asthma: a descriptive study of 425 severe exacerbations. The FACET International Study Group.
The identification, prevention, and prompt treatment of exacerbations are major objectives of asthma management. We looked at change in PEF, symptoms, and use of rescue beta-agonists during the 425 severe exacerbations that occurred during a 12-mo parallel group study (FACET) in which low and high doses of budesonide with and without formoterol were compared in patients with asthma. Oral corticosteroids were prescribed for severe exacerbations, the main study end point, defined as the need for a course of oral corticosteroids (n = 311) or a reduction in morning PEF of > 30% on two consecutive days. PEF, symptoms, and bronchodilator use over the 14 d before and after the exacerbation were obtained from diary cards. Exacerbations were characterized by a gradual fall in PEF over several days, followed by more rapid changes over 2 to 3 d; an increase in symptoms and rescue beta-agonist use occurred in parallel, and both the severity and time course of the changes were similar in all treatment groups. Exacerbations identified by the need for oral corticosteroids were associated with more symptoms and smaller changes in PEF than those identified on the basis of PEF criteria. Female sex was the main patient characteristic associated with an increased risk of having a severe exacerbation. Exacerbations may be characterized predominantly by change in symptoms or change in PEF, but the pattern was not affected by the dose of inhaled corticosteroid or by whether the patient was taking formoterol.
Options:
A: It significantly increases the risk of severe exacerbations requiring oral corticosteroids.
B: It allows for a reduction in the ICS maintenance dose while maintaining asthma control.
C: It leads to a significant increase in withdrawal due to worsening asthma.
D: It has no effect on lung function or asthma control. | B |
494 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What are the potential advantages and disadvantages of using a transverse or oblique incision compared to a midline incision for abdominal surgery? Please answer this question based on the information provided below:
The comparative effects of muscle transection and median upper abdominal incisions on postoperative pulmonary function.
Choice of incision and pain following gallbladder surgery.
A prospective randomized trial compared pain in the first 24 h after gallbladder surgery via an upper midline or a transverse incision. Pain was measured by the patients' self-administered consumption of pethidine, degree of postoperative respiratory impairment and a visual analogue pain scale. The upper midline incision group self-administered significantly more pethidine than the transverse incision group (P less than 0.001), but there was no difference between the groups in respiratory function or visual analogue pain scale results 24 h after operation. Length of hospital stay was not different. An upper midline incision is more painful than a transverse incision in the first 24 h following gallbladder surgery.
Pulmonary function after transverse or midline incision in patients with obstructive pulmonary disease.
Atelectasis and bronchopneumonia occur frequently in patients undergoing aorto-iliac reconstructive surgery. Transverse (T) incisions in upper abdominal surgery are thought to be followed by fewer pulmonary complications than midline incisions (M) but reports remain controversial. We studied the incidence of postoperative pulmonary complications and lung dysfunction after T and M incisions for aorto-iliac surgery in 13 patients with chronic obstructive pulmonary disease (COPD) and 13 control patients with normal lungs (C). For all subjects, we evaluated (1) postoperative clinical or radiological pulmonary events; (2) preoperatively and on postoperative days 2 (D2), 5 (D5), 9 (D9) and 12 (D12) - the forced expiratory volume in 1 s (FEV1), vital capacity (VC), alveolar-arterial oxygen difference (AaPO2), and (3) convenience for the surgeon. Operatively, aortic exposure was excellent with both incisions. Bronchopneumonia occurred only after M in five patients (1 C, 4 COPD). In contrast with the control patients in whom no difference was found between T and M incisions, the FEV1 of COPD patients was significantly less impaired with T than with M incisions (p less than 0.005 on D2 and p less than 0.05 on D5). VC decreased similarly with both incisions on D2 but on D5 the improvement was less with M (p less than 0.005). Changes in AaPO2 were more marked on D2 and D5 for the COPD patients with M incisions. We conclude that (1) in patients with chronic obstructive pulmonary disease, laparotomy with a transverse incision was associated with better postoperative lung function and fewer pulmonary complications; (2) in patients without pulmonary disease, midline and transverse incisions were equivalent.
A randomised controlled trial of transverse skin crease vs. vertical midline incision for right hemicolectomy.
BACKGROUND: A transverse skin crease incision for right hemicolectomy may result in more rapid recovery than traditional vertical midline incision. This hypothesis was tested with a prospective randomised trial.
METHODS: Patients from 2 centres undergoing right hemicolectomy were randomised to received a midline or transverse incision. Incision lengths were sufficient to enable unrestricted resection of the right colon. Patients and carers were blinded to the incisions using strategically placed dressings. Analgesia and oral intake were controlled by the patient. Operative details and recovery parameters were compared.
RESULTS: A total of 28 patients were randomised. Demographic data and tumour characteristics of the two treatment groups were similar. The transverse incision group had a slightly shorter median wound (10 cm vs. 11 cm, p<0.05). Operative time, analgesia requirements, recovery parameters (time to discharge, 6.5 vs. 6.5 days) and frequency of complications were otherwise comparable.
CONCLUSIONS: A transverse skin crease incision for right hemicolectomy results in a slightly smaller wound but no other advantages were demonstrated compared with a traditional vertical midline incision.
Randomized clinical trial of vertical or transverse laparotomy for abdominal aortic aneurysm repair.
BACKGROUND: The objective of this randomized trial was to evaluate the incidence of incisional hernia after transverse or vertical incisions for open aortic aneurysm repair.
METHODS: The study group comprised 69 patients who underwent elective aneurysm repair between November 1998 and November 2000 (60 men, nine women; mean age 72.8 (range 56-95) years). Patients were randomized to a transverse (n = 32) or vertical (n = 37) incision for the procedure. Of the 42 patients who were still alive in February 2004, 37 (15 transverse, 22 vertical incisions) attended for review. Laparotomy scars were assessed both clinically and ultrasonographically by the same examiner, to look for incisional hernia.
RESULTS: Mean follow-up was 4.4 years. A multivariable logistic regression analysis revealed that the type of incision was the only parameter that significantly influenced the rate of incisional hernia: six of 15 patients with a transverse laparotomy versus 20 of 22 with a vertical laparotomy (P = 0.010).
CONCLUSION: The incidence of incisional hernia was high after aortic aneurysm repair, but was lower in patients who had a transverse incision.
Subcostal incision versus midline laparotomy in gallstone surgery: a prospective and randomized trial.
We report the results of a prospective and randomized trial designed to study the incidence of abdominal and pulmonary complications in gallstone surgery comparing subcostal (SI) with midline incision. The need for postoperative analgesia was lower in the SI group. There was no difference in the degree of hypoxaemia in the first two postoperative days, but there was less impairment of pulmonary function in terms of vital capacity and forced expiratory volume in 1 s (P less than 0.0001) in the SI group. SI patients also had a lower incidence of pulmonary or abdominal complications but the difference was not significant. Finally, we found a reduced hospital stay for the SI patients (P less than 0.01), probably related to a reduced postoperative analgesic requirement and an improved pulmonary function. We conclude that subcostal incision is a better approach for biliary tract surgery and should be used whenever possible.
Midline or transverse laparotomy? A random controlled clinical trial. Part I: Influence on healing.
Five hundred and seventy-nine patients undergoing major laparotomy were randomly allocated to have midline or transverse incisions. Transverse incisions took longer to make and caused more bleeding but (in the absence of wound sepsis) no transverse wound burst and there were only 2 incisional hernias. In the midline group, without wound sepsis, there were 2 burst abdomens and 9 incisional hernias. When, however, those patients who suffered wound sepsis were also considered, there were no significant differences between the two groups.
Midline or transverse laparotomy? A random controlled clinical trial. Part II: Influence on postoperative pulmonary complications.
In a series of 579 patients undergoing major laparotomy, the direction of incision (midline or transverse/oblique muscle-cutting) was decided randomly. The severity of postoperative pulmonary complications was expressed by a scoring system which allowed categorization into mild (score 0-3), moderate (score 4-6) and serious (score 7 or more) complications. The important determinants of high scores were found to be male sex, preoperative pulmonary dysfunction, postoperative ventilatory depression, hypovolaemic and septic shock, inhalation of gastric contents and embolism. In no stratum did the direction of incision have any significant effect.
Incisional hernia after upper abdominal surgery: a randomised controlled trial of midline versus transverse incision.
OBJECTIVES: To determine whether a transverse incision is an alternative to a midline incision in terms of incisional hernia incidence, surgical site infection, postoperative pain, hospital stay and cosmetics in cholecystectomy. Incisional hernias after midline incision are commonly underestimated but probably complicate between 2 and 20% of all abdominal wall closures. The midline incision is the preferred incision for surgery of the upper abdomen despite evidence that alternatives, such as the lateral paramedian and transverse incision, exist and might reduce the rate of incisional hernia. A RCT was preformed in the pre-laparoscopic cholecystectomy era the data of which were never published.
METHODS: One hundred and fifty female patients were randomly allocated to cholecystectomy through midline or transverse incision. Early complications, the duration to discharge and the in-hospital use of analgesics was noted. Patients returned to the surgical outpatient clinic for evaluation of the cosmetic results of the scar and to evaluate possible complications such as fistula, wound dehiscence and incisional hernia after a minimum of 12 months follow-up.
RESULTS: Two percent (1/60) of patients that had undergone the procedure through a transverse incision presented with an incisional hernia as opposed to 14% (9/63) of patients from the midline incision group (P = 0.017). Transverse incisions were found to be significantly shorter than midline incisions and associated with more pleasing appearance. More patients having undergone a midline incision, reported pain on day one, two and three postoperatively than patients from the transverse group. The use of analgesics did not differ between the two groups.
CONCLUSIONS: In light of our results a transverse incision should, if possible, be considered as the preferred incision in acute and elective surgery of the upper abdomen when laparoscopic surgery is not an option.
Prospective randomized study of two laparotomy incisions for gastrectomy: midline incision versus transverse incision.
BACKGROUND: We performed a randomized study to evaluate the differences between upper midline incision and transverse incision for gastrectomy.
METHODS: Patients undergoing distal gastrectomy or total gastrectomy for gastric cancer were randomly allocated to have either an upper midline incision or a transverse incision. The times taken to open and close the abdominal cavity, the number of doses of postoperative analgesics, and the incidence of postoperative pneumonia, wound infection, and intestinal obstruction were compared between the patients having the two incisions.
RESULTS: Times for both opening and closing the abdominal cavity were longer with a transverse incision, in both the distal gastrectomy group and total gastrectomy group. In the patients in whom continuous epidural analgesia was used postoperatively, the number of additional doses of analgesics was smaller in the transverse-incision group after distal gastrectomy. The incidence of postoperative pneumonia was lower in the transverse-incision group after distal gastrectomy. The number of patients with postoperative intestinal obstruction was smaller in the transverse-incision group than in the midline-incision group after distal gastrectomy. In contrast to distal gastrectomy, there was no significant difference in the number of doses of postoperative analgesics, incidence of postoperative pneumonia, or incidence of postoperative intestinal obstruction between the two study groups after total gastrectomy.
CONCLUSION: A transverse incision for distal gastrectomy may be more beneficial than an upper midline incision in attenuating postoperative wound pain, decreasing the incidence of postoperative pneumonia, and preventing postoperative intestinal obstruction.
The comparison of type of incision for transperitoneal abdominal aortic surgery based on postoperative respiratory complications and morbidity.
Equal access to the abdominal aorta can be attained through midline and transverse abdominal incisions. The surgical literature suggests that transverse incisions cause less postoperative pain and morbidity. Fifty patients (10 females and 40 males, mean age 67 years) undergoing abdominal aortic surgery were randomised to a midline (n = 25) or transverse (n = 25) incision. All patients were evaluated preoperatively and postoperatively for seven days. Changes in pulmonary function (FVC and FEV1), time to open and close the incision, analgesia used (morphine mg/kg/h), clinical or X-ray evidence of chest infection, and the duration of ICU stay were recorded. In the transverse group there was a reduction in the incidence of chest complications (20% vs. 28%, p = ns) and these incisions took longer to open (13.9 +/- 4.6 vs. 9.9 +/- 5.1, p < 0.05), but overall there was no significant difference between any other parameter in the two groups. Our results show no statistically significant difference in morbidity or analgesia consumption following transverse or midline abdominal incisions and we conclude that the type of incision used can be left to the surgeon's preference.
Midline or transverse abdominal incision for right-sided colon cancer-a randomized trial.
OBJECTIVE: The influence of the type of abdominal incision on post-operative pain and pulmonary function was investigated in patients operated upon for a right-sided cancer of the large bowel.
PATIENTS AND METHODS: Fifty-three patients scheduled for a right hemicolectomy due to a right-sided colon cancer were randomized to a median vertical (M) or a transverse incision (T). Forty patients, 23 with a M and 17 with a T incision, completed the study and could be evaluated. Pain at rest and after physical activity was assessed with a visual analogue scale, and was also measured as reflected in the need for analgesics. Respiratory function was assessed with pre- and post-operative spirometry.
RESULTS: Pain after activity was significantly less in patients with a T incision. This group also needed less analgesia. Vital capacity (VC) and forced expiratory volume in 1 s (FEV 1.0) were profoundly reduced after surgery in both groups of patients, but improvement of respiratory function was faster in patients with a transverse incision. No problem with access to the operative field was noted.
CONCLUSION: We conclude that a transverse incision is preferable to a midline incision and should be used in right hemicolectomy. This abdominal incision reduces effort-induced pain and interferes less with post-operative pulmonary function, and may reduce the risk of pulmonary complications.
Approach to the abdominal aorta: impairment of respiratory function after supraumbilical transverse and midline laparotomy.
Midline and transverse incision are commonly used in upper abdominal surgery. A comparison of the two procedures with respect to the respiratory function, assessed by spirometry, blood gas analysis, inspiratory and expiratory pressures, and thoraco-abdominal respiratory synchronism, was made in two groups of patients after surgery on the abdominal aorta. 32 patients affected by abdominal aortic obstructive or aneurysmatic disease, candidates for aortoiliac revascularization, were randomized into two groups of 17 (group A) and 15 (group B) patients respectively. Group A underwent midline laparotomy and group B supraumbilical transverse laparotomy. Ventilatory function and blood gas analysis were determined on the day before operation and on the second and eight postoperative day. All patients showed a depressed ventilatory function postoperatively, but the impairment was significantly minor after transverse laparotomy.
Transverse versus midline incision for upper abdominal surgery.
PURPOSE: Transverse and midline abdominal incisions are both commonly used for laparotomy to perform surgery on the pancreas and stomach, but comparative data are limited, especially from prospective randomized trials.
METHODS: During a predefined 2-year recruitment period, 94 patients undergoing an elective major laparotomy for disorders of the pancreas or stomach were enrolled in this study. The outcome measures were pulmonary function, incisional pain, and wound characteristics.
RESULTS: The operation groups were equally divided according to the type of incision used. The patients who underwent transverse incision laparotomy had significantly better postoperative pulmonary function and significantly less postoperative incisional pain than those who underwent midline incision laparotomy (P < 0.05), but there were no differences in morbidity and the incidence of wound complications.
CONCLUSION: Performing a transverse incision for surgery on the pancreas or stomach results in better postoperative pulmonary function and less incisional pain than a midline incision, without affecting postoperative morbidity.
Pfannenstiel versus vertical laparotomy in patients undergoing radical retropubic prostatectomy with spinal anesthesia: results of a prospective, randomized trial.
OBJECTIVE: To evaluate the impact of a standard vertical laparotomy versus a Pfannenstiel transverse laparotomy on intra-, peri-operative, and 6-month follow-up outcome in patients undergoing radical retropubic prostatectomy with pelvic lymphadenectomy with spinal anesthesia.
METHODS: Between January 2003 and June 2003, 69 age-matched consecutive patients with clinically localized prostate cancer underwent radical retropubic prostatectomy with pelvic lymphadenectomy with spinal anesthesia and were randomized into Group 1 (vertical laparotomy: 35 patients) and Group 2 (Pfannenstiel laparotomy: 34 patients). An extensive analysis of the critical intra-, peri-operative, and 6-month follow-up clinical parameters was performed.
RESULTS: Both the hemodynamics and the biochemical balance were not significantly different between the two groups. Overall blood loss (p = 0.78), autologous (p = 0.88) and homologous (p = 0.36) blood transfusions were similar regardless of the type of laparotomy. Surgical time was not significantly (p = 0.27) different between the two groups. Similarly, the two forms of laparotomy did not differ regarding the length of the surgical incision (p = 0.21), as measured at the end of the procedure. Post-operative oxygen saturation percentage by pulse oximetry, as well as post-op sedation score, were not significantly different (p = 0.06 and p = 0.97, respectively). Waiting time in the post-operative holding area (p = 0.15), and pain score in the post-operative holding area (p = 0.9) as well as on post-operative day 1 (p = 0.1) were not significantly different between the two groups. The rate of first flatus passage and of unassisted ambulation were similar regardless of the type of laparotomy during post-operative day day 1. The two types of incision made it possible to remove a similar (p = 0.34) number of pelvic lymph nodes and were associated to a similar rate of positive surgical margins among pT2 patients. At the 6-month follow-up the occurrence of a pelvic lymphocele and of deep venous thrombosis was similar in the two groups (p = 0.6 and p = 0.16, respectively). Complete urinary continence and spontaneous erectile function recovery was reported in a similar number of patients regardless of the type of surgical incision (p = 0.59 and p = 0.40, respectively).
CONCLUSIONS: These results suggest that a Pfannenstiel transverse suprapubic laparotomy does not result in a significantly different outcome from a standard vertical laparotomy in patients undergoing a radical retropubic prostatectomy with pelvic lymphadenectomy with L2-L3 spinal anesthesia for clinically localized prostate cancer.
Mini-lap cholecystectomy--an attractive alternative to conventional cholecystectomy.
A prospective study was conducted to determine the safety and efficacy of cholecystectomy through a 5 cm transverse abdominal incision. 181 consecutive patients who underwent elective cholecystectomy for symptomatic gall stone disease in a single surgical unit at the All India Institute of Medical Sciences, New Delhi between December 1990 to February 1992, were prospectively randomized into 5 cm transverse and midline incision groups. Operative time, blood loss, post-operative stay and complications were compared in the two groups. Ninety seven patients were included in the transverse incision group and 84 patients in the midline group. Cholecystectomy could be safely performed through a 5 cm transverse incision in 84 patients (86.8%) without increase in operative complications, morbidity or mortality. In another 84 patients cholecystectomy was performed through a midline incision. The average operating time and blood loss were comparable in both groups. The average post-operative stay in 5 cm transverse incision group was 2.6 days (range 1-4 days) and in the midline group was 4.0 days (range 3-5 days). There were 7 post-operative complications (all wound infections) in the 5 cm transverse group and 12 post-operative complications (10 wound infections and 2 pneumonitis) in the midline group. However, the difference in wound infection rate was not statistically significant (p > 0.1). In Conclusion, Cholecystectomy can be safely performed through a 5 cm transverse incision.
Midline versus transverse incision in major abdominal surgery: a randomized, double-blind equivalence trial (POVATI: ISRCTN60734227).
OBJECTIVE: There are 2 main types of access for patients requiring major open, elective abdominal surgery: the midline or the transverse approach. The aim of this study is to compare both approaches by focusing on postoperative pain, complications, and frequency of incisional hernias.
SUMMARY BACKGROUND DATA: A recent Cochrane review suggested that transverse incisions may be less painful but incisional hernia rates do not differ.
METHODS: Randomized, patient- and observer-blinded, monocentric, equivalence clinical trial. Patients were scheduled for elective primary abdominal incisions. Composite primary end point measured 48 hours after surgery was the total amount of analgesics (piritramide) required in the last 24 hours and pain (Visual Analogue Scale). Secondary end points were early-onset and late complications. This study is registered in the ISRCTN registry and has the ID number ISRCTN60734227.
RESULTS: Two hundred patients (101 midline and 99 transverse) were randomized. Both incision types resulted in similar amounts of required analgesics (95% confidence interval [-0.38; -0.33] was included in the equivalence level). For the Visual Analogue Scale, both the 95% and 90% CI (0-10) were neither within the equivalence levels nor were their differences significant at the 5% level. No relevant differences between midline and transverse incisions were observed for 30-day mortality (2 vs. 2, P = 0.99), mortality after one year (15 vs. 23, P = 0.15), pulmonary complications (13 vs. 17, P = 0.43), median length of hospital stay (11 vs. 12 days, P = 0.08), median time to tolerance of solid food (12 vs. 14 days, P = 0.30), and incisional hernias after one year (13 vs. 8, P = 0.48). More wound infections occurred in the transverse group (15 vs. 5, P = 0.02).
CONCLUSION: The decision about the incision should be driven by surgeon preference with respect to the patient's disease and anatomy.
Abdominal incisions: transverse vs vertical placement and continuous vs interrupted closure.
A previous retrospective review of 2,006 emergency laparotomies had suggested that anesthesia and operative times could be reduced by using a continuous stitch closure for all layers of the incision. A prospective, randomized study was then implemented through use of odd/even digits in the last and next-to-last digits in the hospital number. Of 551 patients subjected to laparotomy because of abdominal trauma, no intraperitoneal injury was found in 212. There was no statistically significant difference in time expended or complications (wound or other, including pulmonary) on contrasting transverse (101) with vertical (111) incisions, or on comparing continuous (104) and interrupted (108) closure, with the exception of an average 26 minutes in time saved by a continuous suture (P = .02). Analysis of these same factors in 339 patients with trauma found at laparotomy could document no statistically significant difference. Such data support the use of a running suture for closure of the abdominal wall as a practical method to save anesthesia and operating time without increased risk of developing a wound or other postoperative complication.
Options:
A: Transverse or oblique incisions may reduce pain and pulmonary compromise but do not significantly affect complication rates or recovery times.
B: Transverse or oblique incisions significantly reduce both early and late postoperative complications compared to midline incisions.
C: Midline incisions are associated with faster recovery times and fewer complications than transverse or oblique incisions.
D: There is no difference in pain, pulmonary function, complication rates, or recovery times between transverse or oblique and midline incisions. | A |
495 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What is the conclusion regarding the use of prophylactic antibiotics in neonates with umbilical venous catheters to reduce mortality and morbidity? Please answer this question based on the information provided below:
[Prophylactic use of antibiotics in umbilical catheterization in newborn infants].
Options:
A: Prophylactic antibiotics significantly reduce mortality and morbidity in neonates with umbilical venous catheters.
B: Prophylactic antibiotics have no effect on mortality and morbidity in neonates with umbilical venous catheters.
C: There is insufficient evidence to support or refute the use of prophylactic antibiotics in neonates with umbilical venous catheters.
D: Prophylactic antibiotics increase the risk of mortality and morbidity in neonates with umbilical venous catheters. | C |
496 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What were the findings regarding the impact of altered dietary salt intake during pregnancy on the risk of developing pre-eclampsia and its complications? Please answer this question based on the information provided below:
Effect of low-sodium diet on uteroplacental circulation.
OBJECTIVE: To study the influence of chronic dietary sodium restriction on uteroplacental circulation.
METHODS: In a randomized trial, Doppler flow velocity waveforms of the uterine and umbilical artery were studied at monthly intervals during pregnancy in 59 women on a low-sodium diet and in 68 controls.
RESULTS: Pulsatility index (PI), resistance index (RI), and A/B ratio of the uterine artery were significantly lower during sodium restriction, whereas PI, RI, and A/B ratio of the umbilical artery were significantly higher.
CONCLUSIONS: The lower resistance indices of the uterine artery during sodium restriction might reflect an increase in pulse pressure/impedance ratio as a result of activation of the renin-angiotensin system. The increase in umbilical artery resistance indices supports the hypothesis that fetal circulation might be altered by chronic dietary sodium restriction.
Urinary prostaglandin excretion in pregnancy: the effect of dietary sodium restriction.
INTRODUCTION: Dietary sodium restriction results in activation of the renin-angiotensin-aldosterone-system. In the non-pregnant situation renin release in response to a low sodium diet is mediated by prostaglandins. We studied the effect of dietary sodium restriction on urinary prostaglandin metabolism in pregnancy.
PATIENTS AND METHODS: In a randomized, longitudinal study the excretion of urinary metabolites of prostacyclin (6-keto-PGF(1 alpha)and 2,3-dinor-6-keto-PGF(1 alpha)) and thromboxane A(2)(TxB(2)and 2,3-dinor-TxB(2)) was determined throughout pregnancy and post partum in 12 women on a low sodium diet and in 12 controls.
RESULTS: In pregnancy the excretion of all urinary prostaglandins is increased. The 6-keto-PGF(1 alpha)/ TxB(2)-ratio as well as the 2, 3-dinor-6-keto-PGF(1 alpha)/ 2,3-dinor-TxB(2)-ratio did not significantly change in pregnancy. CONCLUISION Prostacyclin and thromboxane do not seem to play an important role in sodium balance during pregnancy.
(Patho)physiological implications of chronic dietary sodium restriction during pregnancy; a longitudinal prospective randomized study.
OBJECTIVE: To study the possible pathophysiological implications of long continued dietary sodium restriction in pregnancy.
DESIGN: Longitudinal prospective randomized study of the effects of a low sodium diet compared with unrestricted sodium intake in pregnancy.
SETTING: Academic Department of Obstetrics and Gynaecology at Sint Radboud Hospital, Nijmegen, The Netherlands.
SUBJECTS: 42 healthy nulliparous women.
INTERVENTION: A low sodium diet (20 mmol sodium daily) started in the 14th week of pregnancy and stopped after delivery.
MAIN OUTCOME MEASURES: Maternal weight gain, food intake, blood pressure, cardiac output, systemic vascular resistance, haematocrit and birthweight.
RESULTS: Total maternal weight gain and dietary energy intake during pregnancy and weight at 1 and 6 weeks postpartum were significantly lower in the low sodium group. Blood pressure during pregnancy did not show major differences. Stroke volume and cardiac output during pregnancy were significantly lower in the low sodium group whereas systemic vascular resistance was significantly higher. Haematocrit values in the low sodium group tended to be lower during pregnancy, but were significantly lower at 1 and 6 weeks postpartum than in the unrestricted group. Placental and birthweights were not significantly different between the two groups.
CONCLUSIONS: Chronic dietary sodium restriction during pregnancy is characterized by a diminished body fat accumulation and a reduction in circulating volume, due to a decrease in both plasma and red cell volume, in combination with a high systemic vascular resistance without major effects on blood pressure and birthweight.
Low sodium diet in pregnancy: effects on maternal nutritional status.
In the present study, besides the effect on blood pressure, the effects of a low sodium diet in pregnancy on maternal energy and nutrient intake, calcium metabolism, zinc and magnesium status, weight gain and body fat storage were investigated. No effect of the low sodium diet in pregnancy on the course of blood pressure and the incidence of hypertensive disorders was observed. The reduction in sodium intake also caused a significant reduction in the intake of energy, protein, carbohydrates, fat, calcium, zinc, magnesium, iron and cholesterol. The reduced intake of calcium, zinc and magnesium in the women on the low sodium diet did not result in significant changes in circulating total calcium, ionized calcium, parathyroid hormone, zinc, alkaline phosphatase or magnesium, probably because of homeostatic adaptations by the kidneys. In the women on the low sodium diet non-significant reductions in weight gain (1.5 kg) and fat mass gain (0.9 kg) over pregnancy were observed. These reductions in weight and fat mass gain were more pronounced (3.4 kg (P = 0.003) and 1.3 kg (P = 0.15), respectively) when only the data of the women with good compliance were analyzed. The use of a low sodium diet in pregnancy did not have significant effects on infant birth weight, placental weight or other pregnancy outcome variables.
Dietary sodium restriction in the prophylaxis of hypertensive disorders of pregnancy: effects on the intake of other nutrients.
Dietary sodium restriction is used in the Netherlands in the prophylaxis of preeclampsia. To study the effects of long-term sodium restriction on the intake of other nutrients and the outcome of pregnancy, 68 healthy nulliparous pregnant women were randomly assigned to either a low-sodium diet (20 mmol/24 h) or an unrestricted diet. The diet was consumed between week 14 of gestation and delivery. The dietary intakes of energy, fat, protein, carbohydrate, sodium, potassium, and calcium were estimated with the dietary-history technique. A low-sodium diet reduced the intake of protein (by approximately 15 g/24 h), fat (by 20 g/24 h), and calcium (by 350 mg/24 h) and tended to decrease the energy intake (by approximately 0.7 MJ/24 h). The intakes of carbohydrate and potassium did not differ between the groups. The maternal weight gain was less in the low-sodium group (6.0 +/- 3.7 compared with 11.7 +/- 4.7 kg). Mean birth weight was not significantly different (3.2 +/- 0.5 compared with 3.4 +/- 0.5 kg).
Low-sodium diet in pregnancy: effects on blood pressure and maternal nutritional status.
In ninety-four Dutch nulliparous women the effects of a low-Na diet in pregnancy on blood pressure, energy and nutrient intake, Ca metabolism, Zn and Mg status and body composition were studied longitudinally. The women were randomly divided into an intervention group (n 41), which used a low-Na diet (mean urinary Na excretion 61 mmol/24 h) from week 14 of pregnancy until delivery and a control group (n 53; mean urinary Na excretion 142 mmol/24 h). No effect of the diet on blood pressure was observed. The use of a low-Na diet resulted in significantly reduced intakes of energy, protein, carbohydrates, fat, Ca, Zn, Mg, Fe and cholesterol. However, the women on the low-Na diet appeared to be able to adapt quite well to the reduced intake since Ca, Zn and Mg homeostasis was maintained. In the case of Ca and Mg this was probably due to the observed reduced urinary excretions of these nutrients. Non-significant reductions in weight gain (1.5 kg) and fat-mass gain (0.9 kg) over pregnancy were found in the women on the low-Na diet. No significant effects of the diet on birth weight or placental weight were observed.
Vasopressin and oxytocin levels during normal pregnancy: effects of chronic dietary sodium restriction.
Neurohypophysial hormones are thought to be involved in alterations in fluid balance during pregnancy and delivery. In the course of normal pregnancy intravascular volume is increased whereas sodium restriction is thought to reduce plasma volume and cardiac output. In the present study, we measured the effect of long-term severe sodium restriction on vasopressin (AVP) and oxytocin (OT) levels during normal pregnancy and after delivery. Fifty-nine healthy nulliparous women were randomized either for a low sodium diet (20 mmol sodium daily) or for a normal diet from week 12 of pregnancy onwards. Circulating plasma levels and urinary excretion of AVP and OT, their neurophysins (Np-AVP and Np-OT) and AVP bound to platelets were determined at regular intervals during pregnancy and after delivery. After completion of the study, women on a sodium-restricted diet were compared with control women on a normal diet using repeated measurement ANOVA with adjustment for potentially confounding variables. After randomization, a reduction in urinary sodium excretion of, on average, 40-82% was found. In general, no effect of sodium restriction could be demonstrated on the various parameters (0.53 < P < 0.98) with the exception of a significantly lower 24-h urinary AVP excretion by non-smokers with sodium restriction compared with non-smokers having a normal diet (P = 0.018). For all parameters, clear changes were found in the course of pregnancy and puerperium (P < 0.0001 to P < 0.005). Platelet-bound AVP decreased and Np-OT increased during pregnancy. After birth, free plasma AVP, platelet-bound AVP, OT, osmolality, sodium and potassium increased, while Np-AVP and Np-OT decreased. Although elevated Np-AVP and Np-OT levels during pregnancy seem to indicate increased release of neurohypophysial hormones, pregnancy up to 36 weeks of gestation is accompanied by low circulating AVP and OT levels. Long-term severe sodium restriction diminishes urinary AVP excretion in (non-smoking) pregnant women, without changing circulating levels of AVP and OT, despite the known reduction in circulating volume. The reduced circulating (platelet-bound) AVP levels during pregnancy, whether or not in combination with severe sodium restriction, support the absence of significant non-osmotic stimulation of AVP during pregnancy.
Low sodium diet and pregnancy-induced hypertension: a multi-centre randomised controlled trial.
OBJECTIVE: To examine the effectiveness of the standard policy in the Netherlands to prescribe a sodium restricted diet to prevent or to treat mild pregnancy-induced hypertension.
DESIGN: Multi-centre randomised controlled trial between April 1992 and April 1994.
SETTING: Seven practices of independent midwives and one university hospital.
PARTICIPANTS: The experimental group comprised 184 women given a low sodium diet (< or = 50 mmol sodium/day) and a control group of 177 women given a normal diet. Eligible women for inclusion had had a rise of blood pressure, or excessive weight gain or oedema during the antenatal period. The 361 women in the trial were recruited from 2020 nulliparae, of whom 1512 (75%) gave informed consent at the beginning of their pregnancy to participate in the study.
MAIN OUTCOME MEASURES: The difference between highest diastolic blood pressure after randomisation and diastolic blood pressure at the moment of randomisation; referral and admission to hospital for hypertension.
RESULTS: There was no difference in increase of diastolic blood pressure after randomisation, the percentage of referral and admission to hospital for hypertension, or in obstetric outcome between the two groups. Urinary sodium excretion after randomisation in the normal diet group was significantly higher than in the low sodium group.
CONCLUSION: Prescribing a sodium-restricted diet to prevent or to treat mild pregnancy-induced hypertension is not effective. Therefore there is no need to introduce a salt restricted diet in prenatal care, although increasing evidence shows that a low sodium diet prevents hypertension in non-pregnant individuals.
Options:
A: Reduced dietary salt intake significantly decreased the risk of developing pre-eclampsia.
B: Increased dietary salt intake significantly increased the risk of developing pre-eclampsia.
C: There was insufficient evidence to conclude that altering dietary salt intake had any effect on the risk of developing pre-eclampsia.
D: Both reduced and increased dietary salt intake had significant effects on the risk of developing pre-eclampsia. | C |
497 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What was the primary outcome when evaluating the effectiveness of the six-dose regimen of artemether-lumefantrine for treating uncomplicated falciparum malaria? Please answer this question based on the information provided below:
Comparative clinical trial of two-fixed combinations dihydroartemisinin-napthoquine-trimethoprim (DNP) and artemether-lumefantrine (Coartem/Riamet) in the treatment of acute uncomplicated falciparum malaria in Thailand.
An open randomized comparison of two-fixed dose artemisinin derivative-containing combination regimens was conducted in adults with acute uncomplicated multidrug resistant falciparum malaria in Thailand. DNP, a combination of dihydroartemisinin with napthoquine and trimethoprim developed recently in China, has been evaluated in China, Vietnam, Cambodia and Thailand. This study was performed to compare the safety, tolerability and efficacy of DNP and artemether-lumefantrine/Coartem. One hundred and thirty eligible uncomplicated falciparum malaria patients were enrolled into the study. Patients were randomly assigned in a 2:1 ratio into group A, which received DNP one tablet twice a day for one day; and group B, which received Coartem/Riamet four tablets twice a day for 3 days. The cure rates at 28-day were 99% and 97% in group A and group B, respectively. No serious adverse events occurred. We concluded that both DNP and Coartem/ Riamet were safe, well tolerated and highly efficacious in the treatment of acute uncomplicated falciparum malaria in Thailand.
A clinical and pharmacokinetic trial of six doses of artemether-lumefantrine for multidrug-resistant Plasmodium falciparum malaria in Thailand.
The efficacy-safety and pharmacokinetics of the six-dose regimen of artemether-lumefantrine (Coartem/Riamet; Novartis Pharma AG, Basel, Switzerland) were assessed in a randomized trial in 219 patients (> or = 12 years old) with acute, uncomplicated Plasmodium falciparum malaria in Thailand. One hundred and sixty-four patients received artemether-lumefantrine and 55 received the standard treatment combination of mefloquine-artesunate. Both drugs induced rapid clearance of parasites and malaria symptoms. The 28-day cure rates were 95.5% (90% confidence interval [CI] = 91.7, 97.9%) for artemether-lumefantrine and 100% (90% CI = 94.5, 100%) for mefloquine-artesunate. This high-dose regimen of artemether-lumefantrine was very well tolerated, with very good compliance. The most frequent adverse events were headache, dizziness, nausea, abdominal pain, dyspepsia, vomiting, and skin rash. Overall, only 2% of patients in both groups showed QTc prolongations but without any cardiac complication, and no differences were seen between patients with and without measurable baseline plasma levels of quinine or mefloquine. Plasma levels of artemether, dihydroartemisinin, and lumefantrine were consistent with historical data for the same dose regimen, and were higher, particularly for lumefantrine, than those previously observed with the four-dose regimen, explaining the greater efficacy of the six-dose regimen in a drug-resistant setting. These results confirm the excellent safety and efficacy of the six-dose regimen of artemether-lumefantrine in the treatment of multidrug-resistant P. falciparum malaria.
Randomized comparison of chloroquine plus sulfadoxine-pyrimethamine versus artesunate plus mefloquine versus artemether-lumefantrine in the treatment of uncomplicated falciparum malaria in the Lao People's Democratic Republic.
BACKGROUND: Recent clinical trials in the Lao People's Democratic Republic have demonstrated that chloroquine and sulfadoxine-pyrimethamine, which are national malaria treatment policy, are no longer effective in the treatment of uncomplicated Plasmodium falciparum malaria.
METHODS: A randomized comparison of 3 oral antimalarial combinations--chloroquine plus sulfadoxine-pyrimethamine versus artesunate plus mefloquine versus artemether-lumefantrine--with 42-day follow-up period, was conducted among 330 patients with acute uncomplicated falciparum malaria in southern Laos.
RESULTS: The 42-day cure rates, as determined by intention-to-treat analysis and adjusted for reinfection, were 100%, 97%, and 93% for the groups receiving artesunate plus mefloquine, artemether-lumefantrine, and chloroquine plus sulfadoxine-pyrimethamine, respectively. Of 8 patients receiving chloroquine plus sulfadoxine-pyrimethamine who experienced treatment failure, 6 had early treatment failure. The mean parasite clearance time was significantly longer in patients treated with chloroquine plus sulfadoxine-pyrimethamine (2.9 days; 95% confidence interval [CI], 2.8-3.0 days) than in those treated with artesunate plus mefloquine (2.07 days; 95% CI, 2.0-2.1 days; P<.001) and artemether-lumefantrine (2.08 days; 95% CI, 2.0-2.1 days; P<.001). Cure rates with artemether-lumefantrine were high despite low mean daily dietary fat intake (13.8 g; 95% CI, 12.5-15.1 g) and day 7 plasma lumefantrine concentrations (0.47 mu g/mL; 95% CI, 0.38-0.56 mu g/mL).
CONCLUSION: Oral artesunate plus mefloquine and artemether-lumefantrine are highly effective for the treatment of uncomplicated falciparum malaria in Laos.
Amodiaquine alone, amodiaquine+sulfadoxine-pyrimethamine, amodiaquine+artesunate, and artemether-lumefantrine for outpatient treatment of malaria in Tanzanian children: a four-arm randomised effectiveness trial.
BACKGROUND: Many countries in Africa are considering a change to combination treatment for falciparum malaria because of the increase in drug resistance. However, there are few effectiveness data for these combinations. Our aim was to study the effectiveness of three drug combinations that have proven efficacious in east Africa compared with amodiaquine monotherapy.
METHODS: We undertook a randomised trial of antimalarial drug combinations for children (aged 4-59 months) with uncomplicated malaria in Muheza, Tanzania, an area with a high prevalence of resistance to sulfadoxine-pyrimethamine and chloroquine. Children were randomly allocated 3 days of amodiaquine (n=270), amodiaquine +sulfadoxine-pyrimethamine (n=507), or amodiaquine+artesunate (n=515), or a 3-day six-dose regimen of artemether-lumefantrine (n=519). Drugs were taken orally, at home, unobserved by medical staff. The primary endpoint was parasitological failure by day 14 assessed blind to treatment allocation. Secondary endpoints included day 28 follow-up and gametocyte carriage. Analysis was by intention to treat.
FINDINGS: Of 3158 children screened, 1811 were randomly assigned treatment and 1717 (95%) reached the 14-day follow-up. The amodiaquine group was stopped early by the data and safety monitoring board. By day 14, the parasitological failure rates were 103 of 248 (42%) for amodiaquine, 97 of 476 (20%) for amodiaquine+sulfadoxine-pyrimethamine, 54 of 491 (11%) for amodiaquine+artesunate, and seven of 502 (1%) for artemether-lumefantrine. By day 28, the parasitological failure rates were 182 of 239 (76%), 282 of 476 (61%), 193 of 472 (40%), and 103 of 485 (21%), respectively. The difference between individual treatment groups and the next best treatment combination was significant (p<0.001) in every case. Recrudescence rates by day 28, after correction by genotyping, were 48.4%, 34.5%, 11.2%, and 2.8%, respectively.
INTERPRETATION: The study shows how few the options are for treating malaria where there is already a high level of resistance to sulfadoxine-pyrimethamine and amodiaquine. The WHO-packaged six-dose regimen of artemether-lumefantrine is effective taken unsupervised, although cost is a major limitation.
[Efficacy of therapeutic combinations with artemisinin derivatives in the treatment of non complicated malaria in Burundi].
Faced with the problem of resistance to chloroquine and sulfadoxine-pyrimethamine, the Ministry of Public Health of Burundi decided to study the efficacy of two artemisinin-based combinations, the fixed combination of artemether-lumefantrine and the combination of amodiaquine + artesunate. The efficacy of these combinations for the treatment of uncomplicated falciparum malaria was studied in two sites representative of the country, in Kigobe neighbourhood of Bujumbura, the capital city, and in Buhiga, a rural area. The study followed the standardized WHO protocol from October 2001 to November 2002. A total of 295 children under 5 years were included; 153 children were treated with artesunate and amodiaquine (77 at Buhiga and 76 at Kigobe), and 142 children with the combination of artemether-lumefantrine (64 at Buhiga and 78 at Kigobe). Among the 295 children, 290 were followed up to 14 days. In the group of 149 children treated with artesunate and amodiaquine, 142 (95.3%, 95% CI: 91.9-98.7%) presented with adequate clinical and parasitological response, five (3.3%) with late parasitological failure, one (0.7%) with late clinical failure and one (0.7%) with early treatment failure. Among the 141 children treated with artemether-lumefantrine, 140 (99.3%, 95% CI: 97.9-100%) presented with adequate clinical and parasitological response and one (0.7%) with late parasitological failure at Buhiga. Side-effects were comparable in both groups except for the vomiting. Vomiting was more frequent in the artesunate + amodiaquine on D1 and D2. Both treatments decreased the gametocyte carriage but without getting full clearance in all the patients. During a consensus workshop, the Ministry of Public Health agreed on the combination of artesunate and amodiaquine as the first line drug for the treatment of uncomplicated falciparum malaria in Burundi including epidemic outbreak.
Supervised versus unsupervised intake of six-dose artemether-lumefantrine for treatment of acute, uncomplicated Plasmodium falciparum malaria in Mbarara, Uganda: a randomised trial.
BACKGROUND: The six-dose regimen of artemether-lumefantrine is effective and is among combination therapies prioritised to replace antimalarials that no longer work in Africa. However, its effectiveness has not been assessed in the field, and could be compromised by poor adherence, incorrect timing of doses, and insufficient intake of fatty foods with every dose. Our aim, therefore, was to assess the effectiveness of artemether-lumefantrine prescribed under routine outpatient conditions, compared with its efficacy when given under supervision to inpatients with acute uncomplicated falciparum malaria.
METHODS: We did a randomised trial to compare the efficacy, safety, and pharmacokinetics of artemether-lumefantrine when given in a supervised (all doses observed with fatty-food intake; n=313) or unsupervised (first dose supervised followed by outpatient treatment with nutritional advice; n=644) setting to patients of all ages (weight >10 kg) with acute, uncomplicated falciparum malaria in Mbarara, Uganda. Our primary endpoint was 28 day, PCR-adjusted, parasitological cure rate. Analysis was by intention to treat and evaluability analysis.
FINDINGS: 38 patients were lost to follow-up and one withdrew consent. Day-28 cure rates were 97.7% (296 of 303) and 98.0% (603 of 615) in the supervised and unsupervised groups, respectively. We recorded 15 non-severe, drug-related adverse events, all of which resolved.
INTERPRETATION: Artemether-lumefantrine has a high cure rate irrespective of whether given under supervision with food or under conditions of routine clinic practice. If used as first-line treatment, artemether-lumefantrine could make a substantial contribution to malaria control in Africa, though cost is an issue.
Therapeutic efficacy of artemether-lumefantrine and artesunate-mefloquine for treatment of uncomplicated Plasmodium falciparum malaria in Luang Namtha Province, Lao People's Democratic Republic.
The efficacy of the six-dose regimen of artemether-lumefantrine was compared with the combination of artesunate and mefloquine in a randomised, comparative trial in Luang Namtha Province, Northern Laos. Of 1033 screened patients, 201 were positive for Plasmodium falciparum; 108 patients of all age groups (2-66 years) with acute, uncomplicated P. falciparum malaria were enrolled in the study, 100 of whom were followed-up for 42 days. Fifty-three patients received artemether-lumefantrine and 55 received artesunante-mefloquine. Both drug combinations induced rapid clearance of parasites and malaria symptoms; there was no significant difference in the initial therapeutic response parameters. Both regimes were well tolerated. After 42 days, cure rates were 93.6% (95% CI = 82.5-98.7%; 44 of 47 patients) for artemether-lumefantrine and 100% (95% CI = 93.3-100.0%; 53 of 53 patients) for artesunate-mefloquine. The results show the excellent efficacy and tolerability of both artemether-lumefantrine and artesunate-mefloquine in Northern Laos.
Reduction of malaria transmission to Anopheles mosquitoes with a six-dose regimen of co-artemether.
BACKGROUND: Resistance of malaria parasites to chloroquine (CQ) and sulphadoxine-pyrimethamine (SP) is increasing in prevalence in Africa. Combination therapy can both improve treatment and provide important public health benefits if it curbs the spread of parasites harbouring resistance genes. Thus, drug combinations must be identified which minimise gametocyte emergence in treated cases, and so prevent selective transmission of parasites resistant to any of the partner drugs.
METHODS AND FINDINGS: In a randomised controlled trial, 497 children with uncomplicated falciparum malaria were treated with CQ and SP (three doses and one dose respectively; n = 91), or six doses of artemether in fixed combination with lumefantrine (co-artemether [Coartem, Riamet]) (n = 406). Carriage rates of Plasmodium falciparum gametocytes and trophozoites were measured 7, 14, and 28 d after treatment. The infectiousness of venous blood from 29 children carrying P. falciparum gametocytes 7 d after treatment was tested by membrane-feeding of Anopheles mosquitoes. Children treated with co-artemether were significantly less likely to carry gametocytes within the 4 weeks following treatment than those receiving CQ/SP (30 of 378 [7.94%] versus 42 of 86 [48.8%]; p < 0.0001). Carriers in the co-artemether group harboured gametocytes at significantly lower densities, for shorter periods (0.3 d versus 4.2 d; p < 0.0001) and were less infectious to mosquitoes at day 7 (p < 0.001) than carriers who had received CQ/SP.
CONCLUSIONS: Co-artemether is highly effective at preventing post-treatment transmission of P. falciparum. Our results suggest that co-artemether has specific activity against immature sequestered gametocytes, and has the capacity to minimise transmission of drug-resistant parasites.
No evidence of cardiotoxicity during antimalarial treatment with artemether-lumefantrine.
Artemether-lumefantrine is a new fixed antimalarial combination effective against multidrug-resistant falciparum malaria. A prospective electrocardiographic study was conducted in 150 patients receiving artemetherlumefantrine and 50 treated with artesunate-mefloquine. There was no evidence for clinically significant changes in the electrocardiographic intervals and in particular no relationship between plasma concentrations of lumefantrine and QTc prolongation. Artemether-lumefantrine does not have significant cardiac effects at therapeutic doses.
Artemether-lumefantrine for the treatment of multidrug-resistant falciparum malaria.
The efficacy and safety of the 6-dose regimen of artemether-lumefantrine were assessed in an open randomized trial in children and adults presenting with acute, uncomplicated Plasmodium falciparum malaria in Thailand between November 1997 and March 1998. 200 patients were enrolled in 2 centres: 150 received artemether-lumefantrine (i.e., a median total dose of 9.6 mg/kg [interquartile range 8.7-10.7] and 57.9 mg/kg of lumefantrine [52.4-64.0]) and 50 the standard combination of artesunate (12 mg/kg over 3 d) and mefloquine (25 mg/kg). All patients had rapid initial clinical and parasitological responses. The 28 d cure rates were high: 97.7% (95% confidence interval [95% CI] 93.5-99.5%) for artemether-lumefantrine and 100% (95% CI 92.5-100%) for artesunate-mefloquine. The 6-dose regimen of artemether-lumefantrine was better tolerated than, and as effective as, artesunate-mefloquine, the current standard treatment in this area of multidrug-resistant P. falciparum malaria.
Options:
A: Total failure by day 28 was lower for artemether-lumefantrine compared to amodiaquine and amodiaquine plus sulfadoxine-pyrimethamine.
B: Total failure by day 28 was higher for artemether-lumefantrine compared to chloroquine plus sulfadoxine-pyrimethamine.
C: Total failure by day 28 was the same for artemether-lumefantrine compared to mefloquine plus artesunate.
D: Total failure by day 28 was higher for artemether-lumefantrine compared to dihydroartemisinin-napthoquine-trimethoprim. | A |
498 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What was the conclusion regarding the efficacy of budesonide delivered via nebuliser compared to a large volume spacer for the treatment of chronic asthma in the reviewed studies? Please answer this question based on the information provided below:
Comparative study of budesonide as a nebulized suspension vs pressurized metered-dose inhaler in adult asthmatics.
The study objective was to compare the effect of budesonide administered as a nebulized suspension as compared to a spray with a spacer in adult asthmatics. In a double-blind, double-dummy crossover study, 26 adult patients with moderately severe unstable asthma were randomized to three 4-week treatment periods with budesonide 0.8 mg b.i.d. administered by a pressurized metered-dose inhaler (pMDI) with spacer (Nebuhaler) and budesonide 1 mg and 4 mg b.i.d. administered by a Pari Inhalier Boy jet nebulizer. The nebulizer was activated only during inspiration. The total mass output was similar from the two devices but their fraction of small particles differed by a factor of 2 in favour of pMDI. Effect was evaluated from daily home measurements of peak expiratory flow (PEF), need of beta 2-agonist and symptom scores. Plasma cortisol and budesonide levels were measured in a subgroup of 10 patients. A consistent trend showed the nebulizer treatment to be at least as efficient as the pMDI plus spacer treatment. In actual fact, the apparent order of effect was: 4 mg nebulized suspension treatment > or = 1 mg nebulized suspension treatment > or = 0.8 mg pMDI with spacer treatment. Plasma budesonide and plasma cortisol also exhibited dose-related levels independent of device. The adverse effects reported appeared to be related to the dose rather than delivery device. Accordingly, the effect was related to total mass output, rather than to the small particle fraction of the budesonide aerosol. These results attest to the efficiency of jet-nebulized budesonide suspension, and indicate nebulized budesonide to be equipotent to standard budesonide therapy delivered by pMDI with Nebuhaler, provided nebulization is synchronized with inspiration and no loss of aerosol occurs during expiration.
Drug delivery and adherence in young children.
The aim of this pilot study was to compare a the HaloLite Paediatric Nebulizer (HPN) with a pressurized metered dose inhaler and valved holding chamber (pMDI VHC, Aerochamber) in terms of drug delivery, adherence to treatment, compliance with device, true adherence, and acceptability. Fourteen children aged 11-36 months with asthma on regular treatment with inhaled corticosteroids were enrolled into an open, randomized, crossover trial. They received budesonide for 2 weeks with each delivery system. Both devices incorporated a datalogger which recorded information on how the device was used. The HPN was preprogrammed to deliver 25 microg of budesonide to the patient. A single actuation of budesonide 200 microg was used with the pMDI VHC. The median delivered dose of budesonide was 36 microg (range, 31-45 microg; CV, 15%) for the HPN and 53 microg (range, 17-85 microg; CV, 47%) for the pMDI VHC. The median adherence was 68% (range, 11-96%) with the HPN and 71% (range, 11-100%) with the pMDI VHC. The median device compliance was 30% and 51% and the median true adherence was 23% and 36%, respectively. The shape, size, and weight of the HaloLite Paediatric Nebulizer were generally less acceptable than the shape, size, and weight of the pMDI VHC with datalogger. These results indicate that reproducible quantities of drug can be delivered to very young children using AAD technology such as that incorporated into the HPN. Drug delivery with the pMDI VHC was more variable, but parents preferred this device.
Is high-dose fluticasone propionate via a metered-dose inhaler and Volumatic as efficacious as nebulized budesonide in adult asthmatics?
The efficacy and tolerability of fluticasone propionate (FP) 2 mg daily via a metered-dose inhaler and Volumatic (Glaxo Wellcome) spacer device was compared with nebulized budesonide (nBUD), 2 and 4 mg daily, in a multi-centre, open-label, cross-over study of adult asthmatics. Patients received, in random order, either 4 weeks of treatment with FP followed by 4 weeks of treatment with nBUD, or vice versa, with an intervening 4 week 'wash-out' period between treatments. Thirty patients completed the study, of whom 24 were evaluable. In terms of the primary efficacy parameter, change in mean morning peak expiratory flow (PEF) (l min-1) from baseline to the fourth week of each treatment period, FP was more effective than nBUD [mean difference (FP-nBUD) 21.1 l min-1, P = 0.007, 95% CI (6.5, 35.7)]. Sub-group analysis demonstrated FP to be superior to the 4 mg nBUD [mean treatment difference (FP-nBUD) 42.9 l min-1, P = 0.026, 95% CI (7.1, 78.8)] and at least as efficacious as the 2 mg nBUD sub-group [mean treatment difference (FP-nBUD) 10.2 l min-1, P = 0.211, 95% CI (-6.5, 26.9)]. Furthermore, larger reductions in diurnal variation were observed during FP treatment [mean treatment difference (FP-nBUD) -4.4 percentage points, P = 0.028, 95% CI (-8.4, -0.5)]. There was no significant difference between the treatments for the proportion of symptom-free 24 h periods. Of those expressing a preference, significantly more patients found FP via a metered-dose inhaler and spacer device both easier to administer (78%, P = 0.007) and more convenient to take (76%, P = 0.008) than nebulized budesonide. In addition, cost per patient analysis showed that nebulized budesonide was from 1.7 to 3.5 times more expensive than FP.
Options:
A: Budesonide delivered via nebuliser was less effective than via a large volume spacer.
B: Budesonide delivered via nebuliser was more effective than via a large volume spacer.
C: Budesonide delivered via nebuliser and via a large volume spacer were equally effective.
D: The efficacy of budesonide delivered via nebuliser compared to a large volume spacer could not be determined. | B |
499 | evidence_summarization | You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence. | What were the main findings regarding the efficacy and safety of galantamine in the treatment of Alzheimer's disease and mild cognitive impairment? Please answer this question based on the information provided below:
Galantamine: a randomized, double-blind, dose comparison in patients with Alzheimer's disease.
OBJECTIVES: To investigate whether Galantamine significantly improves the core symptoms of Alzheimer's disease (AD).
BACKGROUND: Galantamine is a reversible, competitive, selective inhibitor of acetylcholinesterase (AChE) that also allosterically modulates nicotinic acetylcholine receptors. This dual mechanism of action provided the rationale for a phase II trial of galantamine in AD.
METHOD: A multicentre, randomized, parallel, double-blind, placebo-controlled trial was carried out to evaluate the efficacy and tolerability of galantamine 18, 24 and 36 mg/day administered for 3 months in 285 patients with mild-to-moderate probable AD. The primary outcome measure was the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog); secondary outcome measures were the Clinical Global Impression of Change (CGIC) and the Progressive Deterioration Scale (PDS).
RESULTS: Patients treated with galantamine 24 mg/day had a significantly better outcome than placebo on ADAS-cog; the treatment difference was 3 points on the intention-to-treat (ITT) analysis ( p = 0.01) and 4.2 points on per protocol analysis ( p = 0.001). Per protocol analysis showed that galantamine had a significantly better outcome than placebo on PDS ( 24-mg/day dose, p < 0.05) and CGIC (36-mg/day dose, p < 0.05). Galantamine was well tolerated at the lower doses of 18 and 24 mg/day where it produced mild, transient effects typical of cholinomimetic agents.
CONCLUSION: This study shows that, relative to placebo, galantamine significantly improves the core symptoms of Alzheimer's disease.
Efficacy and safety of galantamine in patients with mild to moderate Alzheimer's disease: multicentre randomised controlled trial. Galantamine International-1 Study Group.
OBJECTIVE: To evaluate the efficacy and safety of galantamine in the treatment of Alzheimer's disease.
DESIGN: Randomised, double blind, parallel group, placebo controlled trial.
SETTING: 86 outpatient clinics in Europe and Canada.
PARTICIPANTS: 653 patients with mild to moderate Alzheimer's disease.
INTERVENTION: Patients randomly assigned to galantamine had their daily dose escalated over three to four weeks to maintenance doses of 24 or 32 mg.
MAIN OUTCOME MEASURES: Scores on the 11 item cognitive subscale of the Alzheimer's disease assessment scale, the clinician's interview based impression of change plus caregiver input, and the disability assessment for dementia scale. The effect of apolipoprotein E4 genotype on reponse to treatment was also assessed.
RESULTS: At six months, patients who received galantamine had a significantly better outcome on the 11 item cognitive subscale of the Alzheimer's disease assessment scale than patients in the placebo group (mean treatment effect 2.9 points for lower dose and 3.1 for higher dose, intention to treat analysis, P<0.001 for both doses). Galantamine was more effective than placebo on the clinician's interview based impression of change plus caregiver input (P<0.05 for both doses v placebo). At six months, patients in the higher dose galantamine group had significantly better scores on the disability assessment for dementia scale than patients in the placebo group (mean treatment effect 3.4 points, P<0.05). Apolipoprotein E genotype had no effect on the efficacy of galantamine. 80% (525) of patients completed the study.
CONCLUSION: Galantamine is effective and well tolerated in Alzheimer's disease. As galantamine slowed the decline of functional ability as well as cognition, its effects are likely to be clinically relevant.
Galantamine prolonged-release formulation in the treatment of mild to moderate Alzheimer's disease.
The primary objective of this study was to evaluate the efficacy and tolerability of a flexible dosing regimen (16 or 24 mg/day) of galantamine prolonged-release capsule (PRC) compared with placebo in subjects with mild to moderate Alzheimer's disease (AD). This phase III, double-blind, placebo- and active-controlled, parallel-group trial randomized 971 patients to treatment for 6 months. Efficacy endpoints included change in the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog/11), Clinician's Interview-Based Impression of Change plus caregiver input (CIBIC-plus), Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), and Neuropsychiatric Inventory (NPI) scores. Galantamine was associated with significant improvements in the ADAS-cog/11 score but not in the CIBIC-plus or NPI scores. Galantamine PRC was associated with significant improvement in ADCS-ADL scores. Galantamine PRC had similar tolerability and safety profiles compared with twice-daily galantamine, and when administered as a once-daily flexible dosing regimen of 16 or 24 mg/day, was demonstrated to be as safe and effective for the treatment of mild to moderate AD.
Effects of a flexible galantamine dose in Alzheimer's disease: a randomised, controlled trial.
OBJECTIVE: To assess the efficacy and safety of galantamine in Alzheimer's disease at 3 months using flexible dose escalation.
METHODS: A randomised, double blind, placebo controlled trial in 43 centres in the United States, Canada, Great Britain, South Africa, Australia, and New Zealand. Patients with probable Alzheimer's disease (n=386; 171 women) with a score of 11-24 on the mini mental state examination, and a score> or =12 on the cognitive subscale of the Alzheimer's disease assessment scale (ADAS-cog) were randomised to placebo, or galantamine escalated over 4 weeks to a maintenance dose of 24 or 32 mg/day. The primary outcome measures were the change in ADAS-cog score and the clinician's interview based impression of change plus caregiver input (CIBIC-plus) score. Activities of daily living (ADL) and behavioural symptoms were secondary outcomes. To compare the effects of highest levels of dosing, an observed cases (OC) analysis was undertaken, with classic intention to treat (ITT) and ITT with last observation carried forward (LOCF) as confirmatory analyses.
RESULTS: At 3 months, galantamine (24-32 mg/day) produced a significantly better outcome on cognitive function than placebo (treatment difference=1.9 points on ADAS-cog, p=0.002) and a significantly better global response than placebo, as measured by CIBIC-plus (deterioration in 21% of patients on galantamine v 37% on placebo; p<0.001). Galantamine produced significant benefits on basic and instrumental ADL. Behavioural symptoms did not change significantly from baseline levels in either group. Adverse events (primarily gastrointestinal) were of mild to moderate intensity. There were no important differences between the OC, ITT, and ITT/LOCF analyses. Most patients (82%) who were maintained on the higher dose of galantamine completed the study.
CONCLUSIONS: Patients on galantamine, compared with those on placebo, experienced benefits in cognitive function and instrumental and basic activities of daily living. Flexible dose escalation of galantamine was well tolerated.
Efficacy of galantamine in probable vascular dementia and Alzheimer's disease combined with cerebrovascular disease: a randomised trial.
BACKGROUND: Vascular dementia is the second commonest form of dementia, and vascular factors contribute to the development of dementia in many patients with Alzheimer's disease. Galantamine amplifies the acetylcholine response by inhibiting acetylcholinesterase and modulating nicotinic receptors. It has shown broad, sustained benefits in patients with Alzheimer's disease. We investigated the effects of galantamine in patients with a diagnosis of probable vascular dementia or Alzheimer's disease combined with cerebrovascular disease.
METHODS: Eligible patients were randomly assigned galantamine 24 mg/day (n=396) or placebo (n=196) in a multicentre, double-blind, 6-month trial. Primary endpoints were cognition (Alzheimer's disease assessment scale, cognitive subscale [ADAS-cog]) and global functioning (clinician's interview-based impression of change plus caregiver input [CIBIC-plus]). Secondary endpoints included assessments of activities of daily living and behavioural symptoms. Patients were monitored for adverse events. Analyses were on the basis of observed case or last observation carried forward.
FINDINGS: Galantamine showed greater efficacy than placebo on ADAS-cog (galantamine change -1.7 [SE 0.4] vs placebo 1.0 [0.5]; treatment effect 2.7 points; p<0.0001) and CIBIC-plus (213 [74%] vs 95 [59%] patients remained stable or improved, p=0.0001). Activities of daily living and behavioural symptoms were also significantly improved compared with placebo (p=0.002 and p=0.016, respectively). Galantamine was well tolerated.
INTERPRETATION: Galantamine showed a therapeutic effect on all key areas of cognitive and non-cognitive abilities in this group of dementia patients.
Galantamine in AD: A 6-month randomized, placebo-controlled trial with a 6-month extension. The Galantamine USA-1 Study Group.
BACKGROUND: Galantamine is a reversible, competitive cholinesterase inhibitor that also allosterically modulates nicotinic acetylcholine receptors. These mechanisms of action provided the rationale for a therapeutic trial of galantamine in AD.
METHODS: A 6-month, multicenter, double-blind trial was undertaken in 636 patients with mild to moderate AD. Patients were randomly assigned to placebo or galantamine and escalated to maintenance doses of 24 or 32 mg/d. Eligible patients then entered a 6-month, open-label study of the 24 mg/d dose. Primary efficacy measures were the 11-item AD Assessment Scale cognitive subscale (ADAS-cog/11) and the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus). The Disability Assessment for Dementia (DAD) scale was a secondary efficacy variable.
RESULTS: Galantamine significantly improved cognitive function relative to placebo; the treatment effects were 3.9 points (lower dose) and 3.8 points (higher dose) on the ADAS-cog/11 scale at month 6 (p < 0.001 in both cases). Both doses of galantamine produced a better outcome on CIBIC-plus than placebo (p < 0.05). Therapeutic response to galantamine was not affected by APOE genotype. At 12 months, mean ADAS-cog/11 and DAD scores had not significantly changed from baseline for patients who received galantamine 24 mg/d throughout the 12 months. The most common adverse events, which were predominantly gastrointestinal, decreased in frequency during long-term treatment. There was no evidence of hepatotoxicity.
CONCLUSIONS: Galantamine is effective and safe in AD. At 6 months, galantamine significantly improved cognition and global function. Moreover, cognitive and daily function were maintained for 12 months with the 24 mg/d dose.
A 5-month, randomized, placebo-controlled trial of galantamine in AD. The Galantamine USA-10 Study Group.
OBJECTIVE: To investigate the efficacy and tolerability of galantamine, using a slow dose escalation schedule of up to 8 weeks, in 978 patients with mild to moderate AD.
METHODS: A 5-month multicenter, placebo-controlled, double-blind trial. Following a 4-week placebo run-in, patients were randomized to one of four treatment arms: placebo or galantamine escalated to final maintenance doses of 8, 16, or 24 mg/day. Outcome measures included the cognitive subscale of the AD Assessment Scale (ADAS-cog), the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus), the AD Cooperative Study Activities of Daily Living inventory, and the Neuropsychiatric Inventory. Standard safety evaluations and adverse event monitoring were carried out.
RESULTS: After 5 months, the galantamine-placebo differences on ADAS-cog were 3.3 points for the 16 mg/day group and 3.6 points for the 24 mg/day group (p < 0.001 versus placebo, both doses). Compared with placebo, the galantamine 16- and 24-mg/day groups also had a significantly better outcome on CIBIC-plus, activities of daily living, and behavioral symptoms. Treatment discontinuations due to adverse events were low in all galantamine groups (6 to 10%) and comparable with the discontinuation rate in the placebo group (7%). The incidence of adverse events in the galantamine groups, notably gastrointestinal symptoms, was low and most adverse events were mild.
CONCLUSIONS: Galantamine 16 and 24 mg/day significantly benefits the cognitive, functional, and behavioral symptoms of AD as compared with placebo. Slow dose escalation appears to enhance the tolerability of galantamine, minimizing the incidence and severity of adverse events.
Options:
A: Galantamine showed significant improvement in cognitive function and daily living activities in Alzheimer's disease patients, with a similar safety profile to other cholinesterase inhibitors, but it is not recommended for mild cognitive impairment due to an unexplained excess death rate.
B: Galantamine did not show any significant improvement in cognitive function or daily living activities in Alzheimer's disease patients and had a higher incidence of adverse effects compared to other cholinesterase inhibitors.
C: Galantamine showed significant improvement in cognitive function in both Alzheimer's disease and mild cognitive impairment patients, with no significant difference in safety profile compared to other cholinesterase inhibitors.
D: Galantamine showed no significant improvement in cognitive function in Alzheimer's disease patients but was effective in improving daily living activities, with a higher incidence of adverse effects in mild cognitive impairment patients. | A |
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