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200 | 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 pressurised metered dose inhalers (pMDI) compared to other handheld inhaler devices for delivering bronchodilators in patients with stable chronic obstructive pulmonary disease (COPD)? Please answer this question based on the information provided below:
Terbutaline in COPD comparison between Turbuhaler and chlorofluorocarbon (CFC) inhaler.
Patients with chronic obstructive pulmonary disease (COPD) often subjectively benefit from inhaled beta 2-agonists in spite of little or no demonstrable effect in forced expiratory volume in 1 second (FEV1.0). A comparison between the effects of terbutaline administered via a dry powder inhaler (Turbuhaler) and via a chlorofluorocarbon (CFC) inhaler in conjunction with a spacer device (Nebuhaler) was performed in patients with regard to FEV1.0, forced expiratory capacity (FVC), residual volume (RV), and specific conductance (s-Gaw). Fifteen hospitalised patients (11 male) with COPD were studied, each of whom had a diurnal variation in peak expiratory flow (PEF) not exceeding 15% and with a demonstrated volume response to inhaled beta 2-agonists in FVC and/or RV of at least 15%. Patients were administered each of the following five treatments on a single occasion in a randomized order (latin square) in intervals of at least 2 days: placebo, terbutaline via Turbuhaler (1.0 and 2.5 mg) and terbutaline via a CFC inhaler (1.0 mg without and 2.5 mg with Nebuhaler). Inhalation of terbutaline in different doses and from different devices induced a decrease in RV, an increase in FVC, and s-Gaw and a less pronounced increase in FEV1.0. No statistically significant differences between the four terbutaline treatments were seen, but all were significantly different from the placebo. These findings indicate that while patients with COPD may benefit from inhaled terbutaline through decreased hyperinflation, the choice of inhalation device seems to be of little importance for its efficacy.
Terbutaline in COPD comparison between Turbuhaler and chlorofluorocarbon (CFC) inhaler.
Patients with chronic obstructive pulmonary disease (COPD) often subjectively benefit from inhaled beta 2-agonists in spite of little or no demonstrable effect in forced expiratory volume in 1 second (FEV1.0). A comparison between the effects of terbutaline administered via a dry powder inhaler (Turbuhaler) and via a chlorofluorocarbon (CFC) inhaler in conjunction with a spacer device (Nebuhaler) was performed in patients with regard to FEV1.0, forced expiratory capacity (FVC), residual volume (RV), and specific conductance (s-Gaw). Fifteen hospitalised patients (11 male) with COPD were studied, each of whom had a diurnal variation in peak expiratory flow (PEF) not exceeding 15% and with a demonstrated volume response to inhaled beta 2-agonists in FVC and/or RV of at least 15%. Patients were administered each of the following five treatments on a single occasion in a randomized order (latin square) in intervals of at least 2 days: placebo, terbutaline via Turbuhaler (1.0 and 2.5 mg) and terbutaline via a CFC inhaler (1.0 mg without and 2.5 mg with Nebuhaler). Inhalation of terbutaline in different doses and from different devices induced a decrease in RV, an increase in FVC, and s-Gaw and a less pronounced increase in FEV1.0. No statistically significant differences between the four terbutaline treatments were seen, but all were significantly different from the placebo. These findings indicate that while patients with COPD may benefit from inhaled terbutaline through decreased hyperinflation, the choice of inhalation device seems to be of little importance for its efficacy.
Improved delivery of ipratropium bromide using Respimat (a new soft mist inhaler) compared with a conventional metered dose inhaler: cumulative dose response study in patients with COPD.
Respimat (RMT) is a reusable, propellant-free, soft mist inhaler (SMI), a novel device for inhalation therapy. We conducted a three-period cross-over study to evaluate the safety and efficacy of cumulative doses of ipratropium bromide inhaled from RMT (Two dose levels) or from a pressurized metered dose inhaler (MDI), in 36 patients with chronic obstructive pulmonary disease (COPD). The bronchodilator effect of ipratropium bromide was greater when administered via RMT (10 or 20 microg per puff, given double-blind within device, to total doses of 160 or 320 microg) than via MDI (20 microg per puff, total dose 320 microg). The bronchodilator effects of the 160 and 320 microg doses delivered via RMT were similar. Cumulative ipratropium bromide doses of 320 microg given via MDI or RMT and 160 microg given via RMT produced similar safety profiles. Between 45 min after the first drug inhalation and 45 min after the final dose, greater bronchodilatory effect was obtained from half the cumulative dose of ipratropium (RMT 10 microg per puff) when compared with the MDI (20 microg per puff). Therefore, ipratropium bromide delivered by RMT is as safe as, and can be more effective than, the MDI on acute administration in patients with COPD.
Comparison of the bronchodilator effects of salbutamol delivered via a metered-dose inhaler with spacer, a dry-powder inhaler, and a jet nebulizer in patients with chronic obstructive pulmonary disease.
The aim of this study was to compare the bronchodilator effects of salbutamol delivered via three different devices: a dry-powder inhaler (DPI), a metered-dose inhaler (MDI) with a large-volume spacer and a jet nebulizer (NEB) in patients with stable chronic obstructive pulmonary disease (COPD). Ten male patients with stable COPD [age: 67.2 +/- 3.8 years, forced expiratory volume in 1 s (FEV1): 1.56 +/- 0.32 liters] were studied in a randomized, double-blind and crossover manner. Each patient received 200 or 1, 000 microg salbutamol via an MDI with an InspirEaseTM spacer, a RotahalerTM, or a DeVilbiss 646(TM) nebulizer (NEB), or matching placebo on 7 separate days. Spirometry was performed before and 15, 30, 60, 90, 120, and 240 min after inhalation. With the 200- microg dose, only DPI produced a small but greater response in maximum FEV1 and in area under the time-response curve (AUC-FEV1) compared with placebo. With the 1,000- microg dose, DPI and MDI produced equally greater improvements in both maximum FEV1 and AUC-FEV1 than NEB. An equal bronchodilating effect can be obtained using either DPI or MDI with a spacer device, whereas the NEB was less effective when the same dose was administered.
Comparison of the bronchodilator effects of salbutamol delivered via a metered-dose inhaler with spacer, a dry-powder inhaler, and a jet nebulizer in patients with chronic obstructive pulmonary disease.
The aim of this study was to compare the bronchodilator effects of salbutamol delivered via three different devices: a dry-powder inhaler (DPI), a metered-dose inhaler (MDI) with a large-volume spacer and a jet nebulizer (NEB) in patients with stable chronic obstructive pulmonary disease (COPD). Ten male patients with stable COPD [age: 67.2 +/- 3.8 years, forced expiratory volume in 1 s (FEV1): 1.56 +/- 0.32 liters] were studied in a randomized, double-blind and crossover manner. Each patient received 200 or 1, 000 microg salbutamol via an MDI with an InspirEaseTM spacer, a RotahalerTM, or a DeVilbiss 646(TM) nebulizer (NEB), or matching placebo on 7 separate days. Spirometry was performed before and 15, 30, 60, 90, 120, and 240 min after inhalation. With the 200- microg dose, only DPI produced a small but greater response in maximum FEV1 and in area under the time-response curve (AUC-FEV1) compared with placebo. With the 1,000- microg dose, DPI and MDI produced equally greater improvements in both maximum FEV1 and AUC-FEV1 than NEB. An equal bronchodilating effect can be obtained using either DPI or MDI with a spacer device, whereas the NEB was less effective when the same dose was administered.
Options:
A: pMDIs were found to be significantly more effective than dry powder devices for delivering beta2-agonists.
B: Dry powder devices were found to be significantly more effective than pMDIs for delivering beta2-agonists.
C: pMDIs and dry powder devices produced similar outcomes for delivering beta2-agonists, but the evidence was limited.
D: The soft mist device for ipratropium was found to be less effective than pMDIs. | C |
201 | 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 acupuncture in the treatment of adults with lateral elbow pain in terms of pain reduction, improvement in function, grip strength, and adverse effects? Please answer this question based on the information provided below:
Acupuncture treatment in epicondylalgia: a comparative study of two acupuncture techniques.
The purpose of this study was to compare the pain-alleviating effect of classical acupuncture with superficial needle insertion in 82 patients suffering from lateral epicondylalgia. Sessions were 20 min long, two to three times weekly with 10 treatments in all. Five acupuncture points were treated: LI 10, 11, 12, Lu 5, and SJ 5. After 10 treatments significant differences were observed between the groups favoring the classical acupuncture technique in relation to subjective and objective outcome. No such differences could be observed at the follow-ups after 3 months and 1 year. This study showed that classical "deep" acupuncture is superior to superficial needle insertion in the short-term symptomatic treatment of lateral epicondylalgia, but not at 3- and 12-month follow-up.
Acupuncture treatment in epicondylalgia: a comparative study of two acupuncture techniques.
The purpose of this study was to compare the pain-alleviating effect of classical acupuncture with superficial needle insertion in 82 patients suffering from lateral epicondylalgia. Sessions were 20 min long, two to three times weekly with 10 treatments in all. Five acupuncture points were treated: LI 10, 11, 12, Lu 5, and SJ 5. After 10 treatments significant differences were observed between the groups favoring the classical acupuncture technique in relation to subjective and objective outcome. No such differences could be observed at the follow-ups after 3 months and 1 year. This study showed that classical "deep" acupuncture is superior to superficial needle insertion in the short-term symptomatic treatment of lateral epicondylalgia, but not at 3- and 12-month follow-up.
Laser treatment applied to acupuncture points in lateral humeral epicondylalgia. A double-blind study.
Forty-nine patients suffering from lateral humeral epicondylalgia were enrolled in a double-blind study to observe the effects of Ga-As laser applied to acupuncture points. The Mid 1500 IRRADIA laser machine was used, wavelength: 904 nm, mean power output: 12 mW, peak value: 8.3 W; frequency: 70 Hz (pulse train). Localization of points: LI 10, 11, 12, Lu 5 and SJ 5. Each point was treated for 30 sec resulting in a dose of treatment of 0.36 J/point. The patients were treated 2-3 times weekly with 10 treatments in all. Follow-ups were done after 3 months and 1 year. No significant differences were observed between the laser and the placebo group in relation to the subjective or objective outcome after 10 treatments or at the follow-ups.
The analgesic effect of acupuncture in chronic tennis elbow pain.
The immediate analgesic effect of a single non-segmental acupuncture stimulation treatment on chronic tennis elbow pain was studied in a placebo-controlled single-blind trial completed by 48 patients. Before and after treatment, all patients were examined physically by an unbiased independent examiner. Eleven-point box scales were used [13] for pain measurement. Patients in the verum group were treated at non-segmental distal points (homolateral leg) for elbow pain following Chinese acupuncture rules, whereas patients in the placebo group were treated with placebo acupuncture avoiding penetration of the skin with an acupuncture needle. Overall reduction in the pain score was 55.8% (S = 2.95) in the verum group and 15% (S = 2.77) in the placebo group. After one treatment 19 out of 24 patients in the verum group (79.2%) reported pain relief of at least 50% (placebo group: six patients out of 24). The average duration of analgesia after one treatment was 20.2 h in the verum group (S = 21.54) and 1.4 h (S = 3.50) in the placebo group. The results are statistically significant (P < 0.01); they show that non-segmental verum acupuncture has an intrinsic analgesic effect in the clinical treatment of tennis elbow pain which exceeds that of placebo acupuncture.
Options:
A: Acupuncture provides significant long-term pain relief and improvement in function and grip strength.
B: Acupuncture provides short-term pain relief but no significant long-term benefits, and there is insufficient evidence to support its use.
C: Acupuncture has no effect on pain reduction, function, or grip strength, and has significant adverse effects.
D: Acupuncture is more effective than other treatments in providing long-term pain relief and improving function and grip strength. | B |
202 | 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 comparative efficacy and safety of inhaled beclomethasone dipropionate (BDP) and budesonide (BUD) in the treatment of chronic asthma? Please answer this question based on the information provided below:
A comparison of inhaled budesonide and beclomethasone dipropionate in childhood asthma.
The objective of this study was to compare the clinical effects of beclomethasone dipropionate (BDP) and budesonide in asthmatic children using two common ways of administration. Twenty-one children, aged 4-14 years, who regularly used inhaled corticosteroids for their control of asthma were included in the study. The drugs were studied by using a double-blind randomized cross-over design trial with a single-blind placebo period at the end. Each period lasted 3 weeks. The dosage was 100 micrograms b.i.d. for both drugs. Budesonide was administered via a spacer inhaler (Inhalet), and beclomethasone dipropionate via a standard actuator. Compared with placebo, both drugs significantly improved PEFR values for morning (20% for budesonide and 14% for BDP) and evening (14% for budesonide and 9% for BDP). Both morning and/or evening peak flows were significantly higher during the budesonide treatment as compared with the BDP treatment. In comparison with the placebo period, FEV1.0 was significantly improved with budesonide but not with BDP. Plasma cortisol, WBC counts, differential and eosinophilia counts in blood were determined at the beginning and the end of each period. All of the values except for the eosinophil counts were within normal ranges. Candida was looked for but not found in any case. No other adverse effects were registered. For most of the children, a deterioration of the state of their asthma and increased need for concomitant therapy during the placebo period confirmed their steroid dependence. The number of administrations with concomitant anti-asthmatic therapy increased during placebo by 61% as compared with the budesonide therapy, and by 40% compared with the BDP therapy.
Adrenal function in children with bronchial asthma treated with beclomethasone dipropionate or budesonide.
The effect of inhaled beclomethasone dipropionate and budesonide on the adrenal function was studied in 30 children (aged 7 to 15 years) with mild bronchial asthma. The trial was designed as a prospective double-blind parallel study of the effect of stepwise increase of either beclomethasone dipropionate or budesonide from 200 micrograms through 400 micrograms, to 800 micrograms daily in three consecutive periods of 4 weeks. At the end of each period, the adrenal stress response was evaluated by measurements of serum cortisol and androstenedione during a short adrenocorticotropic hormone test. The unstimulated diurnal production of glucocorticosteroids was assessed by measurements of free cortisol in 24-hour urine samples. Free cortisol in urine was found a valid measure of the total diurnal excretion of cortisol metabolites, since it exhibited a good correlation to the fractional cortisol metabolites measured by gas chromatography. The adrenal response to adrenocorticotropic hormone stimulation was unaffected by treatment or dose. The unstimulated diurnal production of glucocorticosteroids demonstrated a highly significant dose-related suppression in response to the inhaled steroids. No significant difference was found between the two topical steroids (probability value 5.3%), and yet the suppression was apparent in the group of children treated with beclomethasone dipropionate but not in the group of children treated with budesonide. Further studies are desirable in order to ascertain whether budesonide offers an improved ratio between beneficial anti-inflammatory effect and unwanted systemic activity.
Methodological aspects on clinical trials with inhaled corticosteroids: results of two comparisons between two steroid aerosols in patients with asthma.
The efficacy of beclomethasone dipropionate aerosol (BDA) 100 micrograms q.i.d. was compared with that of budesonide aerosol 10 micrograms q.i.d. in 17 patients. The efficacy of inhaled BDA 100 micrograms q.i.d. was also compared with that of budesonide 50 micrograms q.i.d. with and without an extension tube (Inhalet) attached to the actuator in 23 patients. Both studies included placebo periods. The trials were performed with the cross-over technique in patients with stable asthma. Each treatment was randomized and given in periods of two weeks starting with a run-in period. The patients recorded peak expiratory flow rates (PEF) twice daily and filled in diary cards for cough, wheeze, breathing difficulties and use of beta 2-receptor stimulant aerosol. In the first study the patients came to the hospital twice weekly throughout the trial for spirometry and interview. In the second study they came every second week. Budesonide and BDA were superior to placebo. Budesonide in doses of 100 micrograms and 50 micrograms were as efficacious as BDA 100 micrograms q.i.d., while budesonide 50 micrograms q.i.d. with Inhalet was slightly more effective. Treatment for two weeks was found to be sufficient. For each parameter the average of the last four days of each period was found to be relevant in the comparison. The placebo period should preferably not be placed at random in the trial, but as the last treatment period.
Comparison of dose-response effects of inhaled beclomethasone dipropionate and budesonide in the management of asthma.
The dose-response effects of inhaled beclomethasone dipropionate (BDP) and budesonide (BUD) administered b.i.d. with the aid of metered dose aerosols were studied in 128 patients (67 men and 61 women, mean age 53 years) suffering from asthma bronchiale. The study was designed as a multi-centre, double-blind, four-period cross-over study, followed by a single-blind double placebo period. BDP was administered in doses of 400 and 1000 micrograms, and BUD in doses of 400 and 800 micrograms. The results in terms of peak expiratory flow (PEF) in the morning and evening, daily symptoms score and use of inhaled beta 2-agonists did not reveal any clinically significant differences between the drugs or between high (800 micrograms BUD, 1000 micrograms BDP) and low (400 micrograms BUD/BDP) doses. However, statistically significant differences were recorded for the corresponding parameters when comparing the placebo with preceding steroid periods. Adverse effects consisting mainly of oropharyngeal candidiasis, hoarseness and cough occurred in 54 of 468 treatment months (12%). The carry-over effects of inhaled steroids are longer lasting than was previously assumed.
Comparison of two high dose corticosteroid aerosol treatments, beclomethasone dipropionate (1500 micrograms/day) and budesonide (1600 micrograms/day), for chronic asthma.
Twenty eight patients with chronic asthma took part in a double blind single crossover controlled trial of inhaled budesonide and inhaled beclomethasone dipropionate, using high doses of 1600 micrograms and 1500 micrograms daily respectively. Both drugs were administered by pressurised aerosol inhaler; the inhaler containing budesonide and its matching placebo were fitted with a collapsible spacer device. There was no significant difference in the control of asthma during the two six week treatment periods. There was no significant difference in FEV1 and forced vital capacity after four and six weeks of treatment or in mean morning and evening peak expiratory flow rates for the last 21 days of treatment. There was a small but statistically significant reduction in the daytime wheeze score while they were taking high dose budesonide but there was no difference for daytime activity, cough, and night symptoms. The mean basal cortisol concentrations were significantly lower after six weeks of high dose treatment than before treatment (budesonide p less than 0.01, beclomethasone p less than 0.05). There was no difference between mean basal cortisol values after six weeks of high dose treatment, and there was no effect on the rise of cortisol obtained after a short tetracosactrin test. High dose inhaled corticosteroids produced few side effects and were well tolerated.
Asthma treatment with a new corticosteroid aerosol, budesonide, administered twice daily by spacer inhaler.
Comparison of a new corticosteroid aerosol, budesonide, with beclomethasone dipropionate in the treatment of chronic asthma.
Effect of inhaled beclomethasone dipropionate and budesonide dry powder on pulmonary function and serum eosinophil cationic protein in adult asthmatics.
The aim of this study was to determine whether the effects of inhaled beclomethasone dipropionate and budesonide dry powder on pulmonary function correlate with those on measurement of serum eosinophil cationic protein (sECP). Thirty-two asthmatic adults in a stable phase, treated daily with 1,000 micrograms beclomethasone dipropionate metered-dose inhaler, completed a 2-week wash-out period and were then randomized to receive a 200 micrograms/dose q.i.d. of either drug, over an 8-week period. Pulmonary function tests (FEV1, FVC, PEFR, FEF25-75% and MEF50) were measured at study entry, before and after every 2 weeks of treatment, while PEFR (morning and evening), symptom scores and salbutamol use PRN were recorded daily on a dairy card. sECP was measured at baseline and after 4 and 8 weeks of treatment. Safety variables included adverse reactions, morning serum cortisol and vital signs (heart rate and blood pressure). FEV1, FVC, PEFR, FEF25-75%, MEF50 and morning PEFR significantly increased (p < 0.05) over baseline in the beclomethasone group, while only FEV1 at week 6 and evening PEFR significantly increased (p < 0.05) in the budesonide group; no significant differences between groups were reported. sECP significantly decreased (p < 0.01) in the beclomethasone group at week 4 and 8 (p < 0.05 between groups). Evidence of statistically significant negative correlation between the FEV1 percent predicted and sECP was assessed at baseline (correlation coefficient r = -0.60, p < 0.05) in the total patient sample, and in the results, expressed as percent change over baseline, obtained at both week 4 and 8 (p < 0.01). A significant decrease in salbutamol use PRN, symptom score and number of daily bronchospasm attacks was also reported in the beclomethasone group (p < 0.05). No adverse reactions or relevant changes in morning cortisol and vital signs were reported in either group. It was concluded that sECP proved to be a reliable marker for monitoring inflammatory events in asthma; inhaled beclomethasone dipropionate dry powder was at least as effective as budesonide in improving lung function and the underlying asthma inflammation.
Endocrine and lung function in asthmatic children on inhaled corticosteroids.
The safety of inhaled corticosteroids in the treatment of chronic asthma has been questioned. In a prospective crossover study asthmatic children not controlled on other medications were commenced on beclomethasone dipropionate (BDP) or budesonide (BUD), both administered at the dose of 200 micrograms twice per day for 2 wk each in randomized order. Recordings at home included twice daily symptom scores, peak expiratory flow readings, and the use of additional antiasthma medications. Before and after each treatment period the patients were admitted for overnight blood sampling for cortisol, ACTH, and growth hormone, 24-h urine collections for cortisol, and detailed lung function tests. A total of 12 children completed the study. The nocturnal serum cortisol production was significantly reduced by 27 and 35% after 2 and 4 wk of treatment (p = 0.005, p = 0.004; Wilcoxon test), and the urinary free cortisol showed a similar reduction of 33 and 48% (p = 0.023, p = 0.005). Such suppression could be shown on both drugs, BDP and BUD, and there was no significant difference between them. The ACTH and growth hormone values were not significantly changed on any treatment. Lung function tests showed an impressive improvement in FVC, FEV1, FEF50, and FEF25 after 2 wk of treatment regardless of the medication. Differences in lung function improvements between the two drugs were very small and not of clinical relevance. The observations indicate that even low-dose inhaled corticosteroids in the form of BDP or BUD have a systemic effect, which emphasizes the importance of using the minimum dose compatible with good control of asthma.
Urine cortisol excretion in children treated with high doses of inhaled corticosteroids: a comparison of budesonide and beclomethasone.
Thirty one children with asthma were treated with inhaled beclomethasone and budesonide in a randomized cross-over study of 2 x 6 weeks' duration. The excretion of free cortisol in two 24 hour urine samples, collected at the end of each treatment period, was significantly higher (mean = 76.3 nmol per day) during budesonide treatment than during beclomethasone treatment (mean = 53.7 nmol per day) (p less than 0.01). The difference between the two drugs was more pronounced in the eight children who received 1,000 and 1,200 micrograms per day than in the 22 children who received 800 micrograms per day. Four children had cortisol excretion below the normal range when treated with beclomethasone. This was seen in one child during budesonide treatment. The age of the child did not influence the result. The long term clinical significance of these findings has yet to be elucidated.
Comparison of budesonide and beclomethasone dipropionate in patients with severe chronic asthma: assessment of relative prednisolone-sparing effects.
The relative prednisolone-sparing effects of inhaled budesonide 400 micrograms daily and beclomethasone dipropionate (BDP) 400 micrograms daily were compared in a double-blind crossover study of 26 patients with chronic asthma requiring treatment with BDP and oral prednisolone in a daily dose of 5 mg or greater. During each period of the trial budesonide and BDP were inhaled via conventional pressurized inhalers in a dose of 100 micrograms four times daily. Prednisolone was reduced by 1 mg per month from the patient's normal maintenance dose to zero or to the point at which asthmatic symptoms became unacceptable. The mean reduction in prednisolone dose during BDP treatment was 2.65 mg compared with 1.8 mg at the end of the budesonide period. The difference between the prednisolone-sparing properties of BDP and budesonide assessed in this way in this group of patients was statistically significant in favour of BDP. The mean minimum prednisolone doses at the end of the treatment periods were 3.46 mg for BDP and 4.3 mg for budesonide. Since inhaled steroids were not withdrawn the absolute prednisolone-sparing properties of the two drugs were not assessed, and thus a pharmacological potency ratio cannot be derived from the results. It is concluded that BDP is marginally more potent than budesonide in its prednisolone-sparing properties.
Clinical efficacy of budesonide Turbuhaler compared with that of beclomethasone dipropionate pMDI with volumatic spacer. A 2-year randomized study in 102 asthma patients.
A total of 102 patients had their asthma treatment with beclomethasone dipropionate (BDP) optimized in order to achieve the best possible control of symptoms. Thereafter, the BDP doses were gradually reduced over a 2-year period (1988-90) to the lowest possible without deterioration of their asthmatic condition. In the beginning of 1990, treatment was changed in 76 patients (group A) to the nearest possible dose of budesonide delivered via Turbuhaler. Twenty-six randomly selected patients (25% of the study population; group B) continued treatment with BDP. In both groups, dose reductions were tried during 1990-2 every third month as long as the patients remained symptom-free and without significant decreases in FEV1 or PEF. In group A, the maintenance dose could be reduced from 1003.9 +/- 325.4 micrograms BDP (mean +/- SD) to 602.9 +/- 454.4 micrograms budesonide Turbuhaler (P < 0.001). In group B, no significant dose reduction was possible; the mean dose was +/- SD 1067.3 +/- 36.6 micrograms in 1990, and 1019.2 +/- 324.7 micrograms in 1992. The results indicate that, in efficacy, 0.6 mg budesonide Turbuhaler corresponds to approximately 1.0 mg BDP with volumatic spacer. This difference is probably due to an improved pulmonary delivery of budesonide with Turbuhaler.
Comparison of budesonide and beclomethasone dipropionate for treatment of asthma.
Beclomethasone dipropionate (BDP) and budesonide (BUD) were each given in a dose of 200 micrograms twice daily by metered dose inhaler to 10 asthmatic children already dependent on treatment with steroids. In a double blind randomised crossover study each course lasted one month. No clinically important differences were found between the two treatments when symptom scores, symptom free days, additional use of salbutamol, and results of lung function tests were considered. Metyrapone mildly reduced the plasma concentration of 11-deoxycortisol in two patients during treatment with budesonide, and in four during treatment with beclomethasone. It is concluded that although they are usually safe, both drugs may cause mild adrenal suppression when given in a dose of 200 micrograms twice daily.
Once daily inhalation of budesonide in the treatment of chronic asthma: a clinical comparison.
In a short-term, open cross-over clinical efficacy study, inhalation of budesonide 800 micrograms once daily was compared to inhalation of budesonide 400 micrograms twice daily and beclomethasone dipropionate 200 micrograms four times daily in 20 patients with stable steroid-dependent chronic asthma. Budesonide was inhaled through a spacer tube. The drugs were given in 3-week periods. Clinical symptoms, consumption of beta 2-agonists and peak flow were measured. In all but one patient, the reduced frequency of budesonide inhalations to only once daily has not given significantly different results compared with more frequent inhalations.
High-dose inhaled steroids in the management of asthma. A comparison of the effects of budesonide and beclomethasone dipropionate on pulmonary function, symptoms, bronchial responsiveness and the adrenal function.
The efficacy of budesonide (800 micrograms b.d.) and beclomethasone dipropionate (750 micrograms b.d.) in controlling the symptoms of asthma, pulmonary function, bronchial responsiveness to histamine, and adrenal function, was assessed in a double-blind, double-dummy cross-over study of 36 adult chronic asthmatic patients. The patients, the majority of whom were assessed to be affected to a severe degree, were insufficiently controlled in their current regimen of inhaled steroids and/or inhaled and oral bronchodilators. A 2 weeks baseline period preceded 6 weeks of treatment with each of the study drugs. Both treatment groups showed improvements from baseline in clinical assessment of lung function carried out after the first 6 weeks of treatment. No significant differences were seen throughout the entire 12 weeks study, when comparing the effects of the treatments on FEV1, FVC, PEF or the histamine PC20. Asthma severity, symptom score and inhaled bronchodilator use showed the same results after both treatments. It is concluded that inhalations of budesonide and beclomethasone dipropionate in high doses are equally potent in the treatment of severe asthma. There is no significant influence on the adrenal function and no significant side effects during a period equal to that of the present study.
[High dose inhaled steroids in the treatment of bronchial asthma. A comparison of the effects of budesonide and beclomethasone dipropionate on pulmonary function, symptoms, bronchial reactivity and adrenocortical function].
The effects of high-dose inhaled budesonide (800 micrograms twice daily) and those of inhaled beclomethasone dipropionate (750 micrograms twice daily) were compared with respect to lung function, symptoms, bronchial reactivity and adrenocortical function in a doubleblind, double-dummy cross-over study. The subjects were 40 adult patients suffering from either allergic or non-allergic asthma. The asthma was categorized as moderate to severe, and the asthma was insufficiently controlled on inhalational steroids given in doses of 300 to 500 micrograms daily. After a two week "run-in" period the patients were randomized to six weeks treatment with either budesonide or beclomethasone dipropionate, followed by six weeks treatment with the opposite drug. Both inhaled budesonide and inhaled beclomethasone dipropionate were able to improve objective measures of lung function and bronchial sensitivity to histamine. Neither drug affected adrenocortical function, and no serious side-effects were noted during the trial. It is concluded that budesonide and beclomethasone dipropionate are safe and effective drugs for the treatment of asthma in adults. The substances are equally effective taken microgram for microgram.
Budesonide inhaled via Turbuhaler: a more effective treatment for asthma than beclomethasone dipropionate via Rotahaler.
BACKGROUND: Chlorofluorocarbon-propelled metered dose inhalers are facing a worldwide ban. Dry powder inhalers have been developed for the agents used in treatment of asthma.
OBJECTIVE: Our objective was to compare the effects of two inhaled glucocorticosteroids in dry power inhalers: budesonide (delivered via Turbuhaler) and beclomethasone dipropionate (delivered via Rotahaler).
METHODS: A randomized, crossover study with two steroid-treatment periods of 8 weeks. At the end of the study, the treatment with the inhaled steroid was stopped for 4 weeks. Sixteen adult patients with moderately severe asthma participated. Before the study all patients were treated with an inhaled steroid in a median dose of 0.60 mg/day (range 0.15-0.80); during the study they received 0.20 mg twice daily. Peak expiratory flow rate was measured twice daily at home throughout the study, lung function was assessed every fourth week and airway responsiveness was measured before and after each period. Preference concerning efficacy and inhaler type was assessed at the end of the study.
RESULTS: Twelve patients completed the study. Lung function, airway responsiveness, and symptoms deteriorated significantly in the steroid-free washout period; this period had to be shortened in 5/12 patients. Mean morning peak expiratory flow was significantly higher during budesonide treatment than during beclomethasone dipropionate treatment, the difference being 17 L/min (95% C.I.: 2-32 L/min, P = .026). Airway responsiveness improved 1.1 doubling concentrations after budesonide treatment, but decreased 0.3 doubling concentrations after beclomethasone dipropionate treatment. The difference between the values after budesonide and beclomethasone dipropionate treatment was 1.4 doubling concentrations (95% C.I.: 0.4-2.4 doubling concentrations, P = .033). Forced expiratory flow in one second improved slightly more during budesonide than during beclomethasone treatment. The difference was 4.3% predicted (95% C.I.: -0.7-9.3%). Most patients reported budesonide Turbuhaler to be more effective (10 versus 0) and easier to use (11 versus 1) than beclomethasone dipropionate Rotahaler.
CONCLUSIONS: As a consequence of the difference in local potency of the steroids and the fact that Turbuhaler deposits more drug particles in the lung than Rotahaler, budesonide inhaled via Turbuhaler appeared to be a more effective steroid formulation than beclomethasone dipropionate inhaled via Rotahaler.
Twice daily inhalation of a new corticosteroid, budesonide, in the treatment of chronic asthma.
The efficacy and side-effects of a new corticosteroid, budesonide, was assessed by comparison with beclomethasone dipropionate in double-blind, cross-over study of 30 patients with chronic asthma. The treatment regimens were budesonide 200 micrograms twice daily by conventional pressurized aerosol with a tube spacer attached and beclomethasone 100 micrograms four times daily via a conventional inhaler. Each treatment was given for four weeks. Results were analyzed using Student's t-test for paired comparisons. No significant differences were found for morning and evening peak flow rates, symptom scores, bronchodilator inhaler usage or forced vital capacity. Forced expiratory volume in one second after 4 weeks on each treatment was significantly higher following budesonide therapy (p less than 0.05), but the absolute changes were small and unlikely to be of clinical relevance. There were no major side-effects during either treatment period, but compared with pre-treatment levels serum creatinine and lactic dehydrogenase levels rose significantly during treatment with budesonide (p less than 0.01 and p less than 0.05 respectively). None of these results reflected clinically important biochemical or haematological changes. There was a significant reduction in neutrophil counts following treatment with beclomethasone (p less than 0.05). In the short term treatment of chronic asthma, budesonide administered twice daily is as effective as four times daily beclomethasone. A twice daily dosage regimen should improve patient compliance with therapy.
Options:
A: BDP was found to be significantly more effective than BUD in improving FEV1, morning PEF, evening PEF, asthma symptoms, and reducing rescue beta2 agonist use.
B: BUD was found to be significantly more effective than BDP in improving FEV1, morning PEF, evening PEF, asthma symptoms, and reducing rescue beta2 agonist use.
C: There was no significant difference between BDP and BUD in improving FEV1, morning PEF, evening PEF, asthma symptoms, and reducing rescue beta2 agonist use.
D: BDP was found to be significantly safer than BUD in terms of side effects and adverse reactions. | C |
203 | 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 inhaled corticosteroids on bone metabolism, bone mineral density, and the development of fractures in adults with asthma or mild chronic obstructive pulmonary disease (COPD)? Please answer this question based on the information provided below:
Long-term treatment with inhaled budesonide in persons with mild chronic obstructive pulmonary disease who continue smoking. European Respiratory Society Study on Chronic Obstructive Pulmonary Disease.
BACKGROUND: Although patients with chronic obstructive pulmonary disease (COPD) should stop smoking, some do not. In a double-blind, placebo-controlled study, we evaluated the effect of the inhaled glucocorticoid budesonide in patients with mild COPD who continued smoking. After a six-month run-in period, we randomly assigned 1277 subjects (mean age, 52 years; mean forced expiratory volume in one second [FEV1], 77 percent of the predicted value; 73 percent men) to twice-daily treatment with 400 microg of budesonide or placebo, inhaled from a dry-powder inhaler, for three years.
RESULTS: Of the 1277 subjects, 912 (71 percent) completed the study. Among these subjects, the median decline in the FEV1 after the use of a bronchodilator over the three-year period was 140 ml in the budesonide group and 180 ml in the placebo group (P=0.05), or 4.3 percent and 5.3 percent of the predicted value, respectively. During the first six months of the study, the FEV1 improved at the rate of 17 ml per year in the budesonide group, as compared with a decline of 81 ml per year in the placebo group (P<0.001). From nine months to the end of treatment, the FEV1 declined at similar rates in the two groups (P=0.39). Ten percent of the subjects in the budesonide group and 4 percent of those in the placebo group had skin bruising (P<0.001). Newly diagnosed hypertension, bone fractures, postcapsular cataracts, myopathy, and diabetes occurred in less than 5 percent of the subjects, and the diagnoses were equally distributed between the groups.
CONCLUSIONS: In patients with mild COPD who continue smoking, the use of inhaled budesonide is associated with a small one-time improvement in lung function but does not appreciably affect the long-term progressive decline.
Differential effects of inhaled budesonide and oral prednisolone on serum osteocalcin.
Inhaled glucocorticosteroids have been developed for the treatment of asthma in an attempt to minimize the suppression of endogenous adrenal function that complicates oral or injected steroid usage, but it is unclear whether this strategy leads to reduced systemic complications in other areas, such as the skeleton. In this study we evaluated serum osteocalcin levels as a marker of skeletal metabolism in healthy volunteers treated with oral and inhaled steroids alone and in response to an oral calcitriol stimulation test. Forty subjects, aged 33 +/- 9 (mean +/- SD) yr were randomized to receive either high or low dose oral prednisolone (40 vs. 10 mg/day) or inhaled budesonide (3.2 vs. 0.8 mg/day). Each dose of budesonide is known to have a greater antiasthmatic potency than the dose of prednisolone with which it was compared. In addition 10 control subjects received placebos containing no active steroid drugs. During the second week of treatment, half of the subjects in each of the 4 steroid-treated groups and all subjects in the control group received oral calcitriol (2.0 micrograms/day). There was a marked dose-dependent reduction in serum cortisol levels, but this reduction was significantly less pronounced during budesonide treatment, such that low dose budesonide was without effect. During the first week of steroid therapy there were significant dose-dependent reductions in serum osteocalcin (P = 0.003), but this reduction was not significantly different between budesonide and prednisolone treatments. In response to calcitriol, serum osteocalcin increased by 35% in the control group (P = 0.06). Osteocalcin levels increased by 56% and 50% in the low dose budesonide and prednisolone groups and by 106% in the high dose budesonide group, but did not change in the high dose prednisolone group. The osteocalcin response to calcitriol was significantly higher in the budesonide groups (P = 0.03, by analysis of variance). High dose prednisolone caused increases in serum 1,25-dihydroxyvitamin D3 (P less than 0.02), urinary calcium excretion (P = 0.07), and urinary hydroxyproline (P less than 0.01). None of these changes was seen during budesonide therapy. There are as yet no data for these variables after long term use of inhaled budesonide in asthmatic patients, but our acute studies suggest that this potent topical glucocorticoid may have considerably less impact on the skeleton than oral prednisolone, even if used at doses high enough to suppress endogenous adrenal function.
Effects of short-term and long-term treatment with inhaled corticosteroids on bone metabolism in patients with airways obstruction. Dutch CNSLD Study Group.
BACKGROUND: Recent reports have suggested short-term changes in serum parameters of bone metabolism with inhaled corticosteroids. The relevance of these findings to the balance between bone formation and resorption during years of corticosteroid treatment remains uncertain.
METHODS: Two novel markers of bone turnover were first compared with conventional markers in a pilot study and subsequently measured in a long-term double blind study of inhaled corticosteroids. In study I 15 patients were newly started on at least 800 micrograms inhaled corticosteroids daily. At entry and after four weeks serum levels of alkaline phosphatase, osteocalcin, and PICP (procollagen type I carboxy terminal propeptide; a procollagen splice product) were measured as markers of bone formation, as well as the urinary hydroxyproline/creatinine ratio and serum levels of ICTP (type I collagen carboxy terminal telopeptide; a collagen degradation product) as markers of bone resorption. In study II 70 patients with airways obstruction received 800 micrograms beclomethasone daily in addition to terbutaline and 85 received bronchodilators only in a double blind fashion. Serum levels of PICP and ICTP were measured before and after 2.5 years of treatment.
RESULTS: In study I a decrease in osteocalcin levels was accompanied by an increase in levels of PICP and a small and non-significant rise in alkaline phosphatase. There were no changes in hydroxyproline or ICTP. In study II no differences were found in serum levels of PICP between the treatment groups; an increase in serum ICTP was found in the group treated without inhaled corticosteroids compared with the group treated with inhaled corticosteroids.
CONCLUSIONS: No detrimental long-term effect of inhaled corticosteroids was found with three conventional and two novel parameters of bone metabolism. The results indicate that long-term changes in bone turnover during treatment with inhaled corticosteroids should not be deduced from short-term studies with single serum parameters of bone metabolism, but well designed long-term studies of, for example, bone densitometry should be awaited before quoting detrimental effects of inhaled corticosteroids on bone metabolism.
Effects of short-term inhaled budesonide and beclomethasone dipropionate on serum osteocalcin in premenopausal women.
Serum osteocalcin, a marker of bone osteoblast function, has been shown to be sensitive to even low doses of oral glucocorticoids. The effect of 1 wk of inhaled glucocorticoid therapy with budesonide (200 micrograms/puff), beclomethasone dipropionate (250 micrograms/puff), and placebo at two puffs b.i.d. and four puffs b.i.d. on 0900 serum osteocalcin were compared in a double-blind randomized fashion. A two-way repeated-measures analysis of variance showed no main effect of drug or dosage but a significant drug-dose interaction (p = 0.023). Post hoc investigation of this interaction demonstrated that the serum osteocalcin level while taking four puffs b.i.d. (2,000 micrograms) of beclomethasone dipropionate was significantly lower than that of placebo or budesonide at four puffs b.i.d. (1,600 micrograms). These results suggest that at lower doses no acute measurable effect of inhaled glucocorticoids on serum osteocalcin can be appreciated but that at higher doses inhaled beclomethasone dipropionate has a depressant effect on bone osteoblast function.
Fluticasone propionate powder and lack of clinically significant effects on hypothalamic-pituitary-adrenal axis and bone mineral density over 2 years in adults with mild asthma.
BACKGROUND: Although inhaled corticosteroids are widely used for the treatment of inflammation in asthma, prospective, long-term, placebo-controlled trials characterizing their systemic safety with chronic use are lacking.
OBJECTIVE: This study was designed to prospectively evaluate the long-term safety of inhaled fluticasone propionate therapy.
METHODS: Fluticasone propionate powder, 500 microgram, or placebo was administered twice daily by means of the Diskhaler for 104 weeks to 64 adults with mild persistent asthma in a randomized, double-blind, parallel-group study. Primary safety variables were measured at baseline and every 6 months thereafter. Although evaluation of efficacy was not an objective of this study, pulmonary function testing was performed at monthly intervals.
RESULTS: Two years of treatment with fluticasone propionate had no significant effects on the skeletal system. No clinically significant changes were observed in ophthalmic parameters (glaucoma and posterior subcapsular cataracts). Mean change from baseline in lumbar spine (L1 to L4 ) bone density at week 104 was not significantly different between fluticasone propionate (-0.006 +/- 0.008 g/cm2) and placebo (-0.007 +/- 0.010 g/cm2). Markers of bone formation (serum osteocalcin) and resorption (urinary N-telopeptide) did not differ significantly between treatment groups. The effects of fluticasone propionate treatment on the hypothalamic-pituitary-adrenal axis were minimal, with no alterations in morning plasma cortisol concentrations and minor but statistically significant decreases in poststimulation mean peak plasma cortisol concentrations (P =.021) and 8-hour plasma cortisol area under the curve values (P =.020) at week 104. Drug-related adverse events were primarily topical effects of inhaled corticosteroids. Pulmonary function improved significantly during 2 years of fluticasone propionate treatment.
CONCLUSION: Fluticasone propionate powder, 500 microgram twice daily for up to 2 years, was efficacious and well tolerated, with no clinically relevant effects on the hypothalamic-pituitary-adrenal axis, bone density, or ophthalmic parameters in adults with mild asthma.
Bone mineral density in subjects with mild asthma randomised to treatment with inhaled corticosteroids or non-corticosteroid treatment for two years.
BACKGROUND: Inhaled corticosteroids are clearly beneficial for patients with asthma of moderate severity, but the risks and benefits of using them in patients with milder asthma are less clear. We have compared the change in bone mineral density over 2 years in adults with mild asthma randomised to receive an inhaled corticosteroid or non-corticosteroid treatment.
METHODS: Subjects with mild asthma (mean forced expiratory volume in one second (FEV(1)) 86% predicted, mean age 35 years, taking beta agonists only) were randomised to receive inhaled budesonide, inhaled beclomethasone dipropionate, or non-corticosteroid treatment for 2 years in a prospective randomised open study in 19 centres in France, New Zealand, Spain, and the UK. The corticosteroid dose was adjusted according to a written self-management plan. The main outcome measure-change in bone mineral density after 6, 12, and 24 months-was measured "blind". Secondary outcomes included lung function, the relation between change in bone density and inhaled steroid dose and change in biochemical markers of bone metabolism.
RESULTS: Of 374 subjects randomised, 239 (64%) completed the study and were included in the analysis. The median daily doses of inhaled budesonide (n=87) and beclomethasone (n=74) were 389 microg and 499 microg, respectively. Subjects treated with an inhaled corticosteroid had better asthma control than those in the reference group (n=78). Change in bone mineral density did not differ between the three groups over the 2 years, nor did it correlate with changes in markers of bone metabolism. The mean change in bone mineral density over 2 years in the budesonide, beclomethasone dipropionate, and reference groups was 0.1%, -0.4%, and 0.4% for the lumbar spine and -0.9%, -0.9%, and -0.4% for neck of the femur. Mean daily dose of inhaled steroid was related to reduction in bone mineral density at the lumbar spine but not at the femoral neck.
CONCLUSION: In subjects with mild asthma an inhaled corticosteroid provided better asthma control than alternative non-corticosteroid treatment with no difference in change in bone mineral density over 2 years. The relation between dose of inhaled corticosteroid and change in bone density at the lumbar spine may be due to a direct effect of inhaled corticosteroids on bone. Since inhaled steroid dose is also related inversely to lung function, an effect of asthma severity on bone density was also possible.
Effects of dose and dosing schedule of inhaled budesonide on bone turnover.
To assess whether the use of larger than usual doses of inhaled steroid to treat severe asthma may adversely affect bone turnover and whether such an effect may be mitigated by altering the dose schedule, we investigated the effects of budesonide (BUD) on serum osteocalcin and the urinary output of hydroxyproline and calcium. Healthy adults were administered 1.2 or 2.4 mg of BUD per day (N = 40) or placebo (N = 8) in a crossover, double-blind comparison of morning versus diurnal dosing schedules for 1 month each. Both BUD doses reduced the 24-hour urinary free-cortisol output (p less than 0.001) and serum osteocalcin (p less than 0.001). The larger dose reduced the morning serum cortisol levels (p = 0.002). Neither dose increased the 8 AM urinary calcium or hydroxyproline output. Osteocalcin and plasma cortisol levels were higher on morning than on diurnal dosing (p = 0.01). The 24-hour urinary free-cortisol output was the same with either schedule (p = 0.96). Additional study is required to assess the clinical importance of the inhibitory effect of BUD on bone formation, as evidenced by the reduction in osteocalcin levels. Of concern is the possibility of serious bone complications resulting from the long-term use of inhaled steroid, particularly in growing children or patients in whom other risk factors for osteoporosis are present. The clinical advantage, if any, of morning dosing remains questionable.
Options:
A: Inhaled corticosteroids at conventional doses increase the risk of bone mineral density loss and fractures.
B: Inhaled corticosteroids at conventional doses have no significant effect on bone mineral density or the development of fractures.
C: Inhaled corticosteroids at conventional doses significantly increase biochemical markers of bone turnover.
D: Inhaled corticosteroids at experimental doses have no effect on biochemical markers of bone turnover. | B |
204 | 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 sensory stimulation programmes for patients in coma or vegetative state? Please answer this question based on the information provided below:
Biochemical and physiological parameters of recovery in acute severe head injury: responses to multisensory stimulation.
We investigated the efficacy of applying a programme of multisensory stimulation to patients with severe diffuse traumatic brain injury, during their admission to a tertiary neurosurgical intensive care unit. We attempted to determine the nature and extent of any physiological or biochemical changes occurring as a result of the multisensory stimulation in the initial period of their comatose state. The findings were inconclusive with no significant treatment effect demonstrated.
Response of head-injured patients to sensory stimulation.
Coma arousal procedure: a therapeutic intervention in the treatment of head injury.
This study reports on the efficacy of a 'coma arousal procedure'. This procedure involved a programme of vigorous sensory stimulation administered to comatose patients by relatives using Comakits. An experimental group of 12 severely head-injured patients received the coma arousal procedure while a matched control group did not. Total duration of coma and weekly Glasgow Coma Scale Scores were recorded for the two groups. Results indicate that the total duration of coma was significantly shorter and that coma lightened more rapidly for the experimental group.
Options:
A: Sensory stimulation programmes are highly effective in improving outcomes for patients in coma or vegetative state.
B: There is no reliable evidence to support or rule out the effectiveness of sensory stimulation programmes for patients in coma or vegetative state.
C: Sensory stimulation programmes are ineffective and should not be used for patients in coma or vegetative state.
D: Sensory stimulation programmes are harmful and worsen the condition of patients in coma or vegetative state. | B |
205 | 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 pedestrian safety education programs in preventing pedestrian-motor vehicle collisions? Please answer this question based on the information provided below:
An evaluation of a safety education program for kindergarten and elementary school children.
OBJECTIVE: To determine the effectiveness of a safety education program, Safety City, that is designed to teach kindergarten and first grade children how to cross the street, call 911 in an emergency, and avoid strangers.
PARTICIPANTS/SETTING: Kindergarten students at 10 urban elementary schools.
DESIGN: Each school was randomized to either the intervention or control group. An evaluation tool was administered to all participants as a pretest. The Safety City program was then presented to the intervention schools. Afterward, the same evaluation tool was used as a post-test. The posttest was administered to the intervention group 6 months after the Safety City program was presented. The control group took the posttest 6 months after the pretest.
MAIN OUTCOME MEASURE: Change in individual test scores.
RESULTS: One hundred eighty-one children completed the pretest and posttest evaluations. There was no statistical difference in the change between pretest and posttest scores of children who participated in the Safety City program and those in the control group (crossing the street, P = .29; calling 911, P = .41; stranger avoidance, P = .57).
CONCLUSIONS: Exposure to the Safety City program did not achieve the desired changes in safety knowledge among participants. This is most likely owing to the fact that Safety City attempts to convey a large amount of relatively complex information to young children in a brief period. We conclude that programs such as Safety City are not sufficient to teach children these behaviors. This report also emphasizes the importance of building an evaluation component into educational programs.
A controlled group study of pedestrian-skill training for the mentally retarded.
An evaluation of the Beltman traffic safety program for children.
An evaluation of the Beltman traffic safety program for children.
Evaluation of the efficacy of simulation games in traffic safety education of kindergarten children.
Using a simulation game designed to teach children to obey certain traffic safety rules, an experimental study was conducted with 136 five-year-old children in four Quebec schools. Within each classroom, subjects were randomly divided into four groups: three intervention groups and one control group. Each of the experimental groups was subjected to a different intervention with outcome measured using three instruments related to attitudes, behavior, and transfer of learning of pedestrian traffic safety. Results suggest that simulation games including role-playing/group dynamics and modeling/training can change attitudes and modify behavior in the area of pedestrian traffic safety in children of this age.
The effectiveness of parents in promoting the development of road crossing skills in young children.
BACKGROUND: Young children show poor judgment when asked to select a safe place to cross the road, frequently considering dangerous sites to be safe. Correspondingly, child pedestrian accidents are over-represented at such locations. Increasing the child's ability to recognise such dangers is a central challenge for road safety education.
AIMS: Practical training methods have proved effective in improving such judgments but are labour-intensive, time-consuming and therefore difficult to implement on a realistic scale. The study examined the possibility that volunteers from the local community might be capable of using such methods to promote children's pedestrian competence.
SAMPLE: Sixty children from the Primary 1 (Reception) classes of three Glasgow schools took part. Volunteers were ordinary parents from the same areas. None had 'formal' experience of working with children other than through being parents.
METHOD: Volunteers received experience of training children at courses organised in each school. Children learned in small groups, receiving two sessions of roadside training followed by four on a table-top model. Pre- and post-tests allowed the effectiveness of training to be assessed.
RESULTS: Significant improvements relative to controls were found in all children following training. Improvements proved robust and no deterioration was observed two months after the programme ended. Comparison with a previous study in which training was undertaken by highly qualified staff showed that the volunteers were as effective as 'expert' trainers.
CONCLUSIONS: Parent volunteers can significantly increase the pedestrian competence of children as young as five years. They constitute a most valuable 'resource' in road safety education. The opportunities afforded by involving the local community in educational interventions should be further explored.
Options:
A: Pedestrian safety education programs significantly reduce the risk of pedestrian-motor vehicle collisions and injuries.
B: Pedestrian safety education programs improve children's knowledge and change observed road crossing behavior, but their impact on reducing pedestrian-motor vehicle collisions and injuries is unknown.
C: Pedestrian safety education programs have no effect on children's knowledge, behavior, or the risk of pedestrian-motor vehicle collisions and injuries.
D: Pedestrian safety education programs are only effective in developing countries and have no impact in developed countries. | B |
206 | 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 routine phenobarbitone administration in people with cerebral malaria according to the study? Please answer this question based on the information provided below:
Effect of phenobarbital on seizure frequency and mortality in childhood cerebral malaria: a randomised, controlled intervention study.
BACKGROUND: Seizures commonly complicate cerebral malaria and are associated with an increased risk of death and neurological sequelae. We undertook a randomised study to assess the efficacy of intramuscular phenobarbital in preventing seizures in childhood cerebral malaria.
METHODS: Children with cerebral malaria admitted to one hospital in Kilifi, Kenya, were randomly assigned a single intramuscular dose of phenobarbital (20 mg/kg) or identical placebo. Clinical tolerance was assessed at the start of the trial, with particular reference to respiratory depression and hypotension. Seizures were timed and recorded, and treated in a standard way. Plasma phenobarbital concentrations were measured. Analyses were by intention to treat.
FINDINGS: 440 children with cerebral malaria were admitted to the hospital; 100 were not recruited to the study. Of the remaining 340, 170 received phenobarbital and 170 placebo. The drug was adequately absorbed and well tolerated. Seizure frequency was significantly lower in the phenobarbital group than in the placebo group (18 [11%] vs 46 [27%] children had three or more seizures of any duration; odds ratio 0.32 [95% CI 0.18-0.58]) but mortality was doubled (30 [18%] vs 14 [8%] deaths; 2.39 [1.28-4.64]). The frequency of respiratory arrest was higher in the phenobarbital group than in the placebo group, and mortality was greatly increased in children who received phenobarbital plus three or more doses of diazepam (odds ratio 31.7 [1.2-814]).
INTERPRETATION: In children with cerebral malaria, phenobarbital 20 mg/kg provides highly effective seizure prophylaxis but is associated with an unacceptable increase in mortality. Use of this dose cannot, therefore, be recommended.
Seizures in cerebral malaria.
Single dose phenobarbitone prevents convulsions in cerebral malaria.
48 patients over 6 years of age with strictly defined cerebral malaria were randomised to receive either a single intramuscular injection of phenobarbitone (3.5 mg/kg) or placebo in a double-blind, placebo-controlled study. Phenobarbitone significantly reduced the incidence of subsequent convulsions from 54% to 12.5%, without adverse effects. A single intramuscular injection of phenobarbitone is a simple, cheap, and effective method for prevention of convulsions in cerebral malaria.
Options:
A: It was associated with fewer convulsions and fewer deaths.
B: It was associated with fewer convulsions but more deaths.
C: It was associated with more convulsions and more deaths.
D: It had no significant effect on convulsions or deaths. | B |
207 | 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 antidepressant medication for treating depression in people with schizophrenia? Please answer this question based on the information provided below:
Implications of the efficacy of thiothixene and a chlorpromazine-imipramine combination for depression in schizophrenia.
The ineffectiveness of antidepressants, and the effectiveness of neuroleptics alone, in the treatment of depressed schizophrenic patients is evidence that a pharmacologically definable depression cannot be demonstrated in schizophrenia. The author reports findings from a double-blind 1-month study of 52 anergic and depressed schizophrenic patients given thiothixene-placebo or chlorpromazine-imipramine. These findings support DSM-III, which does not diagnose intercurrent, secondary depression in the presence of schizophrenia. Consistent with most of the clinical literature, this study also supports the use of a single neuroleptic rather than neuroleptic-antidepressant combinations to treat depressive symptoms secondary to schizophrenia.
Pharmacotherapy of impaired affect in recovering schizophrenic patients.
BACKGROUND: Prominent and persistent anxiety, depression, and/or negative features characterize a substantial minority of recovered or residually psychotic schizophrenic outpatients and contribute to poor outcome. Because extrapyramidal side effects of typical neuroleptic medications often resemble such features, we first systematically studied the contribution of extrapyramidal side effects to these problems and their treatment. For patients who remained distressed, controlled trials of supplemental thymoleptics were undertaken.
METHODS: In trial 1, 92 distressed (depressed and/or anxious) patients and 36 patients in a defect state (patients with negative symptoms) participated in a double-blind, intramuscular challenge that compared centrally acting benztropine mesylate with peripherally acting glycopyrrolate. In trial 2, 57 distressed patients and 22 patients in a defect state were randomly assigned to a double-blind, neuroleptic medication dose-reduction group. In trial 3, 57 chronically distressed patients who were maintained on a low dose of fluphenazine decanoate were randomly assigned to a supplemental desipramine hydrochloride, lithium carbonate, or placebo group under double-blind conditions for 12 weeks.
RESULTS: For patients who were already maintained on antiparkinsonian medication, impaired affect was not resolved by additional benztropine. Only distressed patients with a family history of severe mental disorder (often affective) showed improvement with neuroleptic medication dose reduction. Patients in the defect-state group reported less dysphoria on a reduced neuroleptic medication dose, but negative symptoms persisted. Desipramine improved diverse aspects of mood and residual psychoticism, possibly as a prophylaxis against minor affective exacerbations. Depression improved in women only. Lithium positively affected multiple indexes of anxiety and anxious depression.
CONCLUSION: Most often, persistent affective impairments are neither resistant extrapyramidal side effects nor characterological traits. Thymoleptics improve the nonphasic, chronic types of anxiety and depression in contrast to the acute, episodic forms, for which little support can be found in the literature.
Antidepressants in 'depressed' schizophrenic inpatients. A controlled trial.
Fifty-eight actively psychotic inpatients who initially met criteria for long-standing schizophrenia and subsequently met Research Diagnostic Criteria for a current episode of schizoaffective disorder (mainly schizophrenic) with a depressive syndrome, and who scored at least 30 (mean = 55, SEM = 1.6) on the Brief Psychiatric Rating Scale and 17 (mean = 23, SEM = 0.7) on the Hamilton Rating Scale for Depression, were treated for 5 weeks with haloperidol hydrochloride and benztropine. Haloperidol and benztropine treatment was continued, while those patients who consistently scored greater than 17 on the Hamilton Rating Scale for Depression were randomly assigned to the following double-blind treatment groups for 4 weeks: adjunctive amitriptyline hydrochloride, desipramine hydrochloride, or placebo. Adjunctive desipramine or amitriptyline showed no significant therapeutic advantage, when compared with haloperidol and placebo, on the Brief Psychiatric Rating Scale or the Hamilton Rating Scale for Depression. After 4 weeks of combine therapy, patients receiving adjunctive amitriptyline or desipramine, as compared with those receiving adjunctive placebo, tended to score higher on the Brief Psychiatric Rating Scale hallucinatory behavior item and on the thinking disturbance factor than patients receiving placebo. These results suggest that adjunctive antidepressants are not indicated for the treatment of depressive symptoms in actively psychotic schizophrenic inpatients. Adjunctive antidepressants may retard the rate of resolution of psychosis in this population.
Viloxazine and the depressed schizophrenic--methodological issues.
A pilot study of a small group of schizophrenic patients manifesting symptoms of a depressive nature was treated in a double-blind study in which viloxazine or a placebo was administered in combination with either chlorpromazine or haloperidol. There appeared to be no difference between the viloxazine-treated group and the placebo-treated group, although the study raised some question as to the adequacies of the dosage utilized since there was an absence of any apparent side effects. In view of these issues concerning the clinical merit of the combination, this obviously requires further investigation.
A double-blind, placebo-controlled trial of sertraline for depressive symptoms in patients with stable, chronic schizophrenia.
There have been no studies specifically examining the efficacy of selective serotonin reuptake inhibitor antidepressants for the symptoms of depression in schizophrenia. This study aimed to determine the efficacy and safety of sertraline as a treatment for depressive symptoms in patients with stable, chronic schizophrenia. The Beck Depression Inventory (BDI) was used as the principal outcome measure and other measures of depressive symptoms as secondary outcome measures. Twenty-six patients were entered into a double-blind, placebo-controlled, 8-week trial of sertraline and were included in the intent-to-treat (ITT) analysis (13 in each group). Eight patients in the sertraline group and 12 in the placebo group completed at least four weeks in the study and were considered to have had adequate treatment. On the ITT analysis, the mean score on the BDI fell 14.5% for the sertraline group and 5.6% for the placebo group (p > 0.05); the mean score on the Hamilton Depression Rating Scale (HDRS) fell 16.99% for the sertraline group and 8.3% for the placebo group (p > 0.05). When the analysis was repeated for those who had received adequate treatment, the mean BDI score fell by 28% for the sertraline group and 6% for the placebo group (p = 0.1); the mean HDRS score fell 31% for the sertraline group and 8.6% for the placebo group (p = 0.02). On the Clinical Global Impression-Improvement Scale, 10 of the 13 patients on sertraline improved against four of the 13 in the placebo group (p = 0.05). Sertraline-treated patients showed a significant improvement on the anxiety/ depression subscale of the BPRS on ITT analysis (F = 10.1, p = 0.004). There was no significant effect on negative or positive symptoms. Sertraline was well tolerated. The results suggest that sertraline is useful as a treatment for depressive symptoms in schizophrenia.
Treatment of secondary depression in schizophrenia. A double-blind, placebo-controlled trial of amitriptyline added to perphenazine.
The combination of antidepressants and neuroleptics has been widely recommended and commonly used clinically for the schizophrenic patient who becomes depressed. However, the value of the combination for these patients has not been clearly demonstrated. This report presents results of a double-blind, randomized, placebo-controlled clinical trial designed to evaluate the combination of perphenazine and amitriptyline hydrochloride with that of perphenazine alone in the treatment of 35 ambulatory chronic schizophrenic patients in whom depressive symptoms developed. Results showed that the addition of amitriptyline to perphenazine, when compared with perphenazine alone, was more effective in reducing symptoms of depression after four months of treatment, but less effective in reducing thought disorder. The study concludes that the value of adding an antidepressant to the usual neuroleptic in the treatment of secondary depression in schizophrenia should be reviewed.
Adjunctive imipramine in the treatment of postpsychotic depression. A controlled trial.
The efficacy of adjunctive imipramine hydrochloride treatment for syndromally defined postpsychotic depression was assessed in a six-week, double-blind, placebo-controlled study. All patients had been diagnosed as having schizophrenia or schizoaffective disorder, all were receiving stable doses of fluphenazine decanoate, and all had received benztropine mesylate in an attempt to rule out neuroleptic-induced akinesia. Patients randomized to imipramine therapy fared significantly better in terms of their global improvement and in terms of individual symptoms that are components of the depression syndrome. There were no significant differences in outcome psychosis ratings or side effects. This study indicates the existence of an identifiable syndrome of secondary depression in this patient group that is likely to respond favorably to treatment with adjunctive imipramine.
Options:
A: Antidepressants were significantly better than placebo in reducing depressive symptoms, with no evidence of worsening psychotic symptoms.
B: Antidepressants had no significant effect on depressive symptoms and led to a deterioration of psychotic symptoms.
C: Antidepressants were significantly better than placebo in reducing depressive symptoms, but they caused a high rate of adverse effects.
D: Antidepressants had no significant effect on depressive symptoms and had a high dropout rate among participants. | A |
208 | 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 main conclusion regarding the effectiveness of eating disorder prevention programs for children and adolescents? Please answer this question based on the information provided below:
Prevention of disturbed eating behaviour: a prospective intervention study in 14- to 19-year-old Swiss students.
Subsequent to an epidemiological study on eating behaviour in adolescents, a prospective study was carried out to examine the effect of health promotion lessons on disturbed eating behaviour. From the original sample (t1, n = 1944), a subgroup of 314 students of both sexes, 14-19 years of age, was selected. Participants came from a total of 20 classes in which a high percentage of students exhibited disturbed eating behaviour. Ten classes were then randomly selected to receive health promotion lessons (intervention group, high-risk; IGHR), while the other 10 classes served as controls (control group, high-risk; CGHR). The Eating Attitudes Test (EAT-26), the Giessen Physical Complaint List for Children and Adolescents (GSCL-C) and the Self-Report Symptom Check-List (SCL-90-R) were administered shortly before (t2) and 3 months after (t3) the interventions. The three health promotion lessons dealt with issues concerning beauty ideals, gender differences in psychosexual maturation and body awareness, healthy eating behaviour, physiology of nutrition, early symptoms of eating disorders and therapeutic approaches. The data analyses revealed an improvement on all three symptom scales for both groups between t2 and t3, but there were no significant differences between the IGHR and CGHR groups. When data from high-scoring female participants only were analysed (HRf-IGHR and HRf-CGHR), the multivariate analysis revealed a significant interaction between time and group (15.2% of variance explained). Our experiences in implementing health promotion lessons that conveyed knowledge about eating disorders and addressed physical and psychological issues in a more general way indicated that these interventions can be carried out in schools, and may contribute to increases in physical and psychological well-being in a high-risk population of adolescents.
Middle school primary prevention program for eating disorders: a controlled study with a twelve-month follow-up.
The aim of this pilot study was to evaluate the efficacy of a new school-based eating disorder prevention program designed to reduce dietary restraint and the level of preoccupation with regard to shape and weight. One hundred and six (61 females and 45 males) 11 to 12-year-old students were evaluated, 55 of whom participated in the program (experimental group). An additional 51 students formed the control group. The program met for six sessions, two hours per session. After six months, the experimental group received two booster sessions of two hours in two consecutive weeks. Outcome measures included the Eating Disorder Examination Questionnaire (EDE-Q), the children's version of the Eating Attitudes Test (EAT), the Rosenberg Self-Esteem Scale (RSES), and a Knowledge Questionnaire (KQ) devised by the authors of the program. The questionnaires were administered in both the experimental and control groups, one week before the intervention, one week afterwards, and at six-month and 12-month follow-ups. Unlike a previous school-based eating disorder prevention program, in the experimental group both an increase in knowledge and a decrease in some attitudes were maintained at 12-month follow-up (Eating Concerns EDE-Q scores). Although more intensive interventions seem necessary to modify shape and weight concern and self-esteem, these findings suggest that the intervention had been useful since it led to both an increase in knowledge and a decrease in some dysfunctional eating attitudes.
An attempt to modify unhealthful eating attitudes and weight regulation practices of young adolescent girls.
This is the first long-term, controlled study evaluating the effectiveness of a prevention curriculum designed to modify the eating attitudes and unhealthful weight regulation practices of young adolescent girls. Nine hundred sixty-seven sixth and seventh-grade girls were randomized to experimental healthy weight regulation curriculum or no-treatment control classes. A prevention intervention was developed around three principal components: (1) Instruction on the harmful effects of unhealthful weight regulation; (2) promotion of healthful weight regulation through the practice of sound nutrition and dietary principles and regular aerobic physical activity; (3) development of coping skills for resisting the diverse sociocultural influences that appear linked to the current popular obsessions with thinness and dieting. The intervention failed to achieve the hoped-for impact. We did observe a significant increase in knowledge among girls receiving the intervention and among high-risk students only, there was a small albeit statistically significant effect on body mass index. These findings question the wisdom of providing a curriculum directed at all young adolescents, most of whom are not at risk to develop an eating disorder. Rather than targeting the entire population, a healthy weight curriculum designed to modify the eating attitudes and unhealthful weight regulation practices of young adolescent girls might better focus on "at risk" students.
Primary prevention of disordered eating among preadolescent girls: feasibility and short-term effect of a community-based intervention.
OBJECTIVE: To evaluate a community-based intervention aimed at the primary prevention of disordered eating among preadolescent girls.
DESIGN: Girl Scout troop members were randomized into control and intervention groups. Program feasibility and effect at postintervention and 3-month follow-up were evaluated.
SUBJECTS/SETTING: 226 girls (mean age = 10.6 years, standard deviation = 0.7) from 24 Girl Scout troops.
INTERVENTION: Six 90-minute sessions focusing on media literacy and advocacy skills.
MAIN OUTCOME MEASURES: Evaluation focused on program satisfaction and short-term effect on dieting behaviors, body image attitudes, and media knowledge, attitudes, and habits.
STATISTICAL ANALYSES: Performed t tests, chi 2 tests, and analyses of covariance including troop as a random source of variation.
RESULTS: At baseline, 29% of the girls were trying to lose weight. The program had a notable positive influence on media-related attitudes and behaviors including internalization of sociocultural ideals, self-efficacy to impact weight-related social norms, and print media habits. A modest program effect on body-related knowledge and attitudes was apparent at post-intervention (i.e., on body size acceptance, puberty knowledge, and perceived weight status) but not at follow-up. Significant changes were not noted for dieting behaviors, but they were in the hypothesized direction. Satisfaction with the program was high among girls, parents, and leaders.
APPLICATIONS/CONCLUSIONS: It is feasible to use community youth settings, such as the Girl Scouts, to implement interventions to prevent disordered eating behaviors. The program led to positive trends in outcome variables; however, longer and more intensive interventions are needed for lasting changes in body image and dieting behaviors.
Improving the body image, eating attitudes, and behaviors of young male and female adolescents: a new educational approach that focuses on self-esteem.
OBJECTIVE: This study examines the effect of an interactive, school-based, self-esteem education program on the body image and eating attitudes and behaviors of young male and female adolescents following the program and after 12 months.
METHOD: All 470 eligible students (63% female) aged 11-14 years volunteered to participate. The intervention group students participated in the program, whereas the control group students received their scheduled personal development and health class.
RESULTS: The program significantly improved the body satisfaction of the intervention students and significantly changed aspects of their self-esteem; social acceptance, physical appearance, and athletic ability became less important for the intervention students and more important for control students. Female intervention students rated their physical appearance as perceived by others significantly higher than control students and allowed their body weight to increase appropriately by preventing the age increase in weight-losing behaviors of the control students. One year after the intervention, body image and attitude changes were still present. These findings also held for the 116 students (63% females) with low self-esteem and higher anxiety, who were considered at risk for the development of eating disorders. These students also had significantly lower drive for thinness and greater body satisfaction following the intervention and the decreased importance of physical appearance to their self-esteem was present at 12 months. Control at-risk students significantly decreased their body weight, whereas the weight of the intervention at-risk students significantly increased. The intervention program was effective, safe, having no effect on measures of students' anxiety or depression, and was rated highly by students.
DISCUSSION: This is the first controlled educational intervention to successfully improve body image and to produce long-term changes in the attitudes and self-image of young adolescents. This new approach to prevent the development of eating disorders by improving self-esteem may be effective, particularly if reinforced by teachers and family.
The effects of psychoeducation on disturbed eating attitudes and behavior in young women with type 1 diabetes mellitus.
OBJECTIVE: This study aimed to evaluate the effect of a six-session psychoeducation (PE) program on young women with type 1 diabetes mellitus (DM) and disordered eating attitudes and behavior.
METHOD: Two hundred twelve young women attending a pediatric diabetes clinic were screened for signs of eating disturbance. Of these women, 130 passed the screening and were invited to participate in the intervention phase of the study. Eighty-five subjects were randomized to the PE or treatment-as-usual group. Assessments were conducted before and after treatment and at 6-month follow-up.
RESULTS: Intention-to-treat group by time multivariate analyses of variance (MANOVAs) indicated significant reductions following PE treatment on the Restraint and Eating Concern subscales of the Eating Disorder Examination (EDE) and on the Drive for Thinness and Body Dissatisfaction subscales of the Eating Disorder Inventory (EDI), but no improvement in frequency of purging by insulin omission or hemoglobin A1c levels.
DISCUSSION: The PE group was associated with reductions in eating disturbance, but not with improved metabolic control.
A preventive intervention program in adolescent schoolgirls: a longitudinal study.
BACKGROUND: To explore the impact of a prevention program on the eating and body attitudes of a sample of adolescent schoolgirls.
METHODS: The program involved lessons and group discussions of general adolescent problems and eating disorders. A total of 254 16-year-old schoolgirls were evaluated, of whom 154 participated in the program and a further 154 subjects formed the control group. Variations in weight, Eating Attitudes Test and Eating Disorders Inventory at a 1-year follow-up were compared for the two groups.
RESULTS: Among high-risk subjects, no significant differences were found between the prevention and the control group. The preventive program appeared to reduce significantly body dissatisfaction and to decrease the risk of bulimic attitudes in low-risk subjects.
CONCLUSIONS: Providing schoolgirls with the correct information about eating disorders did not encourage unhealthy attitudes to eating and weight regulation practices. However, for high-risk subjects more intensive and specific intervention may be required, for which further research is needed.
Healthy weight control and dissonance-based eating disorder prevention programs: results from a controlled trial.
OBJECTIVE: Because universal psychoeducational eating disorder prevention programs have had little success, we developed and evaluated two interventions for high-risk populations: a healthy weight control intervention and a dissonance-based intervention.
METHOD: Adolescent girls (N = 148) with body image concerns were randomized to one of these interventions or to a waitlist control group. Participants completed baseline, termination, and 1, 3, and 6-month follow-up surveys.
RESULTS: Participants in both interventions reported decreased thin-ideal internalization, negative affect, and bulimic symptoms at termination and follow-up relative to controls. However, no effects were observed for body dissatisfaction or dieting and effects diminished over time.
DISCUSSION: Results provide evidence that both interventions effectively reduce bulimic pathology and risk factors for eating disturbances.
A preliminary controlled evaluation of a school-based media literacy program and self-esteem program for reducing eating disorder risk factors.
OBJECTIVE: This study compared the efficacy of a media literacy program and a self-esteem program designed to reduce general and specific risk factors for eating disorders.
METHOD: Four classes of 86 grade 8 students (53 boys and 33 girls), mean age of 13 years, were randomly assigned to either a control condition or one of the two intervention conditions. Assessment of general and specific risk factors was carried out at baseline, postintervention and 3-month follow-up.
RESULTS: At postintervention the media literacy group had lower mean scores on weight concern than the control group (p =0.007) but the self-esteem group did not. There were some differences on self-esteem measures at the 3-month follow-up.
DISCUSSION: Media literacy programs combined with an interactive, student-centered framework may potentially be a safe and effective way of reducing risk factors for eating disorders. The impact of teaching style needs to be further evaluated in prevention research.
Options:
A: Eating disorder prevention programs significantly improved healthy eating attitudes and behaviors in children and adolescents.
B: There was a significant reduction in the internalization of societal ideals relating to appearance in some programs, but overall, there was insufficient evidence to support the effectiveness of eating disorder prevention programs.
C: Eating disorder prevention programs had a significant positive impact on both psychological and physical health in children and adolescents.
D: All eating disorder prevention programs demonstrated significant long-term benefits for children and adolescents. | B |
209 | 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 tracheal gas insufflation (TGI) in mechanically ventilated newborn infants in terms of mortality, chronic lung disease (CLD), and duration of mechanical ventilation? Please answer this question based on the information provided below:
Continuous tracheal gas insufflation in preterm infants with hyaline membrane disease. A prospective randomized trial.
In mechanically ventilated neonates, the instrumental dead space is a major determinant of total minute ventilation. By flushing this dead space, continuous tracheal gas insufflation (CTGI) may allow reduction of the risk of overinflation. We conducted a randomized trial to evaluate the efficacy of CTGI in reducing airway pressure over the entire period of mechanical ventilation while maintaining oxygenation. A total of 34 preterm newborns, ventilated in conventional pressure-limited mode, were enrolled in two study arms, to receive or not receive CTGI. Transcutaneous Pa(CO(2)) (tcPa(CO(2))) was maintained at 40 to 46 mm Hg in both groups to ensure comparable alveolar ventilation. Respiratory data were collected several times during the first day and daily until Day 28. Both groups were similar at the time of inclusion. During the first 4 d of the study, the difference between peak pressure and positive end-expiratory pressure was significantly lower in the CTGI group by 18% to 35%, with the same tcPa(CO(2)) level and with no difference in the ratio of tcPa(O(2)) to fraction of inspired oxygen (245 +/- 29 versus 261 +/- 46 mm Hg [mean +/- SD] over the first 4 d). Extubation occurred sooner in the CTGI group (p < 0.05), and the duration of mechanical ventilation was shorter (median: 3.6 d; 25th to 75th quartiles: 1.5 to 12.0 d; versus median: 15.6 d; 25th to 75th quartiles: 7.9 to 22.2; p < 0.05) than in the non-CTGI group. CTGI allows the use of low-volume ventilation over a prolonged period and reduces the duration of mechanical ventilation.
Options:
A: TGI significantly reduced mortality and CLD, and shortened the duration of mechanical ventilation.
B: TGI had no effect on mortality or CLD, but significantly shortened the duration of mechanical ventilation.
C: TGI significantly reduced mortality and CLD, but had no effect on the duration of mechanical ventilation.
D: TGI had no effect on mortality, CLD, or the duration of mechanical ventilation. | B |
210 | 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 early initiation of continuous distending pressure (CDP) in pre-term infants with respiratory distress syndrome (RDS) compared to delayed initiation? Please answer this question based on the information provided below:
Controlled trial of continuous positive airway pressure given by face mask for hyaline membrane disease.
A controlled trial of elective intervention with continuous positive airway pressure (CPAP) was performed on 24 infants with hyaline membrane disease whose arterial oxygen tension (Pao2) fell below 8kPa (60 mmHg) while they were breathing a fractional inspired oxygen concentration (F1O2) greater than 0.60. A face mask was used to apply the CPAP. The progress of the 12 infants who were treated on entry to the trial was compared with that of 12 infants who were treated later. All 12 infants in the early-intervention group and 8 infants in the late-intervention group survived. When CPAP was started, Pao2 increased and the early-treated infants breathed high concentrations of oxygen for a shorter period than the late-treated infants. The 4 infants in the early-intervention group who required mechanical ventilation needed lower mean airway pressures to achieve satisfactory gas exchange than the 7 ventilated infants in the late-intervention group. We conclude that a Pao2 less than 8 kPa while breathing an F1o2 greater than 0.60 is an adequate indication for giving CPAP in hyaline membrane disease, and that early intervention with CPAP allows infants who go on to require mechanical ventilation to be ventilated at lower pressures.
Early versus late introduction of continuous negative pressure in the management of the idiopathic respiratory distress syndrome.
To evaluate the effectiveness of the early application of continuous negative pressure about the thorax, 23 infants with the idiopathic respiratory distress syndrome who had adequate alveolar ventilation were assigned to early or late application of CNP. There were 11 infants in the early CNP and 12 in the late CNP group. There were no differences between the two groups with respect to birth weight, gestational age, age at admission to the study, initial FIO2 requirements, or initial PaO2, PaCo2, and AaPO2. None of the ENCP patients required mechanical ventilation, whereas four of the LCNP group did so. The FIO2 requirements were significantly less for the ECNP infants when compared to the LCNP ones. The mean duration of FIO2 requirements greater than 0.6 was 28.3 hours for those receiving ECNP and 60.7 hours for those in LCNP (P LESS THAN 0.05). This study suggests that the course of RDS may be modified by the early application of CNP.
The effect of continuous positive airway pressure on the course of respiratory distress syndrome: the benefits on early initiation.
The course of idiopathic respiratory distress syndrome (IRDS) treated with continuous positive airway pressure (CPAP) was studied in 38 infants with a respiratory index (RI) based on AaDO2 and PO2 measurements. Thirteen infants were treated with early CPAP (FIO2 = 0.3, PO2 greater than 50 torr (6.7k Pa) at a mean age of 7.1 h and 25 infants received late CPAP (FIO2 = 0.5, PO2 greater than 50 torr) at a mean age of 15.1 h. Significant differences were demonstrated between the two groups in duration of CPAP (42 versus 72 hours) peak RI (3.7 vs. 6.7), time to peak RI from start of therapy (10.0 versus 19.4 h), number of infants ventilated (0 versus 5) and number of air leaks (0 versus 3). The rate of disease worsening as measured by changes in RI/h before CPAP and after CPAP initiation was comparable in the respective treatment groups.
The early use of continuous positive airway pressure in the treatment of idiopathic respiratory distress syndrome.
Infants with IRDS were treated with CPAP early (0.40 FIO2; WITH PaO2 less than 60 mm Hg) or late (0.70 FIO2; with PaO2 less than 60 mm Hg). There was no difference in survival, duration of CPAP therapy, total time of oxygen administration, or complications. The early treated infants needed a lower FIO2 (maximum 0.55) and had a less severe clinical course. The late treated infants were subjected to 0.70 or more FIO2 for an average of 24 hours and were in greater than 0.40 FIO2 significantly longer than those given CPAP early. Infants who weighed less than 1,500 gm and had severe disease did not do well regardless of when CPAP was applied.
Early versus delayed initiation of continuous negative pressure in infants with hyaline membrane disease.
Twenty-three infants with HMD of similar severity, who were less than 24 hours of age and who were breathing spontaneously, were divided by random numbers into early and delayed CNP groups. The infants who were treated with CNP before their PaO2 was less than 50 mm Hg while breathing 70% oxygen experienced a significantly greater increase in PaO2 in response to the initiation of CNP, required less time with O2 therapy, required no mechanical ventilation, and had fewer complications. Based on these results, it is suggested that CNP be initiated in infants with HMD, who are less than 24 hours of age and are breathing spontaneously, before the PaO2 becomes less than 50 mm Hg on 70% O2.
Options:
A: Early CDP significantly reduces the need for intermittent positive pressure ventilation (IPPV) and overall mortality.
B: Early CDP significantly reduces the need for intermittent positive pressure ventilation (IPPV) but has no effect on overall mortality.
C: Early CDP significantly reduces the rates of pneumothorax and bronchopulmonary dysplasia.
D: Early CDP significantly increases the duration of oxygen therapy required. | B |
211 | 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 and safety of D-cycloserine in the treatment of Alzheimer's disease after assessing randomized controlled trials? Please answer this question based on the information provided below:
Evaluation of cycloserine in the treatment of Alzheimer's disease.
This multicenter study evaluated the efficacy and safety of cycloserine and measured its effects on explicit and implicit memory tests in patients with Alzheimer's disease (AD). Four hundred ten patients with AD, aged 50 years or older, were enrolled in this parallel-group, double-blind, placebo-controlled, randomized trial of 5, 15, or 50 mg cycloserine or placebo twice daily, and 403 entered the double-blind treatment phase. Two hundred sixty-five patients completed the entire 26-week treatment phase. There were no baseline differences among the four treatment groups. Cognitive Drug Research (CDR) efficacy assessments showed no differences between active treatments and placebo from baseline to study weeks 2, 6, 14, or 26. Patients receiving 15 mg of cycloserine improved significantly on one section of an implicit memory test. No differences among treatments were observed for any other assessment scales evaluated. The incidence and severity of adverse events were similar across treatment groups. Cycloserine was well tolerated but did not demonstrate consistent evidence of efficacy during the course of therapy. Higher doses may be necessary to achieve efficacy in the AD population and do not appear to be precluded by the adverse event profile seen in this study.
Cognitive and quantified electroencephalographic correlates of cycloserine treatment in Alzheimer's disease.
Cycloserine acts as a potent and selective modulator of the N-methyl-D- aspartate (NMDA) receptor-associated glycine recognition site, which may be a possible mechanism for this compound's positive effects on memory formation and retrieval processes in animals. Studies in normal human volunteers have shown that cycloserine can have significant positive effects on cognitive processing in the elderly and can ameliorate memory deficits induced by subcutaneously administered scopolamine. Based on this profile, a double-blind, placebo controlled, parallel group (three drug dosages) study was conducted as part of a larger study to assess the efficacy and safety, as well as the cognitive and central nervous system (CNS) impact, of 6 months of cycloserine treatment in patients (N = 40) with probable dementia of the Alzheimer type (DAT). The Cognitive Drug Research Computerize Assessment System (CDR System) served as the primary outcome measure of efficacy. CNS activity was assessed using quantified electroencephalography (QEEG). Safety measures included adverse effects documentation and analysis of blood chemistry/hematology. Cycloserine proved to be a safe agent in this population at the doses given but failed to show any statistically significant effects in the areas of cognition and global clinical ratings and did not indicate significant CNS activity on QEEG. These findings suggest that cycloserine has no measurable therapeutic effect on Alzheimer's disease at the doses given.
d-Cycloserine enhances implicit memory in Alzheimer patients.
We tested the ability of d-cycloserine, a partial glycine agonist acting at the N-methyl-D-aspartate (NMDA) receptor complex, to improve implicit memory in Alzheimer patients in a parallel-group, placebo-controlled, double-blind study. One-hundred eight patients with probable Alzheimer's disease of mild to moderate severity received d-cycloserine (5, 15, or 50 mg) or placebo twice daily for 10 weeks. We then evaluated their ability to identify perceptually degraded words, some of which were repeated over multiple trials across 3 days. Implicit memory performance of words repeated across trials was significantly enhanced for the patients who received 15 mg d-cycloserine compared with those who received placebo. These findings support development of NMDA receptor-mediated glutamatergic interventions for the treatment of Alzheimer-related memory disorders.
A preliminary study of D-cycloserine treatment in Alzheimer's disease.
D-cycloserine is a partial agonist on the glycine site of the N-methyl-D-aspartate glutamate receptor. This double-blind crossover study of 15 mg D-cycloserine in Alzheimer's disease patients did not demonstrate clinical benefit. Higher medication dosage or long-term treatment may be required.
Improved cognition in Alzheimer's disease with short-term D-cycloserine treatment.
OBJECTIVE: Glutamatergic neurotransmission is important for memory and cognition and is severely affected in Alzheimer's disease. D-Cycloserine exhibits partial agonist activity at the glycine site of N-methyl-D-aspartate subtype glutamate receptor, facilitating activation of the receptor and improving cognition and memory.
METHOD: Seventeen patients with Alzheimer's disease received a three-phase, double-blind, placebo-controlled trial of 50 mg and 100 mg/day of D-cycloserine.
RESULTS: D-Cycloserine was associated with significant improvement in scores on the cognitive subscale of the Alzheimer's Disease Assessment Scale (improvement of 3.0 points) when given at a dose of 100 mg/day.
CONCLUSIONS: D-Cycloserine has cognitive benefits for patients with Alzheimer's disease.
Options:
A: D-cycloserine showed a significant positive effect on cognitive outcomes and is recommended for the treatment of Alzheimer's disease.
B: D-cycloserine showed no significant positive effect on cognitive outcomes and is not recommended for the treatment of Alzheimer's disease.
C: D-cycloserine showed a significant positive effect on cognitive outcomes but had a high rate of adverse events, making it unsuitable for the treatment of Alzheimer's disease.
D: D-cycloserine showed no significant positive effect on cognitive outcomes but had a low rate of adverse events, making it a safe option for the treatment of Alzheimer's disease. | B |
212 | 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 cognitive-behavioural interventions for improving sleep quality, duration, and efficiency in older adults aged 60 and above? Please answer this question based on the information provided below:
Countercontrol treatment of sleep-maintenance insomnia in relation to age.
We administered countercontrol behavioral therapy for sleep-maintenance insomnia to 34 insomniacs--ranging in age from 35 to 78 years--in small groups. Twenty-two subjects received immediate and 12 received delayed treatment. Three self-report measures of sleep disruption were collected on daily sleep diaries at baseline, termination of treatment, 1-month follow-up, and 12-month follow-up. Although amount of time awake at night was correlated with age (r = .50), response to treatment was not. Even though older people experienced more time awake after sleep onset prior to treatment, they were able to profit from therapy as well as the younger insomniacs. Countercontrol therapy reduced the sleep complaint for the total group by about 30% at the end of treatment, with gradual improvement continuing through a 4-week follow-up. Nevertheless, it appears that sleep-maintenance insomnia may be more difficult to treat than sleep-onset problems.
Relaxation and sleep compression for late-life insomnia: a placebo-controlled trial.
Older adults with insomnia were recruited from the community and randomized to treatments: relaxation, sleep compression, and placebo desensitization. Questionnaire data collected at baseline, posttreatment, and 1-year follow-up and polysomnography data collected at baseline and follow-up yielded the following conclusions: All treatments improved self-reported sleep, but objective sleep was unchanged. Clinical significance analyses yielded the strongest findings supporting the active treatments and suggested that sleep compression was most effective. Results partially supported the conclusion that individuals with high daytime impairment (i.e., fatigue) respond best to treatments that extend sleep, as in relaxation, and individuals with low daytime impairment respond best to treatments that consolidate sleep, as in sleep compression. Strong methodological features including a placebo condition and a treatment implementation scheme elevate the confidence due these findings.
Successful behavioral treatment for reported sleep problems in elderly caregivers of dementia patients: a controlled study.
Although sleep problems are common among dementia caregivers, there has been no research thus far describing treatment of such problems using behavioral techniques. In this study, 36 elderly dementia caregivers with disturbed sleep were randomly assigned to either a brief behavioral intervention or a wait list control. The active treatment consisted of standard sleep hygiene, stimulus control, and sleep compression strategies as well as education about community resources, stress management, and techniques to reduce patient disruptive behaviors. Caregivers in active treatment showed significant improvements in sleep at post-treatment and 3-month follow up. No significant differences between groups were observed for caregiver mood, burden, or patient behavior problems, suggesting that sleep improvements were not an artifact of depression treatment. Treatment responders tended to be younger and more compliant with treatment recommendations than non-responders. Results suggest that behavioral techniques may well be a viable alternative to medication for sleep problems in aging caregivers.
Behavioral and cognitive treatments of geriatric insomnia.
Cognitive-behavior therapy for late-life insomnia.
Twenty-four older adults with persistent psychophysiological insomnia were randomly assigned to an immediate or a delayed cognitive-behavioral intervention in a waiting-list control group design. Cognitive-behavior therapy consisted of an 8-week group intervention aimed at changing maladaptive sleep habits and altering dysfunctional beliefs and attitudes about sleeplessness. Treatment was effective in reducing sleep latency, wake after sleep onset, and early morning awakening, and in increasing sleep efficiency. The magnitude of changes obtained on polysomnographic measures was smaller but in the same direction as that obtained on daily sleep diaries. Sleep improvements obtained by the immediate-treatment group were replicated with the delayed treatment condition. Therapeutic gains were well maintained at 3- and 12-month follow-ups. Clinical validation of outcome was obtained through collateral ratings from the patients and their significant others. The findings indicate that late-life insomnia can be effectively treated with nonpharmacological interventions.
Behavioral and pharmacological therapies for late-life insomnia: a randomized controlled trial.
CONTEXT: Insomnia is a prevalent health complaint in older adults. Behavioral and pharmacological treatments have their benefits and limitations, but no placebo-controlled study has compared their separate and combined effects for late-life insomnia.
OBJECTIVE: To evaluate the clinical efficacy of behavioral and pharmacological therapies, singly and combined, for late-life insomnia.
DESIGN AND SETTING: Randomized, placebo-controlled clinical trial, at a single academic medical center. Outpatient treatment lasted 8 weeks with follow-ups conducted at 3, 12, and 24 months.
SUBJECTS: Seventy-eight adults (50 women, 28 men; mean age, 65 years) with chronic and primary insomnia.
INTERVENTIONS: Cognitive-behavior therapy (stimulus control, sleep restriction, sleep hygiene, and cognitive therapy) (n = 18), pharmacotherapy (temazepam) (n = 20), or both (n = 20) compared with placebo (n = 20).
MAIN OUTCOME MEASURES: Time awake after sleep onset and sleep efficiency as measured by sleep diaries and polysomnography; clinical ratings from subjects, significant others, and clinicians.
RESULTS: The 3 active treatments were more effective than placebo at posttreatment assessment; there was a trend for the combined approach to improve sleep more than either of its 2 single components (shorter time awake after sleep onset by sleep diary and polysomnography). For example, the percentage reductions of time awake after sleep onset was highest for the combined condition (63.5%), followed by cognitive-behavior therapy (55%), pharmacotherapy (46.5%), and placebo (16.9%). Subjects treated with behavior therapy sustained their clinical gains at follow-up, whereas those treated with drug therapy alone did not. Long-term outcome of the combined intervention was more variable. Behavioral treatment, singly or combined, was rated by subjects, significant others, and clinicians as more effective than drug therapy alone. Subjects were also more satisfied with the behavioral approach.
CONCLUSIONS: Behavioral and pharmacological approaches are effective for the short-term management of insomnia in late life; sleep improvements are better sustained over time with behavioral treatment.
Options:
A: Cognitive-behavioural interventions showed no significant effect on sleep quality, duration, and efficiency in older adults.
B: Cognitive-behavioural interventions demonstrated a mild effect on improving sleep quality, duration, and efficiency, particularly for sleep maintenance insomnia.
C: Cognitive-behavioural interventions were found to be more effective than pharmacological treatments for sleep problems in older adults.
D: Cognitive-behavioural interventions were ineffective and had adverse effects on sleep quality in older adults. | B |
213 | 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 helium-oxygen mixtures (heliox) in treating acute exacerbations of chronic obstructive pulmonary disease (COPD) in both ventilated and nonventilated patients? Please answer this question based on the information provided below:
Randomized trial of the use of heliox as a driving gas for updraft nebulization of bronchodilators in the emergent treatment of acute exacerbations of chronic obstructive pulmonary disease.
OBJECTIVE: To determine whether the bronchodilator effects of albuterol and ipratropium bromide are greater if updraft nebulization is driven by 80% helium and 20% oxygen (HELIOX) than if driven by compressed room air (AIR) during the treatment of an acute exacerbations of chronic obstructive pulmonary disease (COPD).
SETTING: The emergency department of a 750-bed inner-city community hospital.
METHODS: Over a 12-month period, a convenience sample of 50 normoxic patients presenting with signs and symptoms of an acute exacerbation of COPD were prospectively randomized to receive either HELIOX or AIR as the driving gas for updraft nebulization of a mixture of albuterol 2.5 mg and ipratropium bromide 0.5 mg. Additional aerosol treatments with albuterol 2.5 mg were given at 20, 40, and 120 mins after randomization using the assigned gas. Spirometry was obtained while breathing room air before the first treatment (baseline) and at 1 hr and 2 hrs after the initiation of treatment. The primary measure of efficacy was the change in percent of predicted forced expiratory volume in 1 sec (FEV1) over the treatment period. A secondary measure of efficacy was the change in percentage of predicted forced expiratory flow after 25% to 75% of vital capacity had been expelled (FEF25-75).
RESULTS: Twenty-five patients were randomized to each treatment group. Three patients (1 HELIOX, 2 AIR) were unable to complete the study. The baseline FEV1was 44% (95% confidence interval, 35% to 52%) of predicted in the HELIOX group and 39 (31% to 46%) of predicted in the AIR group. There were no adverse outcomes observed in either the HELIOX group or the AIR group. There were no significant differences in the change of FEV1 between the two groups by either the 1 hr or 2 hr time point (1 hr, HELIOX + 10% [7% to 13%], AIR + 9% [5% to 13%]; 2 hr HELIOX + 10% [6% to 15%], AIR + 10% [6% to 14%]). The improvement in FEF25-75 was significantly greater in the HELIOX group than in the AIR group at both the 1 hr time point (HELIOX + 14% [7% to 22%] vs. AIR + 7% [3% to 10%], p = .05) and at the 2 hr time point (HELIOX + 15% [8% to 21%] vs. AIR + 7% [4% to 11%], p = .05).
CONCLUSION: Use of HELIOX as a driving gas for the updraft nebulization of bronchodilators during the first 2 hrs of treatment of an acute COPD exacerbation failed to improve FEV1 faster than the use of AIR. The faster improvement in FEF25-75 during the first 2 hrs of treatment was small and of uncertain clinical significance.
Beneficial effects of helium:oxygen versus air:oxygen noninvasive pressure support in patients with decompensated chronic obstructive pulmonary disease.
OBJECTIVE: To test the hypothesis that, in decompensated chronic obstructive pulmonary disease (COPD), noninvasive pressure support ventilation using 70:30 helium:oxygen instead of 70:30 air:oxygen could reduce dyspnea and improve ventilatory variables, gas exchange, and hemodynamic tolerance.
DESIGN: Prospective, randomized, crossover study.
SETTING: Medical intensive care unit, university tertiary care center.
PATIENTS: Nineteen patients with severe COPD (forced 1-sec expiratory volume of 0.83+/-0.3 l) hospitalized in the intensive care unit for noninvasive pressure support ventilation after initial stabilization with noninvasive pressure support for no more than 24 hrs after intensive care unit admission.
INTERVENTIONS: Noninvasive pressure support ventilation was administered in the following randomized crossover design: a) 45 min with air:oxygen or helium:oxygen; b) no ventilation for 45 min; and c) 45 min with air:oxygen or helium:oxygen.
MEASUREMENTS AND MAIN RESULTS: Air:oxygen and helium:oxygen decreased respiratory rate and increased tidal volume and minute ventilation. Helium:oxygen decreased inspiratory time. Both gases increased total respiratory cycle time and decreased the inspiratory/total time ratio, the reduction in the latter being significantly greater with helium:oxygen. Peak inspiratory flow rate increased more with helium:oxygen. PaO2 increased with both gases, whereas PaCO2 decreased more with helium:oxygen (values shown are mean+/-SD) (52+/-6 torr [6.9+/-0.8 kPa] vs. 55+/-8 torr [7.3+/-1.1 kPa] and 48+/-6 torr [6.4+/-0.8 kPa] vs. 54+/-7 torr [7.2+/-0.9 kPa] for air:oxygen and helium:oxygen, respectively; p<.05). When hypercapnia was severe (PaCO2 >56 torr [7.5 kPa]), PaCO2 decreased by > or =7.5 torr (1 kPa) in six of seven patients with helium:oxygen and in four of seven patients with air:oxygen (p<.01). Dyspnea score (Borg scale) decreased more with helium:oxygen than with air:oxygen (3.7+/-1.6 vs. 4.5+/-1.4 and 2.8+/-1.6 vs. 4.6+/-1.5 for air:oxygen and helium:oxygen, respectively; p<.05). Mean arterial blood pressure decreased with air:oxygen (76+/-12 vs. 82+/-14 mm Hg; p<.05) but remained unchanged with helium:oxygen.
CONCLUSION: In decompensated COPD patients, noninvasive pressure support ventilation with helium:oxygen reduced dyspnea and PaCO2 more than air:oxygen, modified respiratory cycle times, and did not modify systemic blood pressure. These effects could prove beneficial in COPD patients with severe acute respiratory failure and might reduce the need for endotracheal intubation.
Options:
A: Helium-oxygen mixtures significantly improve respiratory function and reduce the need for mechanical ventilation in COPD patients.
B: Helium-oxygen mixtures show no significant improvement in respiratory function or reduction in the need for mechanical ventilation in COPD patients.
C: Helium-oxygen mixtures are harmful and increase the risk of complications in COPD patients.
D: Helium-oxygen mixtures are effective only in nonventilated COPD patients but not in ventilated patients. | B |
214 | 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 pre-operative autologous blood donation (PAD) on the need for peri-operative allogeneic red blood cell (RBC) transfusion and overall blood transfusion rates in adult patients scheduled for non-urgent surgery? Please answer this question based on the information provided below:
Preoperative use of recombinant human erythropoietin before total joint arthroplasty.
BACKGROUND: Previous reports have suggested that the use of recombinant human erythropoietin is effective for decreasing the need for perioperative allogeneic blood transfusion. The purpose of this study was to evaluate the efficacy of erythropoietin in combination with, and compared with, preoperative autologous donation for reducing allogeneic blood requirements for total joint arthroplasty.
METHODS: Two hundred and forty patients undergoing primary and revision total hip or knee arthroplasty were enrolled into three groups with different treatment regimens: (1) erythropoietin and preoperative autologous donation (Group 1), (2) erythropoietin alone (Group 2), and (3) preoperative autologous donation alone (Group 3). Patients were evaluated with regard to requirements for allogeneic transfusion, change from the baseline to the lowest postoperative hemoglobin value, postoperative complications, and adverse reactions.
RESULTS: The rate of allogeneic transfusion was 11% in Group 1 (erythropoietin and preoperative autologous donation) compared with 28% in Group 2 (erythropoietin alone) and 33% in Group 3 (preoperative autologous donation alone). Within Group 1, patients who had a unilateral primary arthroplasty had an allogeneic transfusion rate of 4% and those who had a bilateral or revision arthroplasty had an allogeneic transfusion rate of 17%. In Groups 2 and 3, the allogeneic transfusion rates were 14% and 15%, respectively, for the patients who had a unilateral primary arthroplasty and 35% and 47%, respectively, for those who had a bilateral or revision arthroplasty.
CONCLUSIONS: Preoperative use of erythropoietin in conjunction with preoperative autologous donation reduces the need for allogeneic blood transfusion associated with total joint arthroplasty more effectively than does either erythropoietin or preoperative autologous donation alone.
A prospective, randomized study of preoperative autologous donation for hip replacement surgery.
BACKGROUND: Preoperative autologous blood donation is commonly performed to meet potential perioperative transfusion needs and is a common practice prior to total hip arthroplasty. Using standardized transfusion guidelines, we prospectively analyzed the effectiveness of preoperative autologous donation as a method for decreasing allogeneic transfusion among patients undergoing unilateral primary total hip replacement who were eligible to donate autologous blood.
METHODS: Patients who were scheduled for primary total hip replacement surgery and who had a preoperative baseline hemoglobin level >or=120 g/L were randomized either to donate two units of blood (autologous donors) or not to donate any blood (nondonors). The donors and nondonors were compared with regard to demographic data, blood-loss volumes, hemoglobin measurements, and transfusion rates. Randomization continued until data were obtained from at least forty patients per treatment group.
RESULTS: Of the ninety-six patients who completed the study, forty-two were autologous donors and fifty-four were nondonors. There were no significant differences between the donors and nondonors with regard to age, male:female ratio, estimated blood volume, baseline physical condition, or operative blood loss. The hemoglobin values at the time of enrollment (baseline), at the time of hospital discharge, and six weeks postoperatively were not significantly different between the two groups, although values at the time of admission (129 +/- 13 g/L versus 138 +/- 12 g/L) and in the recovery room (104 +/- 12 g/L versus 115 +/- 13 g/L) were significantly lower in the autologous donor group (p < 0.05). No patient in either group required an allogeneic transfusion. Twenty-nine (69%) of the forty-two donors received an autologous transfusion. Thirty-four (41%) of eighty-two autologous units were wasted. At a charge of $379 per autologous unit, there was an additional cost of $758 for each patient in the donor group.
CONCLUSIONS: Preoperative autologous donation provided no benefit for nonanemic patients undergoing primary total hip replacement surgery. Preoperative autologous donation increased the likelihood of autologous transfusion, wastage of predonated units, and costs.
Preoperative autologous blood donation reduces the need for allogeneic blood products: a prospective randomized study.
OBJECTIVE: We sought to assess the efficacy of preoperative autologous blood donation in reducing patient exposure to allogeneic blood products following elective cardiac surgery.
METHODS: We included 48 patients in a prospective study and randomly assigned them into the control or treatment group. We excluded patients with aortic stenosis, main trunk stenosis and unstable angina. Group A (n=23; coronary disease n=21 and valvular disease n=2) was the control group, and group B (n=25; coronary disease n=21, valvular disease n=4) received preoperative autologous blood donation. All patients had cardiopulmonary bypass surgery, and we processed mediastinal blood with a cell-saver device before reinfusion. All patients received aprotinin, and we reinfused blood shed from the mediastinum postoperatively.
RESULTS: No major peri- or postoperative complications occurred. We interrupted preoperative blood donation in 2 patients (8%) because of worsened angina pectoris. The mean time between the first blood donation and surgery was 22.5 (standard deviation [SD] 9.4, range 12-50) days. In group A, 9 patients (39.1%) were exposed to allogeneic blood products. In group B, 11 patients (47.8%) were exposed to blood products (p=0.73), and 4 (16%) were exposed to allogeneic blood products (p=0.036).
CONCLUSION: Preoperative blood donation was completed in 92% of the targeted low-risk population. The procedure significantly reduced exposure to perioperative allogeneic blood products.
Blood transfusions and prognosis in colorectal cancer.
BACKGROUND: Blood transfusions may adversely affect the prognosis of patients treated surgically for cancer, although definite proof of this adverse effect has not been reported.
METHODS: We carried out a randomized trial to investigate whether the prognosis in patients with colorectal cancer would be improved by a program of autologous blood transfusion as compared with the current practice of allogeneic transfusion. Patients in the autologous-transfusion group were required to donate two units of blood before surgery.
RESULTS: A total of 475 patients were evaluated. We found no significant difference in prognosis between the allogeneic-transfusion group (236 patients) and the autologous-transfusion group (239 patients); colorectal cancer-specific survival rates at four years were 67 percent and 62 percent, respectively (P = 0.39). Among the 423 patients who underwent curative surgery, 66 percent of those in the allogeneic-transfusion group and 63 percent of those in the autologous-transfusion group had no recurrence of colorectal cancer at four years (P = 0.93). We also found that the risk of recurrence was significantly increased in patients who received blood transfusions, either allogeneic or autologous, as compared with patients who did not require transfusions; the relative rates of recurrence were 2.1 (P = 0.01) and 1.8 (P = 0.04), respectively; these rates did not differ significantly from each other.
CONCLUSIONS: The use of autologous blood as compared with allogeneic blood for transfusion does not improve the prognosis in patients with colorectal cancer. Regardless of their type, transfusions are associated with poor prognosis, probably because of the circumstances that necessitate them.
The effect of blood transfusions on survival after surgery for colorectal cancer.
The immunosuppressive effect of allogeneic blood transfusions can be associated with a poor prognosis for cancer patients. Predeposit autologous blood transfusions could be a solution to overcome this putative deleterious effect. We performed a randomised clinical study to compare the effects of autologous with allogeneic blood transfusions in colorectal cancer patients. There was no significant difference in disease-free survival between both randomisation arms. However, the transfused patients had a significantly shorter disease-free interval as compared with the non-transfused patients. This association of transfusions with recurrent disease was only the case for local recurrences, whereas the incidence of distant metastases was unaffected. We conclude that the use of a predeposit autologous blood transfusion programme does not improve the prognosis in colorectal cancer patients. The negative association between blood transfusions and cancer recurrence is only true for local recurrences, which suggests that not the blood transfusions themselves but rather the circumstances necessitating them are the real predictors of prognosis.
Autologous blood transfusion in oral and maxillofacial surgery patients with the use of erythropoietin.
BACKGROUND: Autologous blood transfusion presents few infectious or immunologic side effects. The aim of the present study was to determine the impact of autologous blood transfusion with or without recombinant human erythropoietin (rHuEPO) in patients who underwent elective maxillofacial operations.
MATERIAL: Seventy eight consecutive patients (29 men and 49 women) underwent elective maxillofacial operations during the years 1990-95.
STUDY DESIGN AND METHODS: The patients were randomly assigned to three groups: In group 1, 30 patients preoperatively underwent autologous blood predonation with intravenous injection of erythropoietin 600 lU/kg after each blood predonation and autologous blood transfusion intraoperatively; in group 2, 28 patients underwent the same procedure without erythropoietin and in group 3, 20 patients underwent homologous transfusion serving as control group. All patients received ferrous sulphate daily by mouth, preoperatively until one week postoperatively.
RESULTS: Group 1 patients showed higher levels of haematocrit, haemoglobin and red blood cell count pre- and postoperatively than the group 2 patients. It was also shown that the use of rHuEPO contributed to an improvement of the blood parameters of the patients in the group 1 compared with those of the patients in groups 2 and 3.
Perioperative autotransfusion and functional coagulation analysis in total hip replacement.
Functional coagulation analyses like Sonoclot and thromboelastography have not been evaluated during perioperative autotransfusion. We have prospectively studied three different transfusion regimes in 45 patients undergoing total hip arthroplasty. Blood losses were replaced either with heterologous erythrocyte concentrate (group I), intra- and postoperative autotransfusion of blood salvaged with cellsaver technique (group II) or predonated autologous erythrocyte concentrates together with salvaged blood (group III). Routine and functional coagulation analyses with a Sonoclot were performed preoperatively, 6 hours postoperatively (6 h), day 1-5 and 10. An early postoperative hypo- and late postoperative hypercoagulative phase could be detected with Sonoclot signs of platelet function and fibrin deposition in all groups. Sonoclot coagulation analyses better correlated to both blood loss and dextran dosage than APTT and platelet count in the routine coagulation analyses. Functional coagulation analysis has a potential use in individualizing plasmasubstitution and thromboprophylaxis regimes during autotransfusion in THR.
Predonation autologous blood in hip arthroplasty.
In a prospective randomized study of elderly patients, a total of 130 units of blood were donated by 45 patients prior to a total hip arthroplasty. Fifteen patients served as controls (no phlebotomy). The average age was 71 (60-82) years. No major complication occurred with phlebotomy. All the patients were able to maintain their hematologic and chemical parameters within the normal range throughout the donation period. The autologous blood covered all the peroperative transfusion needs and 97 percent of the total transfusion requirements. There was less postoperative blood loss, as well as total blood loss, in the autologous groups compared with the control group. There was no difference in the rate of postoperative complications between the groups. The use of predeposited autologous blood in elective orthopedics, regardless of patient age, is feasible, cost effective, and avoids the risks associated with homologous blood transfusion.
Elderly patients' responses to preoperative autologous blood collection.
OBJECTIVE: To follow the haematological response in elderly patients to preoperative autologous blood collection.
DESIGN: A prospective, randomised study.
SETTING: Malmö General Hospital, Sweden.
PATIENTS: Sixty patients with a mean age of 71 years (range, 60-82 years) who were to undergo total hip replacement were randomly divided into four groups of 15. One group served as control. Three units of blood were collected from patients in the other three groups, the first unit at least 30 days before the planned operation, with an average interval of 10 days between collections. Iron supplementation was given to one group as a substitution remedy, another group was given iron and folic acid and the third group was without supplementation during the collection period.
MAIN OUTCOME MEASURES: Haematological and biochemical tests were performed on blood samples taken at the time of each collection, on the morning of the hip replacement operation, and ten days after and six weeks after the operation.
RESULTS: No major complication was encountered with blood collection. The patients tolerated the procedure very well including the substitution remedies. Haematological and biochemical parameters remained within the normal range during the collection period and after the operation. No patient in the autologous groups needed homologous blood during the operation; three units of homologous blood were used after the operation in these patients.
CONCLUSION: Preoperative blood collection from the elderly is safe and well tolerated. The procedure should be encouraged in elective orthopaedic operations regardless of age.
Autologous blood transfusion in hip replacement. No effect on blood loss but less increase of plasminogen activator inhibitor in a randomized series of 80 patients.
80 patients underwent total hip replacement (THR) for primary coxarthrosis. In a randomized study, half of them donated 2 units of blood before operation. One unit was collected 4 weeks and one 2 weeks before the scheduled THR. All except 1 patient tolerated the predonations well. Total blood losses were similar in both groups. Additional bank blood was given in 7/38 in the predonation group, compared to 29/40 in the control group. Hemostatic parameters were studied in 10 consecutive patients in each group. Plasminogen activator inhibitor 1 (PAI-1), a possible risk parameter for thromboembolism, was significantly more increased postoperatively in the control group, which received only homologous blood. Platelet count, prothrombin complex, antithrombin III and von Willebrand factor antigen were significantly reduced and C reactive protein increased after surgery in both groups. We recommend predonation of 2 autologous units before a primary THR. In most cases, such predonation makes homologous blood transfusion unnecessary. The use of predonated blood causes no reduction of blood loss in THRs, but the increase in PAI-1 seen after homologous transfusions is avoided.
Blood transfusion-modulated tumor recurrence: first results of a randomized study of autologous versus allogeneic blood transfusion in colorectal cancer surgery.
PURPOSE: Allogeneic blood transfusions have reportedly been associated with a poor prognosis in patients with curatively resected cancer. To control for immunosuppression induced by a speculatively causal allogeneic blood transfusion, we designed a randomized study in which the control group received autologous blood transfusions not related to any condition of immunosuppression.
PATIENTS AND METHODS: One hundred twenty patients with potentially curative resectable colorectal cancer and the capability to predeposit autologous blood were randomly selected to receive either standard allogeneic blood transfusion or predeposited autologous blood.
RESULTS: In curatively resected cancer patients, the number who needed allogeneic blood transfusions was reduced from 60% in the allogeneic blood group to 33% in the autologous blood group (P = .009). After a median follow-up duration of 22 months (range, 8 to 48) tumor recurrence was observed in 28.9% of the allogeneic blood group and 16.7% of the autologous blood group. Life-table analysis established a tendency toward a shorter tumor-free survival for the allogeneic blood group (log-rank P = .11). The problem with this analysis was the strong association of allogeneic blood transfusions with tumor recurrence, which interfered in 33% of patients in the autologous blood group who required additional allogeneic blood transfusions. Multivariate analysis of established risk factors for tumor recurrence and surgery-related variables reflecting potential immunosuppressive conditions showed that only pT stage (relative risk, 6.61; 95% confidence interval [CI], 1.82 to 23.99; P = .004), pN stage (relative risk, 8.39; 95% CI, 3.15 to 22.33; P < .001), and the need for allogeneic blood (relative risk, 6.18; 95% CI, 2.20 to 17.37; P < .001) were independent predictors of tumor recurrence. Subgroup analysis of patients who received a transfusion of < or = 2 U blood found a significantly higher risk of tumor recurrence in the allogeneic blood group (relative risk, 5.16; 95% CI, 1.13 to 23.62; P = .034), which was reduced to borderline significance (relative risk, 3.54; 95% CI, 0.76 to 16.51; P = .107) by adjustment for tumor (T) and node (N) stage.
CONCLUSION: As indicated by these first results, the blood transfusion modality has a significant effect on tumor recurrence after surgical treatment of colorectal cancer. A change in the practice of blood transfusion might thus potentially surpass the impact of any recent adjuvant treatment strategies.
Beneficial effect of autologous blood transfusion on infectious complications after colorectal cancer surgery.
Homologous blood transfusion has been associated with an increased risk of postoperative infectious complications. To test the clinical consequences of this apparently immunosuppressive effect of homologous blood in a controlled trial, we designed a study in which the control group deposited autologous blood before their operations for use should transfusion be needed. We enrolled 120 patients with apparently curable colorectal cancer who were able to predeposit autologous blood (haemoglobin > 12.5 g/dL). 62 patients were assigned to receive homologous blood if blood transfusions were needed during operation, and the other 58 to receive their own predeposited blood followed, if necessary, by homologous blood [corrected]. Despite the similarity between the groups in factors known to affect the risk of postoperative infections, there was a significant difference in postoperative infection rate between the homologous and autologous blood groups (17 [27%] vs 7 [12%], p < 0.05; unadjusted odds ratio 2.75 [95% CI 1.07-7.11). The rates of non-infectious complications were similar Probably because their preoperative blood depositing caused the autologous blood patients to have lower haemoglobin concentrations, they were more likely to require transfusion than were the homologous blood group (53 [91%] vs 37 [60%], p < 0.001; relative risk 1.53 [1.24-1.89]). 20 (35%) required homologous as well as autologous blood. To adjust for the many infection-related factors, we did multivariate regression analysis; tumour location, preoperative ASA index, and study group assignment were the only significant risk factors. The odds ratio for postoperative infections adjusted for these factors was 2.84 (1.02-7.98, homologous vs autologous). Testing of delayed-type hypersensitivity responses before and after surgery showed decreases in both mean diameter and number of positive reactions in recipients of homologous blood and slight increases in those who received autologous blood. This study shows the clinical potential of blood-transfusion-mediated immunomodulation, which may be important also in tumour immunology.
Influence of autologous blood transfusion on natural killer and lymphokine-activated killer cell activities in cancer surgery.
BACKGROUND AND OBJECTIVES: Immunosuppression associated with blood transfusion may influence postoperative infection rates. It may also affect the prognosis of patients treated surgically for colorectal cancer. To control this effect, study protocols have applied autologous blood donation programs, which are thought to be immunologically neutral. However, evidence has emerged that blood donation itself might have suppressive effects on natural killer (NK) cell activities. At present, there are no data available on the effects of autologous blood transfusion on NK or lymphokine-activated killer (LAK) cells. This might be of interest as LAK cells may be active in tumor control.
MATERIALS AND METHODS: 26 patients who underwent surgical resection for colorectal cancer, were assigned at random into two groups: (1) autologous blood donation and transfusion, or (2) allogeneic blood transfusion. NK and LAK activities were determined before blood donation, at surgery, and on the 3rd and 8th postoperative day.
RESULTS: Blood donation induced a small decrease in NK and LAK activities. The postoperative courses of the two groups differed. In the allogeneic group, NK activity (-50%, p = 0.018) and LAK activity decreased (-60.7%, p = 0.043), whereas in the autologous group the decline in LAK was less pronounced (-33.7%, p = 0.091), and their NK activity even increased (+17.4%, p = 0.315). NK activity was modulated differently in the two study groups (0.0036). Differences in LAK activities were found between the 3rd and 8th day postoperatively (p = 0.354).
CONCLUSIONS: In patients receiving autologous blood transfusion, postoperative suppressed NK and LAK activities were modulated. This implies that autologous blood transfusion is not immunologically neutral, but has an intrinsic immunomodulatory potential.
Modulation of immune response by blood transfusion: evidence for a differential effect of allogeneic and autologous blood in colorectal cancer surgery.
Even though blood transfusion-associated immunomodulatory effects have been reported, the basic immune mechanism is still not understood. Data from studies on the clinical effects of allogeneic blood-induced immunosuppression are contradictory. However, there are indications that autologous blood transfusion is not immunologically neutral but has intrinsic immunomodulatory potential. Therefore we investigated in vivo different immunological mediators in 56 randomized patients of a study comparing autologous and allogeneic blood transfusion in colorectal cancer surgery. Soluble IL-2 receptor, which is an indicator of general immune activation and the following immunologic refractory phase, indicated immunosuppression was more elevated at the seventh postoperative day in patients with allogeneic transfusions (p = .013) and autologous transfusions (p = .0003). The immunologic determination of TNF-alpha showed a significant postoperative increase in patients with autologous transfusions only (p = .0031). However, postoperative increase of soluble TNF-receptors p55 and p75 was also significant in patients transfused with allogenic blood (p = .022; p = .0014). The response to tetanus toxoid vaccination, an indicator of humoral immunity, was higher in patients transfused with allogeneic rather than autologous blood (p = .082), whereas responses of patients with autologous transfusions were even lower than in nontransfused patients. The reciprocal was already found for cell-mediated immunity determined by epicutaneously tested delayed-type hypersensitivity-reactions. IL-10 levels, an indicator of cellular immunosuppression, were determined in 27 additional patients before operation, immediately postoperative, and at the seventh postoperative day. IL-10 was found elevated immediately postoperative in allogeneic (p = .011) and nontransfused patients only (p = .042). The data from this study substantiate recent findings of a different immunomodulatory potential of allogeneic and autologous blood transfusion. They furthermore support the hypothesis that autologous blood transfusion does not contain immunologically neutral effects of allogeneic blood, but itself exerts an immunomodulatory effect.
Feasibility of a predeposit autologous blood donation program in colorectal cancer patients: results from a randomized clinical study.
The hematologic and transfusion data of a multicenter randomized trial investigating the effect of blood transfusions on the 5-year survival were used to study the feasibility of an autologous blood donation program in colorectal cancer patients. Three hundred and ten patients were randomized for autologous blood transfusions (predeposition of 2 units) or homologous blood transfusions, and transfusion rules were standardized. The Hb level in the patients who donated blood decreased by 20.1 +/- 1.3 g/l (mean +/- SEM) preoperatively and 4.5 +/- 1.8 g/l postoperatively, and in controls 3.7 +/- 1.1 g/l and 16.5 +/- 1.9 g/l (significantly different between the two groups, both pre- and postoperatively: p less than 0.01). Because blood loss and number of transfusions were similar in both groups, this indicated that either preoperative or postoperative erythropoiesis is stronger in patients who had donated blood. Twenty-three percent of the autologous patients and 61% of the homologous patients were exposed to homologous blood. The effectiveness of the procedure differed per tumor localization. In patients with a right-sided colon carcinoma, 22% of the control patients needed homologous blood, compared to 10% of the autologous patients. In patients with other colon carcinomas, this was 52 and 16%, respectively, and in patients with a rectal carcinoma 85 and 41%. We conclude that predeposition of 2 units of blood for colorectal cancer surgery is feasible and useful to prevent homologous blood usage in a significant number of patients with left colon carcinoma or rectal carcinoma.
Autologous blood transfusion for hepatectomy in patients with cirrhosis and hepatocellular carcinoma: use of recombinant human erythropoietin.
BACKGROUND: We evaluated the benefit of autologous blood transfusion and the effect of recombinant human erythropoietin (rh-EPO) on preoperative autologous blood donation for hepatectomy in patients with cirrhosis.
METHODS: Forty-two patients with cirrhosis and hepatocellular carcinoma underwent hepatectomy, 21 of whom (group A) donated autologous blood before operation. Eleven of these patients (group A1) were administered rh-EPO before operation, and ten patients (group A2) were untreated. Twenty-one patients (group B) did not donate autologous blood.
RESULTS: The frequency of homologous blood transfusion was 24% in group A and 62% in group B (p < 0.05). Preoperative erythropoiesis increased markedly in group A1, and postoperative erythropoietin production was not suppressed in this group. Postoperative hematocrits recovered significantly more rapidly in patients transfused with only autologous blood. Postoperative serum total bilirubin concentrations were significantly higher in patients with transfused homologous blood.
CONCLUSIONS: Autologous blood transfusion yields clinically superior results for hepatectomy in patients with cirrhosis when compared with homologous transfusion. Preoperative rh-EPO administration minimizes presurgical decreases in hematocrit caused by autologous blood donation.
Effect of packed red blood cells transfusion on plasma fibronectin during liver resection.
Our study aimed at evaluating the effect of blood transfusion - allogeneic or autologous - on plasma levels of fibronectin during liver resections. Thirty-five patients scheduled for liver resection were randomly allocated to receive autologous (group autologous blood transfusion (ABT), n= 19) or allogeneic (homologous) (homologous blood transfusion (HBT), n= 16) packed red blood cell to maintain serum haemoglobin concentration above 9 g. Serum levels of fibronectin were measured before induction of anaesthesia, at the end of operation and at first, third and sixth postoperative day. Perioperative morbidity and survival rate were also recorded. Serum fibronectin levels were significantly higher (P < 0.05) in the autologous group than in the allogeneic, at the first (134 +/- 49 microg mL(-1) vs. 89 +/- 31 microg mL(-1)) and third (178 +/- 51 microg mL(-1) vs. 96 +/- 41 microg mL(-1)) postoperative day. No differences in survival and complication rate between the two groups were observed. Concentrations of serum fibronectin seem to be adversely affected by allogeneic blood transfusion during liver resection surgery, although this does not seem to affect patients' morbidity and mortality.
[A comparison of autologous transfusion procedures in hip surgery].
The risks associated with transfusion can be minimized with autologous blood. The efficiency of preoperative deposit, preoperative hemodilution and intra- and postoperative autotransfusion in reducing homologous transfusions has been demonstrated. There seem to be few studies, however, that compared the different methods of autologous transfusion. This study was designed to evaluate the comparative efficiency of these methods. PATIENTS AND METHODS. Sixty-four patients scheduled for total hip arthroplasty were randomly divided into four groups: group I--preoperative autologous deposit: group II--preoperative hemodilution; group III--intra- and postoperative autotransfusion; group IV--control. Preoperative autologous donations were stored in CPDA-1 buffer. Three units of 450 ml were requested. A predonation hemoglobin (Hb) concentration of 11 g dl was required. Surgery was carried out in the 5th week after the first donation. Preoperative hemodilution to Hb 9 g/dl was carried out after induction of anesthesia and initial circulatory stabilization. A cell separator was used for intra- and postoperative autotransfusion. Postoperative autotransfusion of drainage blood was continued until 6 h after the beginning of the operation. Polygeline was used for volume resuscitation. If the Hb concentration fell below 9 g/dl in the operating room and intensive care unit or below 10 g/dl in the general ward, autologous blood or homologous packed red cells were transfused. Autologous blood collected with the cell separator was retransfused at the end of the operation and after the autotransfusion period irrespective of the actual Hb concentration. RESULTS. The general data of the patients, blood loss, and Hb concentration at the beginning of the study and postoperatively were comparable in the four groups. Homologous transfusion requirements amounted to 0 (0-1250) ml (median, range) packed red cells in group I (preoperative deposit). 500 (0-2000) ml in group II (hemodilution), 125 (0-1000) ml in group III (autotransfusion) and to 500 (0-1500) ml in group IV (control). In group I 14 of 16 patients, in group II 1 of 16, in group III 8 of 16 patients, in group IV 5 of 15 patients did not require homologous transfusion. The difference between group I and IV was significant (p = 0.004 and p = 0.003). Global coagulation tests, antithrombin III, and total serum protein were comparable in the four groups. DISCUSSION. The efficiency of preoperative hemodilution to reduce homologous transfusion requirements is limited]. In the present study, as in two other recent studies, hemodilution did not reduce homologous transfusion requirements. Autotransfusion with a cell separator can save approximately 50% of the erythrocytes lost during hip arthroplasty and 70% of the drainage loss. The homologous transfusion requirements for the autotransfused group reported here were less than in the control group; the difference, however, was not statistically significant. Patients participating in preoperative autologous deposit did not require homologous blood for hip arthroplasty in 62%-70% of cases in other investigations; in the present study 88% of the patients did not require homologous blood. CONCLUSION. Under the conditions studied, preoperative autologous deposit was the most efficient method of autologous transfusion for hip arthroplasty. It should be employed primarily.
Options:
A: PAD reduces the risk of receiving an allogeneic blood transfusion and decreases the overall transfusion rates.
B: PAD reduces the risk of receiving an allogeneic blood transfusion but increases the overall transfusion rates.
C: PAD increases the risk of receiving an allogeneic blood transfusion and increases the overall transfusion rates.
D: PAD has no significant impact on the risk of receiving an allogeneic blood transfusion or the overall transfusion rates. | B |
215 | 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 and safety of indomethacin for the treatment of Alzheimer's disease based on the analysis of the available trial? Please answer this question based on the information provided below:
Clinical trial of indomethacin in Alzheimer's disease.
In a 6-month, double-blind, placebo-controlled study, 100 to 150 mg/d indomethacin appeared to protect mild to moderately impaired Alzheimer's disease patients from the degree of cognitive decline exhibited by a well-matched, placebo-treated group. Over a battery of cognitive tests, indomethacin patients improved 1.3% (+/- 1.8%), whereas placebo patients declined 8.4% (+/- 2.3%)--a significant difference (p < 0.003). Caveats include adverse reactions to indomethacin and the limited scale of the trial.
Options:
A: Indomethacin significantly improved cognitive function in Alzheimer's disease patients without any serious side effects.
B: Indomethacin showed no significant improvement in cognitive function and had a higher dropout rate due to gastrointestinal adverse events.
C: Indomethacin significantly reduced the progression of Alzheimer's disease but had a higher incidence of death.
D: Indomethacin had no effect on Alzheimer's disease and was well tolerated with no significant adverse events. | B |
216 | 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 paracetamol in treating fever in children, specifically in terms of fever clearance time, febrile convulsions, and adverse events? Please answer this question based on the information provided below:
Efficacy of tepid sponging versus paracetamol in reducing temperature in febrile children.
A block randomized clinical trial to compare the efficacy of tepid sponging with the use of paracetamol in febrile children was undertaken at the Queen Elizabeth Central Hospital, Blantyre. Eighty children aged between 6 and 54 months with axillary temperatures of between > or = 38.5 degrees C and < or = 40 degrees C and a clinical diagnosis consistent with upper respiratory tract infection and/or malaria were block randomized to receive either oral paracetamol (15 mg/kg) or tepid sponging. Children receiving tepid sponging were sponged from head to toe (except the scalp) by leaving a thin layer of water on the body. If the body became dry it was repeated and continued until the axillary temperature fell to < 38.5 degrees C. Axillary temperature and assessment of discomfort (convulsions, crying, irritability, vomiting and shivering) were recorded every 30 minutes for 2 hours. A significantly greater and more rapid reduction of fever was demonstrated with paracetamol than with tepid sponging. Tepid sponging without antipyretics is often used to reduce fever, but our results suggest that this is effective only during the 1st 30 minutes. Paracetamol is clearly more effective than tepid sponging in reducing body temperature in febrile children in a tropical climate.
Evaluation of sponging and antipyretic medication to reduce body temperature in febrile children.
Two hundred and twenty-four children aged 6 months to 5 years, with rectal temperatures greater than or equal to 30 degrees (104 degrees F), were randomly treated with sponging alone or with medication including a single oral dose of aspirin 15 mg/kg, or paracetamol 15 mg/kg, or ibuprofen 8 mg/kg. Twenty-three children were excluded from the final analysis because they did not complete the study. Demographic characteristics of the patients were found to be comparable in all groups. Rectal temperatures were recorded every 30 min for a 3 h period. During the first 30 min of intervention, sponging was found to be more effective than all of the three medications. After 60 min, the effects of each medication became superior to sponging with tepid water in reducing body temperature. Twenty-three children were excluded from the final analysis because they did not complete the study. Comparing the effect of the three different medications, it was seen that the antipyretic efficacy of aspirin and ibuprofen were significantly more than paracetamol 3 h after intervention (P < 0.05). For the management of fever over 39 degrees C, it is therefore recommended to give children an antipyretic drug, preferably ibuprofen, and at the same time to begin sponging to provide a rapid and sustained antipyresis
Effect of paracetamol on parasite clearance time in Plasmodium falciparum malaria.
BACKGROUND: Routine antipyretic therapy in children with infectious diseases has long been the source of controversy. Each year, in addition to antimalarial medication, millions of children with Plasmodium falciparum malaria receive paracetamol to reduce fever. However, the usefulness of this practice has not been proven.
METHODS: In a randomised trial in Lambaréné, Gabon, 50 children with P falciparum malaria were treated with intravenous quinine, and received either mechanical antipyresis alone, or in combination with paracetamol. Rectal body temperature and parasitaemia were recorded every 6 h for 4 days. Plasma concentrations and inducible concentrations of tumour necrosis factor (TNF) and interleukin-6 were measured every 24 h. In addition, production of oxygen radicals was measured in both groups.
FINDINGS: The mean fever clearance time was 32 h for children treated with paracetamol and 43 h for those who received mechanical antipyresis alone; however, this 11 h difference was not significant (95% CI -2 to 24 h; p = 0.176). Parasite clearance time was significantly prolonged in patients who received paracetamol with a difference of 16 h (8-24 h; p = 0.004). Plasma concentrations of TNF and interleukin-6 were similar in both groups during the study. However, the induced concentrations of TNF, and the production of oxygen radicals, were significantly lower in children treated with paracetamol than those who received mechanical antipyresis alone.
INTERPRETATION: These data suggest that paracetamol has no antipyretic benefits over mechanical antipyresis alone in P falciparum malaria. Moreover, paracetamol prolongs parasite clearance time, possibly by decreased production of TNF and oxygen radicals.
A comparative evaluation of indomethacin, acetaminophen and placebo as antipyretic agents in children.
Acetaminophen: more harm than good for chickenpox?
STUDY OBJECTIVE: To determine whether acetaminophen affects the duration or severity of childhood varicella.
DESIGN: Randomized, double-blind, placebo-controlled trial.
SETTING: Office- and hospital-based pediatric practices.
PATIENTS: Seventy-two children between 1 and 12 years of age entered the study. One child was withdrawn because of high fever, and three children did not complete the study; 31 received placebo and 37 received acetaminophen.
INTERVENTIONS: Acetaminophen, 10 mg/kg/dose, was given at 8 AM, 12 PM, 4 PM, and 8 PM for 4 days. Placebo was given to the control group. Itching, appetite, activity, and overall condition were measured for 6 days. The time to last vesicle formation, time to total scabbing, and time to total healing were measured until complete resolution of the exanthem.
MEASUREMENTS AND MAIN RESULTS: The following results were better in the placebo group (p less than .05): time to total scabbing 5.6 days (SD 2.5) versus 6.7 days (SD 2.3) in the acetaminophen group, and itching on day 4 in the placebo group (symptom score 2.9 (SD 0.20) vs 2.2 (SD 0.26]. Activity was better in the acetaminophen group on day 2 (3.13 (SD 0.23) vs 2.82 (SD 0.24].
CONCLUSIONS: These results provide evidence that acetaminophen does not alleviate symptoms in children with varicella and may prolong illness.
Efficacy of sponging vs acetaminophen for reduction of fever. Sponging Study Group.
Seventy-three children with acute febrile illnesses were enrolled in a study to compare the efficacy of sponging, sponging plus acetaminophen, and acetaminophen alone as methods of lowering body temperature. The greatest temperature reduction was seen in the combined acetaminophen plus sponging group. The smallest temperature reduction was noted in children who received sponging alone. We urge reconsideration of routine sponging of febrile young patients.
Antipyretic efficacy of ibuprofen vs acetaminophen.
OBJECTIVE: To compare the antipyretic efficacy of ibuprofen, placebo, and acetaminophen.
DESIGN: Double-dummy, double-blind, randomized, placebo-controlled trial.
SETTING: Emergency department and inpatient units of a large, metropolitan, university-based, children's hospital in Michigan.
PARTICIPANTS: 37 otherwise healthy children aged 2 to 12 years with acute, intercurrent, febrile illness.
INTERVENTIONS: Each child was randomly assigned to receive a single dose of acetaminophen (10 mg/kg), ibuprofen (7.5 or 10 mg/kg), or placebo.
MEASUREMENTS/MAIN RESULTS: Oral temperature was measured before dosing, 30 minutes after dosing, and hourly thereafter for 8 hours after the dose. Patients were monitored for adverse effects during the study and 24 hours after administration of the assigned drug. All three active treatments produced significant antipyresis compared with placebo. Ibuprofen provided greater temperature decrement and longer duration of antipyresis than acetaminophen when the two drugs were administered in approximately equal doses. No adverse effects were observed in any treatment group.
CONCLUSION: Ibuprofen is a potent antipyretic agent and is a safe alternative for the selected febrile child who may benefit from antipyretic medication but who either cannot take or does not achieve satisfactory antipyresis with acetaminophen.
Management of feverish children at home.
OBJECTIVES: To compare the acceptability and effects on temperature of advice to unwrap children and give paracetamol or warm sponging treatments in the management of feverish illness at home.
DESIGN: A randomised, open, parallel group study using factorial design comparison of unwrapping, warm sponging plus unwrapping, paracetamol plus unwrapping, and paracetamol and warm sponging plus unwrapping.
SETTING: Homes of willing families with a feverish child recruited after consulting one of 21 participating general practitioners in Southampton.
SUBJECTS: 52 children aged from 3 months to 5 years with axillary temperatures before treatment of > or = 37.8 degrees C and < 40 degrees C.
MAIN OUTCOME MEASURES: Response to advice assessed over four hours; temperature assessed by continuous data logging from an axillary thermistor; acceptability of treatment to child and parent scored on Likert scales immediately after treatment and on return to health.
RESULTS: Response to treatment advice varied; unwrapping alone had little effect on temperature. Paracetamol increased the time below 37.2 degrees C in four hours by 109 (95% confidence interval 74 to 145) minutes compared with unwrapping; warm sponging caused the fastest reduction in temperature. Parents discriminated between treatments, preferring paracetamol.
CONCLUSION: Advice to give paracetamol is more effective than sponging or unwrapping in controlling temperature in children at home and is more acceptable to parents. Warm sponging has an additive effect and reduces fever more quickly than paracetamol.
Risks and benefits of paracetamol antipyresis in young children with fever of presumed viral origin.
To examine whether antipyretic therapy in young children is associated with potential risks (interference with enhanced host defences at febrile temperatures) or benefits (improved comfort and behaviour), a randomised, double-blind, placebo-controlled trial of paracetamol was conducted among 225 children 6 months to 6 years of age who presented with acute (less than or equal to 4 days) fever (greater than or equal to 38 degrees C per rectum) without evident bacterial focus of infection. Parents were asked to give paracetamol liquid 10-15 mg/kg or placebo every 4 h as needed for fever and to avoid bathing, sponging, or other pharmacological agents. Parents kept temperature and symptom diaries and recorded changes in child comfort and behaviour according to a pretested, 5-category Likert-type questionnaire 1-2 h after every dose. There were no significant differences between treated and placebo groups in mean duration of subsequent fever (34.7 vs 36.1 h) or other symptoms (72.9 vs 71.7 h). Paracetamol-treated children were more likely to be rated by their parents as having at least a 1-category improvement in activity (38 vs 11%; p = 0.005) and alertness (33 vs 12%; p = 0.036) but no significant differences were noted in mood, comfort, appetite, or fluid intake. That overall improvement in behaviour and comfort with paracetamol was not impressive is underscored by the inaccuracy of parents' "guess" at the end of the trial as to which agent their child had received-45% correct guesses for paracetamol and 52% for placebo. The data suggest that the clinically relevant hazards and benefits of paracetamol antipyresis have been exaggerated.
Evaluation of sponging and of oral antipyretic therapy to reduce fever.
Ibuprofen, acetaminophen, and placebo treatment of febrile children.
A double-blind, parallel-group, triple-dummy-designed, single-oral-dose study compared the efficacy, tolerability, safety, and dose-response of 5 mg/kg (n = 32) and 10 mg/kg (n = 28) ibuprofen suspension, 10 mg/kg acetaminophen elixir (n = 33), and placebo liquids (n = 34) in 127 children (2 to 11 years of age) with fever (101 degrees to 104 degrees F). Blood samples, oral temperatures, pulse, blood pressure, and respiration were obtained before and 1/2, 1, 2, 3, 4, 5, 6, and 8 hours after the dose was administered. The study was terminated early if oral temperature was greater than 104 degrees F or if it increased 1 degree F above baseline. All agents were well tolerated and more effective than placebo (p less than 0.05) for fever control. Ibuprofen, 10 mg/kg, was favored over 10 mg/kg acetaminophen (p less than 0.05). For temperatures greater than 102.5 degrees F, a dose-response relationship for 5 and 10 mg/kg ibuprofen was demonstrated in terms of percentage of fever reduction and in terms of the initial 2-hour rate of decrease in temperature. Antipyretic efficacy for temperatures greater than 102.5 degrees F was 10 mg/kg ibuprofen greater than 5 mg/kg greater than 10 mg/kg acetaminophen greater than placebo. All treatments were well tolerated. No significant clinical or laboratory abnormalities were noted. Ibuprofen suspension may be a safe and effective antipyretic in children.
Single-dose, placebo-controlled comparative study of ibuprofen and acetaminophen antipyresis in children.
Ibuprofen was evaluated as an antipyretic agent in 178 children (aged 3 months to 12 years) to compare dosage (5 vs 10 mg/kg), establish absolute efficacy (with a placebo control group), determine relative efficacy (ibuprofen vs acetaminophen), evaluate maximum efficacy, and identify potential confounding variables. Ibuprofen 5 mg/kg was minimally effective in children less than 6 years of age who had an initial temperature of at least 38.8 degrees C (101.9 degrees F). Ibuprofen 10 mg/kg was more effective for febrile children. The area under the curve for temperature (or change in temperature) captured the net effect of each drug and provided the best estimate for efficacy comparison during a defined period. A linear correlation between initial temperature and measures of efficacy was observed. A twofold increase in efficacy was observed for children with an initial temperature less than 38.8 degrees C. A similar effect was noted for each treatment group. Age was also found to have confounding effects on antipyretic response. A complex interaction between antipyretic response, initial temperature, and age raises questions about the pharmacodynamics of the antipyretic response. We conclude that the most important variable in antipyretic study design is initial temperature. The influence of initial temperature on the magnitude of the response to an antipyretic drug is a previously unappreciated finding with potential impact on pharmacodynamic investigations of antipyretic medications. We describe this finding as nonlinear pharmacodynamics.
Options:
A: Paracetamol significantly reduced fever clearance time and the risk of febrile convulsions compared to placebo and physical methods.
B: Paracetamol showed a superior antipyretic effect compared to placebo, but no significant difference was found when compared to physical methods.
C: There was insufficient evidence to show that paracetamol influenced the risk of febrile convulsions, and no significant difference in fever clearance time was found between paracetamol and physical methods.
D: Paracetamol was associated with a higher number of severe adverse events compared to placebo and physical methods. | C |
217 | 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 electrical stimulation (ES) for improving muscle strength and function in patients with rheumatoid arthritis (RA) based on the reviewed studies? Please answer this question based on the information provided below:
Rehabilitation of atrophied muscle in the rheumatoid arthritic hand: a comparison of two methods of electrical stimulation.
This study compares the effectiveness of two therapeutic electrotherapies which result in plastic adaptation in the atrophied muscle of rheumatoid arthritic hands. The natural discharge pattern of a fatigue-resistant motor unit (eutrophic electrotherapy) was more effective than a uniform 10 Hz electrotherapy. It was concluded that uniform 10 Hz electrotherapy ignored the information carried in the motor unit action potential spike train, which was the signal inducing rapid and behaviourally effective plastic adaptation.
Options:
A: ES showed no significant benefit compared to a control group in terms of muscle strength and fatigue resistance.
B: ES demonstrated significant benefit in muscle strength and fatigue resistance, particularly with patterned stimulation, but the evidence is limited due to the low quality of the trial.
C: ES was found to be harmful and led to increased muscle atrophy and fatigue in RA patients.
D: ES had significant benefits, but the side effects were severe and outweighed the positive outcomes. | B |
218 | 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 of anterior and posterior surgical approaches for inserting a hemiarthroplasty to the hip in terms of clinical outcomes? Please answer this question based on the information provided below:
Internal fixation versus hemiarthroplasty for the displaced subcapital fracture of the femur. A prospective randomised study.
A prospective randomised trial of surgical treatment for the displaced subcapital femoral fracture in patients of 70 years or more is presented. Two hundred and eighteen patients were randomly allocated into one of three treatment groups: manipulative reduction and internal fixation using Garden screws; Thompson hemiarthroplasty through a posterior (Moore) approach; and Thompson hemiarthroplasty through an anterolateral (McKee) approach. There is no significant difference in the mortality of the internal fixation and posterior arthroplasty groups. Both groups showed a significantly higher mortality than patients operated on through the anterior approach. The technical results of operation were worse in the internally fixed group, with only 40 per cent being satisfactory. Mobilisation was best achieved after the posterior approach. It is concluded that Thompson hemiarthroplasty, using an anterolateral approach, is the safest operation in this group of patients.
Options:
A: The anterior approach showed significantly better clinical outcomes and lower mortality rates.
B: The posterior approach showed significantly better clinical outcomes and lower mortality rates.
C: There was no significant difference in clinical outcomes between the anterior and posterior approaches.
D: There is insufficient evidence to determine the optimum surgical approach for inserting a hemiarthroplasty to the hip. | D |
219 | 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 main conclusion regarding the effectiveness of non-surgical interventions for late radiation cystitis in patients who have received radical radiotherapy to the pelvis? Please answer this question based on the information provided below:
Post-irradiation cystitis improved by instillation of early placental extract in saline.
21 patients with chronic cystitis due to irradiation therapy for carcinoma of the cervix had symptomatic and cystoscopic improvement from instillations of early placental extract in saline. There was a statistically significant difference between these patients and a control group.
Flavoxate hydrochloride for urinary urgency after pelvic radiotherapy: comparison of 600 mg versus 1200 mg daily dosages.
This preliminary communication reports on a non-randomized pilot type trial of 34 females with urgency after pelvic radiotherapy who were treated with flavoxate hydrochloride for 4 weeks. A dosage of 600 mg/day was given to 21 patients and 1200 mg/day to 13 patients. Clinically, both regimens achieved comparable results. Urodynamically (first desire volume, bladder capacity and pressure at capacity) treatment with 1200 mg/day was significantly superior to 600 mg/day. Both schedules were equally well tolerated by patients and no treatment interruption occurred. A randomized double-blind trial comparing 600 and 1200 mg/day flavoxate hydrochloride is currently underway the results of which will be reported in due course.
Options:
A: There is strong evidence from multiple randomized controlled trials supporting the effectiveness of non-surgical interventions.
B: There is limited evidence from a few non-randomized studies, making it difficult to draw firm conclusions about the effectiveness of non-surgical interventions.
C: There is no evidence supporting the effectiveness of non-surgical interventions for late radiation cystitis.
D: There is conclusive evidence from retrospective case series supporting the effectiveness of non-surgical interventions. | B |
220 | 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 observed effects of inspiratory muscle training on patients with bronchiectasis in terms of endurance exercise capacity, PiMax, and quality of life? Please answer this question based on the information provided below:
Exercise training and inspiratory muscle training in patients with bronchiectasis.
BACKGROUND: Bronchiectasis is a chronic suppurative lung disease often characterised by airflow obstruction and hyperinflation, and leading to decreased exercise tolerance and reduced health status. The role of pulmonary rehabilitation (PR) and inspiratory muscle training (IMT) has not been investigated in this group of patients.
METHODS: Thirty two patients with idiopathic bronchiectasis were randomly allocated to one of three groups: PR plus sham IMT (PR-SHAM), PR plus targeted IMT (PR-IMT), or control. All patients (except the control group) underwent an 8 week training programme of either PR or PR plus targeted IMT. Exercise training during PR was performed three times weekly at 80% of the peak heart rate. IMT was performed at home for 15 minutes twice daily over the 8 week period.
RESULTS: PR-SHAM and PR-IMT resulted in significant increases in the incremental shuttle walking test of 96.7 metres (95% confidence interval (CI) 59.6 to 133.7) and 124.5 metres (95% CI 63.2 to 185.9), respectively, and in endurance exercise capacity of 174.9% (95% CI 34.7 to 426.1) and 205.7% (95% CI 31.6 to 310.6). There were no statistically significant differences in the improvements in exercise between the two groups. Significant improvements in inspiratory muscle strength were also observed both in the PR-IMT group (21.4 cm H2O increase, 95% CI 9.3 to 33.4; p = 0.008) and the PR-SHAM group (12.0 cm H2O increase, 95% CI 1.1 to 22.9; p = 0.04), the magnitude of which were also similar (p = 0.220). Improvements in exercise capacity were maintained in the PR-IMT group 3 months after training, but not in the PR-SHAM group.
CONCLUSION: PR is effective in improving exercise tolerance in bronchiectasis but there is no additional advantage of simultaneous IMT. IMT may, however, be important in the longevity of the training effects.
Options:
A: Inspiratory muscle training had no significant effect on endurance exercise capacity, PiMax, or quality of life.
B: Inspiratory muscle training improved endurance exercise capacity, PiMax, and quality of life.
C: Inspiratory muscle training decreased endurance exercise capacity, PiMax, and quality of life.
D: Inspiratory muscle training only improved endurance exercise capacity but had no effect on PiMax or quality of life. | B |
221 | 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 penicillin regimens in preventing rheumatic fever recurrence and streptococcal throat infections in patients with a history of rheumatic fever? Please answer this question based on the information provided below:
A controlled study of three methods of prophylaxis against streptococcal infection in a population of rheumatic children. II. Results of the first three years of the study, including methods for evaluating the maintenance of oral prophylaxis.
PROPHYLAXIS OF RECURRENT RHEUMATIC FEVER: INEFFECTIVENESS OF INTERMITTENT "THERAPEUTIC" ORAL PENICILLIN.
Discontinuation of antistreptococcal prophylaxis. A double-blind study in rheumatic patients free of heart disease.
Prophylaxis of recurrent rheumatic fever. Therapeutic-continuous oral penicillin vs monthly injections.
Rheumatic fever prophylaxis using benzathine penicillin G (BPG): two- week versus four-week regimens: comparison of two brands of BPG.
OBJECTIVE: This prospective study was aimed at answering two important questions: 1) Is a biweekly schedule of 1.2 million U intramuscular benzathine penicillin G (BPG) superior to a 4-week one in the prevention of upper respiratory Group A beta-hemolytic streptococcal (GABHS) infections and rheumatic fever (RF) recurrences? 2) Is there a difference in the bioavailability of BPG obtained from different manufacturers?
METHODOLOGY: Three hundred sixty rheumatic patients aged 4 to 20 years were randomly assigned to either a biweekly (190 patients) or 4-week (160 patients) BPG prophylactic schedule and were followed-up monthly for 2 years by clinical examination, throat swab culture for GABHS and measurement of antistreptolysin O titer to detect GABHS infection and/or recurrences of RF (according to revised Jones' Criteria). Thereafter, 34 rheumatic subjects, aged 8 to 16 years were randomly assigned to receive a 4-week injection of 1.2 million U of either a locally manufactured BPG brand (22 patients) or an imported one (12 patients). Sera of all patients were tested for penicillin level by plate diffusion method on days 1, 2, 3, 4, 5, 6, 7, 14, 21, and 28 after the intramuscular injection of BPG.
RESULTS: The GABHS infection rate was found to be 0.2% and 0.3% for patients on the biweekly and 4-week BPG schedules, respectively, with no significant differences between them. However, the RF recurrence rate/patient/year for the 4-week schedule patients (0.12) was double that for the biweekly schedule ones (0.06). Estimation of the bioavailability of the two different brands of BPG demonstrated a difference in their pharmacokinetics and a decrease in the serum penicillin concentration below the minimum inhibitory concentration 3 weeks after the injection of either brand.
CONCLUSION: Although a biweekly schedule may not be superior in preventing upper respiratory GABHS infection, it may play a role in preventing the sequelae of such infections. The short duration of penicillinemia explains the superiority of the 2-week schedule in RF prophylais. The difference in the pharmacokinetics of penicillin brands might contribute to the high recurrence rate of RF reported in Egypt.
Prophylaxis of recurrences of rheumatic fever with penicillin given orally; final report of a five year study.
Rheumatic fever recurrences: controlled study of 3-week versus 4-week benzathine penicillin prevention programs.
To compare the merits of 3-week versus 4-week injections of benzathine penicillin G in preventing recurrence of rheumatic fever, 179 patients aged 4 to 19 years were assigned to one of the two programs. Age, weight, cardiac status, and streptococcal infections among the patients and their family members studied in each program were comparable. Eight-two patients and their family members were monitored for streptococcal infections. Compliance in the two programs was comparable. Of the 63 patients who stayed in the 4-week program, RF recurred in six, as a result of prophylaxis failure in five and associated with partial compliance in one. Of the 90 patients in the 3-week program, RF recurred in one, associated with partial compliance; no failures occurred (P = 0.01). We recommended that for RF chemoprophylaxis in individuals at great risk, regardless of age, benzathine penicillin injections should be administered every 3 rather than every 4 weeks.
Long-term outcome of patients with rheumatic fever receiving benzathine penicillin G prophylaxis every three weeks versus every four weeks.
OBJECTIVE: To compare the efficacy of injections of 1.2 million units of benzathine penicillin G given every 3 weeks versus every 4 weeks for secondary prevention of rheumatic fever, based on the long-term outcome of patients receiving such prophylaxis.
METHODS: A total of 249 consecutive patients with rheumatic fever, randomly assigned to either a 3-week or a 4-week regimen, were examined every 3 to 6 months, and followed for 794 and 775 patient-years, respectively.
RESULTS: Compliance with each regimen was comparable: 83 (66.9%) of 124 patients in the 3-week group versus 92 (73.6%) of 125 patients in the 4-week group stayed in the program (p > 0.05). Streptococcal infections occurred less frequently in those receiving the 3-week regimen: 7.5 versus 12.6 per 100 patient-years (p < 0.01). Prophylaxis failed in 2 patients receiving the 3-week regimen and in 10 receiving the 4-week regimen (0.25 and 1.29 per 100 patient-years respectively; p = 0.015). Serum penicillin levels were adequate (> or = 0.02 micrograms/ml) in 100 (56%) of 179 samples obtained 21 days after penicillin injection in the 3-week regimen, and in 51 (33%) of 155 samples obtained 28 days after injection in the 4-week regimen (p < 0.01). Of 71 patients with mitral regurgitation in the 3-week regimen, 47 (66%) no longer had the murmur; of 87 patients in the 4-week regimen, 40 (46%) no longer had the murmur (p < 0.05).
CONCLUSIONS: This 12-year controlled study indicates that the outcome of patients with rheumatic fever is better with a 3-week than with a 4-week penicillin prophylaxis regimen. Greater emphasis and more widespread use of the 3-week regimen should be recommended.
Three- versus four-week administration of benzathine penicillin G: effects on incidence of streptococcal infections and recurrences of rheumatic fever.
OBJECTIVE: To investigate the effects of 3-week versus 4-week administration of benzathine penicillin G (BPG) on the incidence of Group A streptococcal infections and the recurrences of rheumatic fever (RF).
STUDY DESIGN: We started, in 1979, randomly allocating all patients with RF to a 3-week or 4-week BPG prophylaxis program. They were examined at the RF clinic, every 3 to 6 months, and at any time they did not feel well. During 1979 to 1989, throat cultures and sera for antistreptolysin O and streptozyme titers were obtained at each clinic visit. Chest radiographs, electrocardiogram, color Doppler echocardiograms, and acute phase reactants were obtained.
SUBJECTS: Two hundred forty-nine patients fulfilled the revised Jones criteria and were followed until December 1991: 124 in the 3-week and 125 in the 4-week program. Their age, sex, weight, percentage with history of RF, severity of cardiac involvement, follow-up duration, and compliance to program were comparable. Eight hundred eighty throat cultures were collected in the 3-week program and 770 were collected in the 4-week program. Six hundred sixteen and 627 sera were determined in each program for antistreptolysin O, and 582 and 592 sera for streptozyme titers.
RESULTS: True streptococcal infections occurred in both programs: 39 infections in the 3-week program, and 59 infections in the 4-week program (7.5 vs 12.7 per 100 patient-years). Four infections with no antibody response occurred in the 3-week program, and three such infections in the 4-week program. Nine RF recurrences occurred in 8 patients in the 3-week program, and 16 recurrences in 16 patients in the 4-week program. Prophylaxis failure occurred in 2 of 124 patients in the 3-week program, and in 10 of 125 patients in the 4-week program (0.25 vs 1.29 per 100 patient-years). The overall recurrences/infections rate in each program was comparable, 13.6% vs 15.5%, but the recurrences/ infections rate due to prophylaxis failure was higher in the 4-week program than in the 3-week program, 3.0% versus 9.7%.
CONCLUSIONS: This 12-year prospective and controlled study documented that streptococcal infections and RF recurrences occurred more often in the 4-week program than in the 3-week program. The risk of prophylaxis failure was fivefold greater in the 4-week program than in the 3-week program.
Epidemiology and prophylaxis of rheumatic fever in Delhi--a five year follow-up.
Options:
A: Oral penicillin was more effective than intramuscular penicillin in preventing rheumatic fever recurrence and streptococcal throat infections.
B: Intramuscular penicillin was more effective than oral penicillin in preventing rheumatic fever recurrence and streptococcal throat infections.
C: There was no difference in effectiveness between oral and intramuscular penicillin in preventing rheumatic fever recurrence and streptococcal throat infections.
D: Four-weekly intramuscular penicillin injections were more effective than 2-weekly or 3-weekly injections in preventing rheumatic fever recurrence and streptococcal throat infections. | B |
222 | 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 of the meta-analysis comparing primary repair to fecal diversion in the management of penetrating colon injuries in terms of morbidity and mortality? Please answer this question based on the information provided below:
Management of penetrating colon injuries. A prospective randomized trial.
Fifty-six patients with penetrating colon injuries were entered into a randomized prospective study. Management of the colon injury was not dependent on the number of associated injuries, amount of fecal contamination, shock, or blood requirements. Twenty-eight patients were treated with primary repair or resection and anastomosis and 28 patients were treated by diversion (24 colostomy, 3 ileostomy, 1 jejunostomy). The average Penetrating Abdominal Trauma Index score was 23.9 for the diversion group and 26 for the primary repair group. There were five (17.9%) septic-related complications in the diversion group. This included four intra-abdominal abscesses and one subcutaneous wound infection. There were six (21.4%) septic-related complications in the primary repair group. This included one wound infection, two positive blood cultures, and three intra-abdominal abscesses. There were no episodes of suture line failure in the primary repair/anastomosis group. The authors conclude that, independent of associated risk factors, primary repair or resection and anastomosis should be considered for treatment of all patients in the civilian population with penetrating colon wounds.
Colorectal trauma: primary repair or anastomosis with intracolonic bypass vs. ostomy.
This prospective, randomized, controlled study was undertaken to compare primary repair or anastomosis with intracolonic bypass vs. ostomy in severe colon and intraperitoneal rectal injury. Patients were randomized at surgery following confirmation of injury. Data collected included demographics, mechanism and location of injury, trauma score (TS), injury severity score (ISS), penetrating abdominal trauma index (PATI), complications, length of hospital stay, and hospital charges. Twenty-two patients were studied: 11 with intracolonic bypass and 11 controls. The experimental and control groups were statistically similar in demographics and mechanism of injury, severity of injury (TS = 13.8 vs. 12.8; ISS = 27.5 vs. 24.2; PATI = 40.5 vs. 35.0), and complication rate. Length of stay (12.2 days vs. 20.7 days) and charges $27,885 vs. $53,599) tended to be greater in controls, and the comparison did not include subsequent colostomy closure. This study supports intracolonic bypass as a safe alternative to ostomy in severe colon and intraperitoneal rectal trauma.
Further evaluation of colostomy in penetrating colon injury.
Our objective was to compare, in a randomized prospective format, complication rates associated with primary repair versus fecal diversion in penetrating colon injury. During a 72-month period, 181 patients with penetrating colon injuries were entered in a randomized prospective study at an urban Level I trauma center. After intraoperative identification of colon injuries, patients were randomized to a primary repair or a diversion group. Randomization was independent of previously identified risk factors, including severity of colon injury, presence of hypotension, blood loss, extent of fecal contamination, and time from injury to operation. Five patients initially entered in the study protocol were removed because they died in the immediate postoperative period (< 24 hours). One hundred seventy-six patients were studied, of which 89 were randomized to primary repair and 87 to diversion. The average age in the diversion group was 26.4 years and it was 28.0 years in the primary repair group (P > 0.05). The average Penetrating Abdominal Trauma Index for the diversion group was 22.3, and it was 23.7 for the primary repair group (P > 0.05). There were 18 (21%) septic related complications in the diversion group and 16 (18%) in the primary repair group (P > .05). With respect to risk factors, complication rates were not higher in one study group versus the other. We conclude that, in the civilian population, all penetrating colon injuries should be managed with primary repair.
Randomized clinical trial to determine if delay from time of penetrating colonic injury precludes primary repair.
BACKGROUND: There is often a delay of more than 12 h in transferring patients with penetrating colonic injury from outlying hospitals to a regional referral centre. The aim of this prospective study was to determine whether primary suture of a penetrating colonic injury in the presence of delayed presentation, shock, peritoneal contamination or associated injuries leads to increased morbidity and mortality rates.
METHODS: Patients with penetrating colonic injuries were randomized to primary closure or colostomy. Patients were compared with regard to interval from injury to operation, associated injuries, duration of operation, postoperative complications and hospital stay.
RESULTS: Two hundred and forty patients were seen over a 69-month period. The interval from injury to operation ranged from 3 to 56 h, and was similar in the two treatment groups. Postoperative complications were similar in the two groups but there were significant differences in operation time (mean(s.d.) 127.1(45.8) min for primary repair and 142.3(43.0) min for colostomy; P = 0.009) and length of hospital stay (mean (range) 9 (6-56) versus 26 (13-64) days respectively; P < 0.001).
CONCLUSION: Delay from time of penetrating colonic injury is not a contraindication to primary repair. :
Primary repair of colon injuries: a prospective randomized study.
Due to the results of a 6-year experience with civilian penetrating colon injuries at Mount Carmel/Grace Hospital, in Detroit, Michigan, which had favored primary repair of colon injuries, a prospective randomized study was performed. Seventy-one patients with penetrating colon injuries were entered in a prospective randomized study. Forty-three patients were treated with primary repair or resection and anastomosis, and 28 patients were treated with diversion. The average Penetrating Abdominal Trauma Index score was 25.5 for the primary repair and 23.4 for the diversion groups. The majority of injuries as assessed by the Colon Injury Score (CIS) for the primary repair group were grades 2 (58%) and 3 (28%). The diversion group predominantly had grades 2 (64%) and 3 (25%). There was no significant difference between the two groups. There were 8 (19%) patients with colon and noncolon-related complications in the primary repair group, and 10 (36%) patients with colon, noncolon, and colostomy-related complications in the diversion group. In addition, there were 2 (7%) patients with complications following colostomy reversal. Independent risk factors for adverse outcomes were compared and used to calculate the probability for adverse outcomes with respect to the mode of treatment. The probability for adverse outcomes was statistically greater in the diversion group. An analysis was also made within the primary repair group comparing the subgroups of primary repair with, and without, resection of colon. It appears that the primary repair with resection of colon may have fewer complications; however, this conclusion is based on a statistically insufficient sample size. The authors contend that primary repair or resection with anastomosis is the method of choice for treatment of all penetrating colon injuries in the civilian population despite any associated risk factors for adverse outcomes.
Management of perforating colon trauma: randomization between primary closure and exteriorization.
During a 44 month trial, 268 patients with wounds of the colon were entered into a prospective, randomized, nonblinded study. Consideration for primary closure demanded that: preoperative shock was never profound, blood loss was less than 20% of estimated normal volume, no more than two intra-abdominal organ systems had been injured, fecal contamination was minimal, operation was begun within eight hours, and wounds of colon and abdominal wall were never so destructive as to require resection. Once such criteria had been satisfied, colon wound management was dictated by last digit in the randomly assigned hospital number; odd indicated primary closure; even, exteriorization of the wound or primary closure with protection by a proximal vent. Results obtained in 139 determinant patients eligible for randomization revealed that primary closure (67 patients) had a lower infection rate of the incision (48% vs S7%, p > 0.05) and a still lower infection rate for the abdomen proper (15% vs 29%, p < 0.05) on comparison to the 72 patients with a randomized colostomy. Morbidity otherwise for the randomized colostomy was tenfold greater than if a primary closure had been performed. Average postoperative stay was six days longer (p < 0.01) if a colostomy had been created, exclusive of subsequent hospitalization for colostomy closure; while the total extra cost for management of the colon wound by colostomy was approximately $2,700.00. Although immediate mortalities were identical, one late death occurred following colostomy closure. These data not only confirm the safety of primary closure for colon wounds in selected cases, but also indicate that such should become the preferred method of treatment whenever specific criteria have been met.
Options:
A: Primary repair was associated with significantly higher mortality and more complications compared to fecal diversion.
B: Primary repair showed no significant difference in mortality but had significantly fewer total complications and infectious complications compared to fecal diversion.
C: Primary repair had significantly higher mortality and fewer complications compared to fecal diversion.
D: Primary repair showed no significant difference in both mortality and total complications compared to fecal diversion. | B |
223 | 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 nebulized morphine in reducing dyspnoea in patients with end-stage interstitial lung disease? Please answer this question based on the information provided below:
Low-dose nebulized morphine does not improve exercise in interstitial lung disease.
Recent reports have suggested that low-dose nebulized morphine may improve exercise tolerance in patients with interstitial lung disease (ILD) by acting on peripheral opioid-sensitive pulmonary receptors. We therefore examined whether the administration of low-dose nebulized morphine would influence dyspnea or the breathing pattern during exercise of subjects with ILD and improve their exercise performance. Each of six subjects with ILD underwent three maximal incremental cycle ergometer tests, each test separated from the last by at least 3 d. Each exercise test was similar except that 30 min before exercise, the subjects received nebulized saline (control), morphine 2.5 mg, or morphine 5.0 mg, respectively, in double-blinded fashion. No significant differences were noted in exercise duration, maximal workload, or sense of dyspnea at the end of exercise in the control test and the tests with either morphine 2.5 mg or morphine 5.0 mg. Nor were significant differences noted in resting, submaximal, or end-exercise measurements of oxygen uptake (VO2), carbon dioxide output (VCO2), end-tidal CO2 (PETCO2), oxygen saturation (SaO2), minute ventilation (VI), respiratory frequency (f), tidal volume (VT), or heart rate (HR) in the three tests. Low-dose nebulized morphine did not alter the subjects' breathing pattern or affect the relationship between dyspnea and ventilation during exercise. No significant side effects were noted. The administration of low-dose nebulized morphine to subjects with ILD neither relieves their dyspnea during exercise nor improves their maximal exercise performance.
Options:
A: Nebulized morphine significantly improved dyspnoea and exercise performance.
B: Nebulized morphine had no effect on dyspnoea but improved exercise performance.
C: Nebulized morphine had no significant effect on dyspnoea or exercise performance.
D: Nebulized morphine worsened dyspnoea and reduced exercise performance. | C |
224 | 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 short-acting beta agonists in treating infants under 2 years of age with recurrent wheeze? Please answer this question based on the information provided below:
Controlled trial of nebulized albuterol in children younger than 2 years of age with acute asthma.
To determine the response to nebulized beta 2 agonist, 28 children younger than 2 years of age who visited the emergency department during an episode of acute asthma were studied. Each subject had a previous history of recurrent wheezing episodes. They were randomly assigned to receive two administrations of either nebulized albuterol (0.15 mg/kg per dose) or placebo (normal saline) with oxygen, 1 hour apart. After two nebulizations, the albuterol-treated patients had a greater improvement in clinical status (respiratory rate, degree of wheezing and accessory muscle use, total clinical score, and arterial oxygen saturation) than the placebo group. None of the patients in the albuterol group experienced a decrease of arterial oxygen saturation of greater than or equal to 2%. It is concluded that a trial of nebulized beta 2 agonists is warranted in the treatment of acute asthma in infants and young children.
Inhaled salbutamol for wheezy infants: a randomised controlled trial.
BACKGROUND: Salbutamol is frequently used as a bronchodilator for infants who wheeze. Many single dose studies have questioned its effectiveness.
AIMS: To investigate the response of wheezy infants to salbutamol over an extended time period in order to elucidate either symptomatic relief or a protective effect.
METHODS: Eighty infants under 1 year, with persistent or recurrent wheeze and a personal or family history of atopy, were recruited to a randomised, double blind, cross over, placebo controlled trial. Salbutamol (200 microg three times daily) or placebo were administered regularly over two consecutive treatment periods of four weeks via a spacer and mask. Symptoms of wheeze and cough were recorded in a diary. At the end of the study pulmonary function tests were performed before and after salbutamol (400 microg).
RESULTS: Forty eight infants completed the diary study; 40 infants underwent pulmonary function testing. No difference in mean daily symptom score was observed between the salbutamol and placebo periods. There was no difference in the number of symptom free days. Compliance and forced expiratory flows remained unchanged and resistance increased following salbutamol. There was no relation between the response measured by symptom score or pulmonary function in individual patients.
CONCLUSION: In wheezy infants with an atopic background, there was no significant beneficial effect of salbutamol on either clinical symptoms or pulmonary function. Clinical effects could not be predicted from pulmonary function tests. Salbutamol cannot be recommended as the bronchodilator of choice in this age group.
Delivery of salbutamol by metered dose inhaler and valved spacer to wheezy infants: effect on bronchial responsiveness.
The efficacy of a new valved spacer device, the Babyhaler inhaler (Glaxo) for administering metered dose inhaler treatment via a facemask to infants was assessed. In a double blind, single dose study, salbutamol (800 micrograms) or placebo were given on separate days to 12 sedated, sleeping, wheezy infants during a symptom free interval. Lung function was measured before and after administration and the bronchial response to aerosol challenge with methacholine was then assessed using the squeeze technique. A small increase in heart rate and a drop in arterial oxygen tension followed salbutamol administration. No other change in lung volume or air flow obstruction was detected. Bronchial responsiveness decreased significantly after the administration of salbutamol by Babyhaler, the PC30 (provoking concentration of methacholine causing a 30% fall in maximal flow at functional residual capacity by the squeeze technique) increasing from a median of 3.8 g/l after placebo to 12.5 g/l after salbutamol. The Babyhaler is an effective device for administering bronchodilator to wheezy infants. The small scale of the response may be attributable to the uncertain effect of beta agonists in this population. Furthermore, pulmonary deposition of inhaled aerosols may be reduced in nose breathing, sleeping infants.
Treatment of recurrent acute wheezing episodes in infancy with oral salbutamol and prednisolone.
UNLABELLED: The aim of this study was to investigate the role of oral salbutamol and prednisolone in the treatment of acute episodes of wheezing in infants under 15 months of age. Sixty-two acute episodes of wheezing were studied in 59 babies (age range 3-14 months; mean 7 months), who had all suffered at least one previous wheezy episode. Patients were randomised to receive either salbutamol and prednisolone, salbutamol and placebo or double placebo. Parents were requested to keep a diary card record of twice daily scoring of their baby's symptoms over the next 14 days. A significantly greater number of treatment failures occurred in the placebo group compared to babies treated with oral salbutamol (relative risk 2.51; 95% confidence intervals for relative risk 1.09-5.79). There was no difference in the number of treatment failures between babies treated with a combination of salbutamol and placebo and those treated with salbutamol and prednisolone (relative risk 0.71; 95% confidence intervals for relative risk 0.18-2.80).
CONCLUSION: This study demonstrates that oral salbutamol is beneficial in the treatment of acute episodes of wheezing in infancy. A combination of oral salbutamol and oral prednisolone appeared to have no additional benefit over treatment with oral salbutamol alone.
Short-term effect of albuterol, delivered via a new auxiliary device, in wheezy infants.
In a double-blind, placebo-controlled study, the response of lung function to albuterol, topically administered by a metered-dose inhaler (MD) through a baby-adapted auxiliary device, was evaluated in 36 wheezy infants (1.6 to 25.2 months of age; median 8.1 months). The auxiliary device contains an air chamber of 350 ml and two low-resistant valves separating the inspiratory from the expiratory line. After baseline lung function measurements by infant whole-body plethysmography, the patients were randomly assigned to inhale either three times two puffs albuterol (100 micrograms/puff) or three times two puffs placebo at 5-min intervals. Changes in the degree of pulmonary hyperinflation, estimated by thoracic gas volume (TGV) and/or in the degree of bronchial obstruction, estimated by thoracic gas volume (TGV) and/or in the degree of bronchial obstruction, estimated by airway conductance (Gaw), were measured at 5-min intervals for up to 30 min. TGV and Gaw were expressed as standard deviation scores (SDS) of values predicted, and patients improving TGV and/or Gaw more than 2 SD were considered responders. In comparison with placebo, a significant percentage improvement in TGV (by the mean 26 to 53%) and a significant percentage improvement in Gaw (by the mean 34 to 51%) could be found in the active treatment groups. The study documents the usefulness of a new auxiliary device for the administration of aerosolized bronchodilators to wheezy infants.
Clinical and physiological improvement after inhalation of low-dose beclomethasone dipropionate and salbutamol in wheezy infants.
UNLABELLED: Twenty-nine of initially 42 infants with recurrent wheeze (20 male and 9 female) with an age range of 2.1-25.2 months were randomly assigned to receive either 100 micrograms beclomethasone dipropionate (BDP) combined with 200 micrograms salbutamol (group BDP-S, n = 9), 200 micrograms salbutamol (group S, n = 8), or placebo (group P, n = 6) 3 times daily for a 6 weeks' treatment period. Six infants had to be treated openly with BDP-S (group O, n = 6) because of deterioration in the disease state. Ten babies were excluded because of incomplete data and poor drug compliance and further 3 because of needed rescue medication. The drugs were inhaled from a metered dose inhaler through a baby-adapted spacer device, the Babyhaler. Control was assessed by symptom diaries, and infant whole-body plethysmography. Values of thoracic gas volume (TGV), airway conductance (Gaw) and specific airway conductance (sGaw) were calculated numerically independent of age and body length in percent predicted and in standard deviation scores using regression equations taken from healthy infants previously evaluated. Functional improvement was considered to have occurred when either TGV, and/or Gaw improved more than 2 SD from baseline. There was a significant improvement in the symptom score (p < 0.05), particularly concerning cough, in addition to a significant decrease in pulmonary hyperinflation (TGV: p < 0.05) and improvement of Gaw (p < 0.01) and sGaw (p < 0.01) in the BDP-S group when compared to the P group. No significant differences were found between the BDP-S and S group and/or between the S and P groups.
CONCLUSIONS: In wheezy infants BDP improves clinical status and lung function, when given in combination with salbutamol by a baby-adapted spacer device.
Beta 2-agonists for the treatment of wheezy bronchitis?
Nebulized albuterol (salbutamol) for the treatment of wheezy bronchitis was evaluated in a double-blind trial comprising 28 acutely ill children younger than 18 months and in 13 children 18 to 36 months of age. No significant difference in clinical effect was shown between albuterol and saline in the youngest group of children. Albuterol had some beneficial effect in children older than 18 months.
Airway responsiveness in wheezy infants: evidence for functional beta adrenergic receptors.
The effect of nebulised salbutamol on the bronchial response to nebulised histamine was studied in five wheezy infants aged 3-12 months. The response to doubling concentrations of up to 8 g/l of histamine was assessed by the change in the maximum flow at FRC (VmaxFRC), measured by flow-volume curves produced during forced expiration with a pressure jacket. The concentration of histamine required to provoke a 30% fall in VmaxFRC (PC30) was measured. All of the infants responded to low concentrations of histamine during control tests before and after nebulised saline (mean PC30 1.07 and 0.51 g/l). On a separate day there was a similar response to histamine before salbutamol (PC30 0.57 g/l), but after salbutamol the response was completely abolished up to the maximum concentration of histamine in all subjects (PC30 greater than 8 g/l). Thus wheezy infants have highly effective beta 2 adrenoceptors in intrathoracic airways.
Options:
A: Short-acting beta agonists significantly improve respiratory rate, symptom scores, and reduce hospital admissions.
B: Short-acting beta agonists show no clear benefit in managing recurrent wheeze in infants under 2 years of age.
C: Short-acting beta agonists are highly effective in reducing bronchial reactivity and improving oxygen saturation in all settings.
D: Short-acting beta agonists are effective only when administered regularly at home. | B |
225 | 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 ursodeoxycholic acid (UDCA) and/or antibiotics in prolonging stent patency and survival in patients with malignant biliary strictures treated with endoscopic stenting? Please answer this question based on the information provided below:
Randomised trial of prevention of biliary stent occlusion by ursodeoxycholic acid plus norfloxacin.
Biliary stents are liable to clog. We investigated whether a choleretic plus an antibiotic could delay clogging. 20 consecutive patients with a malignant biliary stricture were randomised after endoscopic insertion of a polyethylene stent to receive ursodeoxycholic acid plus norfloxacin (13-15 mg/kg and 400 mg, daily) or conservative treatment. The drug combination was associated with: a longer median patency of first (49 vs 6 weeks) and all stents (38 vs 7 weeks); a prolonged median survival (67 vs 18 weeks); and a shorter mean hospital stay (0.2 vs 1.0 days per week of survival). Thus ursodeoxycholic acid plus norfloxacin may prevent stent clogging.
Prevention of biliary stent occlusion by ursodeoxycholic acid plus norfloxacin: a multicenter randomized trial.
We report a prospective randomized multicenter trial that tested the efficacy of combining ursodeoxycholic acid and norfloxacin in the prevention of polyethylene stent clogging in patients with obstructive jaundice due to an unresectable malignancy at the level of the common bile duct. After insertion of a 10-Fr straight polyethylene stent, patients were allocated to receive oral treatment with ursodeoxycholic acid and norfloxacin, or conservative treatment. The primary outcome measure was stent blockage within six months. Thirty-three patients (group I) received ursodeoxycholic acid and norfloxacin, and 29 received conservative treatment (group II). At six months, cumulative stent patency rate did not differ significantly between group I (47+/-11%, mean +/- SE, median 149 days) and group II patients (24+/-10%, mean +/- SE, median 100 days, P = 0.23, log-rank test). Four stents were clogged by ursodeoxycholic acid. Survival did not differ between the two groups. Combined therapy with ursodeoxycholic acid and norfloxacin failed to improve stent patency. Moreover, ursodeoxycholic acid can cause stent obstruction.
Prevention of biliary stent occlusion using cyclical antibiotics and ursodeoxycholic acid.
This study reports an open randomised controlled trial of cyclical antibiotics and ursodeoxycholic acid in prevention of plastic biliary stent occlusion. Seventy patients with malignant distal bile duct obstruction were randomised to either active treatment with cyclical antibiotics (ampicillin, metronidazole, ciprofloxacin) and ursodeoxycholic acid or no treatment after successful stent insertion. The two groups were well matched. The follow up was complete with stent occlusion or death being the end points. There was no difference in the incidence of stent occlusion between the two groups and the overall survival was similar. In conclusion, this study did not show any benefit of treatment with antibiotics and ursodeoxycholic acid in prolonging stent patency or improving survival.
A combination of ciprofloxacin and Rowachol does not prevent biliary stent occlusion.
BACKGROUND: Endoscopic insertion of biliary prostheses is now an established palliative treatment for frail and elderly patients with distal extrahepatic malignant biliary strictures who are unable to tolerate major surgery. The major limitation to long-term biliary stenting is late stent occlusion caused by bacterial adherence followed by encrustation with amorphous bacterial products. We studied the effect on the duration of stent patency of combination therapy with ciprofloxacin and Rowachol, a choleretic agent, in a group of patients who underwent stent insertion for extrahepatic malignant biliary strictures.
METHODS: Patients with this diagnosis were randomized to either active treatment with ciprofloxacin (500 mg twice daily) and Rowachol (2 tablets 3 times daily) or no drug treatment (control group). They were followed up prospectively and the end points of the study were stent occlusion and patient survival.
RESULTS: Forty-eight patients who had successful stent placement were recruited; 8 patients were excluded from the final analysis because of death in less than 1 month (5 patients) or stent replacement within a month because of persistent jaundice (3 patients). Twenty patients were randomized to the active and control groups. One patient in the active group withdrew because of nausea. The 2 groups were comparable with regard to age, gender, causes of extrahepatic malignant biliary strictures, and levels of serum alkaline phosphatase and bilirubin. There were significant reductions in mean serum bilirubin and alkaline phosphatase concentrations 1 month after stent placement. At the time of analysis, 12 patients were still alive (7 patients from the control group). Median survival was 23 weeks in both the active treatment group and the control group. There were 9 episodes (45%) of stent occlusions in the active treatment group and 10 episodes (50%) in the control group. The median time to stent occlusion was 23 (range 7 to 68) weeks for the active treatment group and 21 (range 6 to 56) weeks for the control group, p = 0.23. There was no significant difference in the duration of patient survival and of stent patency between the 2 groups. The lack of difference between treated and untreated patients in survival duration and stent patency was also shown if the results were analyzed on an intent-to-treat basis and the 8 patients who were excluded in the final analysis were also analyzed.
CONCLUSIONS: Prophylactic therapy with ciprofloxacin and Rowachol does not prolong stent patency or patient survival.
Long-term ciprofloxacin treatment for the prevention of biliary stent blockage: a prospective randomized study.
OBJECTIVE: In vitro experimental and animal studies have shown that quinolones reduce the adherence of bacteria on a polyethylene tube and prevent stent blockage. Our aim was to see whether ciprofloxacin prevents stent blockage in patients with malignant stricture of the biliary tract.
METHODS: Patients with inoperable biliary or pancreatic tumor not involving the bifurcation of the common hepatic duct were recruited. They were randomized to receive either endoscopic stenting alone or stenting with prophylactic treatment of ciprofloxacin (200 mg i.v. before stenting, followed by 250 mg orally twice per day). In each follow-up visit, clinical symptoms of cholangitis were documented and blood samples taken for blood counts, serum levels of bilirubin, and alkaline phosphatase. Stent blockage was defined as clinical symptom(s) of cholangitis with biochemical or radiological evidence of stent dysfunction.
RESULTS: Fifty-eight patients were recruited into the study. Three patients in the stenting group and three in the ciprofloxacin group were excluded after randomization. Eleven patients received stenting alone and five patients receiving ciprofloxacin had previous endoscopic stenting. Thirteen patients (50%) in the ciprofloxacin group and eight patients (31%) in the stenting group died before stent blockage. Ten patients (38%) in each group had stent blockage during the follow-up at 20 wk. The median stent patency was 11.6 wk and 11.9 wk in the ciprofloxacin group and the stenting group, respectively. Kaplan-Meier analysis of stent patency showed no difference between the two groups. Among patients who received endoscopic stenting for the first time, there was a trend favoring ciprofloxacin treatment, but the difference was not significant. The 30-day and 20-wk mortality between the groups were comparable.
CONCLUSION: Long-term use of ciprofloxacin does not prevent blockage of polyethylene biliary stents.
Options:
A: UDCA and/or antibiotics significantly prolong stent patency and improve survival.
B: UDCA and/or antibiotics have no significant effect on stent patency or survival.
C: UDCA alone significantly prolongs stent patency but does not affect survival.
D: Antibiotics alone significantly improve survival but do not affect stent patency. | B |
226 | 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 versus injectable ovulation induction agents for treating unexplained subfertility? Please answer this question based on the information provided below:
Late low-dose pure follicle stimulating hormone for ovarian stimulation in intra-uterine insemination cycles.
At present, there is general agreement that ovarian stimulation improves pregnancy rates after intra-uterine insemination (IUI). Also, ovulation induction with gonadotrophins is associated with higher success rates than clomiphene citrate in IUI cycles. However, the drawbacks to the use of gonadotrophin stimulation before IUI include the risks of ovarian hyperstimulation and multiple gestation, and the relative cost of a treatment cycle in a view of the medication costs and the need for increased monitoring by hormone assays and ultrasonographic measurements. In the present prospective randomized trial, the efficacy and safety of ovarian stimulation with clomiphene citrate (50 mg/day for 5 days) and IUI (clomiphene/IUI group) were compared with those of late low-dose pure follicle stimulating hormone (FSH, 75 IU/day from day cycle 7 until the leading follicle reached > 17 mm in diameter) and IUI (FSH/IUI group) in ovulatory women who were infertile because of unexplained infertility (n = 40) or male subfertility (n = 60). The mean length of treatment in the FSH group was 6.4 +/- 2.5 days. Multiple follicular development was seen in 25% of clomiphene-stimulated cycles but only in 8% of those treated with FSH. Pregnancy rate per cycle in clomiphene/IUI and FSH/IUI groups was 4% (4/98) and 13% (12/94) respectively (P = 0.02). All pregnancies obtained were singleton. There were two and one clinical abortions in the clomiphene/IUI (50%) and FSH/IUI (8%) groups respectively. No patient developed ovarian hyperstimulation syndrome. Use of our therapeutic scheme, which proved to be efficacious, safe and economic for ovarian stimulation in IUI cycles, is advocated before the institution of in-vitro fertilization (IVF) or gamete intra-Fallopian transfer (GIFT) therapy in infertile patients with patient Fallopian tubes. This late low-dose technique of administering pure FSH is suitable for use in offices without immediate access to oestradiol results.
A randomized prospective study comparing pregnancy rates after clomiphene citrate and human menopausal gonadotropin before intrauterine insemination.
OBJECTIVE: To determine whether hMG offers an advantage over clomiphene citrate (CC) in achieving pregnancy after IUI with husband's sperm.
DESIGN: Randomized prospective trial.
SETTING: Infertility patients in a university teaching hospital.
PATIENT(S): Fifty-eight women under 39 years old undergoing ovulation induction before IUI.
INTERVENTION(S): The women were assigned randomly to one of two treatment groups. Patients in group I (CCHH) received CC for the first two cycles and hMG for the last two cycles. Patients in group II (HHCC) received hMG for the first two cycles and CC for the last two cycles.
MAIN OUTCOME MEASURE(S): Cycle fecundity rates for the two treatment modalities were compared statistically with use of life-table analysis.
RESULT(S): Of the 174 cycles studied, overall cycle fecundity rate was 11.11 (9 of 81 cycles) in the CCHH group and 10.75 (10 of 93 cycles) in the HHCC group. The difference was not statistically significant. The cycle fecundity rate was 14.44% (13 of 90 cycles) for cycles with CC and 7.14% (6 of 84) with hMG. The difference was not statistically significant.
CONCLUSION(S): These data suggest that CC is an effective alternative to hMG in the population examined.
A prospective randomized trial of artificial insemination versus intercourse in cycles stimulated with human menopausal gonadotropin or clomiphene citrate.
OBJECTIVE: To determine the relative efficacy of intrauterine insemination (IUI), direct intraperitoneal insemination, and intercourse in cycles stimulated with clomiphene citrate (CC) or human menopausal gonadotropins (hMG).
DESIGN: A prospective randomized trial with a 2(3) factorial design with eight different treatment alternatives. Only one cycle per couple was performed.
SETTINGS: The Departments of Obstetrics and Gynecology, Central Hospital, Västerås and Akademiska Hospital, Uppsala University, Uppsala, Sweden.
PATIENTS: Of 157 randomized couples with unexplained infertility including 51 cases with minimal or mild endometriosis, 148 were selected for comparison.
MAIN OUTCOME MEASURE: Pregnancy rate (PR).
RESULTS: Follicular stimulation with hMG gave a higher PR than with CC in the insemination cycles, 19% (10/52) and 4% (2/49), respectively, but the PRs in intercourse cycles were not significantly different for hMG and CC, 13% (3/24) and 17% (4/23), respectively. Insemination cycles and intercourse cycles had a similar overall PR, 12% (12/101) and 13% (7/47), respectively. Furthermore, IUI and direct intraperitoneal insemination did not differ in efficacy.
CONCLUSION: Follicular stimulation with hMG is more effective than CC in insemination cycles, but insemination as such seems to have no beneficial effect on the PR in stimulated cycles for treatment of unexplained infertility.
A prospective randomized trial of artificial insemination versus intercourse in cycles stimulated with human menopausal gonadotropin or clomiphene citrate.
OBJECTIVE: To determine the relative efficacy of intrauterine insemination (IUI), direct intraperitoneal insemination, and intercourse in cycles stimulated with clomiphene citrate (CC) or human menopausal gonadotropins (hMG).
DESIGN: A prospective randomized trial with a 2(3) factorial design with eight different treatment alternatives. Only one cycle per couple was performed.
SETTINGS: The Departments of Obstetrics and Gynecology, Central Hospital, Västerås and Akademiska Hospital, Uppsala University, Uppsala, Sweden.
PATIENTS: Of 157 randomized couples with unexplained infertility including 51 cases with minimal or mild endometriosis, 148 were selected for comparison.
MAIN OUTCOME MEASURE: Pregnancy rate (PR).
RESULTS: Follicular stimulation with hMG gave a higher PR than with CC in the insemination cycles, 19% (10/52) and 4% (2/49), respectively, but the PRs in intercourse cycles were not significantly different for hMG and CC, 13% (3/24) and 17% (4/23), respectively. Insemination cycles and intercourse cycles had a similar overall PR, 12% (12/101) and 13% (7/47), respectively. Furthermore, IUI and direct intraperitoneal insemination did not differ in efficacy.
CONCLUSION: Follicular stimulation with hMG is more effective than CC in insemination cycles, but insemination as such seems to have no beneficial effect on the PR in stimulated cycles for treatment of unexplained infertility.
Options:
A: Oral agents are significantly more effective than injectable agents in achieving pregnancy and live birth.
B: Injectable agents are significantly more effective than oral agents in achieving pregnancy and live birth.
C: There is insufficient evidence to suggest that oral agents are inferior or superior to injectable agents in terms of efficacy and safety.
D: Injectable agents have significantly higher risks of detrimental outcomes such as miscarriage and multiple births compared to oral agents. | C |
227 | 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 continuation rates of the contraceptive vaginal sponge compared to the diaphragm used with nonoxynol-9? Please answer this question based on the information provided below:
A comparative trial of the Today contraceptive sponge and diaphragm.
A comparative trial was conducted in the United States to compare the Today contraceptive sponge and the diaphragm used with spermicide. Subjects were randomly assigned to contraceptive methods and were followed up for 1 year. None of the subjects were previous sponge users, but about 30% were previous diaphragm users. The overall cumulative 1-year life-table pregnancy rate was higher for sponge users compared to diaphragm users. No serious side effects occurred with either product. The discontinuation rates for allergic-type reactions and discomfort were higher for sponge users. Similar rates of method-related complaints and discontinuation rates for personal and product-related reasons suggest there were no differences in the acceptability of the two products. In this trial, the allowable use time for the sponge was 2 days. The sponge is now recommended for 1-day use. The overall results of the study indicate the sponge to be a safe and acceptable method of contraception with an effectiveness rate in the range of that for other vaginal contraceptives.
Options:
A: The sponge was more effective than the diaphragm in preventing pregnancy, and had lower discontinuation rates.
B: The sponge was less effective than the diaphragm in preventing pregnancy, and had higher discontinuation rates.
C: The sponge and the diaphragm had similar efficacy in preventing pregnancy, but the sponge had higher discontinuation rates.
D: The sponge and the diaphragm had similar efficacy in preventing pregnancy, and similar discontinuation rates. | B |
228 | 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 iodised salt in preventing iodine deficiency disorders in comparison to other forms of iodine supplementation or placebo? Please answer this question based on the information provided below:
Salt: an ineffective vehicle for iodine delivery to young children in rural Sarawak.
The urinary iodine excretions of women (15-40 y) and young children (< or = 6 y) from two longhouse villages in the iodine-deficient district of Lubok Antu, Sarawak, were compared. One longhouse (Mengkak) was provided with freshly produced iodized salt every two months (one kg per family) while the other (Menjiling) was provided with iodized water via fortification of the village piped-water supply. Spot urines were collected for iodine determination at baseline and at 6 and 12 months after the start of the study. Salt and water samples were collected at monthly intervals. Goiter assessment was performed on the women at the start and end of the one-year study. The mean iodine concentrations in the salt samples from Mengkak and Menjiling were, respectively, 47.1 +/- 9.7 mg/kg (n = 60) and 0.8 +/- 3.4 mg/kg (n = 60) while the mean iodine concentration in the water samples from Menjiling was 138.6 +/- 43.2 micrograms/L (n = 24); iodine could not be detected in the water samples from Mengkak. There were significant and sustained increases in median urinary iodine excretions of both women and young children in Menjiling; in Mengkak, however, significant and sustained increases in median urinary iodine excretions were observed only in women while the median urinary iodine excretions of children remained essentially unchanged throughout the study period. Goiter prevalences in the women were reduced in both longhouses. The above observations reveal the inadequacy of iodized salt as a vehicle for iodine delivery to young rural Sarawakian children and indicate the need for other means of delivering supplemental iodine to this age group in areas where salt iodization is the only strategy for IDD control. In contrast, iodization of village water supply by itself is adequate in delivering iodine uniformly to the whole community.
Effect of voluntary intake of iodinated salt on prevalence of goitre in children.
The availability of iodinated salt containing 20 mg of iodine as iodate/kg salt consumed on a voluntary basis enabled us to investigate its effect on goitre prevalence and iodine excretion in urine in a longitudinal, prospective, randomized study over 4 years. With this salt, under the assumption of a consumption of 5 g salt per day and person, an additional intake of 100 micrograms of iodine can be achieved. The study was performed on initially 334 children (168 boys, 166 girls) at the age of 10 years living in an area of iodine deficiency. After 4 years, 286 children still participated in the study. Initially, goitre prevalence as assessed by palpation was found to be 30.5% (37.4% in girls and 23.8% in boys). Neck circumference was found to be significantly higher in children with goitre compared with those without (30.2 +/- 1.4 vs 29.4 +/- 1.4 cm; P less than 0.001). Iodine excretion in the urine was significantly lower in children with goitre compared with those without (40.4 +/- 16.7 micrograms/g creatinine vs 46.1 +/- 24.9 micrograms/g creatinine; x +/- SD; P less than 0.05). The children were randomly assigned to two different groups: group A (N = 146) was asked to use iodinated salt, group B (N = 188) non-iodinated salt. Over the 4 years, a continuous increase in iodine excretion in urine could be demonstrated in group A.(ABSTRACT TRUNCATED AT 250 WORDS)
The effects of iodoprophylaxis on thyroid size during pregnancy.
Thyroid gland size was ultrasonographically determined in 35 pregnant women who live in an area with moderate iodine deficiency. Iodide salt was administered to group A (n = 17), whereas group B (n = 18) was used as a control. Each group was tested for thyroid-stimulating hormone serum levels, iodine excretion, and thyroid volume. In both groups thyroid-stimulating hormone levels were similar and did not change throughout pregnancy. The iodine excretion at the third trimester in the treated group was significantly (p less than 0.01) higher than that of group B (100.0 +/- 39.0 versus 50.0 +/- 37.0 micrograms iodine per 24 hours, respectively). Initially, thyroid volume did not differ between the two groups. At the end of pregnancy, no difference was found in thyroid size in group A, whereas in the untreated women it increased significantly (p less than 0.0001) with a mean increase of 1.6 +/- 0.6 ml (16.2% +/- 6.0%). These results show that the increased thyroid size in the control group was mainly a result of relative iodine deficiency and that iodoprophylaxis should be warranted even in areas with moderate iodine deficiency to prevent the increase in thyroid size and, probably, to avoid the risk of maternal and fetal hypothyroidism.
PRELIMINARY REPORT OF AN EXPERIMENT IN THE KANGRA VALLEY FOR THE PREVENTION OF HIMALAYAN ENDEMIC GOITRE WITH IODIZED SALT.
This report incorporates the results of an investigation designed to test the effectiveness of potassium iodide and potassium iodate in the control of Himalayan endemic goitre when these compounds are added in small physiological doses to the domestic salt habitually consumed by the people in the endemic belt. In a prospective study lasting five years, a striking reduction in the prevalence of goitre was observed in areas receiving salt fortified with either potassium iodide or potassium iodate. During the same period, goitre prevalence remained unchanged in the control zone, which received plain, unfortified salt. The study has an important bearing on the problem of goitre control in developing countries that use moist, coarsely crystalline salt.
Randomized clinical trial comparing different iodine interventions in school children.
OBJECTIVE: The purpose of this trial was to compare three different iodine interventions.
DESIGN: School children aged 8-10 years were randomized into one of three groups: group A was provided with iodized salt by researchers with an iodine concentration of 25 ppm; group B purchased iodized salt from the market; and group C was similar to group B with the exception that they were given iodized oil capsules containing 400 mg iodine at the beginning of the study. Salt iodine content was measured bimonthly for 18 months and indicators of iodine deficiency were measured at baseline and 6, 9, 12 and 18 months after randomization.
RESULTS: The prevalence of abnormal thyroid volumes, based on the World Health Organization (WHO) body surface area reference >97th percentile, was 18% at baseline and declined to less than 5% by 12 months in groups A and C, and to 9% after 18 months in group B. Results for goitre by palpation were similar. The median urinary iodine was 94 microg l(-1) at baseline and increased in all groups to > 200 microg l(-1) at the 6-month follow-up.
CONCLUSIONS: In this population of school children with initially a low to moderate level of iodine deficiency, the group receiving salt with 25 ppm (group A) was not iodine deficient on all indicators after 18 months of study. When the iodine content of the salt varied, such as in group B, by 18 months thyroid sizes had not yet achieved normal status.
Options:
A: Iodised salt significantly reduced goitre rates and improved iodine status in all studies.
B: Iodised salt showed a tendency towards goitre reduction and improved iodine status in most studies, but not all results were statistically significant.
C: Iodised salt had no effect on goitre rates or iodine status in any of the studies.
D: Iodised salt caused adverse effects in a significant number of participants. | B |
229 | 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 dopamine to prevent renal dysfunction in preterm newborn infants treated with indomethacin? Please answer this question based on the information provided below:
Can dopamine prevent the renal side effects of indomethacin? A prospective randomized clinical study.
BACKGROUND: Indomethacin therapy for closure of a patent ductus arteriosus in preterm neonates is responsible for transient renal insufficiency. Dopamine theoretically reduces the renal side effects of indomethacin therapy.
PATIENTS: 33 neonates with a mean gestational age of 28.5 weeks who received indomethacin for treatment of a symptomatic PDA were included in a prospective randomized controlled clinical study.
METHOD: 15 patients were treated with indomethacin alone (control group), 18 patients with indomethacin and dopamine (study group). Indomethacin was given in a dose of 0.2 mg/kg/dose intravenously, all patients received three doses with intervall of 12 hours. The dose of dopamine was in all patients 4 micrograms/kg per minute commencing 2 hours prior to the first dose of indomethacin and continuing for 12 hours after the third dose.
RESULTS: Indomethacin induced a significant increase in serum creatinin (76.3 mumol/l vs 99.7 mumol/l for the control group, and 70.7 mumol/l vs 93.0 mumol/l for the study group), and weight (1259 g vs 1316 g for the control group, and 1187 g vs 1221 g for the study group). The increase systolic blood pressure (61 mmHg vs 65.7 mmHg) in the study group was significant (p < 0.05) but remained unchanged in the control group. The changes between the study group and the control group were not significant either in serum creatinin, fractional excretion of sodium, or weight gain. The failure rate of ductal closure was not different between the two groups.
CONCLUSION: The additional use of dopamine does not reduce the renal side effects of indomethacin.
Effect of dopamine on failure of indomethacin to close the patent ductus arteriosus.
To test the hypotheses that administering dopamine before and concurrently with indomethacin therapy would (1) increase successful ductal closure rate, (2) act by maintaining a diuresis, and (3) prevent oliguria or high serum creatinine concentrations, we conducted a randomized, controlled trial in infants whose gestational age was <36 weeks and who had hemodynamically significant ductus arteriosus. Thirty-six infants were selected to receive a continuous infusion of either placebo or dopamine at either a low dosage of 2 micrograms/kg per minute or a higher dosage of 5 micrograms/kg per minute, beginning 6 hours before the use of indomethacin and continuing until 12 hours after the third dose of indomethacin. A total of 12 patients were selected to receive placebo, 14 were selected to receive "low dopamine," and 10 were selected to receive "high dopamine." The three groups were similar in their initial characteristics. Serum creatinine concentrations, urine output, and fractional excretion of sodium were not different in the three groups after indomethacin treatment. Two patients receiving placebo required a second course of indomethacin compared with four patients in the low-dopamine group and one in the high-dopamine group. The proportion of failures of medical treatment was not statistically different among the three groups. We conclude that concomitant dopamine therapy neither decreases the failure rate in indomethacin-treated infants nor reduces the magnitude of the indomethacin-induced oliguria.
The use of dopamine for the prevention of the renal side effects of indomethacin in premature infants with patent ductus arteriosus.
To determine if dopamine would prevent the renal side effects of indomethacin, fifteen preterm infants were randomized into two groups: seven received indomethacin alone, and eight received indomethacin together with low dose dopamine infusion. Infants who received indomethacin together with dopamine had significantly higher UV (p less than 0.005), CNa (p less than 0.005), Cosm (p less than 0.005) and FENA (p less than 0.005) than those of infants who received indomethacin alone. There was, however, no significant difference in Ccr and FNa between the groups. These data indicate that dopamine overcomes indomethacins renal side effects of tubular origin, but it cannot prevent the renal vasoconstrictive action of vasoconstrictor hormones following the inhibition of prostaglandin synthesis by indomethacin. Considering that RBF and GFR turn to normal approximately 12 hours after the last dose of indomethacin, and that with the use of dopamine systemic blood pressure and peripheral circulation can also be normalized and to some extent myocardiac contractility improved, low doses of dopamine can be used instead of furosemide in the sick preterm infant with PDA when indomethacin therapy is indicated.
Options:
A: Dopamine significantly improves renal function and prevents renal dysfunction in these infants.
B: Dopamine has no significant effect on preventing renal dysfunction in these infants.
C: Dopamine significantly worsens renal function and increases the risk of renal dysfunction in these infants.
D: Dopamine significantly reduces the incidence of oliguria and improves serum creatinine levels in these infants. | B |
230 | 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 maternal antibiotic regimens for intraamniotic infection on maternal and perinatal morbidity and mortality? Please answer this question based on the information provided below:
A randomized trial of intrapartum versus immediate postpartum treatment of women with intra-amniotic infection.
A randomized trial of intrapartum versus postpartum antibiotic treatment of women with intra-amniotic infection was conducted. Intra-amniotic infection was treated with ampicillin and gentamicin during labor (at the time of diagnosis) in 26 women and immediately after umbilical cord clamping in 19 women. Intrapartum treatment led to a lower incidence of neonatal sepsis (0 versus 21%; P = .03) and a shorter neonatal hospital stay (3.8 versus 5.7 days; P = .02) when compared with postpartum treatment. There were no significant differences in the microbiologic results, the gestational age, or the birth weight between the groups. Intrapartum-treated mothers had a shorter mean postpartum stay, a lower mean number of febrile days, and a lower mean peak postpartum temperature than did postpartum-treated mothers; these differences were all statistically significant (P = .05). The treatment of clinical intra-amniotic infection during labor results in improved outcome.
Anaerobic coverage for intra-amnionic infection: maternal and perinatal impact.
Although intrapartum antibiotics are beneficial to both the mother and newborn, there is no consensus as to the most efficacious antibiotic regimen in the treatment of intra-amnionic infection, especially with regard to anaerobic coverage. We randomized pregnant women with intra-amnionic infection to receive either dual agent therapy (ampicillin and gentamicin) or triple agent therapy (ampicillin, gentamicin, and clindamycin). The frequency of vaginal and cesarean delivery was similar in both groups. There was no significant difference in the incidence of endometritis between the two groups (10 of 69 versus 5 of 64; p = NS). There were no significant differences in either neonatal morbidity or mortality. The addition of clindamycin to provide anaerobic coverage for intra-amnionic infection does not significantly alter the incidence of endometritis in women delivered by cesarean section, although it may have an impact on women delivering vaginally.
Options:
A: Intrapartum antibiotic treatment significantly reduced neonatal sepsis and pneumonia compared to postpartum treatment.
B: There was no statistically significant difference in neonatal sepsis, pneumonia, or maternal bacteremia between intrapartum and postpartum antibiotic treatments.
C: Antibiotic regimens with anaerobic activity significantly reduced neonatal sepsis and death compared to those without anaerobic activity.
D: Postpartum antibiotic treatment significantly reduced the incidence of post-partum endometritis compared to intrapartum treatment. | B |
231 | 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 relative effectiveness of different methods of anaesthesia for treating distal radial fractures in adults? Please answer this question based on the information provided below:
Regional anesthesia preferable for Colles' fracture. Controlled comparison with local anesthesia.
In a prospective randomized study of 99 displaced Colles' fractures, regional intravenous block was compared with local anesthesia in the fracture hematoma. Patients treated with regional intravenous block had less pain during the manipulation of the fracture and better grip strength at the 6-month follow-up. The anatomic end result (dorsal angulation) was better after regional anesthesia.
Bier's block: a change of injection site.
Bier's block or intravenous regional anesthesia is a well-proven technique that is useful in the traumatic setting to provide upper limb anesthesia in the manipulation of distal radial fractures. In this situation, the traditional injection site in the dorsum of the hand can present difficulties with subsequent plaster application and with venous access caused by swelling or pain. One hundred patients were randomly allocated into two groups of 50. The first group was injected into the dorsum of the hand and the second into the antecubital fossa, in each case on the injured side. Effectiveness of anesthesia at both the fractures site and the cuff was assessed using a visual analog scale. Results analyzed using Student's t test, showed no difference in anesthesia between the two groups. In addition, there were fewer technical problems associated with venous access and subsequent plaster application in the antecubital fossa group.
Intravenous diazepam: its use in the reduction of fractures of the lower end of the radius.
Local anaesthetic infiltration versus Bier's block for Colles' fractures.
Bier's block--an improved technique.
A simple modification to the method of regional anaesthesia known as Bier's block is presented. This was applied to patients with Colles' fractures. In a controlled trial the technique produced anaesthesia more quickly than the other method.
Clonidine as adjuvant for mepivacaine, ropivacaine and bupivacaine in axillary, perivascular brachial plexus block.
PURPOSE: To evaluate the effects of clonidine on three local anesthetics (mepivacaine 1%, ropivacaine 0.75% and bupivacaine 0.5%) with comparable potency and almost the same concentration-response relationship.
METHODS: One hundred and twenty trauma-patients were randomly allocated into six groups. In the control-groups (Mo/Ro/Bo) brachial plexus was performed using 40 mL of local anesthetic plus 1 mL of NaCL 0.9%. In the clonidine-groups (Mc/Rc/Bc) brachial plexus was performed using each 40 mL of drug plus 1 mL (0.150 mg) of clonidine. Onset-time and the duration of the sensory block were recorded. Data are expressed as mean +/- SD.
RESULTS: According to the average sensory block determined by a visual analog scale in the median, ulnar and radial nerve distributions and ranging from 100 (no sensory blockade) to 0 (complete sensory blockade), both mepi-groups showed a rapid onset (at 10 min: -Mo 20 +/- 15/Mc 19 +/- 14; at 30 min: -Mo 3 +/- 4/Mc 5 +/- 4). The ropi-and bupi- groups both had a longer onset time (at 10 min: -Ro 23 +/- 19/Rc 25 +/- 22/Bo 24 +/- 15; at 30 min -Ro 10 +/- 6/ Rc 11 +/- 6 /Bo 12 +/- 4). The onset time in group-Bc was significantly prolonged (at 10 min: -45 +/- 21; at 30 min: -20 +/- 6). Duration of motor blockade was prolonged by clonidine only in the mepivacaine and bupivacaine groups; (in minutes: Mo 212 +/- 47 -Mc 468 +/- 62; Ro 702 +/- 52 -Rc 712 +/- 82; Bo 728 +/- 36 -Bc 972 +/- 72).
CONCLUSION: The present study shows that the addition of clonidine has a different impact on each of the three local anesthetics investigated in terms of onset and duration of block.
A prospective trial to compare three anaesthetic techniques used for the reduction of fractures of the distal radius.
The aim of this study was to compare prospectively haematoma blocks alone and haematoma blocks with sedation with general anaesthesia for the reduction of distal radius fractures in adult patients, with respect to pain perception before, during and after manipulation using a visual analogue scale, radiological position, waiting time, procedure time and cost. Fifty-eight adult patients with closed, displaced distal radius fractures were included in the study. Pain experienced during manipulation was greatest in patients who received haematoma blocks alone compared with the other two groups. Post-manipulation pain was significantly greater in patients who received a general anaesthetic. Radiological correction was as good in those patients receiving a haematoma block with or without sedation as a general anaesthetic. The waiting and manipulation times and resource costs were greater in those receiving a general anaesthetic. There were no complications related to any of these anaesthetic methods. Patient acceptance is greater with a correctly performed haematoma block and sedation technique compared to general anesthesia. It is also more efficient with regard to time and the resources required. This is particularly important for a progressively increasing ambulatory, elderly population who require prompt, safe, effective and painless management.
Cubital nerve block vs haematoma block for the manipulation of Colles' fracture.
Blocking efficacy and acute toxicity of prilocaine (15 ml of 10 mg/ml prilocaine) was examined in 35 (16 + 19) patients by using blocks of the radial, ulnar and median nerves in the elbow region (Group 1), or the haematoma block method (Group 2) for the manipulation of Colles' fracture. In Group 1 vs Group 2, the reposition was painless in 44% (7/16) vs 68% (13/19), moderate pain occurred in 38% (6/16) vs 21% (4/19), and severe pain in 19% (3/16) vs 11% (2/19). At 15 minutes there was a higher degree of block, on average, at the median and ulnar nerve innervation areas in Group 1. Complete motor block at peripheral innervation regions of all three nerves was achieved in only one patient in Group 1 and in no case in Group 2. Despite this, the surgeons assessed the relaxation at the wrist satisfactory for reposition of the fracture in all but one patient (Group 2). The highest individual prilocaine plasma concentration in Group 1 was 0.68 microgram/ml at ten minutes, whereas the highest individual value in Group 2 was 0.77 microgram/ml at ten minutes. Systemic toxicity from the local anaesthetic did not occur.
Comparison of bupivacaine and prilocaine used in Bier block--a double blind trial.
The value of Bier blocks for the manipulation of fractures and for operations on the upper limb is well recognized. Two anaesthetic agents, bupivacaine and prilocaine, are widely used for this purpose. A prospective double blind trial of 200 patients has been carried out to compare the efficacy of each drug and the incidence of side effects. The study shows that bupivacaine was associated with a greater number of successful fracture reductions than prilocaine with little difference in their analgesic effects, but this was balanced by more minor side effects with bupivacaine. There was little difference in the time from injection to analgesia in the two groups. All intravenous regional analgesia procedures were carried out by junior orthopaedic or accident and emergency doctors. The overall success rate for analgesia was 91 per cent but marked cuff discomfort occurred in 9 per cent of patients. There was a clear association between failure of analgesia and two of the doctors carrying out the procedure.
The addition of tenoxicam to prilocaine for intravenous regional anaesthesia.
The analgesic effects of tenoxicam 20 mg added to prilocaine in a standard Bier's block (group 2) was studied in 45 patients who had their Colles' fractures reduced under intravenous regional anaesthesia, and compared both to a control group (group 1), and to a group who received a standard Bier's block combined with the same dose of tenoxicam given intravenously into the contralateral arm (group 3). Patients in group 2 obtained significantly better analgesia than group 1, as judged by a longer time before first additional analgesia was required (p < 0.05), less total analgesic consumption (p < 0.01), and lower pain scores (p < 0.01). These benefits were not obtained by patients in group 3.
Haematoma block or Bier's block for Colles' fracture reduction in the accident and emergency department--which is best?
OBJECTIVE: To offer clear guidance on the anaesthetic management of Colles' fractures in the accident and emergency (A&E) department in the light of the conflict between existing reports and current trends, and to address the issue of alkalinisation of haematoma blocks.
METHODS: This was a two centre, prospective, randomised clinical trial with consecutive recruitment of adult patients with Colles' fractures requiring manipulation to receive either Bier's block or haematoma block. There was subsequent blinded randomisation to alkalinised or non-alkalinised haematoma block.
RESULTS: 72 patients were recruited into the Bier's block group, and 70 into the haematoma block group. Bier's block was less painful to give than the haematoma block (median pain score 2.8 v 5.3; P << 0.001), and fracture manipulation was also less painful in the Bier's block group (median pain score 1.5 v 3.0; P < 0.01). There was no significant difference in overall A&E transit time between the two groups. There was better initial radiological outcome in terms of dorsal angulation in the Bier's block group (-3.6 degrees v 2.1 degrees; P = 0.003). More remanipulations were required in the haematoma block group (17/70 v 4/72; P = 0.003). There was a trend towards decreased pain on administration of the alkalinised haematoma block when compared with non-alkalinised haematoma block, but this did not reach significance. There was no difference in pain score on fracture manipulation. There were no complications in either group.
CONCLUSIONS: Bier's block is superior to haematoma block in terms of efficacy, radiological result, and remanipulation rate; transit times are equal, both procedures are practical in the A&E environment, and there were no complications. Bier's block is the anaesthetic management of choice for Colles' fractures requiring manipulation within the A&E department.
Anaesthetic for Colles' fracture.
Hyaluronidase (Hyalase): a useful addition in haematoma block?
OBJECTIVE: To investigate whether hyaluronidase (Hyalase) is a useful and justified addition to haematoma block for pain relief.
METHODS: The study was a randomised double blind trial of 33 consecutive patients attending the accident and emergency department for manipulation of distal radius fracture under haematoma block. Control patients received 1% lignocaine; the treatment group received 1% lignocaine plus 1500 IU hyaluronidase. Manipulation occurred 10 minutes after instituting the block.
RESULTS: 16 patients received hyaluronidase, 17 received lignocaine only. One patient with unsuccessful manipulation was excluded. There was no significant difference between the two groups for any of three methods of pain assessment (P > 0.05, Mann Whitney).
CONCLUSIONS: The addition of hyaluronidase does not increase the efficacy of the haematoma block when 10 minutes are allowed to elapse before manipulation, and the increased cost of adding (and risk of allergy) is not justified by any theoretical increased speed of analgesia.
Muscle relaxants and Bier's block.
The use of muscle relaxant to supplement local anaesthetics for Bier's blocks.
In searching for the 'ideal' muscle relaxant for use with intravenous regional anaesthesia, muscle relaxation was assessed with and without the addition of Atracurium to Bier's Block in four volunteers. This was followed by a clinical study of 36 patients with wrist fractures to confirm the drug's safety and examine the possible clinical advantages of using a muscle relaxant. The addition of 2 mg of Atracurium to the Bier's Block improved the ease of reduction (P less than 0.025) and the quality of analgesia (P less than 0.05) (Mann-Whitney U test). The authors conclude that the addition of Atracurium to a Bier's Block is useful in selected patients with a wrist fracture.
Brachial plexus block using a new subclavian perivascular technique: the proximal cranial needle approach.
We describe the proximal cranial needle approach for brachial plexus blockade; clear surface markings and cranial direction of the needle lead to satisfactory results with a low incidence of complications.
Analgesia for the reduction of Colles fracture. A comparison of hematoma block and intravenous sedation.
OBJECTIVE: An alternative to general anesthesia was tested against conventional sedation by a double-blind, randomized clinical trial in reduction of Colles fracture.
SETTINGS: A large teaching hospital where cases of Colles fracture are not different from those seen in district hospitals.
PATIENTS: Sixty-six out of 80 consecutive cases with this fracture were selected from March to August 1990 on the basis of: 1) informed consent; 2) no contraindication to any method of analgesia; 3) no analgesic during the past 8 hours; 4) injury duration less than 96 hours; 5) no mental, auditory, or visual impairment; and 6) no associated injury.
INTERVENTIONS: Patients were randomized into 2 equal groups. After tests for Xylocaine (Astra brand of lidocaine hydrochloride) sensitivity in both groups, the A group received 30 mg of pentazocine with 5 mg of diazepam intravenously on the dorsum of the affected wrist (sedation group), whereas the B group received 20 cc of 1.5% Xylocaine into the fracture hematoma. Five minutes later the fracture was reduced and immobilized by Lakhtakia or A. Singh.
MAIN OUTCOME MEASURES: Thirteen to 15 hours later Manglik, blinded to the analgesia status of the patient, recorded pain before, during, and after reduction using Visual Analogue Scale (VAS).
MAIN RESULTS: Statistically, randomization and blinding were found to be effective. The pain scores during reduction in the local anesthetic group (median = 1.8) were significantly less than those in the sedation group (median = 8.7), P < 0.001 using the Wilcoxon rank sum test. The difference persisted in regression analysis. The 2 methods proved comparable in safety and other measures of effectiveness.
CONCLUSIONS: Hematoma block by local anesthetic is a safe and effective alternative to sedation in reduction of Colles fracture.
[Intravenous regional analgesia compared to infiltration analgesia in the reduction of distal forearm fractures].
Comparison of local anaesthetic techniques in the reduction of Colles' fracture.
A trial comparing the use of Bier's block and the direct infiltration of the fracture site with local anaesthetic was carried out to assess their effectiveness in the reduction of Colles' fracture. This showed Bier's block to be superior in terms of patient acceptability and in ease of reduction. The results of the reduction were also significantly better using the Bier's block, as judged by the measurement of the residual displacement on the X-ray.
Options:
A: Haematoma block provides better analgesia and easier fracture reduction compared to intravenous regional anaesthesia (IVRA).
B: There is robust evidence from randomised trials establishing the relative effectiveness of different methods of anaesthesia.
C: There is insufficient robust evidence from randomised trials to establish the relative effectiveness of different methods of anaesthesia.
D: General anaesthesia is conclusively more effective than haematoma block and sedation for treating distal radial fractures. | C |
232 | 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 main findings regarding the use of tissue adhesives compared to standard wound closure for traumatic lacerations in terms of cosmetic outcome, pain, procedure time, and complications? Please answer this question based on the information provided below:
Randomised trial of histoacryl blue tissue adhesive glue versus suturing in the repair of paediatric lacerations.
OBJECTIVE: To compare histoacryl blue tissue adhesive glue with suturing in the repair of simple paediatric lacerations.
METHODOLOGY: Prospective, randomised controlled trial in tertiary paediatric emergency department. Children 4 years old or older with non-ragged lacerations <5 cm in length, <12-h-old and not involving eyelid or mucous membrane. A total of 163 patients were randomly allocated to either glue (83 cases) or sutures (80 controls) to repair their laceration. Primary outcome measures were cosmetic outcome at 3 and 12 months with secondary outcomes-length of time to perform procedure, and pain assessment of procedure by doctor, nurse, parent and child.
RESULTS: Cases and controls were similar in age, wound length and width and body part involved, but more females received glue (P = 0.013). Time taken to repair the wound was faster in the glue group (median 0-2 mins vs. 6-10 min suture, P<0.001). Doctors (P = 0.02), nurses (P<0.01) and parents (P = 0.02) but not the children themselves (P = 0.24) rated glue repair as less distressing. Complications at 1 week (wound dehiscence, redness and discharge) were the same for both groups (P>0.2). Cosmetic outcome was the same for both groups at 3 (n = 65) and 12 (n = 65) months (P>0.7).
CONCLUSION: Tissue adhesive glue is faster and probably less painful than suturing. Tissue adhesive glue has the same cosmetic result as suturing when used for the repair of simple lacerations in children.
Randomised trial of histoacryl blue tissue adhesive glue versus suturing in the repair of paediatric lacerations.
OBJECTIVE: To compare histoacryl blue tissue adhesive glue with suturing in the repair of simple paediatric lacerations.
METHODOLOGY: Prospective, randomised controlled trial in tertiary paediatric emergency department. Children 4 years old or older with non-ragged lacerations <5 cm in length, <12-h-old and not involving eyelid or mucous membrane. A total of 163 patients were randomly allocated to either glue (83 cases) or sutures (80 controls) to repair their laceration. Primary outcome measures were cosmetic outcome at 3 and 12 months with secondary outcomes-length of time to perform procedure, and pain assessment of procedure by doctor, nurse, parent and child.
RESULTS: Cases and controls were similar in age, wound length and width and body part involved, but more females received glue (P = 0.013). Time taken to repair the wound was faster in the glue group (median 0-2 mins vs. 6-10 min suture, P<0.001). Doctors (P = 0.02), nurses (P<0.01) and parents (P = 0.02) but not the children themselves (P = 0.24) rated glue repair as less distressing. Complications at 1 week (wound dehiscence, redness and discharge) were the same for both groups (P>0.2). Cosmetic outcome was the same for both groups at 3 (n = 65) and 12 (n = 65) months (P>0.7).
CONCLUSION: Tissue adhesive glue is faster and probably less painful than suturing. Tissue adhesive glue has the same cosmetic result as suturing when used for the repair of simple lacerations in children.
A new tissue adhesive for laceration repair in children.
To determine the effectiveness of a new tissue adhesive, 2-Octylcyanoacrylate (2-OCA), for laceration repair, 83 children presenting to T.C. Thompson Children's Hospital Emergency Department with lacerations meeting eligibility requirements between February and June 1996 were randomized to receive 2-OCA or nonabsorbable sutures/staples. The length of time for repair was recorded. The length of time for laceration repair was decreased (2.9 minutes 2-OCA vs 5.8 minutes suture/staple; p < 0.001), the parents' assessment of the pain felt by their children in the 2-OCA group was less, and the wounds closed with tissue adhesive had slightly lower cosmesis scores. 2-OCA is an acceptable alternative to conventional methods of wound repair with comparable cosmetic outcome.
Comparison of tissue adhesive and suturing in the repair of lacerations in the emergency department.
The objective of this study was to compare the applications of Histoacryl Blue (HAB) and suturing regarding cosmetic outcome, cost and patient and physician satisfaction in the emergency department (ED). A total of 92 consecutive adult patients with lacerations equal to or shorter than 5 cm were enrolled in the study. Patients were randomized to either HAB or suturing. Ten-day and three-month cosmetic outcomes were evaluated via visual analogue scale (VAS) by a blinded surgeon. Cosmetic outcome, cost and patient and physician satisfaction of both groups were compared. Only 52 patients completed the follow-up at three months. Twenty-eight had been repaired with sutures and 24 with HAB. The differences regarding ten-day and three-month cosmetic outcome scales between the patients repaired with HAB and sutures were not statistically significant. Application of HAB resulted in greater satisfaction of the patient and the physician (p=0.007 and p=0.0001, respectively). Costs of HAB were significantly lower than sutures (p=0.0001). It is concluded that HAB is a cheaper method of laceration repair and results in greater satisfaction of both patients and physicians, while cosmetic outcomes were comparable. These results suggest that HAB is a viable alternative to suturing for selected lacerations in the ED.
Cosmetic outcomes of facial lacerations repaired with tissue-adhesive, absorbable, and nonabsorbable sutures.
The objective of this study was to compare the 9- to 12-month cosmetic outcome of facial lacerations closed with rapid-absorbing gut suture (RG), octylcyanoacrylate (OC), or nylon suture (NL). We hypothesized that no important differences would exist between these methods. This prospective, randomized study enrolled consecutive patients with facial lacerations when experienced physician assistants were on duty for wound closure. Patients returned at 9 to 12 months for cosmetic evaluation. Two blinded physicians performed visual analog cosmesis scale (VACS) scoring, and the patient completed a VAS satisfaction score. One hundred forty-five patients were enrolled. Nine-month follow up occurred in 84 patients. The maximum difference within each evaluator's set of scores was 3.6 mm, well below the minimum clinically important difference (MCID) of 10 to 15 mm. We did not detect clinically important differences in cosmetic outcome at 9 to 12 months in patients with facial lacerations closed with RG, OC, or NL, although RG or OC could be preferred to eliminate follow-up visits for suture removal.
A randomised, controlled trial comparing a tissue adhesive (2-octylcyanoacrylate) with adhesive strips (Steristrips) for paediatric laceration repair.
OBJECTIVE: To compare the tissue adhesive 2-octylcyanoacrylate (Dermabond) with adhesive strips, Steristrips in paediatric laceration repair.
METHOD: Children with suitable lacerations were randomly allocated for wound closure with either a tissue adhesive or adhesive strips. Thirty children were treated in each group. Linear Visual Analogue Scores were used to judge parents' and nurses' opinions of the application of each treatment. A similar scoring system was used to judge the cosmetic outcome as viewed by parents and a plastic surgeon. Complications and trial failures were noted.
RESULTS: Complete data were available for 44 of the children. Parents viewed the treatments as equally acceptable. In contrast those performing the procedure judged the tissue adhesive more difficult to apply. Scores of cosmetic outcome by both parents and the plastic surgeon showed no significant difference in the treatment method used. There were four children in the tissue adhesive group and one from the adhesive strip group in whom the wounds were unable to be closed.
CONCLUSION: Both tissue adhesives and adhesive strips are excellent "no needle" alternatives for the closure of suitable paediatric lacerations. This study suggests that the techniques are similar in efficacy, parental acceptability, and cosmetic outcome. The choice as to which is used may come down to economics and operator preference.
A randomized, clinical trial comparing butylcyanoacrylate with octylcyanoacrylate in the management of selected pediatric facial lacerations.
OBJECTIVE: To compare two tissue adhesives, butylcyanoacrylate and octylcyanoacrylate, in the treatment of small (<4 cm) superficial linear traumatic facial lacerations in children.
METHODS: This was a randomized, clinical trial with parallel design. 94 children <18 years of age seen in the ED of a tertiary care pediatric hospital with a facial laceration suitable for tissue adhesive closure underwent laceration closure using either butylcyanoacrylate or octylcyanoacrylate. The primary outcome was the cosmetic result at three months rated from photographs by a plastic surgeon on a visual analog scale (VAS). Secondary outcomes included the time to perform the procedure, the perceived difficulty of the procedure, the pain perceived by the patient, and a wound evaluation score at ten to 14 days and three months.
RESULTS: Ninety-four patients were randomized with 47 in each group. The two groups were similar for baseline demographic and clinical characteristics. There was no difference in the three-month cosmesis VAS (median, 70.0 mm for n-butyl-2-cyanoacrylate vs 67.5 mm for octylcyanocrylate, p = 0.84). There was no difference between the groups for time to complete the procedure (p = 0.88), parent/patient-perceived pain of the procedure (p = 0.37), or physician-perceived difficulty of the procedure (p = 0.33). Similarly, there was no difference between the groups for the percentage of early (p = 0.58) or late (p = 0.71) optimal wound evaluation scores.
CONCLUSIONS: In the closure of small linear pediatric facial lacerations, octylcyanoacrylate is similar to butylcyanoacrylate in ease of use and early and late cosmetic outcomes. The superior physical properties of octylcyanoacrylate appear to add little benefit to the management of these selected lacerations. Physician preference and differing costs may dictate use for these small selected lacerations.
A randomized, controlled trial comparing a tissue adhesive with suturing in the repair of pediatric facial lacerations.
STUDY OBJECTIVE: To compare the tissue adhesive Histoacryl Blue with suturing in the repair of pediatric facial lacerations.
DESIGN: Prospective, randomized controlled trial.
SETTING: Emergency department of a pediatric teaching hospital.
PARTICIPANTS: Eighty-one children presenting with clean facial lacerations less than 4 cm in length and 0.5 cm in width.
INTERVENTIONS: Patients were allocated randomly to have their lacerations repaired with sutures or Histoacryl Blue.
RESULTS: The two groups were similar for demographic and clinical characteristics. Photographs taken at three months were rated by two plastic surgeons blinded to the method of closure. There was no difference between groups for appearance scores on a visual analog scale (60.5 mm for Histoacryl Blue versus 57.2 mm for suture, P = .45) or on a categorical scale (Histoacryl Blue versus sutures: unacceptable, 11% versus 13%; acceptable, 59% versus 71%; excellent, 30% versus 16%; P = .76). Measures of observer agreement produced Pearson correlations of .72 and .94 on the visual analog scale and kappa coefficients of .46 and .73 on the categorical scale. Histoacryl Blue was assessed as less painful on a visual analog scale (24.7 versus 43.7 mm, P < .01) and faster (7.9 versus 15.6 minutes, P < .001).
CONCLUSION: Histoacryl Blue is a faster and less painful method of facial laceration repair that has cosmetic results similar to the use of sutures.
A randomized trial comparing octylcyanoacrylate tissue adhesive and sutures in the management of lacerations.
OBJECTIVE: To assess the effectiveness of a new tissue adhesive for laceration closure.
DESIGN: A prospective, randomized controlled trial.
SETTING: An adult teaching hospital.
PARTICIPANTS: One hundred thirty patients with 136 lacerations who consented to enrollment during a 5-month period. The lacerations included all eligible nonmucosal facial lacerations, as well as selected extremity and torso lacerations (not on hands, feet, or joints). One hundred six lacerations were available for early follow-up, and 98 were available for 3-month evaluation.
INTERVENTIONS: Lacerations were randomly allocated to have skin closure with octylcyanoacrylate adhesive or monofilament suture.
MAIN OUTCOME MEASURE: A 3-month photograph of the wound was assigned a cosmesis score on a previously validated 100-mm visual analog cosmesis scale by a plastic surgeon who was unaware of the method of wound closure.
RESULTS: There were no differences in the mean visual analog cosmesis scores (67 mm for octylcyanoacrylate vs 68 mm for sutures; P=.65). Similarly, there was no difference in the percentage of early (80% vs 82%; P=.80) or late (72% vs 75%; P=.74) optimal wound evaluation scores. The tissue adhesive was a faster method of wound repair (3.6 vs 12.4 minutes; P<.001) as well as being less painful (visual analog pain scores, 7.2 vs 18.0 mm; P<.001).
CONCLUSIONS: Octylcyanoacrylate tissue adhesive effectively closes selected lacerations. This relatively painless and fast method of wound repair can replace the need for suturing several million lacerations each year.
Tissue adhesive versus suture wound repair at 1 year: randomized clinical trial correlating early, 3-month, and 1-year cosmetic outcome.
STUDY OBJECTIVE: To compare the 1-year cosmetic outcome of wounds treated with octylcyanoacrylate tissue adhesive and monofilament sutures and to correlate the early, 3-month, and 1-year cosmetic outcomes.
METHODS: We prospectively randomized 136 cases of traumatic laceration to repair with octylcyanoacrylate tissue adhesive or 5-0 or smaller monofilament suture. A wound score was assigned by a research nurse, and validated by a second nurse blinded to the treatment, at 5 to 10 days after injury (early), 3 months, and 1 year. Standardized photographs were taken at 3 months and 1 year and shown to a cosmetic surgeon blinded to the method of closure, who rated the wounds on a validated cosmesis scale.
RESULTS: We were able to examine 77 lacerations at 1 year for follow-up. No differences were found in the demographic or clinical characteristics between groups. Likewise, at 1 year no difference was found in the optimal wound scores (73% versus 68%, P =.60) or in visual analog scale cosmesis scores (69 versus 69 mm, P =.95) for octylcyanoacrylate and sutures, respectively. Agreement was poor between early and 3-month wound scores (kappa=.34; 95% confidence interval [CI],.10 to.58) but a strong association existed between 3-month and 1-year wound scores (kappa=.71; 95% CI,.52 to.90). We noted a moderate correlation between 3-month and 1-year results on the visual analog cosmesis scale (intraclass correlation,.48; 95% CI, .30 to.63).
CONCLUSION: One year after wound repair, no difference is noted in the cosmetic outcomes of traumatic lacerations treated with octylcyanoacrylate tissue adhesive and sutures. The assessment of wounds 3 months after injury and wound repair provides a good measure of long-term cosmetic outcome.
[Tissue glue in minor skin lesions. A prospective controlled comparison between tissue glue and the suturing of skin minor lesions].
Laceration repair using a tissue adhesive in a children's emergency department.
OBJECTIVE: To determine the effectiveness of a tissue adhesive, Histoacryl Blue (HAB), for laceration repair in children.
DESIGN: Prospective, randomized clinical trial.
SETTING: A tertiary care pediatric emergency center at Egleston Children's Hospital.
PARTICIPANTS: Children who presented for laceration repair between October 1994 and February 1995 were prospectively evaluated. Patients less than 1 or greater than 18 years of age, those with lacerations greater than 5 cm, and those with lacerations located on the eyelids, ears, nose, lips, hands, feet, joints, or perineum were excluded.
INTERVENTIONS: Following consent and routine wound management, including subcutaneous closure when deemed necessary, patients were randomized to receive skin sutures or HAB for cutaneous closure.
METHODS: Length of time required for laceration repair was recorded. Parental perception of the pain experienced by their child was assessed using a visual analogue scale. Photographic documentation of scar appearance at the 2-month follow-up visit was evaluated by plastic surgeons using a visual analogue scale.
RESULTS: Sixty-one children were enrolled: HAB group (N = 30), suture group (N = 31). No differences occurred between groups in laceration length, depth, location, or patient demographics. Length of time required for repair was decreased (median, HAB 7 minutes vs suture 17.0 minutes) and parental assessment of their child's pain was significantly less in the HAB group. Parents were more likely to recommend HAB over suturing to other parents or guardians. Cosmetic outcome in the HAB group was assessed to be as good as, or better than, the cosmetic outcome in the suture group as evaluated by two plastic surgeons.
CONCLUSION: The use of HAB for laceration repair is an acceptable alternative to conventional suturing with a comparable cosmetic outcome. Advantages include less pain to the child, no need for suture removal, and more efficient use of physician time. Parents were also more likely to recommend HAB over suturing for laceration repair.
Long-term appearance of lacerations repaired using a tissue adhesive.
BACKGROUND: Histoacryl Blue (HAB), a tissue adhesive, has been shown to decrease laceration repair time, cause less pain to the child, eliminate the need for suture removal, and result in a similar short-term cosmetic outcome compared with conventional suturing. Reports suggest that poor correlation can exist between the short-term and long-term cosmetic outcomes for lacerations repaired by conventional suturing. Therefore, this study compares the long-term cosmetic outcome of HAB to conventional suturing for laceration repair in children.
DESIGN: Prospective, randomized clinical trial.
PARTICIPANTS: Children presenting an urban pediatric emergency department for laceration repair between October 1994 and February 1995 were eligible. Patients less than 1 or more than 18 years old, those with lacerations more than 5 cm in length, or in areas of high tension or mobility were excluded.
INTERVENTIONS: After routine wound management, including subcutaneous closure when deemed necessary, patients were randomized to receive skin sutures or HAB for cutaneous closure. Photographs taken at the 2-month and 1-year follow-up visits were evaluated for cosmetic appearance by two plastic surgeons blinded to the method of repair.
RESULTS: Sixty-one children were enrolled: HAB (N = 30), suture (N = 31). Thirty HAB and 25 sutured patients were assessed at 2 months, while 17 HAB and 15 sutured patients were reevaluated at 1 year. Patients that followed-up at 2 months and 1 year were comparable to those with no follow-up in: treatment group (HAB vs suture), demographics, wound characteristics, and initial parental satisfaction. The two plastic surgeons graded the cosmetic appearance of the wounds repaired by HAB to be comparable to those repaired by conventional suturing at both the 2-month and 1-year follow-up.
CONCLUSIONS: The use of HAB is an ideal alternative to conventional suturing for the cutaneous closure of low tension lacerations in children with a long-term cosmetic outcome comparable to conventional suturing.
Lacerations against Langer's lines: to glue or suture?
This study evaluated the effects of initial wound orientation on the cosmetic outcome of facial lacerations repaired with histoacryl blue (HAB), a tissue adhesive, vs. conventional suturing. This was a retrospective analysis of patients from a prospective randomized clinical trial on the use of HAB. Children in the initial cohort who had facial lacerations and were also evaluated for cosmetic appearance at a 2-month follow-up appointment were eligible. Orientation along Langer's Lines, which define the functional anatomy of the underlying structures to the skin, was determined by two investigators blinded to the initial method of repair. Photographs of the wounds were reviewed and the wounds were categorized as being: Langer (+) (<20 degrees deviated from Langer's Lines) or Langer (-) (> or =20 degrees deviated from Langer's Lines). Photographic appearance at follow-up was evaluated using a 100-mm visual analog scale (0=best, 100=worst) by two plastic surgeons blinded to the method of repair. Sixty-one patients were enrolled in the initial cohort, with 55 (90%) evaluated at the 2-month follow-up. Forty-eight of the 55 (87%) had facial lacerations, therefore meeting present study criteria: [HAB (n=26), Suturing (n=22), Langer (+) (n=27), Langer (-) (n=21)]. Langer (+) patients were comparable to Langer (-) for demographics, wound characteristics, and method of repair. There was no difference in overall cosmetic appearance of facial wounds closed with HAB vs. conventional suturing. Follow-up appearance was significantly worse for sutured Langer (-) vs. Langer (+) wounds. In contrast, cosmetic appearance of lacerations closed by HAB were comparable between Langer (-) and Langer (+) wounds. In conclusion, initial wound orientation had a greater impact on the cosmetic appearance for lacerations closed by suturing compared to HAB. HAB may be the preferred method of cutaneous closure for facial lacerations oriented against Langer's Lines.
Application of tissue adhesives: rapid attainment of proficiency. Stony Brook Octylcyanoacrylate Study Group.
OBJECTIVE: To evaluate the 3-month cosmetic outcome following laceration repair with a new tissue adhesive, 2-octylcyanoacrylate, as a function of physician experience with this tissue adhesive.
METHODS: The authors prospectively enrolled consecutive patients >1 year of age with non-bite, non-crush-induced lacerations who presented <6 hours after injury and were treated with 2-octylcyanoacrylate. Structured closed-question data sheets were completed at the time of laceration repair and at 3-month follow-up. Long-term cosmetic appearance (>3 months) was assessed by patients using a 100-mm visual analog scale. The cosmetic outcomes were evaluated as a function of the physician application using ANOVA or chi2 tests, as appropriate. This study had 80% power to detect a 10-mm difference between the 2-octylcyanoacrylate and suture groups (alpha, 0.05).
RESULTS: Seven physicians applied 2-octylcyanoacrylate to 63 patients; 61 patients received sutures. Patients were similar in the 2 groups (age, gender, race, history, and wound characteristics; p > 0.05 for all). At long-term follow-up, the cosmetic outcomes were similar in the 2-octylcyanoacrylate and suture groups according to patients (VAS 83.8 +/- 19.4 mm vs 82.5 +/- 17.6 mm; p = 0.72) and physicians (optimal score, 77% vs 80%; p = 0.67), and independent of physician experience with the 2-octylcyanoacrylate. One wound developed an infection and one wound necessitated reclosure due to dehiscence. Neither occurred with the first application.
CONCLUSIONS: The 3-month cosmetic appearance of wounds treated with 2-octylcyanoacrylate is equivalent to that with sutures and does not improve as physicians become more experienced with use of this tissue adhesive. These data suggest that physicians can develop competence in application of tissue adhesives with a brief training period.
Prospective, randomized, controlled trial of tissue adhesive (2-octylcyanoacrylate) vs standard wound closure techniques for laceration repair. Stony Brook Octylcyanoacrylate Study Group.
OBJECTIVE: To compare a new tissue adhesive, 2-octylcyanoacrylate, with standard wound closure techniques for the repair of traumatic lacerations.
METHODS: A prospective, randomized, controlled clinical trial enrolled consecutive patients > 1 year of age with non-bite, non-crush-induced lacerations who presented < 6 hours after injury. Structured closed-question data sheets were completed at the time of laceration repair and suture removal. Patients were randomly assigned to treatment with either 2-octylcyanoacrylate or standard wound closure. Infection was determined at the time of suture removal. Long-term cosmetic appearance (> 3 months) was assessed by physicians using a previously validated categorical cosmetic scale and by patients using a 100-mm visual analog scale.
RESULTS: There were 63 patients randomized to the octylcyanoacrylate group and 61 patients treated with standard wound closure techniques. The 2 treatment groups were similar with respect to age, gender, race, medical history, and wound characteristics. At the 5-to-10-day follow-up, only 1 wound was infected and only 2 wounds required reclosure due to dehiscence. These 3 patients received treatment with octylcyanoacrylate. At long-term follow-up, the cosmetic appearances were similar according to the patients (octylcyanoacrylate, 83.8 +/- 19.4 mm vs standard techniques, 82.5 +/- 17.6 mm; p = 0.72) and the physicians (optimal cosmetic appearance, 77% vs 80%; p = 0.67).
CONCLUSIONS: Wounds treated with octylcyanoacrylate and standard wound closure techniques have similar cosmetic appearances 3 months later.
Evaluation of a new high-viscosity octylcyanoacrylate tissue adhesive for laceration repair: a randomized, clinical trial.
OBJECTIVE: Tissue adhesives have recently been approved for skin closure. Their low viscosity may result in inadvertent migration. The authors compared the tendency of the adhesive to migrate after laceration closure with a high- or low-viscosity octylcyanoacrylate (OCA).
METHODS: This was a randomized, clinical trial set in university and community-based emergency departments. Participants included patients with simple traumatic lacerations. Patients were randomized to laceration closure with low- or high-viscosity OCA tissue adhesive. The outcome measured was immediate adhesive migration (interobserver agreement, kappa = 0.90). Data analysis was performed with proportions compared with chi-square and Fisher's exact tests.
RESULTS: Eighty-four patients were randomized to low- (n = 42) or high- (n = 42) viscosity OCA tissue adhesive. Groups were similar in baseline patient and wound characteristics. The high-viscosity OCA was less likely to migrate than the lower-viscosity agent (21% vs. 78%, p < 0.001; odds ratio = 0.3, 95% confidence interval = 0.1 to 0.5). The proportion of patients who noted a sensation of heat during OCA application was higher in the high-viscosity groups (44% vs. 26% respectively, p = 0.11); however, all such patients in both groups would use the device again. At 14 days, there were no wound infections in either group. There was one dehiscence in the high-viscosity group.
CONCLUSIONS: The high-viscosity OCA tissue adhesive was less likely to migrate than the lower-viscosity device. Wound dehiscence and infection rates were acceptably low in both treatment groups.
Randomized controlled comparison of cosmetic outcomes of simple facial lacerations closed with Steri Strip Skin Closures or Dermabond tissue adhesive.
OBJECTIVE: To compare the short-term complications and long-term cosmetic outcomes of simple facial lacerations closed with 3M Steri Strip Skin Closures or Dermabond.
METHODS: Prospective, randomized controlled trial of children ages 1 to 18 presenting to a pediatric emergency department with simple low-tension lacerations of the face. After standard wound care, patients received wound closure with either Steri Strip Skin Closure or Dermabond. Pain associated with closure was evaluated on a 100-mm visual analogue scale (0 = no pain, 100 = worst pain). A follow-up telephone call was made a week after enrollment to determine short-term complications. Patients returned 2 months after would closure for wound photography. Cosmetic outcomes were evaluated by 2 plastic surgeons blinded to the method of wound closure on a 100-mm visual analogue scale (0 = best scar, 100 = worst scar).
RESULTS: One hundred children aged 1 to 18 were enrolled. Ninety-seven patients had results analyzed. Forty-eight received Steri Strip Skin Closures and 49 received Dermabond. Patient demographics and wound characteristics were similar between groups. Pain scores on a 100-mm visual analogue scale were 9.0 mm for the Steri Strip group and 6.2 mm for the Dermabond group (P = ns). At short-term follow-up, there was one wound complication in the Steri Strip group and 7 complications in the Dermabond group (P = 0.06). Eighty-nine patients received 2-month evaluation (41 Steri Strip, 45 Dermabond). There was no difference in the mean visual analogue scale cosmesis scores: 37.2 mm (95% CI = 30.8-43.7) versus 43.8 mm (95% CI = 38.4-49.2) (P = 0.12).
CONCLUSIONS: Steri Strip Skin Closures and Dermabond provide similar cosmetic outcomes for closure of simple facial lacerations. Steri Strip Skin Closure may represent a low-cost alternative for closure of simple facial lacerations.
Randomized controlled comparison of cosmetic outcomes of simple facial lacerations closed with Steri Strip Skin Closures or Dermabond tissue adhesive.
OBJECTIVE: To compare the short-term complications and long-term cosmetic outcomes of simple facial lacerations closed with 3M Steri Strip Skin Closures or Dermabond.
METHODS: Prospective, randomized controlled trial of children ages 1 to 18 presenting to a pediatric emergency department with simple low-tension lacerations of the face. After standard wound care, patients received wound closure with either Steri Strip Skin Closure or Dermabond. Pain associated with closure was evaluated on a 100-mm visual analogue scale (0 = no pain, 100 = worst pain). A follow-up telephone call was made a week after enrollment to determine short-term complications. Patients returned 2 months after would closure for wound photography. Cosmetic outcomes were evaluated by 2 plastic surgeons blinded to the method of wound closure on a 100-mm visual analogue scale (0 = best scar, 100 = worst scar).
RESULTS: One hundred children aged 1 to 18 were enrolled. Ninety-seven patients had results analyzed. Forty-eight received Steri Strip Skin Closures and 49 received Dermabond. Patient demographics and wound characteristics were similar between groups. Pain scores on a 100-mm visual analogue scale were 9.0 mm for the Steri Strip group and 6.2 mm for the Dermabond group (P = ns). At short-term follow-up, there was one wound complication in the Steri Strip group and 7 complications in the Dermabond group (P = 0.06). Eighty-nine patients received 2-month evaluation (41 Steri Strip, 45 Dermabond). There was no difference in the mean visual analogue scale cosmesis scores: 37.2 mm (95% CI = 30.8-43.7) versus 43.8 mm (95% CI = 38.4-49.2) (P = 0.12).
CONCLUSIONS: Steri Strip Skin Closures and Dermabond provide similar cosmetic outcomes for closure of simple facial lacerations. Steri Strip Skin Closure may represent a low-cost alternative for closure of simple facial lacerations.
Options:
A: Tissue adhesives result in significantly better cosmetic outcomes, less pain, shorter procedure time, and fewer complications compared to standard wound closure.
B: Tissue adhesives result in similar cosmetic outcomes, less pain, shorter procedure time, and a small but statistically significant increased rate of dehiscence compared to standard wound closure.
C: Tissue adhesives result in worse cosmetic outcomes, more pain, longer procedure time, and more complications compared to standard wound closure.
D: Tissue adhesives result in similar cosmetic outcomes, more pain, longer procedure time, and fewer complications compared to standard wound closure. | B |
233 | 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 dopamine in term newborn infants with suspected perinatal asphyxia in terms of mortality and long-term neurodevelopmental outcomes? Please answer this question based on the information provided below:
The cardiovascular effects of dopamine in the severely asphyxiated neonate.
The cardiovascular effects of dopamine were evaluated in 14 severely asphyxiated neonates. After a period of stabilization, either dopamine 2.5 micrograms/kg/minute or placebo was infused in a randomized double-blind protocol. In seven dopamine-treated infants, echocardiographically determined shortening fraction and mean velocity of circumferential fiber shortening increased when compared to preinfusion values (P less than 0.05). There was no significant change in these echo indices of cardiac function in the placebo-treated group. Systolic blood pressure rose in the dopamine group when compared to predopamine infusion values and to the postinfusion values of the placebo group (P less than 0.001 and 0.025, respectively). Diastolic blood pressure increased to a small degree in the dopamine group. There was no significant change in heart rate or echocardiographically measured systolic time intervals. Low doses of dopamine increase cardiac performance and raise systolic blood pressure in the severely asphyxiated neonate.
The cardiovascular effects of dopamine in the severely asphyxiated neonate.
The cardiovascular effects of dopamine were evaluated in 14 severely asphyxiated neonates. After a period of stabilization, either dopamine 2.5 micrograms/kg/minute or placebo was infused in a randomized double-blind protocol. In seven dopamine-treated infants, echocardiographically determined shortening fraction and mean velocity of circumferential fiber shortening increased when compared to preinfusion values (P less than 0.05). There was no significant change in these echo indices of cardiac function in the placebo-treated group. Systolic blood pressure rose in the dopamine group when compared to predopamine infusion values and to the postinfusion values of the placebo group (P less than 0.001 and 0.025, respectively). Diastolic blood pressure increased to a small degree in the dopamine group. There was no significant change in heart rate or echocardiographically measured systolic time intervals. Low doses of dopamine increase cardiac performance and raise systolic blood pressure in the severely asphyxiated neonate.
Options:
A: Dopamine significantly reduces mortality and improves long-term neurodevelopmental outcomes.
B: Dopamine significantly reduces mortality but has no effect on long-term neurodevelopmental outcomes.
C: Dopamine has no significant effect on mortality or long-term neurodevelopmental outcomes.
D: Dopamine significantly improves long-term neurodevelopmental outcomes but has no effect on mortality. | C |
234 | 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 introduction of early versus delayed oral fluids and food after caesarean section in terms of postoperative recovery outcomes? Please answer this question based on the information provided below:
Safety and efficacy of early postoperative solid food consumption after cesarean section.
Traditionally patients have received a physician-dictated regimen of gradual expansion of their diets following cesarean section. This has been based upon concern about the possibility of ileus from expanding the diet too rapidly. Given the economic necessity of earlier postoperative discharge following abdominal delivery, many patients have solid food reintroduced in their diets around the time they leave the hospital. This prospective, randomized, controlled study compared a traditional, gradual dietary expansion scheme with patient-determined reintroduction of solid food, which was offered within eight hours of surgery. The hypotheses were that women would eat more rapidly after cesarean section when given the opportunity and that early solid food consumption would reduce the need for analgesia. The results indicated that both hypotheses were correct. Given the opportunity, women will eat solid food very soon after cesarean section (mean +/- SD 10.2 +/- 5.2 hours from surgery to onset of solid food consumption) as compared to women on a traditional dietary expansion regimen (mean +/- SD 41.5 +/- 16.0 hours, P < .001). Women offered food within hours of cesarean section required less patient-requested injectable narcotic postoperatively than did women on gradual dietary expansion (median, 75 mg versus 225 mg meperidine, P < .05). There was no evidence of compromise of safety or comfort from introducing solid food early and allowing the patient to decide when to eat postoperatively. The conclusion from these data is that early postoperative feeding after cesarean section is a safe and effective alternative for most women, who now face early hospital discharge.
Immediate postoperative oral hydration after caesarean section.
A study was carried out to assess the effects of immediate postoperative oral rehydration in 51 unpremedicated women undergoing caesarean section under epidural anesthesia. The patients were randomly assigned to 2 groups: group 1 (n = 22)--fasting at least until 24 hours after the end of the operation, and group 2 (n = 29)--receiving immediate oral intake of fluids (water, tea or coffee with sugar) without limitation of quantity. The 2 groups were compared for the occurrence of postoperative nausea and vomiting, onset of peristalsis, rectal gas emission, first bowel movement, and possible complications. The results demonstrate no significant differences between the parturients who drank immediately postoperatively as compared to those in whom oral fluid intake was delayed for 24 hours or more. It is concluded that immediate postoperative oral rehydration had no harmful effect upon peristalsis post-caesarean section.
Postoperative management of cesarean patients: the effect of immediate feeding on the incidence of ileus.
OBJECTIVE: To evaluate the effect of immediate feeding on gastrointestinal function in patients undergoing cesarean delivery.
METHODS: A prospective study was conducted in which patients were randomized to one of two groups, either early feeding or delayed feeding, ie, feeding according to the institution's current protocol. Questionnaires were filled out by the subjects on the day of discharge. Fisher exact test was used to compare the two groups with respect to the type of anesthetic used and to compare the incidence of gastrointestinal symptoms. A one-sided exact binomial confidence interval was used to determine the upper bound of the likelihood of paralytic ileus. Logistic regression analysis was used to evaluate the presence of ileus symptoms when controlling for the type of anesthetic used.
RESULTS: There were no significant differences between the control and study groups. There was no significant difference in the number of gastrointestinal symptoms between the two groups. The incidence of postoperative paralytic ileus was zero in both the study and control groups.
CONCLUSION: Routine early feeding of subjects undergoing cesarean delivery can be implemented without an increase in gastrointestinal symptoms or paralytic ileus.
Early feeding after cesarean: randomized trial.
OBJECTIVE: To study the rate of ileus symptoms and hospital course of women who are offered solid food shortly after cesarean delivery.
METHODS: This study involved women delivered by cesarean under regional anesthesia. Exclusion criteria included general anesthesia, magnesium sulfate, intra-operative bowel injury or bowel surgery, or other conditions that precluded early feeding. Early-fed women were offered regular diets within 8 hours of surgery, and controls were given nothing by mouth for 12-24 hours, advanced to clear liquids on the first postoperative day, and then given solid food on the second or third postoperative day.
RESULTS: Sixty women were assigned randomly to each method. Early-fed women received solid food sooner after surgery, 5.0 +/- 1.2 hours versus 40.0 +/- 10.6 hours. The incidences of mild ileus symptoms and postoperative complications were similar in both groups; however, the study did not have an adequate sample size to definitively assess safety concerns. Women in the early-fed group had shorter hospital stays (49.5 +/- 12.7 hours versus 75.0 +/- 12.3 hours, P <.001), and shorter time intervals from surgery to bowel movement, 34.5 hours (interquartile range 25.3-48.8) versus 51.0 (43.3-62.0) hours, P <.001. In the early-fed group, women whose operative times exceeded 40 minutes were more likely to have symptoms of mild ileus.
CONCLUSION: Early initiation of solid food after cesarean delivery appears to be well tolerated and may be associated with a shorter hospital stay. Early-fed women whose operations exceed 40 minutes may be more likely to have mild ileus symptoms.
Early feeding after cesarean: randomized trial.
OBJECTIVE: To study the rate of ileus symptoms and hospital course of women who are offered solid food shortly after cesarean delivery.
METHODS: This study involved women delivered by cesarean under regional anesthesia. Exclusion criteria included general anesthesia, magnesium sulfate, intra-operative bowel injury or bowel surgery, or other conditions that precluded early feeding. Early-fed women were offered regular diets within 8 hours of surgery, and controls were given nothing by mouth for 12-24 hours, advanced to clear liquids on the first postoperative day, and then given solid food on the second or third postoperative day.
RESULTS: Sixty women were assigned randomly to each method. Early-fed women received solid food sooner after surgery, 5.0 +/- 1.2 hours versus 40.0 +/- 10.6 hours. The incidences of mild ileus symptoms and postoperative complications were similar in both groups; however, the study did not have an adequate sample size to definitively assess safety concerns. Women in the early-fed group had shorter hospital stays (49.5 +/- 12.7 hours versus 75.0 +/- 12.3 hours, P <.001), and shorter time intervals from surgery to bowel movement, 34.5 hours (interquartile range 25.3-48.8) versus 51.0 (43.3-62.0) hours, P <.001. In the early-fed group, women whose operative times exceeded 40 minutes were more likely to have symptoms of mild ileus.
CONCLUSION: Early initiation of solid food after cesarean delivery appears to be well tolerated and may be associated with a shorter hospital stay. Early-fed women whose operations exceed 40 minutes may be more likely to have mild ileus symptoms.
The PROEF diet--a new postoperative regimen for oral early feeding.
OBJECTIVE: The purpose of this study was to determine if immediate postoperative feeding of a new oral elemental diet (PROEF diet) would be tolerated by patients and to determine its effect on gastrointestinal function after cesarean section.
STUDY DESIGN: One hundred eighteen patients undergoing cesarean section were randomly assigned by a computer-generated list of numbers to receive either the PROEF diet (60 patients) or routine postoperative dietary management (58 patients). Gastrointestinal morbidity was analyzed by an independent-samples t test.
RESULTS: The PROEF diet group has a more rapid return of normal bowel sounds, 10.3 versus 14.5 hours (p = 0.001), and earlier acceptance of a regular diet, 2.0 versus 2.3 days (p = 0.008).
CONCLUSION: The PROEF diet was well tolerated in cesarean section patients with no increase in gastrointestinal morbidity when compared with a control group of patients. This dispels the classic teaching that postoperative patients may not have oral intake until the return of normal bowel function. Further study is necessary to support the theoretic benefits that may accrue from early feeding of an elemental diet.
The PROEF diet--a new postoperative regimen for oral early feeding.
OBJECTIVE: The purpose of this study was to determine if immediate postoperative feeding of a new oral elemental diet (PROEF diet) would be tolerated by patients and to determine its effect on gastrointestinal function after cesarean section.
STUDY DESIGN: One hundred eighteen patients undergoing cesarean section were randomly assigned by a computer-generated list of numbers to receive either the PROEF diet (60 patients) or routine postoperative dietary management (58 patients). Gastrointestinal morbidity was analyzed by an independent-samples t test.
RESULTS: The PROEF diet group has a more rapid return of normal bowel sounds, 10.3 versus 14.5 hours (p = 0.001), and earlier acceptance of a regular diet, 2.0 versus 2.3 days (p = 0.008).
CONCLUSION: The PROEF diet was well tolerated in cesarean section patients with no increase in gastrointestinal morbidity when compared with a control group of patients. This dispels the classic teaching that postoperative patients may not have oral intake until the return of normal bowel function. Further study is necessary to support the theoretic benefits that may accrue from early feeding of an elemental diet.
Options:
A: Early oral fluids or food were associated with reduced time to first food intake, reduced time to return of bowel sounds, reduced postoperative hospital stay, and a trend to reduced abdominal distension.
B: Early oral fluids or food were associated with increased time to first food intake, increased time to return of bowel sounds, increased postoperative hospital stay, and a trend to increased abdominal distension.
C: Early oral fluids or food showed no significant differences in time to first food intake, time to return of bowel sounds, postoperative hospital stay, or abdominal distension.
D: Early oral fluids or food were associated with increased nausea, vomiting, and paralytic ileus. | A |
235 | 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 infliximab for the treatment of rheumatoid arthritis after 6 and 12 months of treatment? Please answer this question based on the information provided below:
Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group.
BACKGROUND: Neutralization of tumor necrosis factor a (TNF-alpha) for three to six months reduces the symptoms and signs of rheumatoid arthritis. However, the capacity of this approach to effect a more sustained benefit and its effect on joint damage are not known.
METHODS: We treated 428 patients who had active rheumatoid arthritis despite methotrexate therapy with placebo or infliximab, a chimeric monoclonal antibody against TNF-alpha, in intravenous doses of 3 or 10 mg per kilogram of body weight every 4 or 8 weeks in combination with oral methotrexate for 54 weeks. We assessed clinical responses with use of the criteria of the American College of Rheumatology, the quality of life with a health-status questionnaire, and the effect on joint damage radiographically.
RESULTS: The combination of infliximab and methotrexate was well tolerated and resulted in a sustained reduction in the symptoms and signs of rheumatoid arthritis that was significantly greater than the reduction associated with methotrexate therapy alone (clinical response, 51.8 percent vs. 17.0 percent; P<0.001). The quality of life was also significantly better with infliximab plus methotrexate than with methotrexate alone. Radiographic evidence of joint damage increased in the group given methotrexate, but not in the groups given infliximab and methotrexate (mean change in radiographic score, 7.0 vs. 0.6, P<0.001). Radiographic evidence of progression of joint damage was absent in infliximab-treated patients whether or not they had a clinical response.
CONCLUSIONS: In patients with persistently active rheumatoid arthritis despite methotrexate therapy, repeated doses of infliximab in combination with methotrexate provided clinical benefit and halted the progression of joint damage.
Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis.
OBJECTIVE: To evaluate the efficacy, pharmacokinetics, immunogenicity, and safety of multiple infusions of a chimeric monoclonal anti-tumor necrosis factor alpha antibody (cA2) (infliximab; Remicade, Centocor, Malvern, PA) given alone or in combination with low-dose methotrexate (MTX) in rheumatoid arthritis (RA) patients.
METHODS: In a 26-week, double-blind, placebo-controlled, multicenter trial, 101 patients with active RA exhibiting an incomplete response or flare of disease activity while receiving low-dose MTX were randomized to 1 of 7 groups of 14-15 patients each. The patients received either intravenous cA2 at 1, 3, or 10 mg/kg, with or without MTX 7.5 mg/week, or intravenous placebo plus MTX 7.5 mg/week at weeks 0, 2, 6, 10, and 14 and were followed up through week 26.
RESULTS: Approximately 60% of patients receiving cA2 at 3 or 10 mg/kg with or without MTX achieved the 20% Paulus criteria for response to treatment, for a median duration of 10.4 to >18.1 weeks (P < 0.001 versus placebo). Patients receiving cA2 at 1 mg/kg without MTX became unresponsive to repeated infusions of cA2 (median duration 2.6 weeks; P=0.126 versus placebo). However, coadministration of cA2 at 1 mg/kg with MTX appeared to be synergistic, prolonging the duration of the 20% response in >60% of patients to a median of 16.5 weeks (P < 0.001 versus placebo; P=0.006 versus no MTX) and the 50% response to 12.2 weeks (P < 0.001 versus placebo; P=0.002 versus no MTX). Patients receiving placebo infusions plus suboptimal low-dose MTX continued to have active disease, with a Paulus response lasting a median of 0 weeks. A 70-90% reduction in the swollen joint count, tender joint count, and C-reactive protein level was maintained for the entire 26 weeks in patients receiving 10 mg/kg of cA2 with MTX. In general, treatment was well tolerated and stable blood levels of cA2 were achieved in all groups, except for the group receiving 1 mg/kg of cA2 alone, at which dosage antibodies to cA2 were observed in approximately 50% of the patients.
CONCLUSION: Multiple infusions of cA2 were effective and well tolerated, with the best results occurring at 3 and 10 mg/kg either alone or in combination with MTX in approximately 60% of patients with active RA despite therapy with low-dose MTX. When cA2 at 1 mg/kg was given with low-dose MTX, synergy was observed. The results of the trial provide a strategy for further evaluation of the efficacy and safety of longer-term treatment with cA2.
Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group.
BACKGROUND: Not all patients with rheumatoid arthritis can tolerate or respond to methotrexate, a standard treatment for this disease. There is evidence that antitumour necrosis factor alpha (TNFalpha) is efficacious in relief of signs and symptoms. We therefore investigated whether infliximab, a chimeric human-mouse anti-TNFalpha monoclonal antibody would provide additional clinical benefit to patients who had active rheumatoid arthritis despite receiving methotrexate.
METHODS: In an international double-blind placebo-controlled phase III clinical trial, 428 patients who had active rheumatoid arthritis, who had received continuous methotrexate for at least 3 months and at a stable dose for at least 4 weeks, were randomised to placebo (n=88) or one of four regimens of infliximab at weeks 0, 2, and 6. Additional infusions of the same dose were given every 4 or 8 weeks thereafter on a background of a stable dose of methotrexate (median 15 mg/week for > or =6 months, range 10-35 mg/wk). Patients were assessed every 4 weeks for 30 weeks.
FINDINGS: At 30 weeks, the American College of Rheumatology (20) response criteria, representing a 20% improvement from baseline, were achieved in 53, 50, 58, and 52% of patients receiving 3 mg/kg every 4 or 8 weeks or 10 mg/kg every 4 or 8 weeks, respectively, compared with 20% of patients receiving placebo plus methotrexate (p<0.001 for each of the four infliximab regimens vs placebo). A 50% improvement was achieved in 29, 27, 26, and 31% of infliximab plus methotrexate in the same treatment groups, compared with 5% of patients on placebo plus methotrexate (p<0.001). Infliximab was well-tolerated; withdrawals for adverse events as well as the occurrence of serious adverse events or serious infections did not exceed those in the placebo group.
INTERPRETATION: During 30 weeks, treatment with infliximab plus methotrexate was more efficacious than methotrexate alone in patients with active rheumatoid arthritis not previously responding to methotrexate.
Options:
A: Infliximab significantly reduced RA disease activity and had an acceptable safety profile, with improved radiographic scores and fewer patients showing radiographic progression.
B: Infliximab showed no significant difference in RA disease activity compared to controls, and had a higher rate of adverse events.
C: Infliximab was effective in reducing RA disease activity but had a high rate of withdrawals due to adverse events.
D: Infliximab had no impact on RA disease activity and showed no difference in safety profile compared to controls. | A |
236 | 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 of the study comparing thalidomide to placebo in the treatment of toxic epidermal necrolysis? Please answer this question based on the information provided below:
Randomised comparison of thalidomide versus placebo in toxic epidermal necrolysis.
BACKGROUND: Toxic epidermal necrolysis (TEN) is associated with a 30% death rate. Tumour necrosis factor alpha (TNF-alpha) has been implicated in the pathogenesis of TEN. Thalidomide is a potent inhibitor of TNF-alpha action. We did a double-blind, randomised, placebo-controlled study of thalidomide in TEN.
METHODS: The patients received a 5-day course of thalidomide 400 mg daily or placebo. The main endpoint was the progression of skin detachment after day 7. Secondary endpoints were the severity of the disease, evaluated with the simplified acute physiology score (SAPS), and the mortality. TNF-alpha and interleukin 6 were measured.
FINDINGS: The study was stopped because there was excess mortality in the thalidomide group--ten of 12 patients died compared with three of ten in the placebo group (Fisher's exact test with Katz's approximation, relative risk=2.78, p=0.03). After adjustment for SAPS, mortality remained significantly higher in the thalidomide group than in the placebo group (exact logistic regression mid-p=0.007; 95% CI for odds ratio 2.7 to infinity). Plasma TNF-alpha concentration was higher in the thalidomide group than the placebo group on day 2, though the difference was not significant (Wilcoxon rank-sum test p=0.07).
INTERPRETATION: Even though few patients were included, our data suggest that thalidomide is detrimental in TEN, possibly because of a paradoxical enhancement of TNF-alpha production.
Options:
A: Thalidomide was found to be significantly more effective than placebo in reducing mortality and severity of the disease.
B: Thalidomide showed no significant difference compared to placebo in terms of mortality and disease severity.
C: Thalidomide was associated with significantly higher mortality compared to placebo.
D: Thalidomide was found to be effective in reducing the progression of skin detachment but had no impact on overall mortality. | C |
237 | 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 plasma exchange in the treatment of myasthenia gravis based on the available evidence? Please answer this question based on the information provided below:
[Long-term effects of plasma exchange in myasthenia. Results of a randomized study].
A randomized study was carried out in 14 myasthenia patients to compare the long-term effects of two therapeutic regimens. Group I patients received prednisone 1 mg/kg/24 h for one month, then in decreasing dosage; in case of failure at the end of the first month, cyclophosphamide 2 mg/kg/24 h was added to the prednisone treatment. Group II patients received the same treatment associated with 3 plasma exchanges over a 10-day period; these were continued, if required, at the rate of once a week. The minimum follow up was one year. The results (greater improvement in muscular strength and vital capacity) were better after one month in group I and thereafter similar in both groups. However, the mean daily dose of prednisone was higher in Group I. The number of exacerbations of myasthenia was greater in group II (11 versus 2 in group I over a 24-months period). The mean fall in anti-R Ach ab was about the same in both groups. This study confirms the rapid effectiveness of plasma exchanges and their value in severe myasthenia. The higher incidence of exacerbations in Group II was probably due to a rebound phenomenon and points to the need for combined immuno-suppressive treatment.
Clinical trial of plasma exchange and high-dose intravenous immunoglobulin in myasthenia gravis. Myasthenia Gravis Clinical Study Group.
We have conducted a trial to randomly assess the efficacy and tolerance of intravenous immunoglobulin (i.v.Ig) or plasma exchange (PE) in myasthenia gravis (MG) exacerbation and to compare two doses of i.v.Ig. Eighty-seven patients with MG exacerbation were randomized to receive either three PE (n = 41), or i.v.Ig (n = 46) 0.4 gm/kg daily further allocated to 3 (n = 23) or 5 days (n = 23). The main end point was the variation of a myasthenic muscular score (MSS) between randomization and day 15. The MSS variation was similar in both groups (median value, +18 in the PE group and +15.5 in the i.v.Ig group, p = 0.65). Similar efficacy, although slightly reduced in the 5-day group was observed with both i.v.Ig schedules. The tolerance of i.v.Ig was better than that of PE with a total of 14 side effects observed in 9 patients, 8 in the PE group and 1 in the i.v.Ig group (p = 0.01). Although our trial failed to show a pronounced difference in the efficacy of both treatments, it exhibited a very limited risk for i.v.Ig. i.v.Ig is an alternative for the treatment of myasthenic crisis. The small sample sizes in our trial, however, could explain why a difference in efficacy was not observed. Further studies are needed to compare PE with i.v.Ig and to determine the optimal dosage of i.v.Ig.
Immunoglobulin treatment versus plasma exchange in patients with chronic moderate to severe myasthenia gravis.
The purpose of this study was to compare the efficacy of high-dose intravenous immunoglobulin (IVIG) treatment with plasma exchange in patients suffering from moderate to severe myasthenia gravis (MG) in a stable phase. There are no controlled studies comparing IVIG with plasma exchange in patients who despite immunosuppressive treatment have persistent incapacitating MG symptoms. This was a controlled crossover study. Twelve patients with generalized moderate to severe MG on immunosuppressive treatment for at least 12 months were included. The patients were evaluated clinically using a quantified MG clinical score (QMGS) before and at follow-up visits after each treatment. One week after the treatments, the patients who received plasma exchange treatment showed a significant improvement in QMGS compared to baseline but although some improvement was seen after IVIG this did not reach statistical significance. Four weeks after both plasma exchange and IVIG treatments, there was a significant improvement in QMGS compared to baseline. One week and 4 weeks after treatment, no significant difference between the 2 treatments was found. Both treatments have a clinically significant effect 4 weeks out in patients with chronic MG, but the improvement has a more rapid onset after plasma exchange than after IVIG.
Options:
A: Plasma exchange significantly improved muscle scores and reduced relapses in the long term.
B: Plasma exchange showed no significant improvement in muscle scores and had more relapses compared to prednisone alone in the first year.
C: Plasma exchange was found to be ineffective in both short-term and long-term treatment of myasthenia gravis.
D: Plasma exchange was confirmed to be beneficial in both short-term and long-term treatment of myasthenia gravis. | B |
238 | 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 overall effect of mechanical ventilation (MV) on mortality in newborn infants with severe respiratory failure due to pulmonary disease, particularly in those with a birth weight of more than 2 kg? Please answer this question based on the information provided below:
A controlled trial of assisted ventilation using an oro-nasal mask.
Mechanical ventilation in the respiratory distress syndrome: a controlled trial.
A controlled trial of artificial respiration in the respiratory-distress syndrome of the newborn.
A controlled trial of management of respiratory distress syndrome in a body-enclosing respirator. I. Evaluation of safety.
Early correction of hypoxemia and acidemia in infants of low birth weight: a controlled trial of oxygen breathing, rapid alkali infusion, and assisted ventilation.
Options:
A: MV increased mortality in all newborn infants regardless of birth weight.
B: MV had no significant effect on mortality in newborn infants with a birth weight of more than 2 kg.
C: MV significantly reduced mortality in newborn infants with a birth weight of more than 2 kg.
D: MV had no significant effect on mortality in any newborn infants. | C |
239 | 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 short-term effects of snoezelen on the behaviors of people with dementia based on the reviewed trials? Please answer this question based on the information provided below:
A randomized controlled trial of the effects of multi-sensory stimulation (MSS) for people with dementia.
OBJECTIVES: To investigate short-term effects of Multi-Sensory Stimulation (MSS) on behaviour, mood and cognition of older adults with dementia, the generalization of effects to day hospital and home environments and the endurance of any effects over time.
DESIGN: A randomized controlled trial comparing MSS with a credible control of one-to-one activities.
METHODS: Fifty patients with diagnoses of moderate to severe dementia were randomized to either MSS or Activity groups. Patients participated in eight 30-minute sessions over a 4-week period. Ratings of behaviour and mood were taken before, during and after sessions to investigate immediate effects. Pre, mid, post-trial, and follow-up assessments were taken to investigate any generalization of effects on cognition, behaviour at the day hospital and behaviour and mood at home and endurance of effects once sessions had ceased.
RESULTS: Immediately after MSS and Activity sessions patients talked more spontaneously, related better to others, did more from their own initiative, were less bored/inactive, and were more happy, active or alert. Both groups were more attentive to their environment than before, with a significantly greater improvement from the MSS group. At the day hospital, patients in the Activity group improved on their 'speech skills' (amount of speech; initiation of speech), whereas the MSS group remained unchanged during the trial. The MSS group showed a significant improvement in mood and behaviour at home compared to the Activity group whose behaviour deteriorated. No longer-term benefits were shown; indeed, behaviour declined sharply during the month follow-up period.
CONCLUSIONS: Both MSS and Activity sessions appear to be effective and appropriate therapies for people with dementia.
Effects of multi-sensory stimulation for people with dementia.
BACKGROUND: Over recent years multi-sensory stimulation (MSS) has become an increasingly popular approach to care and is used in several centres throughout Europe. This popularity could be explained by the limited alternatives available to staff and a widely held belief that MSS is a friendly and highly humane approach. A randomized controlled trial was therefore essential to evaluate the effectiveness and extent of the benefits of MSS.
AIM: To assess whether MSS is more effective in changing the behaviour, mood and cognition of older adults with dementia than a control of activity (playing card games, looking at photographs, doing quizzes, etc.).
METHODS: A total of 136 patients from three countries [United Kingdom (UK), the Netherlands and Sweden] were randomized to MSS or activity groups. Patients participated in eight 30-minute sessions over 4 weeks. Ratings of behaviour and mood were taken before, during and after sessions to investigate immediate effects. Pre-, mid-, post-trial and follow-up assessments were taken to investigate any generalization of effects to cognition and behaviour and mood at home/on the ward or at the day hospital.
RESULTS: There were limited short-term improvements for both the MSS and activity groups immediately after sessions, and limited short-term improvements between the groups during sessions. There were no significant differences between the groups when assessing change in behaviour, mood or cognition at home/on the ward or at the day hospital. In the UK, however, behaviour at the day hospital for both groups remained stable during the trial but deteriorated once the sessions had stopped, and active/disturbed behaviour at home improved but likewise deteriorated once sessions had stopped.
CONCLUSIONS: Overall, MSS was found to be no more effective than an activity in changing the behaviour, mood or cognition of patients with dementia in the short- or long-term.
Effects of snoezelen, integrated in 24 h dementia care, on nurse-patient communication during morning care.
OBJECTIVE: To investigate the effectiveness of snoezelen, integrated in 24-hour care, on the communication of Certified Nursing Assistants (CNAs) and demented nursing home residents during morning care.
METHODS: A quasi-experimental pre- and post-test design was conducted, comparing sic psychogeriatric wards, that implemented snoezelen, to six control wards, that continued in giving usual care. Measurements were performed at baseline and 18 months after a training 'snoezelen for caregivers'. Independent assessors analysed 250 video-recordings directly from the computer, using an adapted version of the Roter Interaction Analysis System (RIAS) and non-verbal measurements.
RESULTS: Trained CNAs showed a significant increase of resident-directed gaze, affective touch and smiling. The total number of verbal utterances also increased (more social conversation, agreement, talking about sensory stimuli, information and autonomy). Regarding residents, a significant treatment effect was found for smiling, CNA-directed gaze, negative verbal behaviours (less disapproval and anger) and verbal expressed autonomy.
CONCLUSION: The implementation of snoezelen improved the actual communication during morning care.
PRACTICE IMPLICATIONS: Teaching CNAs to provide snoezelen has added value for the quality of care. Morning care by trained CNAs appeared to take more time. This suggests that (some) time investment might be required to achieve positive effects on CNA- resident communication.
Behavioral and mood effects of snoezelen integrated into 24-hour dementia care.
OBJECTIVES: To investigate the effectiveness of snoezelen, integrated in 24-hour daily care, on the behavior and mood of demented nursing home residents.
DESIGN: Quasiexperimental pre- and posttest design.
SETTING: Twelve psychogeriatric wards of six nursing homes, spread over different parts of the Netherlands.
PARTICIPANTS: One hundred twenty-five patients with moderate to severe dementia and care dependency were included in the pretest and 128 in the posttest; 61 were completers (included in both pre- and posttest).
INTERVENTION: Experimental subjects received an individual 24-hour snoezel program, based on family history taking and stimulus preference screening. Caregivers were trained, and (organizational) adaptations were made to fulfill the conditions for resident-oriented snoezel care. The control group received usual nursing home care.
MEASUREMENTS: Observations were made on the wards using subscales of the Dutch Behavior Observation Scale for Psychogeriatric Inpatients, the Dutch version of the Cohen-Mansfield Agitation Inventory, and the Cornell Scale for Depression in Dementia. Independent assessors observed video recordings of morning care and rated residents' behavior and mood using INTERACT and FACE, respectively.
RESULTS: Residents receiving snoezel care demonstrated a significant treatment effect with respect to their level of apathetic behavior, loss of decorum, rebellious behavior, aggressive behavior, and depression. During morning care, the experimental subjects showed significant changes in well-being (mood, happiness, enjoyment, sadness) and adaptive behavior (responding to speaking, relating to caregiver, normal-length sentences).
CONCLUSION: Snoezel care particularly seems to have a positive effect on disturbing and withdrawn behavior. The results suggest that a 24-hour integrated snoezel program has a generalizing effect on the mood and behavior of demented residents.
Options:
A: The pooled results were significant and strongly favored the treatment.
B: The pooled results were insignificant, but the trend favored the treatment.
C: The pooled results were insignificant and did not favor the treatment.
D: The pooled results were significant and did not favor the treatment. | B |
240 | 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 physical exercise in improving sleep problems among adults aged 60 and above? Please answer this question based on the information provided below:
Moderate-intensity exercise and self-rated quality of sleep in older adults. A randomized controlled trial.
OBJECTIVE: To determine the effects of moderate-intensity exercise training on self-rated (subjective) sleep quality among healthy, sedentary older adults reporting moderate sleep complaints.
DESIGN: Randomized controlled trial of 16 weeks' duration.
SETTING: General community.
PARTICIPANTS: Volunteer sample of 29 women and 14 men (of 67 eligible subjects) aged 50 to 76 years who were sedentary, free of cardiovascular disease, and reported moderate sleep complaints. No participant was withdrawn for adverse effects.
INTERVENTION: Randomized to 16 weeks of community-based, moderate-intensity exercise training or to a wait-listed control condition. Exercise consisted primarily of four 30- to 40-minute endurance training sessions (low-impact aerobics; brisk walking) prescribed per week at 60% to 75% of heart rate reserve based on peak treadmill exercise heart rate.
MAIN OUTCOME MEASURE: Pittsburgh Sleep Quality Index (PSQI).
RESULTS: Compared with controls (C), subjects in the exercise training condition (E) showed significant improvement in the PSQI global sleep score at 16 weeks (baseline and posttest values in mean [SD] for C=8.93 [3.1] and 8.8 [2.6]; baseline and posttest values for E=8.7 [3.0] and 5.4 [2.8]; mean posttest difference between conditions=3.4; P<.001; 95% confidence interval, 1.9-5.4), as well as in the sleep parameters of rated sleep quality, sleep-onset latency (baseline and posttest values for C=26.1 [20.0] and 23.8 [15.3]; for E=28.4 [20.2] and 14.6 [13.0]; net improvement=11.5 minutes), and sleep duration baseline and posttest scores for C=5.8 [1.1] and 6.0 [1.0]; for E=6.0 [1.1] and 6.8 [1.2]; net improvement=42 minutes) assessed via PSQI and sleep diaries (P=.05).
CONCLUSIONS: Older adults with moderate sleep complaints can improve self-rated sleep quality by initiating a regular moderate-intensity exercise program.
Options:
A: Physical exercise significantly improved sleep onset latency, total sleep duration, and global sleep quality scores, but not sleep efficiency.
B: Physical exercise had no significant impact on any measures of sleep quality or duration.
C: Physical exercise significantly improved sleep efficiency but had no impact on sleep onset latency or total sleep duration.
D: Physical exercise worsened sleep onset latency and total sleep duration, but improved sleep efficiency. | A |
241 | 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 contraceptive efficacy and safety of the Prentif cap and FemCap compared to the diaphragm? Please answer this question based on the information provided below:
A comparative study of the safety and efficacy of FemCap, a new vaginal barrier contraceptive, and the Ortho All-Flex diaphragm. The FemCap Investigators' Group.
The FemCap is a new silicone rubber barrier contraceptive shaped like a sailor's hat, with a dome that covers the cervix, a rim that fits into the fornices, and a brim that conforms to the vaginal walls around the cervix. It was designed to result in fewer dislodgments and less pressure on the urethra than the cervical cap and diaphragm, respectively, and to require less clinician time for fitting. This was a phase II/III, multicenter, randomized, open-label, parallel group study of 841 women at risk for pregnancy. A subset of 42 women at one site underwent colposcopy. Women were randomized to use the FemCap or Ortho All-Flex contraceptive diaphragm, both with 2% nonoxynol-9 spermicide, for 28 weeks. The objectives were to compare the two devices with regard to their safety and acceptability and to determine whether the probability of pregnancy among FemCap users was no worse than that of the diaphragm (meaning not more than 6 percentage points higher). The 6-month Kaplan-Meier cumulative unadjusted typical use pregnancy probabilities were 13.5% among FemCap users and 7.9% among diaphragm users. The adjusted risk of pregnancy among FemCap users was 1.96 times that among diaphragm users, with an upper 95% confidence limit of 3.01. Clinical equivalence (noninferiority) of the FemCap compared with the diaphragm, as defined in this study, would mean that the true risk of pregnancy among FemCap users was no more than 1.73 times the pregnancy risk of diaphragm users. Because the observed upper 95% confidence limit (and even the point estimate) exceeded 1.73, the probability of pregnancy among FemCap users, compared with that among diaphragm users, did not meet the definition of clinical equivalence used in this study. The FemCap was believed to be safe and was associated with significantly fewer urinary tract infections. More women reported problems with the FemCap with regard to insertion, dislodgement, and especially removal, although their general assessments were positive. The two devices were comparable with regard to safety and acceptability, but a 6-point difference in the true 6-month pregnancy probabilities of the two devices could not be ruled out. Further studies are needed to determine whether design modifications can simplify insertion and removal.
Options:
A: Both the Prentif cap and FemCap were found to be as effective as the diaphragm in preventing pregnancy, and both were medically safe.
B: The Prentif cap was as effective as the diaphragm in preventing pregnancy, but the FemCap was not. Both cervical caps were medically safe.
C: Neither the Prentif cap nor the FemCap were as effective as the diaphragm in preventing pregnancy, but both were medically safe.
D: The Prentif cap was not as effective as the diaphragm in preventing pregnancy, but the FemCap was. Both cervical caps were medically safe. | B |
242 | 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 adverse effects of single-dose dipyrone in adults with moderate to severe renal colic pain? Please answer this question based on the information provided below:
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.
Nifedipine in the treatment of renal colic.
A double-blind randomized, clinical trial was conducted in 43 patients to evaluate the efficacy of sublingual nifedipine in the treatment of pain in renal colic. Comparison was made with a combination of dipyrone, pitofenone and fenpipramide, which is usually administered intravenously in Spain. With nifedipine, pain completely disappeared in 44% of the cases, and with the combination of drugs, in 89% (p less than 0.005). More adverse effects were noted with the combination than with nifedipine. Both treatments brought about a slight drop in arterial pressure without leading to hypotension in any case. There was no change in heart rate. The possible causes of the relatively low level of success with nifedipine were analyzed. The possibility of using nifedipine under certain circumstances in which other drugs are contraindicated or when their administration is unfeasible is suggested.
[A double-blind study of the analgesic efficacy in kidney colic of the combination of dipyrone and spasmolytic with ketorolac trometamol].
We conducted a double-blind study in 34 patients to compare the analgesic efficacy in acute renal colic using 2.5 g dipyrone combined with a spasmolytic agent and 30 mg ketorolac tromethamine, diluted in 100 ml saline solution and injected intravenously. Clinical criteria and the observation of red cells in urine were used for the diagnosis. The intensity of the pain and its development were measured using visual analogue scales (VAS) and a scale of items showing patient improvement. The side effects were spontaneously mentioned by the patients and elicited by direct questioning. It can be confirmed with a beta error of 0.10 that the analgesic effect obtained by both treatments is similar. Nevertheless, the combination of dipyrone and spasmolytic produces more side effects, possibly due to the spasmolytic agent.
Diclofenac versus dipyrone in acute renal colic: a double-blind controlled trial.
A randomized, double-blind clinical trial in 50 patients was done to compare the efficacy and tolerance of single doses of intramuscular diclofenac 75 mg and dipyrone 2 g in acute renal colic. Both drugs were equally effective, but diclofenac was better in terms of complete relief of pain. Vital signs were affected according to the stress and pain.
[Flurbiprofen: therapeutic alternative in nephritic colic].
A double blind randomized study was conducted in 52 patients with renoureteric colic to compare the therapeutic efficacy of two analgesics given in a single intramuscular dose. Following the administration of 2 gm dipirone plus 20 mg hyoscine N-butylbromide (n = 26) or 150 mg flurbiprofen (n-26), the patients were assessed for pain intensity, relief and pain status for a period of one hour. Both treatments afforded a similar analgesic effect, with pain remitting in 76.9% of the cases. No significant differences were observed for the latency periods or degree of pain at 5, 10, 30 and 60 minutes following treatment. Additional analgesic therapy was required in 34.6% of the patients who received dipirone and 26.9% of the flurbiprofen group, the difference not being statistically significant. Overall both drugs were well tolerated and only local adverse effects were observed, pain being the most frequent.
[Flubiprofen vs dipyrone combined with hyoscine: the analgesic efficacy in renal colic].
OBJECTIVE: We compared the efficacy of flurbiprofen (NSAID) versus dipirone + hyoscine N-butylbromide in the treatment of nephric colic.
METHODS: The study comprised 135 patients, aged 18 to 75 yrs, with intense nephric colic. The patients were observed 60 min after a single IM dose of 150 mg flurbiprofen (n = 67) or 2 gm dipirone + 20 mg hyoscine N-butylbromide.
RESULTS: Both treatment modalities were well-tolerated and afforded significant pain relief. Flurbiprofen, however, was faster-acting and superior to dipirone + hyoscine in the overall evaluation of good and excellent therapeutic response rates.
CONCLUSION: The results of the study show that IM flurbiprofen is a useful alternative to dipirone + hyoscine N-butylbromide in the treatment of nephric colic.
Comparison of the onset and duration of the analgesic effect of dipyrone, 1 or 2 g, by the intramuscular or intravenous route, in acute renal colic.
In a double-blind, double-dummy randomized controlled clinical trial, the onset and duration of the analgesic effect of dipyrone, 1 or 2 g, and diclofenac sodium, 75 mg, by either the i.m. or the i.v. route were compared in 293 patients (aged 18-70 years) with acute renal colic. A level of > or = 50 mm on the 100-mm visual analogue scale was required for inclusion in the study. Patients were randomly allocated to six treatment groups, receiving dipyrone 1 g i.m., dipyrone 1 g i.v., dipyrone 2 g i.m.;, dipyrone 2 g i.v., diclofenac sodium 75 mg i.m.; and diclofenac sodium 75 mg i.v., respectively. Evaluations were performed at 10, 20, 30, and 60 min and 2, 4, and 6 h after treatment (time 0). Primary efficacy end points included course of pain, total pain, percentage of patients with a pain improvement of 50% or more at each evaluation time, pain intensity evaluated by the investigator on a 0-3 scale, and differences in pain intensity. The analgesic response was more marked and prolonged among patients receiving dipyrone 2 g i.m. or dipyrone 2 g i.v. There were no significant differences between dipyrone 1 g and diclofenac sodium 75 mg, by either the i.m. or the i.v. route. All treatment regimens were well tolerated.
Intramuscular diclofenac sodium versus intravenous Baralgin in the treatment of renal colic.
A comparative, randomized, double-blind study of diclofenac sodium 75 mg im versus Baralgin (a combination drug composed of dipyrone and two spasmolytics) 5 mL iv was performed on 57 patients with renal colic. Both groups were comparable as to age, sex, pain evolution time before treatment, and no treatment for renal colic in the six hours preceding trial drug administration. No significant differences were found between the two groups with respect to the evolution of pain after the first dose or in the frequency of administration of a second dose. Tolerability was good in both groups, but sweating and pain throughout the vein were observed in one patient in the Baralgin group. We concluded that diclofenac sodium constitutes an excellent alternative to pyrazolone analgesics, with the advantages of being monotherapy and having good tolerability, when used as intramuscular injection in ambulatory patients.
Double-blind study with dipyrone versus tramadol and butylscopolamine in acute renal colic pain.
To investigate the combined analgesic and spasmolytic effect of dipyrone, 104 patients suffering from "severe" or "excruciating" colic pain due to a confirmed calculus in the upper urinary tract were randomized to receive i.v. either 2.5 g dipyrone (36 patients), 100 mg tramadol (35 patients), or 20 mg butylscopolamine (33 patients) in a multicentre, observer-blind, parallel-group study conducted in 8 German centres. The three treatment groups were homogeneous when analyzed by age, sex, height, and baseline pain intensity. Dipyrone was significantly more effective than tramadol in reducing pain for the primary endpoint, pain intensity differences (PID) at 20, 30, and 50 min after drug administration, and was significantly more effective than butylscopolamine at 30 and 50 min for the secondary efficacy endpoint, pain intensity differences on a categorical scale. Dipyrone had the highest SPID0-2 h of the three drugs (P < 0.05). Only 5 patients receiving dipyrone needed "rescue" medication as compared with 13 patients given tramadol and 11 patients receiving butylscopolamine. Adverse events were observed in 4 patients receiving butylscopolamine and in 1 patient each given dipyrone and tramadol. "Distinct" pain relief as assessed on a visual analogue scale (VAS) is a reliable method of determining the onset of analgesic action in the colic pain model.
Options:
A: Single-dose dipyrone was found to be less effective than other analgesics and had a high incidence of severe adverse effects.
B: Single-dose dipyrone was found to be of similar efficacy to other analgesics used in renal colic pain, with commonly reported adverse effects being dry mouth and somnolence.
C: Single-dose dipyrone was found to be significantly more effective than other analgesics and had no reported adverse effects.
D: Single-dose dipyrone combined with antispasmolytic agents was found to be more effective than dipyrone alone, with no adverse effects reported. | B |
243 | 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 anti-cholinergic agents compared to beta2-sympathomimetic agents in treating acute exacerbations of COPD? Please answer this question based on the information provided below:
Effects of combined treatment with glycopyrrolate and albuterol in acute exacerbation of chronic obstructive pulmonary disease.
STUDY OBJECTIVE: To investigate whether the addition of a single aerosolized dose of glycopyrrolate leads to a greater improvement in pulmonary function than treatment with albuterol alone for patients with acute exacerbation of chronic obstructive pulmonary disease (COPD).
DESIGN: Prospective, randomized, blinded, controlled study. Fifty-seven patients with acute exacerbation of COPD were entered into the study. All patients received three aerosol treatments. Patients were randomized to receive 2 mg aerosolized glycopyrrolate (combination therapy group) or aerosolized placebo in addition to their first 2.5-mg albuterol aerosol treatment. All patients received 2.5 mg of aerosolized albuterol alone for the next two treatments.
SETTING: Urban teaching hospital emergency department.
RESULTS: We found no difference in pretreatment 1-second fractional expired volume (FEV1) between the control and glycopyrrolate groups. There was no significant difference in the absolute value of the FEV1 at 1 hour or at 3 hours between the two groups; however, patients who received combination therapy had a greater percent increase from the pretreatment value of FEV1 (56%) as measured in milliliters than did control patients (19%; P = .008).
CONCLUSION: The combination of glycopyrrolate and albuterol produces a greater improvement in FEV1 than does albuterol alone in the treatment of patients with acute exacerbation of COPD.
A comparison of the effects of ipratropium bromide and metaproterenol sulfate in acute exacerbations of COPD.
Thirty-two patients presenting with acute exacerbations of chronic obstructive pulmonary disease were entered into the following double-blind, crossover study. First (time 0), patients inhaled either ipratropium bromide (54 micrograms) or metaproterenol sulfate (1.95 mg) via a metered dose inhaler (MDI) attached to a device (Inspirease) (phase 1). After 90 minutes, they inhaled whichever of the two medications they had not received in phase 1. This is referred to as phase 2. Pulmonary function (FEV1 and FVC) was measured at time 0, and at 30, 60, and 90 minutes following phase 1 treatment, and at 30, 60, and 90 minutes following phase 2 treatment (120, 150, and 180 minutes from the start of the study). Arterial blood gas samples (n = 20) were obtained at entry into the study and 30 and 90 minutes after phase 1 medication. The groups did not differ in age, degree of airway obstruction, hypoxemia, or theophylline usage at the start of the study. In phase 1, at 90 minutes, pulmonary function in both groups significantly and similarly improved. For ipratropium, FEV1 improved from 0.62 +/- 0.08 L to 0.88 +/- 0.11 L (p less than 0.01) and for metaproterenol FEV1 improved from 0.69 +/- 0.06 to 0.92 +/- 0.09 L (p less than 0.01). There was no further improvement with phase 2 treatment for either group. Thirty minutes after inhaling ipratropium, there was a small but significant rise in PO2 (5.8 +/- 3.0 mm Hg; p less than 0.05) while metaproterenol inhalation resulted in a 6.2 +/- 1.2 mm Hg decline in PO2 (p less than 0.05). These changes were not sustained at 90 minutes. We concluded that for acute exacerbations of COPD, both ipratropium and metaproterenol are effective medications when administered via an MDI attached to a device (Inspirease). However, ipratropium may be a safer choice as it initially did not cause a decline in blood oxygenation.
Effect of three different bronchodilators during an exacerbation of chronic obstructive pulmonary disease.
This study evaluates the effect of three different bronchodilators (beta 2-adrenergic, anticholinergic and methylxanthine) alone and in randomized sequence, during an exacerbation in thirteen patients with chronic obstructive pulmonary disease. Dose-response curves were obtained for inhaled salbutamol and inhaled ipratropium bromide. The bronchodilator effect of a perfusion of aminophylline was also assessed. When a plateau of bronchodilatation was achieved with one agent, one dose of a second bronchodilator was administered to see whether additional bronchodilation could be achieved. The increments in FEV1 and FVC were similar with the three agents. The addition of a second bronchodilator did not result in significant increments in most of the patients. In at least half of the patients the doses of salbutamol and ipratropium that produced the maximal bronchodilatation were twice that currently employed.
Comparison of nebulised salbutamol and ipratropium bromide with salbutamol alone in the treatment of chronic obstructive pulmonary disease.
BACKGROUND: Patients admitted with acute exacerbation of chronic obstructive pulmonary disease (COPD) are often prescribed ipratropium bromide in combination with a beta 2 agonist such as salbutamol. Studies have not shown any benefit in adding ipratropium bromide to salbutamol in acute exacerbations of COPD, but these studies have only assessed patients for 60-90 minutes and short term studies may not predict long term clinical response. Combination therapy with the two drugs was compared with salbutamol alone in the treatment of acute exacerbations of COPD during a hospital admission.
METHODS: Seventy patients admitted to hospital with an acute exacerbation of COPD were randomly allocated to receive either nebulised salbutamol 5 mg and ipratropium bromide 500 micrograms, or nebulised salbutamol 5 mg alone (all four times a day) on admission. All other treatment was prescribed at the discretion of the attending physician. Length of stay in hospital and spirometric values on days 1, 3, 7, 14, and discharge were assessed. Patients completed a subjective symptom score each day.
RESULTS: There was no difference between the two groups in the mean (SD) length of stay (salbutamol 10.5 (4.7) days, salbutamol + ipratropium bromide 11.8 (4.4) days; 95% CI -1.02 to 3.62). There was no difference in spirometric values on days 1, 3, 7, 14, or discharge between the two groups. The subjective improvement was similar with both treatments.
CONCLUSIONS: The routine addition of nebulised ipratropium bromide to salbutamol appears to be of no benefit in the treatment of acute exacerbations of COPD.
Nebulised salbutamol with and without ipratropium bromide in acute airflow obstruction.
103 patients with acute airflow obstruction (56 asthma, 47 chronic obstructive pulmonary disease [COPD]) completed a double-blind trial of nebulised bronchodilator treatment in a hospital accident and emergency department. Each patient was randomised to receive either 10 mg of salbutamol nebuliser solution in 2 ml of saline or 10 mg of salbutamol in 2 ml (0.5 mg) of preservative-free ipratropium bromide. Peak flow rate (PFR) was recorded before treatment and 1 hour after beginning nebulised treatment. In 23 asthmatic patients given salbutamol alone PFR rose by a mean 31% 1 hour after treatment whereas in 33 such patients given combined treatment it rose by a mean 77% (95% confidence interval for the difference 8-84%). Patients whose PFR was below 140 l/min at entry gained maximum benefit from the combined treatment. For COPD patients the PFR rise was almost identical for both treatments. In acute asthma the immediate PFR response to a mixture of salbutamol and ipratropium bromide was better than the response to nebulised salbutamol alone. For COPD patients, the two treatments were of equal benefit.
Severe exacerbations of COPD and asthma. Incremental benefit of adding ipratropium to usual therapy.
Single dose studies have assessed the utility of ipratropium bromide alone or with beta agonists in the short- and long-term management of chronic obstructive lung disease and asthma. We performed a randomized, double-blind trial to assess the incremental benefit over 24 hours of adding ipratropium vs placebo to a standardized regimen of medications commonly used in the acute and subsequent hospital management of COPD and asthma. Sixty-eight subjects received nebulized salbutamol, intravenous methylprednisolone, intravenous aminophylline, and antibiotics and were randomized to receive either 80 micrograms of ipratropium or placebo via metered dose inhaler and spacing device with each salbutamol treatment (6 to 8 times per day). Among the 50 patients who completed the study, there were no significant differences between ipratropium and placebo groups with respect to baseline FEV1, FVC, and PaCO2. The improvement of FEV1 from baseline to 24 hours was 294 (SD = 568) ml in the ipratropium group vs 393 (SD = 622) ml in placebo group. Adjusting FEV1 by age, gender, and smoking did not significantly alter the findings. Those with an admission diagnosis of asthma showed larger 24 hour FEV1 responses (487 ml in ipratropium vs 801 ml in placebo) than those with COPD (149 ml ipratropium vs 102 ml in placebo). However, within these two strata, there were no significant differences in FEV1 improvement between ipratropium and placebo groups. This study suggests that if ipratropium is used in the initial emergency treatment of COPD or asthma, it could safely be discontinued by 24 hours in order to reduce the cost and complexity of therapy.
Nebulized anticholinergic and sympathomimetic treatment of asthma and chronic obstructive airways disease in the emergency room.
The effectiveness of nebulized anticholinergic and sympathomimetic regimens was evaluated in a double-blind study of 199 patients with acute airways obstruction. Patients were assigned to one of three treatment regimens according to a randomized schedule: 0.5 mg of ipratropium bromide, 1.25 mg of fenoterol hydrobromide, and 0.5 mg of ipratropium plus 1.25 mg of fenoterol. In 148 patients with acute exacerbations of asthma (mean one-second forced expiratory volume, 1.18 +/- 0.64 liters), all three regimens produced significant improvement in one-second forced expiratory volume (p less than 0.001). The greatest improvement followed treatment with the ipratropium-fenoterol combination (0.53 +/- 0.40 liters at 45 minutes; 0.57 +/- 0.51 liters at 90 minutes) and was significantly greater than that following either ipratropium alone (p less than 0.001) or fenoterol alone (p less than 0.05). In 51 patients with acute exacerbations of chronic obstructive pulmonary disease (mean one-second forced expiratory volume, 0.67 +/- 0.29 liter), each regimen produced significant improvement in one-second forced expiratory volume at both 45 and 90 minutes (for all, p less than 0.05), but there was no significant difference among the three treatment regimens. It is concluded that, in patients with acute asthma, combination therapy with sympathomimetic and anticholinergic agents is more efficacious than either one alone. In patients with acute exacerbations of chronic obstructive pulmonary disease, although either sympathomimetic or anticholinergic therapy provides bronchodilatation, no further benefit could be demonstrated from combination therapy.
Decreased duration of emergency department treatment of chronic obstructive pulmonary disease exacerbations with the addition of ipratropium bromide to beta-agonist therapy.
STUDY OBJECTIVES: To determine the benefit of the addition of ipratropium bromide to beta-agonist therapy of acute exacerbations of chronic obstructive pulmonary disease.
DESIGN: The trial was randomized and double blinded.
SETTING: The study was conducted in the emergency department of Parkland Memorial Hospital, a busy, inner-city, county hospital.
INTERVENTIONS: Patients were treated in the medicine emergency department with either the standard regimen of nebulized isoetharine, 0.5 mL of a 1% solution (5.0 mg) diluted to 2.0 mL with normal saline every hour (control group) or with the same regimen plus ipratropium bromide, 54 micrograms (three puffs) after the first isoetharine treatment and 36 micrograms (two puffs) after the second and fourth (experimental group). A placebo metered-dose inhaler used in the same manner as the ipratropium blinded the study to both the patients and medical personnel.
MEASUREMENTS AND MAIN RESULTS: The group treated with the addition of ipratropium (30) was discharged from the ED an average of 91 minutes (P less than .05) sooner than the control group (25) and required on the average one less isoetharine treatment (P less than .05). The pulmonary functions tested, forced expiratory volume in the first second, and the forced vital capacity were the same in the two groups initially and on discharge, as identical discharge criteria were used in each group.
CONCLUSION: The addition of ipratropium to standard beta-agonist treatment of chronic obstructive pulmonary disease exacerbations shortens the duration of treatment required in the ED.
Options:
A: Anti-cholinergic agents were significantly more effective than beta2-sympathomimetic agents in improving lung function.
B: Beta2-sympathomimetic agents were significantly more effective than anti-cholinergic agents in improving lung function.
C: There was no significant difference in the effectiveness of anti-cholinergic agents and beta2-sympathomimetic agents in improving lung function.
D: The combination of anti-cholinergic agents and beta2-sympathomimetic agents significantly improved lung function compared to either agent used alone. | C |
244 | 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 chemotherapy to radiotherapy on the survival of adults with high-grade glioma, and did any specific patient subgroups benefit more from the treatment? Please answer this question based on the information provided below:
Radiotherapy and CCNU in the treatment of high-grade supratentorial astrocytomas.
Forty-one consecutive patients with supratentorial primary brain tumors (38 Grade III and IV astrocytomas, one giant-cell astrocytoma, and two cases with insufficient tissue for diagnosis) were randomly allocated within 2 weeks of surgery to one of three therapeutic groups. Group 1 (15 patients) received radiation therapy totaling 4000 to 4500 rads in 4 to 5 weeks. Group 2 (13 patients) received 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea CCNU) 130 mg/sq m orally every 6 weeks. Group 3 (13 patients) received radiation therapy plus CCNU as for Groups 1 and 2. When the disease progressed, patients in Groups 1 and 2 were crossed over to receive CCNU and irradiation respectively. The median survival time in these groups was 188, 259, and 252 days, and the mean survival 263, 262, and 329 days. The median time from diagnosis to crossover (Groups 1 and 2) or to progression (Group 3) was 163, 99, and 220 days, and the mean time was 172, 108, and 231 days. There was no statistically significant difference between the means or medians in any of these situations.
Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial.
A controlled, prospective, randomized study evaluated the use of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and/or radiotherapy in the treatment of patients who were operated on and had histological confirmation of anaplastic glioma. A total of 303 patients were randomized into this study, of whom 222 (73%) were within the Valid Study Group (VSG), having met the protocol criteria of neuropathology, corticosteroid control, and therapeutic approach. Patients were divided into four random groups, and received BCNU (80 mg/sq m/day on 3 successive days every 6 to 8 weeks), and/or radiotherapy (5000 to 6000 rads to the whole brain through bilateral opposing ports), or best conventional care but no chemotherapy or radiotherapy. Analysis was performed on all patients who received any amount of therapy (VSG) and on the Adequately Treated Group (ATG), who had received 5000 or more rads radiotherapy, two or more courses of chemotherapy, and had a minimum survival of 8 or more weeks (the interval that would have been required to have received either the radiotherapy or chemotherapy). Median survival of patients in the VSG was, best conventional care: 14 weeks (ATG: 17.0 weeks); BCNU: 18.5 weeks (ATG: 25.0 weeks); radiotherapy: 35 weeks (ATG: 37.5 weeks); and BCNU plus radiotherapy: 34.5 weeks (ATG: 40.5 weeks). All therapeutic modalities showed some statistical superiority compared to best conventional care. There was no significant difference between the four groups in relation to age distribution, sex, location of tumor, diagnosis, tumor characteristics, signs or symptoms, or the amount of corticosteroid used. An analysis of prognostic factors indicates that the initial performance status (Karnofsky rating), age, the use of only a surgical biopsy, parietal location, the presence of seizures, or the involvement of cranial nerves II, III, IV, and VI are all of significance. Toxicity included acceptable, reversible thrombocytopenia and leukopenia.
Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery.
Within three weeks of definitive surgical intervention, 467 patients with histologically proved malignant glioma were randomized to receive one of four treatment regimens: semustine (MeCCNU), radiotherapy, carmustine (BCNU) plus radiotherapy, or semustine plus radiotherapy. We analyzed the data for the total randomized population and for the 358 patients in whom the initial protocol specifications were met (the valid study group). Observed toxicity included acceptable skin reactions secondary to radiotherapy and reversible leukopenia and thrombocytopenia due to chemotherapy. Radiotherapy used alone or in combination with a nitrosourea significantly improved survival in comparison with semustine alone. The group receiving carmustine plus radiotherapy had the best survival, but the difference in survival between the groups receiving carmustine plus radiotherapy and semustine plus radiotherapy was not statistically significant. The combination of carmustine plus radiotherapy produced a modest benefit in long-term (18-month) survival as compared with radiotherapy alone, although the difference between survival curves was not significiant at the 0.05 level. This study suggests that it is best to use radiotherapy in the post-surgical treatment of malignant glioma and to continue the search for an effective chemotherapeutic regimen to use in addition to radiotherapy.
Comparisons of carmustine, procarbazine, and high-dose methylprednisolone as additions to surgery and radiotherapy for the treatment of malignant glioma.
Within 3 weeks of definitive surgery, 609 patients with histologically demonstrated, supratentorial malignant glioma were randomized to receive, in addition to 6000 rads of radiotherapy, one of four treatment regimens: carmustine (BCNU), high-dose methylprednisolone, procarbazine, or BCNU plus high-dose methylprednisolone. We analyzed the data for the total randomized population and for the 527 patients (87% with glioblastoma multiforme) in whom the initial protocol specifications were met (the valid study group). Significantly longer survival was experienced by patients receiving procarbazine or BCNU alone compared to those receiving only high-dose methylprednisolone. No other pairwise comparisons demonstrated differences significant at the 0.05 level. However, the combination of BCNU plus high-dose methylprednisolone tended to be less effective than BCNU alone in patients with poor prognosis. This study indicates that BCNU and procarbazine are moderately useful agents in conjunction with radiotherapy for patients with malignant glioma. In addition, future protocols may allow use of corticosteroids in conventional dosages for treating cerebral edema and controlling symptoms; conclusions based on survival as the endpoint are unlikely to be affected by administering steroids at somewhat greater than the usual dose. More effective regimens for the treatment of malignant glioma should be sought.
Combined radiotherapy and chemotherapy with dibromodulcitol and CCNU in the postoperative treatment of malignant gliomas.
Within 4 weeks after definitive surgery, 91 patients with supratentorial glioblastomas and malignant astrocytomas were randomized to one of three treatment arms: Group 1 received radiotherapy alone; Group 2 received dibromodulcitol (DBD) during radiotherapy, and treatment was then continued with DBD; and Group 3 received DBD during radiotherapy, followed by combination chemotherapy of CCNU and DBD. No severe myelotoxicity occurred, but combined treatment with CCNU and DBD occasionally caused a transient myelosuppression. Statistical analysis of 84 evaluable patients showed a significantly longer survival period in those who received chemotherapy during and after irradiation. Median survival times in the three groups were 40, 57, and 60 weeks, respectively; the corresponding p value for Groups 2 and 3 was 0.025 and 0.0015. The ratio of patients surviving over 18 and 24 months was highest in Group 3. This study suggests that the administration of DBD during irradiation might have been the main factor in improving survival times.
Evaluation of CCNU, VM-26 plus CCNU, and procarbazine in supratentorial brain gliomas. Final evaluation of a randomized study. European Organization for Research on Treatment of Cancer (EORTC) Brain Tumor Group.
This prospective and randomized trial reports the effects of three chemotherapeutic regimens on three different clinical parameters in adults with supratentorial malignant brain gliomas: 1) duration of the interval between surgery and relapse (the "free interval"); 2) total survival time; and 3) rate and length of objective remissions. All patients were irradiated with 5500 to 6000 rads after neurosurgery aimed at an optimum removal. The administration of VM-26, 60 mg/sq m on Day 1, plus CCNU, 130 mg/sq m on Day 2, repeated every 6 weeks, had no significant effect on the length of the free interval between surgery and relapse. Thus, the median duration of this period was 39 weeks in the group of 61 patients who received adjuvant chemotherapy and 30 weeks in 55 controls without treatment. Neither was the total survival time prolonged by the administration of early chemotherapy. The best prognostic factor for the duration of the free interval and survival was age: patients under 50 years old survived statistically significantly longer. The rate of the objective remission, defined as a clear-cut clinical improvement persisting 6 weeks after complete discontinuation of steroids, was measured after tumor relapse. In patients who were not previously treated with chemotherapy, CCNU alone or VM-26 plus CCNU produced objective remissions in only 15% of treated patients. Out of 17 cases treated previously by VM-26 plus CCNU, none responded to procarbazine after relapse.
Adjuvant therapy with dibromodulcitol and BCNU increases survival of adults with malignant gliomas. EORTC Brain Tumor Group.
OBJECTIVE: We tested adjuvant chemotherapy combining dibromodulcitol (DBD) and bischloroethylnitrosourea (BCNU) given postoperatively to adults with newly diagnosed supratentorial malignant gliomas.
METHODS: We enrolled 269 patients, 255 of whom were eligible. After surgery, we treated all patients with radiation therapy, using a median dose of 60 Gy given in 30 fractions. After randomization, patients in the chemotherapy group also received (1) six weekly courses, administered during irradiation, of DBD 700 mg/m2 and (2) one to nine (median, four) courses, administered during the first year following radiation therapy, of DBD 1,000 mg/m2 on day 1 and BCNU 150 mg/m2 on day 2, with the course being repeated every 6 weeks.
RESULTS: Patients treated with radiation therapy along with DBD plus BCNU (group 2) had significantly longer survival time (p = 0.044) and time to progression (p = 0.003) than did those treated with radiation therapy alone (group 1). The median survival time was 13.0 months for group 2 and 10.4 months for group 1; the median time to progression was 8.1 months for group 2 and 6.7 months for group 1. The percentage of patients alive at 18 and 24 months was 34% and 21% in group 2 compared with 21% and 12% in group 1.
CONCLUSION: DBD plus BCNU is an effective adjuvant therapy for malignant glioma.
Controlled study with BCNU vs. CCNU as adjuvant chemotherapy following surgery plus radiotherapy for glioblastoma multiforme.
From September, 1972 to December, 1976, 102 consecutive patients operated on for glioblastoma multiforme were randomized, after total or subtotal tumor resection, to receive irradiation alone, irradiation plus BCNU or irradiation plus CCNU. BCNU and CCNU adjuvant chemotherapy was repeated every 6--8 weeks as long as the patients remained in complete remission. Patients were comparable for median age, type of surgery, and histological grade III and IV. Radiotherapy was administered at the tumor dose of about 5000 rads in all three groups. The percent of optimal dose administered was 96% for BCNU and 93% for CCNU. In the group treated with radiotherapy alone (32 cases) the median survival was 10.5 months, while in the groups treated with BCNU (34 cases) and CCNU (36 cases) the median survival was 12 and 16 months, respectively. Both relapse-free (P = 0.05) and total survival (P = 0.03) were significantly improved only in patients who were treated with radiotherapy plus CCNU compared to patients receiving radiotherapy alone after surgery. Present results show that in resectable glioblastoma multiforme, a slightly improved survival rate can be achieved by the prolonged use of adjuvant CCNU following maximal surgical resection and radiotherapy. The cure rate was not improved.
Postoperative radiotherapy and radiotherapy combined with CCNU chemotherapy for treatment of brain gliomas.
A prospective, randomized trial evaluates the effects of two postoperative treatment regimens on survival in 198 adult patients with supratentorial gliomas. All patients were irradiated with 6,000 rads after possibly radical removal of tumors. CCNU administration in the doses of 100 mg/sq m of body surface every 6-8 weeks following surgery proved to have no significant effect on the survival of patients. The median survival time in patients receiving radiation therapy alone was 61 +/- 7 weeks, while in those receiving additional chemotherapy was 56 +/- 4 weeks. Tumor histological malignancy and patients age were found to be the only important prognostic factors, irrespective of the treatment modality.
Comparison of postoperative radiotherapy and combined postoperative radiotherapy and chemotherapy in the multidisciplinary management of malignant gliomas. A joint Radiation Therapy Oncology Group and Eastern Cooperative Oncology Group study.
Recently, the RTOG and ECOG concluded a joint randomized study on malignant gliomas that was in progress for the past five years. A total of 626 patients entered this protocol. Sixty-seven percent of the 535 evaluable patients have died and thus this represents a preliminary report of a major joint clinical trial. The objective of this study was to evaluate the efficacy after neurosurgery of three new treatment options as compared with control treatment of radiotherapy alone. The four options were: (1) control radiation; 6000 rad/6-7 weeks to whole brain; (2) a higher radiation dose; Control dose plus a booster dose of 1000 rad/1-2 weeks to the tumor; (3) control radiation dose plus BCNU (80 mg/m2/day IV X 3 and repeat BCNU every 8 weeks); (4) Control radiation dose plus combination methyl-CCNU (125 mg/m2/day orally X 1 and repeat methyl-CCNU every 8 weeks), and DTIC (150 mg/m2/day IV X 5 and repeat DTIC every 4 weeks). All pertinent patient characteristics were studied and several important prognostic factors have been identified. Notably, age, histologic type (Astrocytoma with anaplastic foci, versus glioblastoma multiforme), initial performance status, time since first symptoms and presence or absence of seizure. At this time, it appeared that there was no treatment option which was significantly better than the control. The study identified that age was the most important prognostic factor. Patients who were younger than age 40 years had an 18-month survival of 64%, patients who were age 40-60 years had an 18-month survival of 20%, and patients who were older than age 60 had an 18-month survival of 8%. The study also demonstrated that a modified histologic classification of anaplastic astrocytoma versus glioblastoma provided better prognostic information than the astrocytoma grading system of Kernohan. Patients with anaplastic astrocytoma had a median survival of 27 months as compared to 8 months for patients with glioblastoma. In further evaluation of any beneficial effect of chemotherapy, it was identified that only among the 40-60-year-old groups, BCNU treated patients appeared to have significantly increased survival than patients in the control groups (P = 0.01, one-sided). Similarly, methyl-CCNU + DTIC was suggestively better than the control (P = 0.08, one-sided). The higher radiation dose, 7000 rad/8-9 weeks appeared to give no significantly better survival over the control dose option. Both BCNU and methyl-CCNU + DTIC produced some toxicity. The combination of methyl-CCNU + DTIC was more toxic than BCNU, producing severe or worse thrombocytopenia in 23% of the patients as compared to 6% on BCNU.
Options:
A: Chemotherapy significantly prolonged survival with a 15% relative decrease in the risk of death, and no specific patient subgroups benefited more than others.
B: Chemotherapy had no significant effect on survival, and no specific patient subgroups benefited more than others.
C: Chemotherapy significantly prolonged survival with a 15% relative decrease in the risk of death, and younger patients benefited more than older patients.
D: Chemotherapy significantly prolonged survival with a 15% relative decrease in the risk of death, and patients with better performance status benefited more. | A |
245 | 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 terbutaline pump maintenance therapy after threatened preterm labor in preventing preterm birth and its complications? Please answer this question based on the information provided below:
Terbutaline pump maintenance therapy for prevention of preterm delivery: a double-blind trial.
OBJECTIVE: This study's aim was to determine whether maintenance therapy with terbutaline administered by pump prolongs gestation in women after treatment with intravenous magnesium sulfate tocolysis for suspected preterm labor.
STUDY DESIGN: Consenting women with a singleton gestation and intact membranes who had uterine contractions and >1 cm cervical dilation, 80% effacement, or progressive cervical change and whose contractions were successfully arrested with intravenous magnesium were randomly assigned to receive either terbutaline or normal saline solution placebo by subcutaneous infusion pump. Pump therapy was administered with a standardized protocol. Pump therapy was discontinued and parenteral magnesium was resumed if recurrent preterm labor developed while women were on the therapeutic regimen at <34 weeks' gestation and no contraindication for tocolysis existed. If recurrent labor was arrested, pump therapy was restarted according to the original treatment group. A sample size of 48 women was required to detect a 2-week intergroup difference in mean time to delivery. Analyses were based on intent to treat.
RESULTS: Fifty-two women received terbutaline (n = 24) or placebo (n = 28). At random assignment the groups were similar with respect to age, race, parity, previous preterm delivery, gestational age, and cervical examination. Overall there was a 1-day difference in mean time to delivery between the groups (terbutaline 29 +/- 22 days and placebo 28 +/- 23 days, P = .78). There were no differences in the rates of preterm delivery at <34 and <37 weeks' gestation. Neonatal outcomes were similar.
CONCLUSIONS: Maintenance terbutaline therapy administered by pump does not prolong gestation in women successfully treated for suspected preterm labor.
A placebo-controlled randomized trial of the terbutaline pump for prevention of preterm delivery.
To determine the efficacy of the terbutaline pump for the prevention of preterm delivery, patients in preterm labor defined by progressive cervical change underwent intravenous magnesium sulfate tocolysis (with or without oral indomethacin, as necessary), and once labor was arrested, were randomized to one of three treatment arms: terbutaline by pump, saline by pump (blinded), or oral terbutaline. If recurrent preterm labor occurred despite maximization of therapy, the treatment arm was determined and therapy was changed; saline pump and oral terbutaline were switched to terbutaline pump, terbutaline pump was switched to oral terbutaline. Patients who continued to labor were readmitted for aggressive intravenous therapy. Women randomized to the terbutaline pump (n = 15), saline pump (n = 12), and oral terbutaline (n = 15) groups were similar in terms of gravidity, parity, days of tocolysis before study entry, gestational age at entry, and cervical dilatation at entry. The mean gestational age at delivery was the same in all three groups (35 weeks), as were neonatal outcomes. Terbutaline by pump, saline by pump, and oral terbutaline appear equivalent for the prevention of preterm delivery. The terbutaline pump should remain experimental.
Options:
A: Terbutaline pump maintenance therapy significantly decreases the risk of preterm birth and its complications.
B: Terbutaline pump maintenance therapy offers no significant advantages over saline placebo or oral terbutaline in preventing preterm birth and its complications.
C: Terbutaline pump maintenance therapy increases the risk of preterm birth and its complications.
D: Terbutaline pump maintenance therapy is highly effective and safe, with substantial cost benefits. | B |
246 | 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 safety and effectiveness of nonoxynol-9 (N-9) in preventing vaginal acquisition of HIV infection by women from men? Please answer this question based on the information provided below:
Efficacy of nonoxynol 9 contraceptive sponge use in preventing heterosexual acquisition of HIV in Nairobi prostitutes.
OBJECTIVE: To determine the efficacy of the nonoxynol 9 contraceptive sponge in preventing sexual acquisition of the human immunodeficiency virus (HIV).
DESIGN: Prospective, randomized placebo-controlled trial.
SETTING: Research clinic for prostitutes in Nairobi, Kenya.
PATIENTS AND INTERVENTIONS: One hundred thirty-eight HIV-seronegative women were enrolled, of whom 74 were assigned to nonoxynol 9 sponge use and 64 to placebo use. These two groups did not significantly differ with respect to demographic characteristics, sexual practices, or prevalence of genital infections at enrollment, except for a lower number of sex partners per week and a higher initial prevalence of genital ulcers among women assigned to nonoxynol 9 sponge use. Among the 116 women who returned for follow-up, the mean durations of follow-up were 14 and 17 months for the two groups, respectively.
MAIN OUTCOME MEASURE: HIV seroconversion.
RESULTS: Nonoxynol 9 sponge use was associated with an increased frequency of genital ulcers (relative risk [RR], 3.3; P less than .0001) and vulvitis (RR, 3.3; P less than .0001) and a reduced risk of gonococcal cervicitis (RR, 0.4; P less than .0001). Twenty-seven (45%) of 60 women in the nonoxynol 9 sponge group and 20 (36%) of 56 women in the placebo group developed HIV antibodies. The hazard ratio for the association between nonoxynol 9 sponge use and HIV seroconversion was 1.7 (95% confidence interval [CI], 0.9 to 3.0). Using multivariate analysis to control for the presence of genital ulcers at enrollment, the adjusted hazard ratio for the association between nonoxynol 9 sponge use and seroconversion was 1.6 (95% CI, 0.8 to 2.8).
CONCLUSIONS: Genital ulcers and vulvitis occurred with increased frequency in nonoxynol 9 sponge users. We were unable to demonstrate that nonoxynol 9 sponge use was effective in reducing the risk of HIV infection among highly exposed women.
A controlled trial of nonoxynol 9 film to reduce male-to-female transmission of sexually transmitted diseases.
BACKGROUND: Nonoxynol 9 is a proved spermicide, but whether it is also a microbicide is uncertain. A truly effective vaginal microbicide would reduce the susceptibility of women to sexually transmitted diseases, including infection with the human immunodeficiency virus (HIV).
METHODS: We enrolled 1292 HIV-negative female sex workers in Cameroon and enrolled them in a double-blind, placebo-controlled study in which the participants were randomly assigned to use either a film containing 70 mg of nonoxynol 9 or a placebo film, inserted into the vagina before intercourse. All of the women were provided with latex condoms and were instructed to have their male sexual partners use them. At monthly follow-up visits, we examined the women with a colposcope for genital lesions, tested endocervical specimens for gonorrhea and chlamydia infection with DNA probes, tested for HIV infection, and treated the women for curable sexually transmitted diseases.
RESULTS: The rates of HIV infection (cases per 100 woman-years) were 6.7 in the nonoxynol 9 group and 6.6 in the placebo group (rate ratio, 1.0; 95 percent confidence interval, 0.7 to 1.5). The rates of genital lesions were 42.2 cases per 100 woman-years in the nonoxynol 9 group and 33.5 in the placebo group (rate ratio, 1.3; 95 percent confidence interval, 1.0 to 1.6). The rates of gonorrhea were 33.3 and 31.1 cases per 100 woman-years in the nonoxynol 9 and placebo groups, respectively (rate ratio, 1.1; 95 percent confidence interval, 0.8 to 1.4). The corresponding rates of chlamydia infection in the nonoxynol 9 group and the placebo group were 20.6 and 22.2 per 100 woman-years (rate ratio, 0.9; 95 percent confidence interval, 0.7 to 1.3). The women reported that condoms were used during 90 percent of sexual acts.
CONCLUSIONS: The use of a nonoxynol 9 vaginal film did not reduce the rate of new HIV, gonorrhea, or chlamydia infection in this group of sex workers who used condoms and received treatment for sexually transmitted diseases.
Effect of nonoxynol-9 gel on urogenital gonorrhea and chlamydial infection: a randomized controlled trial.
CONTEXT: Nonoxynol-9 has been suggested as a vaginal microbicide to protect against common sexually transmitted infections.
OBJECTIVE: To compare nonoxynol-9 gel and condom use (gel group) vs condom use alone (condom group) for the prevention of male-to-female transmission of urogenital gonococcal and chlamydial infection.
DESIGN AND SETTING: Randomized controlled trial conducted at 10 community clinics and 10 pharmacies in Yaoundé, Cameroon, between October 1998 and September 2000, with 6 months of follow-up.
PARTICIPANTS: High-risk population of 1251 women (excluding sex workers) being treated for or who had symptoms of sexually transmitted infections. Three were excluded from the gel group (0.5%) and 7 from the condom group (1%) because of no follow-up data.
INTERVENTIONS: Nonoxynol-9 gel (100 mg) and condoms or condoms only.
MAIN OUTCOME MEASURE: A positive test result for gonococcal or chlamydial infection by the ligase chain reaction assay; secondary outcome measure was a positive test result for human immunodeficiency virus (HIV).
RESULTS: The rate ratio (RR) for new urogenital infections was 1.2 for the gel group vs condom group (95% confidence interval [CI], 0.9-1.6; P =.21). The gel group had 116 diagnosed gonococcal infections, chlamydial infections, or both for a rate of 43.6 per 100 person-years, and the condom group had 100 infections for a rate of 36.6 per 100 person-years. The RR for gonococcal infection in the gel group vs the condom group was 1.5 (95% CI, 1.0-2.3) and for chlamydial infection was 1.0 (95% CI, 0.7-1.4). There were 5 new cases of HIV infections in the gel group and 4 in the condom group. Three women in each group became pregnant during the study.
CONCLUSION: Nonoxynol-9 gel did not protect against urogenital gonococcal or chlamydial infection.
Options:
A: N-9 significantly reduced the risk of HIV infection and had no impact on genital lesions.
B: N-9 had no significant effect on the risk of HIV infection but increased the risk of genital lesions.
C: N-9 significantly increased the risk of HIV infection and had no impact on genital lesions.
D: N-9 had no significant effect on the risk of HIV infection and had no impact on genital lesions. | B |
247 | 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 nonoxynol-9 (N-9) in preventing vaginal acquisition of sexually transmitted infections (STIs) in women? Please answer this question based on the information provided below:
A follow-up study of methods of contraception, sexual activity, and rates of trichomoniasis, candidiasis, and bacterial vaginosis.
A randomized, clinical trial was conducted to evaluate the spermicidal agent nonoxynol 9 as prophylaxis for sexually transmitted diseases. Eight hundred eighteen women using birth control who attended a sexually transmitted disease clinic were evaluated monthly for trichomoniasis, candidiasis, and bacterial vaginosis for 6 months. Women using the active spermicide experienced a somewhat lower incidence rate of trichomoniasis (relative rate 0.83; 95% confidence interval 0.61 to 1.12) and bacterial vaginosis (relative rate 0.86; 95% confidence interval 0.69 to 1.12) as compared with placebo users. The rate of candidiasis was nearly identical for spermicide and placebo users (relative rate 1.02; 95% confidence interval 0.77 to 1.35). The number of sexual partners during the preceding month was related directly to the occurrence of trichomoniasis (p = 0.047) and bacterial vaginosis (p = 0.009) but not candidiasis (p = 0.99). Subjects using oral contraceptives experienced a statistically significant lower rate of trichomoniasis than did women using an intrauterine contraceptive device or who had had a tubal ligation (relative rate 0.56; 95% confidence interval 0.39 to 0.81).
Efficacy of nonoxynol 9 contraceptive sponge use in preventing heterosexual acquisition of HIV in Nairobi prostitutes.
OBJECTIVE: To determine the efficacy of the nonoxynol 9 contraceptive sponge in preventing sexual acquisition of the human immunodeficiency virus (HIV).
DESIGN: Prospective, randomized placebo-controlled trial.
SETTING: Research clinic for prostitutes in Nairobi, Kenya.
PATIENTS AND INTERVENTIONS: One hundred thirty-eight HIV-seronegative women were enrolled, of whom 74 were assigned to nonoxynol 9 sponge use and 64 to placebo use. These two groups did not significantly differ with respect to demographic characteristics, sexual practices, or prevalence of genital infections at enrollment, except for a lower number of sex partners per week and a higher initial prevalence of genital ulcers among women assigned to nonoxynol 9 sponge use. Among the 116 women who returned for follow-up, the mean durations of follow-up were 14 and 17 months for the two groups, respectively.
MAIN OUTCOME MEASURE: HIV seroconversion.
RESULTS: Nonoxynol 9 sponge use was associated with an increased frequency of genital ulcers (relative risk [RR], 3.3; P less than .0001) and vulvitis (RR, 3.3; P less than .0001) and a reduced risk of gonococcal cervicitis (RR, 0.4; P less than .0001). Twenty-seven (45%) of 60 women in the nonoxynol 9 sponge group and 20 (36%) of 56 women in the placebo group developed HIV antibodies. The hazard ratio for the association between nonoxynol 9 sponge use and HIV seroconversion was 1.7 (95% confidence interval [CI], 0.9 to 3.0). Using multivariate analysis to control for the presence of genital ulcers at enrollment, the adjusted hazard ratio for the association between nonoxynol 9 sponge use and seroconversion was 1.6 (95% CI, 0.8 to 2.8).
CONCLUSIONS: Genital ulcers and vulvitis occurred with increased frequency in nonoxynol 9 sponge users. We were unable to demonstrate that nonoxynol 9 sponge use was effective in reducing the risk of HIV infection among highly exposed women.
A clinical trial of nonoxynol-9 for preventing gonococcal and chlamydial infections.
A randomized, double-blind, placebo-controlled trial was conducted to evaluate the spermicidal agent nonoxynol-9 as prophylaxis for cervical infections caused by Chlamydia trachomatis and Neisseria gonorrhoeae. Eight hundred eighteen women were recruited from a sexually transmitted disease clinic. Only subjects who were using reliable birth control methods (oral contraceptives, intrauterine device, or sterilization) were eligible. Subjects were randomly assigned to use either a commercially available spermicidal agent containing nonoxynol-9 or a placebo preparation. Subjects were followed up for six months; specimens were collected monthly for culture of the two pathogens. Women assigned to the nonoxynol-9 group were less likely to become infected with N. gonorrhoeae (relative rate, 0.75; 90% confidence limits, 0.58 and 0.96) and C. trachomatis (relative rate, 0.79; 90% confidence limits, 0.64 and 0.97). Among women who used their assigned gel for the majority of coital episodes, a stronger protective effect was observed.
Use of nonoxynol-9 and reduction in rate of gonococcal and chlamydial cervical infections.
The spermicide nonoxynol-9 (N-9) has been used as a contraceptive for over 30 years, but the use of a vaginal spermicide and condoms for the prevention of sexually transmitted infections has not been examined in randomised studies. We report a single-blind randomised field trial to assess the effect of N-9 film on the rate of gonococcal and chlamydial cervical infection in women at high risk of these diseases. 343 women were randomly assigned to use either condoms and N-9 (186 women) or condoms and a placebo (157). Compliance with condom use was much the same in the two groups. Overall, N-9 reduced the rate of cervical infection by 25% (rate ratio [RR] 0.75, 95% confidence interval [Cl] 0.5-1.1); in women who used N-9 for more than 75% of their coital acts the infection rate was reduced by 40% (RR 95% Cl 0.3-1.0). The rate of yeast vulvovaginitis or genital ulcers was not higher in N-9 users than in placebo users, but the rate of symptomatic irritation was increased by 70% (RR 95% Cl 1.1-2.6) among N-9 users. Condom use was more protective against cervical infection than N-9 use. The rate of infection was 50% (RR 95% Cl 0.3-0.7) lower with 75% than with 0-50% condom compliance. The use of a vaginal N-9 spermicide with condoms whenever possible seems to be a better strategy than the use of condoms only for prevention of gonococcal and chlamydial cervical infection.
A controlled trial of nonoxynol 9 film to reduce male-to-female transmission of sexually transmitted diseases.
BACKGROUND: Nonoxynol 9 is a proved spermicide, but whether it is also a microbicide is uncertain. A truly effective vaginal microbicide would reduce the susceptibility of women to sexually transmitted diseases, including infection with the human immunodeficiency virus (HIV).
METHODS: We enrolled 1292 HIV-negative female sex workers in Cameroon and enrolled them in a double-blind, placebo-controlled study in which the participants were randomly assigned to use either a film containing 70 mg of nonoxynol 9 or a placebo film, inserted into the vagina before intercourse. All of the women were provided with latex condoms and were instructed to have their male sexual partners use them. At monthly follow-up visits, we examined the women with a colposcope for genital lesions, tested endocervical specimens for gonorrhea and chlamydia infection with DNA probes, tested for HIV infection, and treated the women for curable sexually transmitted diseases.
RESULTS: The rates of HIV infection (cases per 100 woman-years) were 6.7 in the nonoxynol 9 group and 6.6 in the placebo group (rate ratio, 1.0; 95 percent confidence interval, 0.7 to 1.5). The rates of genital lesions were 42.2 cases per 100 woman-years in the nonoxynol 9 group and 33.5 in the placebo group (rate ratio, 1.3; 95 percent confidence interval, 1.0 to 1.6). The rates of gonorrhea were 33.3 and 31.1 cases per 100 woman-years in the nonoxynol 9 and placebo groups, respectively (rate ratio, 1.1; 95 percent confidence interval, 0.8 to 1.4). The corresponding rates of chlamydia infection in the nonoxynol 9 group and the placebo group were 20.6 and 22.2 per 100 woman-years (rate ratio, 0.9; 95 percent confidence interval, 0.7 to 1.3). The women reported that condoms were used during 90 percent of sexual acts.
CONCLUSIONS: The use of a nonoxynol 9 vaginal film did not reduce the rate of new HIV, gonorrhea, or chlamydia infection in this group of sex workers who used condoms and received treatment for sexually transmitted diseases.
Effect of nonoxynol-9 gel on urogenital gonorrhea and chlamydial infection: a randomized controlled trial.
CONTEXT: Nonoxynol-9 has been suggested as a vaginal microbicide to protect against common sexually transmitted infections.
OBJECTIVE: To compare nonoxynol-9 gel and condom use (gel group) vs condom use alone (condom group) for the prevention of male-to-female transmission of urogenital gonococcal and chlamydial infection.
DESIGN AND SETTING: Randomized controlled trial conducted at 10 community clinics and 10 pharmacies in Yaoundé, Cameroon, between October 1998 and September 2000, with 6 months of follow-up.
PARTICIPANTS: High-risk population of 1251 women (excluding sex workers) being treated for or who had symptoms of sexually transmitted infections. Three were excluded from the gel group (0.5%) and 7 from the condom group (1%) because of no follow-up data.
INTERVENTIONS: Nonoxynol-9 gel (100 mg) and condoms or condoms only.
MAIN OUTCOME MEASURE: A positive test result for gonococcal or chlamydial infection by the ligase chain reaction assay; secondary outcome measure was a positive test result for human immunodeficiency virus (HIV).
RESULTS: The rate ratio (RR) for new urogenital infections was 1.2 for the gel group vs condom group (95% confidence interval [CI], 0.9-1.6; P =.21). The gel group had 116 diagnosed gonococcal infections, chlamydial infections, or both for a rate of 43.6 per 100 person-years, and the condom group had 100 infections for a rate of 36.6 per 100 person-years. The RR for gonococcal infection in the gel group vs the condom group was 1.5 (95% CI, 1.0-2.3) and for chlamydial infection was 1.0 (95% CI, 0.7-1.4). There were 5 new cases of HIV infections in the gel group and 4 in the condom group. Three women in each group became pregnant during the study.
CONCLUSION: Nonoxynol-9 gel did not protect against urogenital gonococcal or chlamydial infection.
Effect of the contraceptive sponge on chlamydial infection, gonorrhea, and candidiasis. A comparative clinical trial.
To investigate the effect of the nonoxynol 9-impregnated contraceptive sponge on the incidence of chlamydial infection, gonorrhea, and candidiasis, we conducted a randomized comparative study among high-risk women in Bangkok, Thailand. The first (parallel) portion of the study covered 434 woman-weeks among sponge users and 494 woman-weeks among nonusers. As compared with women not using the sponge, sponge users were found to be less likely to become infected with chlamydia (relative rate, 0.67; 95% confidence interval, 0.42 to 1.07) and gonorrhea (relative rate, 0.31 [0.16 to 0.60]) but more likely to become infected with Candida (relative rate, 2.76 [0.96 to 7.98]). Women who continued in the study were crossed over to the alternate group, with former nonusers starting to employ the sponge and vice versa. The results of this second phase were similar to those of the larger parallel study. Overall, these results suggest that women using the sponge are protected against the two most common sexually transmitted pathogens, which are also those with the most serious health consequences. However, women using the sponge should be advised they may have an increased likelihood of a vaginal infection with Candida.
Options:
A: N-9 is highly effective in preventing STIs and has no significant adverse effects.
B: N-9 is moderately effective in preventing STIs but has some adverse effects.
C: N-9 is not effective in preventing STIs and may increase the risk of genital lesions.
D: N-9 is effective in preventing some STIs but not others, with no significant adverse effects. | C |
248 | 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 therapy-based rehabilitation services on stroke patients living at home within one year of stroke onset or discharge from hospital? Please answer this question based on the information provided below:
Can readmission after stroke be prevented? Results of a randomized clinical study: a postdischarge follow-up service for stroke survivors.
BACKGROUND AND PURPOSE: About 50% of stroke survivors are discharged to their homes with lasting disability. Knowledge, however, of the importance of follow-up services that targets these patients is sparse. The purpose of the present study was to evaluate 2 models of follow-up intervention after discharge. The study hypothesis was that intervention could reduce readmission rates and institutionalization and prevent functional decline. We report the results regarding readmission.
METHODS: This randomized study included 155 stroke patients with persistent impairment and disability who, after the completion of inpatient rehabilitation, were discharged to their homes. The patients were randomized to 1 of 2 follow-up interventions provided in addition to standard care or to standard aftercare. Fifty-four received follow-up home visits by a physician (INT1-HVP), 53 were provided instructions by a physiotherapist in their home (INT2-PI), and 48 received standard aftercare only (controls). Baseline characteristics for the 3 groups were comparable. Six months after discharge, data were obtained on readmission and institutionalization.
RESULTS: The readmission rates within 6 months after discharge were significantly lower in the intervention groups than in the control group (INT1-HVP 26%, INT2-PI 34%, controls 44%; P=0.028). Multivariate analysis of readmission risk showed a significant favorable effect of intervention (INT1-HVP or INT2-PI) in interaction with length of hospital stay (P=0.0332), indicating that the effect of intervention was strongest for patients with a prolonged inpatient rehabilitation.
CONCLUSIONS: Readmission is common among disabled stroke survivors. Follow-up intervention after discharge seems to be a way of preventing readmission, especially for patients with long inpatient rehabilitation.
Domiciliary occupational therapy for patients with stroke discharged from hospital: randomised controlled trial.
OBJECTIVE: To establish if a brief programme of domiciliary occupational therapy could improve the recovery of patients with stroke discharged from hospital.
DESIGN: Single blind randomised controlled trial.
SETTING: Two hospital sites within a UK teaching hospital.
SUBJECTS: 138 patients with stroke with a definite plan for discharge home from hospital.
INTERVENTION: Six week domiciliary occupational therapy or routine follow up.
MAIN OUTCOME MEASURES: Nottingham extended activities of daily living score and "global outcome" (deterioration according to the Barthel activities of daily living index, or death).
RESULTS: By eight weeks the mean Nottingham extended activities of daily living score in the intervention group was 4.8 points (95% confidence interval -0.5 to 10.0, P=0.08) greater than that of the control group. Overall, 16 (24%) intervention patients had a poor global outcome compared with 30 (42%) control patients (odds ratio 0.43, 0.21 to 0.89, P=0.02). These patterns persisted at six months but were not statistically significant. Patients in the intervention group were more likely to report satisfaction with a range of aspects of services.
CONCLUSION: The functional outcome and satisfaction of patients with stroke can be improved by a brief occupational therapy programme carried out in the patient's home immediately after discharge. Major benefits may not, however, be sustained.
Outcomes of elderly stroke patients. Day hospital versus conventional medical management.
BACKGROUND AND PURPOSE: Much controversy exists over the value of geriatric day hospitals in the rehabilitation of elderly patients, and cerebrovascular accident is a particularly common diagnosis among patients referred to these day hospitals. We carried out a prospective, randomized study to compare the outcomes of elderly stroke patients managed by a geriatric team using a day hospital facility versus conventional medical management.
METHODS: One hundred twenty elderly patients with acute stroke were randomized to inpatient care on a stroke ward under the care of either a neurologist or a geriatric team. Those under the care of neurologists were hospitalized until the attending physician felt that the patients had reached full rehabilitation potential. Patients under the care of the geriatric team were discharged home as soon as the team felt they were able to cope and given follow-up rehabilitation at the day hospital. Family or community support was arranged when necessary for both treatment groups. On recruitment, patient demographics, medical history, clinical features related to stroke, and functional ability as measured by the Barthel Index were noted. Subjects were reviewed at 3 and 6 months to assess functional level, hospital and outpatient services received, general well-being, mood, and level of satisfaction. Costs of treatment of the two groups were also compared.
RESULTS: Functional improvement (Barthel Index score) was greater in the group managed by the geriatricians with a day hospital facility compared with the conventional group at 3 months (P = .03). There were also fewer outpatient visits among the day hospital patients at 6 months (P = .03). No significant difference was found in costs between the two treatment groups.
CONCLUSIONS: Compared with conventional medical management, care in the geriatric day hospital hastened functional recovery and reduced outpatient visits in elderly stroke patients without additional cost.
A randomized, controlled pilot study of a home-based exercise program for individuals with mild and moderate stroke.
BACKGROUND AND PURPOSE: Many stroke survivors have minimal to moderate neurological deficits but are physically deconditioned and have a high prevalence of cardiovascular problems; all of these are potentially modifiable with exercise. The purposes of this randomized, controlled pilot study were (1) to develop a home-based balance, strength, and endurance program; (2) to evaluate the ability to recruit and retain stroke subjects; and (3) to assess the effects of the interventions used.
METHODS: Twenty minimally and moderately impaired stroke patients who had completed inpatient rehabilitation and who were 30 to 90 days after stroke onset were randomized to a control group or to an experimental group that received a therapist-supervised, 8-week, 3-times-per-week, home-based exercise program. The control group received usual care as prescribed by the patients' physicians. Baseline and postintervention assessments included the Fugl-Meyer Motor Assessment, the Barthel Index of Activities of Daily Living (ADL), the Lawton Scale of Instrumental ADL, and the Medical Outcomes Study-36 Health Status Measurement. Functional assessments of balance and gait included a 10-m walk, 6-Minute Walk, and the Berg Balance Scale. Upper extremity function was evaluated by the Jebsen Test of Hand Function.
RESULTS: Of 22 patients who met study criteria, 20 completed the study and 2 refused to participate. The experimental group tended to improve more than the control group in motor function (Fugl-Meyer Upper Extremity: mean change in score, 8. 4 versus 2.2; Fugl-Meyer Lower Extremity: 4.7 versus -0.9; gait velocity: median change, 0.25 versus .09 m/s; 6-Minute Walk: 195 versus 114 ft; Berg Balance Score: 7.8 versus 5; and Medical Outcomes Study-36 Health Status Measurement of Physical Function: 15. 5 versus 9). There were no trends in differences in change scores by the Jebsen Test of Hand Function, Barthel Index, and Lawton Instrumental ADL Scale.
CONCLUSIONS: This study demonstrated that a randomized, controlled clinical trial of a poststroke exercise program is feasible. Measures of neurological impairments and lower extremity function showed the most benefit. Effects of the intervention on upper extremity dexterity and functional health status were equivocal. The lasting effects of the intervention were not assessed.
Remedial therapy after stroke: a randomised controlled trial.
Of 1094 patients with a confirmed stroke admitted to Northwick Park, a district general hospital, 364 (33%) died while in hospital, 215 (20%) were fully recovered when discharged, and 329 (30%) were too frail or too ill from diseases other than stroke to be considered for active rehabilitation. Only 121 (11%) were suitable for intensive treatment. They and 12 patients referred direct to outpatients were allocated at random to one of three different courses of rehabilitation. Intensive was compared with conventional rehabilitation and with a third regimen which included no routine rehabilitation, but under which patients were encouraged to continue with exercises taught while in hospital and were regularly seen at home by a health visitor. Progress at three months and 12 months was measured by an index of activities of daily living. Improvement was greatest in those receiving intensive treatment, intermediate in those receiving conventional treatment, and least in those receiving no routine treatment. Decreasing intensity of treatment was associated with a significant increase in the proportions of patients who deteriorated and in the extent to which they deteriorated. Probably only a few stroke patients, mostly men, are suitable for intensive outpatient rehabilitation, but for those patients the treatment is effective and realistic.
A randomized controlled trial of enhanced Social Service occupational therapy for stroke patients.
OBJECTIVE: To determine whether stroke patients referred to the Social Service occupational therapy service would benefit from an enhanced service compared to the usual service.
DESIGN: Randomized controlled study allocating patients to the enhanced service or the usual service.
SUBJECTS: Stroke patients discharged home from hospital and referred to Social Service occupational therapy department.
OUTCOME MEASURES: The sections and total score from the Nottingham Extended Activities of Daily Living Scale (EADL), the Barthel Index, the General Health Questionnaire (GHQ) and the number of pieces of equipment provided were analysed.
RESULTS: One hundred and eleven stroke patients were recruited to this study. Fifty-three were randomly allocated to the enhanced service and 58 to the usual service. Patients receiving the enhanced service were seen more quickly after referral, for longer, and received significantly more visits (p < 0.01) than those receiving the usual service. Three months after entry to the study the enhanced service group had better EADL (p < 0.01) than the usual service group. This benefit remained significant in only the mobility section of the EADL at six months. Careers of the stroke patients in the enhanced group had lower GHQ scores (p < 0.05) than those in the usual group at six months.
CONCLUSIONS: This trial supports the use of domiciliary occupational therapy for stroke patients after discharge from hospital in terms of improvements in functional outcomes in the short term, but the long-term benefits remain unclear.
Occupational therapy for stroke patients not admitted to hospital: a randomised controlled trial.
BACKGROUND: Patients who have a stroke are not always admitted to hospital, and 22-60% remain in the community, frequently without coordinated rehabilitation. We aimed to assess the efficacy of an occupational therapy intervention for patients with stroke who were not admitted to hospital.
METHODS: In this single-blind randomised controlled trial, consecutive stroke patients on a UK community register in Nottingham and Derbyshire were allocated randomly to up to 5 months of occupational therapy at home or to no intervention (control group) 1 month after their stroke. The aim of the occupational therapy was to encourage independence in personal and instrumental activities of daily living. Patients were assessed on outcome measures at baseline (before randomisation) and at 6 months. The primary outcome measure was the score on the extended activities of daily living (EADL) scale at 6 months. Other outcome measures included the Barthel index, the general health questionnaire 28, the carer strain index, and the London handicap scale. All assessments were done by an independent assessor who was unaware of treatment allocation. The analysis included only data from completed questionnaires.
FINDINGS: 185 patients were included: 94 in the occupational therapy group and 91 in the control group. 22 patients were not assessed at 6 months. At follow-up, patients who had occupational therapy had significantly higher median scores than the controls on: the EADL scale (16 vs 12, p<0.01, estimated difference 3 [95% CI 1 to 4]); the Barthel index (20 vs 18, p<0.01, difference 1, [0-1]); the carer strain index (1 vs 3, p<0.05, difference 1 [0 to 2]); and the London handicap scale (76 vs 65, p<0.05, difference 7, [0.3 to 13.5]). There were no significant differences on the general health questionnaire between the patient or carer.
INTERPRETATION: Occupational therapy significantly reduced disability and handicap in patients with stroke who were not admitted to hospital.
Stroke Transition after Inpatient Rehabilitation.
This article describes a 3-year study testing the efficacy of a system of home-based, case-managed care for stroke survivors returning to the community following inpatient poststroke rehabilitation. The Stroke Transition after Inpatient Rehabilitation (STAIR) study was a randomized, controlled trial of a postdischarge management strategy carried out in a group of 55 stroke patients, aged 65 or older, who did not have serious residual cognitive or language impairments and returned to the community following inpatient rehabilitation with the assistance of a primary caregiver. The program was shown to facilitate improvement in the general social activity level of the patients in the experimental group at 6 months compared to the control, and there was a trend for this effect to persist at 1 year. Strong relationships were identified between residual disability, social activity level, patients' perceptions of efficacy, and caregiver stress.
The effectiveness of community-based rehabilitation for stroke patients who remain at home: a pilot randomized trial.
OBJECTIVE: To assess the effectiveness of community-based rehabilitation for stroke patients who were not admitted to hospital in South London.
DESIGN: Randomized controlled trial.
SETTING: Patients' homes in South London.
SUBJECTS: Stroke patients not admitted to hospital after a stroke.
INTERVENTION: Rehabilitation at home by rehabilitation team for up to three months or usual care.
MAIN OUTCOME MEASURES: The primary outcome measure was the Barthel score. Secondary measures included the Motricity Index, Rivermead ADL, Hospital Anxiety and Depression score and Nottingham Health Profile.
RESULTS: Forty-three patients who remained at home were randomized to rehabilitation team (23) or 'usual' care (20). The mean number of physiotherapy sessions was three (range 1-14) for the rehabilitation team group and two for the usual care group. Patients (with a deficit) in the rehabilitation arm of the trial were more likely to receive occupational, physical and speech therapy than those in the control arm (p = 0.03, 0.01 and 0.008, respectively). For those patients actually receiving therapy, there was no evidence that the amount received differed between the groups. However, the number of patients in each of these comparisons was very small. The outcome for patients in the rehabilitation team arm of the trial was nonsignificantly higher (0.05 < p < 0.2) than for those in the control arm for the areas of Nottingham Health Profile, anxiety, depression, caregiver strain and the proportion of patients living at home. Based on the data observed here, a trial with approximately 150 patients in each arm would be needed to have adequate power to detect a 33% difference between intervention and control groups in these outcomes.
CONCLUSION: Community therapy support for patients not admitted to hospital is feasible but to determine whether it is cost- or clinically effective would require trials of adequate size.
A multicentre randomized controlled trial of leisure therapy and conventional occupational therapy after stroke. TOTAL Study Group. Trial of Occupational Therapy and Leisure.
OBJECTIVE: To evaluate the effects of leisure therapy and conventional occupational therapy (OT) on the mood, leisure participation and independence in activities of daily living (ADL) of stroke patients 6 and 12 months after hospital discharge.
DESIGN: Multicentre randomized controlled trial.
SETTING AND PARTICIPANTS: Four hundred and sixty-six stroke patients from five UK centres.
MAIN OUTCOME MEASURES: The General Health Questionnaire (12 item), the Nottingham Extended ADL Scale and the Nottingham Leisure Questionnaire, assessed by post, with telephone clarification.
RESULTS: Four hundred and forty (94%) and 426 (91%) subjects were alive at 6 and 12 months, respectively. Three hundred and seventy-four (85% of survivors) and 311 (78% of survivors) responded at 6 and 12 month follow-up respectively. At six months and compared to the control group, those allocated to leisure therapy had nonsignificantly better GHQ scores (-1.2: 95% CI -2.9, +0.5), leisure scores (+0.7, 95% CI -1.1, +2.5) and Extended ADL scores (+0.4: 95% CI -3.8, +4.5): the ADL group had nonsignificantly better GHQ scores (-0.1: 95% CI -1.8, +1.7) and Extended ADL scores (+1.4: 95% CI -2.9, +5.6) and nonsignificantly worse leisure scores (-0.3: 95% CI -2.1, +1.6). The results at 12 months were similar.
CONCLUSION: In contrast to the findings of previous smaller trials, neither of the additional OT treatments showed a clear beneficial effect on mood, leisure activity or independence in ADL measured at 6 or 12 months.
An investigation of involvement in leisure activities after a stroke.
The purpose of this study was to determine the efficacy of occupational therapy intervention related to the leisure activities of stroke survivors. Forty discharged stroke patients were randomly assigned to an experimental group, which received occupational therapy intervention related to leisure activities, or to a control group. An independent evaluator assessed the patients' involvement in activities and satisfaction with that involvement on three separate occasions. The results showed no statistically significant differences between the experimental and control groups in activity involvement or satisfaction with that involvement. There are likely two reasons for these findings. First, the intervention was limited in scope (i.e., only five therapist visits), and second, many environmental factors strongly influence activity participation and satisfaction.
Options:
A: Therapy-based rehabilitation services have no significant effect on the independence of stroke patients in personal activities of daily living.
B: Therapy-based rehabilitation services increase the odds of a poor outcome for stroke patients living at home.
C: Therapy-based rehabilitation services reduce the odds of a poor outcome and improve independence in personal activities of daily living for stroke patients living at home.
D: Therapy-based rehabilitation services only improve the mental health of stroke patients living at home, without affecting their physical independence. | C |
249 | 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 clinical efficacy of air filtration units as a pet allergen control measure in the homes of people with pet-allergic asthma? Please answer this question based on the information provided below:
Clinical effects of air cleaners in homes of asthmatic children sensitized to pet allergens.
BACKGROUND: Exposure to cat and dog allergens is very common in the Western World and is a serious cause of asthma in sensitized subjects.
OBJECTIVE: We sought to study the clinical effects of air cleaners in living rooms and bedrooms of asthmatic children sensitized to cat or dog allergens.
METHODS: Twenty asthmatic children sensitized to pet allergens (cat/dog) and with an animal at home participated in a double-blind, placebo-controlled, cross-over study in which the effects of air cleaners placed in the living room and bedroom for 3 months were compared with the effects of sham air cleaners. Before and after each study period, lung function, airway hyperresponsiveness (adenosine monophosphate), and peak flow variation were recorded. Cat and dog allergen levels were assessed in the filters of the air cleaners.
RESULTS: After a 3-month intervention with active air cleaners, airway hyperresponsiveness decreased significantly, showing a 1.2 doubling dose increase of PC(20 )adenosine (P =.003). Peak flow amplitude also decreased (P =. 045). Substantial amounts of airborne cat and dog allergen were captured by the air cleaners in living rooms and bedrooms as well. Allergen levels in floor dust were not changed.
CONCLUSION: In young asthmatic patients sensitized and exposed to pets in the home, application of air cleaners in living rooms and bedrooms was accompanied by a significant improvement in airway hyperresponsiveness and a decrease in peak flow amplitude.
A placebo-controlled trial of a HEPA air cleaner in the treatment of cat allergy.
To evaluate the effect of a room high-efficiency particulate air (HEPA) cleaner on cat-induced asthma and rhinitis, 35 cat-allergic subjects who were living with one or more cats were studied in a double-blind, placebo controlled trial. After a 1 mo baseline period, subjects' bedrooms were equipped with an active or placebo air cleaner for the following 3 mo. Evaluations included monthly measurement of cat-allergen levels, daily morning, afternoon, and nighttime nasal- and chest-symptom scores, twice-daily measurement of peak-flow rates, daily medication scores, monthly spirometry, and methacholine (MCh) challenge testing before and after the study. Airborne allergen levels were reduced in the active-filter group as compared with the placebo group (p = 0.045). However, no differences were detected in settled-dust allergen levels (p = 0.485), morning, afternoon, or nighttime nasal-symptom scores (p = 0.769, 0.534, and 0.138), chest-symptom scores (p = 0.388, 0.179, and 0.215), sleep disturbance (p = 0.101), morning or afternoon peak-flow rates (p = 0. 424 and 0.679), or rescue medication use (nasal, p = 0.164, chest, p = 0.650), respectively. Although the combination of a HEPA room air cleaner, mattress and pillow covers, and cat exclusion from the bedroom did reduce airborne cat-allergen levels, no effect on disease activity was detected for any parameter studied.
Options:
A: Air filtration units significantly reduced allergen levels and improved asthma symptoms.
B: Air filtration units had no significant impact on allergen levels or asthma symptoms.
C: Air filtration units worsened asthma symptoms due to increased allergen levels.
D: Air filtration units were effective in reducing allergen levels but had no impact on asthma symptoms. | B |
250 | 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 area-wide traffic calming schemes in reducing road traffic crashes, injuries, and deaths? Please answer this question based on the information provided below:
Safety effects of speed reducing measures in Danish residential areas.
On May 1, 1977 a new code was introduced into the Danish Road Traffic Act. The result was a change in layout and speed limits in a great number of residential streets; in most cases the streets were transformed into 30 km/h streets and in few cases into 15 km/h streets. In addition to speed signs, both types of streets were equipped with speed reducing measures. Based on experiences from a selection of experimental streets, mostly 30 km/h streets, different, but very positive effects were found. Overall there was a reduction in the mean speed in these areas of 11 km/h. On the 223 km, 30 km/h streets there was a reduction of 77 accidents and 88 casualties within a period of three years. These reductions were caused by the implementation of speed signs, speed reducing measures, and a reduction in traffic. On the basis of 44 experimental streets, where traffic was recorded both before and after the changes, the reduction in risk of casualties, i.e. the number of casualties per road user km, was 72%, while the risk of accidents seemed to be unchanged. Considering serious injuries alone, a very high reduction of 78% was found. Accidents included in the study consist of all police reported accidents, i.e. accidents with personal injury as well as damage only accidents.
Safety impact of engineering treatments on undivided rural roads.
This article presents an evaluation of the safety impacts of four engineering treatments implemented in the Autonomous Community of Madrid (Spain): highway upgrading; updating and improvement of traffic signing; repainting of pavement markings and pavement resurfacings. This evaluation was carried out using the Empirical Bayes method with a comparison group. The functioning of a methodology to test the significance of the safety impact is described. The results show that highway upgrading has a positive and significant safety impact, while the updating and improvement of traffic signing, the repainting of road markings and pavement resurfacings do not exhibit a significant impact on safety.
Safety effects of 30 Km/H zones in The Netherlands.
Since 1983, Dutch municipal authorities can institute a maximum speed of 30 km/h on roads or in zones within built-up areas. The safety effects of 30 km/h zones are supposed to be positive. In order to be sure about this, the Ministry of Transport has stimulated 15 municipalities to implement a 30 km/h zone and set up an evaluation of the safety effects of these zones. The evaluation research is coordinated by the Institute for Road Safety Research (SWOV). The evaluation concerns the changes in traffic flows, opinions of residents, conflicts, and accidents. This paper gives the results of the evaluation.
Options:
A: Area-wide traffic calming schemes significantly reduce the number of road traffic crashes, injuries, and deaths.
B: Area-wide traffic calming schemes have no significant effect on the number of road traffic crashes, injuries, and deaths.
C: Area-wide traffic calming schemes may reduce the number of road traffic injuries and deaths, but further rigorous evaluations are needed to confirm their effectiveness.
D: Area-wide traffic calming schemes increase the number of road traffic crashes, injuries, and deaths. | C |
251 | 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 and safety of vinpocetine in the treatment of patients with cognitive impairment and dementia? Please answer this question based on the information provided below:
Efficacy and tolerance of vinpocetine in ambulant patients suffering from mild to moderate organic psychosyndromes.
The efficacy and tolerance of orally administered vinpocetine was investigated in patients suffering from mild to moderate organic psychosyndromes including primary dementia. Two hundred and three patients were included in a placebo-controlled, randomized double-blind, multicentre trial and received every day for 16 weeks either: 3 x 10 mg doses of vinpocetine, 3 x 20 mg doses of vinpocetine, or 3 x placebo. Patients were assessed on ratings of clinical global impression, cognitive performance and on measures of the quality of life including depressive illness. There were no clinically relevant side-effects reported and the frequencies of adverse events between patients treated with vinpocetine (30 mg or 60 mg) and placebo were comparable. Statistically significant improvements were found in favour of both active treatment groups compared to placebo in both confirmatory evaluations of efficacy of treatment: the "Global Improvement" (on the CGI scale) and cognitive performance (SKT). Vinpocetine was also superior to placebo in ratings of the "severity of illness". This study demonstrates the usefulness and efficacy of vinpocetine in the management of patients with moderate organic psychosyndromes. An apparently greater therapeutic efficacy of 3 x 10 mg vinpocetine compared with the higher vinpocetine dosage is statistically not significant.
Options:
A: Vinpocetine showed significant beneficial effects and is recommended for clinical use in treating cognitive impairment and dementia.
B: Vinpocetine demonstrated some potential benefits, but the evidence is inconclusive and does not support its clinical use.
C: Vinpocetine was found to have no beneficial effects and is associated with significant adverse effects.
D: Vinpocetine showed clear benefits for vascular dementia but not for Alzheimer's disease. | B |
252 | 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 non-surgical treatments have been shown to provide significant short-term benefit for individuals with carpal tunnel syndrome? Please answer this question based on the information provided below:
Treatment of carpal tunnel syndrome with nerve and tendon gliding exercises.
OBJECTIVE: To assess the effect of nerve and tendon gliding exercises in carpal tunnel syndrome.
DESIGN: The study was a prospective, randomized, before-and-after treatment trial. A total of 28 patients with the diagnosis of carpal tunnel syndrome in 36 hands were randomly assigned to two groups. A custom made neutral volar wrist splint was given to group 1 and group 2. The patients were instructed to wear the splints all night and during the day as much as possible for 4 wk. The patients in group 2 were also instructed to perform series of nerve and tendon gliding exercises in addition to the splint treatment. Patients were evaluated with clinical parameters, a functional status scale, and a symptom severity scale.
RESULTS: At the end of treatment, statistically significant improvement was obtained in all parameters in both groups. The improvement in group 2 was slightly greater, but the difference between the groups was not significant, except for the lateral pinch strength value. Patient satisfaction was investigated during the follow-up period, ranging from 5 to 11 mo, with a mean of 8 mo. A total of 72% of the patients in group 1 and 93% of the patients in group 2 reported good or excellent results. The difference between the two groups was not statistically significant.
CONCLUSION: Although the results in group 2 were better than group 1, the difference was not statistically significant. Further investigations are required to establish the role of nerve and tendon gliding exercises in the treatment of carpal tunnel syndrome.
Splinting for carpal tunnel syndrome: in search of the optimal angle.
Carpal tunnel syndrome (CTS) is the most common of the compression neuropathies. Several studies have demonstrated the efficacy of wrist splinting in relieving the symptoms of CTS; however, the chosen angle of immobilization has varied. Wick catheter measurements of carpal tunnel pressures suggest that the neural position has less pressure and, therefore, greater potential to provide relief from symptoms. This study is a prospectively gathered, blind trial comparing the symptom relief experienced by wearers of splints immobilized at 20 degrees extension and at neutral. The results indicate that the neutral angle provided superior symptom relief, and that the relief did not often improve between 2 weeks and 2 months of wear. Relief of symptoms was not related to the length of time that the patient had experienced of CTS symptoms. The results also indicate that the results of the electromyography/nerve conduction study (EMG/NCS) do not provide information about the subjects' likely response to splinting.
The effectiveness of magnet therapy for treatment of wrist pain attributed to carpal tunnel syndrome.
We conducted a double-blind placebo-controlled randomized clinical trial in which 30 patients with pain attributed to carpal tunnel syndrome had either a 1000 gauss magnet or a placebo metal disk applied to the carpal tunnel area using a Velcro wrap for a period of 45 minutes. Pain was measured on a visual analogue scale using 0 and 10 as anchors. Presenting symptoms including numbness, tingling, burning, and pain did not differ significantly between the 2 groups. There was significant pain reduction across the 45-minute period for both groups. However, t test comparisons found no significant differences between the groups for beginning pain, pain at 15 minutes, pain at 30 minutes, or pain at 45 minutes. The use of a magnet for reducing pain attributed to carpal tunnel syndrome was no more effective than use of the placebo device.
Oral drug of choice in carpal tunnel syndrome.
BACKGROUND: Conservative treatment of mild to moderate carpal tunnel syndrome (CTS) is variable.
OBJECTIVE: To evaluate the effectiveness of commonly used oral medications such as diuretics, nonsteroid anti-inflammatory drugs (NSAIDs), and steroids in the treatment of CTS.
METHODS: Prospective, randomized, double-blind and placebo-controlled study of patients with clinical symptoms and signs of CTS, confirmed by standard electrodiagnosis. Baseline assessments included a standardized symptom questionnaire, rating five categories of symptoms (pain, numbness, paresthesia, weakness/clumsiness, and nocturnal awakening) on a scale from 0 (no symptoms) to 10 (severe). The total score in each of the five categories was termed the global symptom score (GSS). After baseline assessment, patients were randomized to the following treatment arms: 1) 4 weeks of placebo (n = 16); 2) 4 weeks of diuretic (trichlormethiazide, 2 mg daily; n = 16); 3) 4 weeks of NSAID-slow release (SR) (tenoxicam-SR, 20 mg daily; n = 18); and 4) 2 weeks of prednisolone, 20 mg daily, followed by another 2-week dosage of 10 mg daily (n = 23). Results of follow-up assessments in the second and the fourth weeks were identical to baseline scores. The changes in GSS were analyzed to determine the statistical difference.
RESULTS: No significant reduction from baseline GSS was seen at second, and fourth weeks in the placebo, NSAID-SR, and diuretic groups. However, the mean score at 4 weeks in the steroid group decreased significantly from a baseline of 27.9 +/- 6.9 to 10 +/- 7.4.
CONCLUSION: For patients with mild to moderate CTS who opt for conservative treatment, corticosteroids are of greater benefit.
Comparative efficacy of conservative medical and chiropractic treatments for carpal tunnel syndrome: a randomized clinical trail.
OBJECTIVE: To compare the efficacy of conservative medical care with chiropractic care in the treatment of carpal tunnel syndrome.
DESIGN: Two-group, randomized, single-blind trial with 9 wk of treatment and a 1-month follow-up interview.
SETTING: Wolfe-Harris Center for Clinical Studies at Northwestern College of Chiropractic in Bloomington, Minnesota.
PATIENTS: Ninety-one of 96 eligible subjects who reported symptoms that were confirmed by clinical exam and nerve conduction studies.
INTERVENTIONS: Interventions included ibuprofen (800 mg 3 times a day for 1 wk, 800 mg twice a day for 1 wk and 800 mg as needed to a maximum daily dose of 2400 mg for 7 wk) and nocturnal wrist supports for medical treatment. Chiropractic treatment included manipulation of the soft tissues and bony joints of the upper extremities and spine (three treatments/week for 2 wk, two treatments/week for 3 wk and one treatment/week for 4 wk), ultrasound over the carpal tunnel and nocturnal wrist supports.
MAIN OUTCOME MEASURES: Outcome measures were pre- and postassessments of self-reported physical and mental distress, nerve conduction studies and vibrometry.
RESULTS: There was significant improvement in perceived comfort and function, nerve conduction and finger sensation overall, but no significant differences between groups in the efficacy of either treatment.
CONCLUSIONS: Carpal tunnel syndrome associated with median nerve demyelination but not axonal degeneration may be treated with commonly used components of conservative medical or chiropractic care.
Ultrasound treatment for treating the carpal tunnel syndrome: randomised "sham" controlled trial.
OBJECTIVE: To assess the efficacy of ultrasound treatment for mild to moderate idiopathic carpal tunnel syndrome.
DESIGN: Randomised, double blind, "sham" controlled trial with assessments at baseline, after 2 weeks' and 7 weeks' treatment, and at a follow up assessment 6 months later (8 months after baseline evaluation).
SETTING: Outpatient clinic of a university department of physical medicine and rehabilitation in Vienna.
SUBJECTS: 45 patients with mild to moderate bilateral carpal tunnel syndrome as verified by electroneurography.
INTERVENTION: 20 sessions of ultrasound (active) treatment (1 MHz, 1.0 W/cm2, pulsed mode 1:4, 15 minutes per session) applied to the area over the carpal tunnel of one wrist, and indistinguishable sham ultrasound treatment applied to the other. The first 10 treatments were performed daily (5 sessions/week); 10 further treatments were twice weekly for 5 weeks.
MAIN OUTCOME MEASURES: Score of subjective symptom ratings assessed by visual analogue scale; electroneurographic measures (for example, motor distal latency and sensory antidromic nerve conduction velocity).
RESULTS: Improvement was significantly more pronounced in actively treated than in sham treated wrists for both subjective symptoms (P < 0.001, paired t test) and electroneurographic variables (motor distal latency P < 0.001, paired t test; sensory antidromic nerve conduction velocity P < 0.001, paired t test). Effects were sustained at 6 months' follow up.
CONCLUSION: Results suggest there are satisfying short to medium term effects due to ultrasound treatment in patients with mild to moderate idiopathic carpal tunnel syndrome. Findings need to be confirmed, and ultrasound treatment will have to be compared with standard conservative and invasive treatment options.
Yoga-based intervention for carpal tunnel syndrome: a randomized trial.
CONTEXT: Carpal tunnel syndrome is a common complication of repetitive activities and causes significant morbidity.
OBJECTIVE: To determine the effectiveness of a yoga-based regimen for relieving symptoms of carpal tunnel syndrome.
DESIGN: Randomized, single-blind, controlled trial.
SETTING: A geriatric center and an industrial site in 1994-1995.
PATIENTS: Forty-two employed or retired individuals with carpal tunnel syndrome (median age, 52 years; range, 24-77 years).
INTERVENTION: Subjects assigned to the yoga group received a yoga-based intervention consisting of 11 yoga postures designed for strengthening, stretching, and balancing each joint in the upper body along with relaxation given twice weekly for 8 weeks. Patients in the control group were offered a wrist splint to supplement their current treatment.
MAIN OUTCOME MEASURES: Changes from baseline to 8 weeks in grip strength, pain intensity, sleep disturbance, Phalen sign, and Tinel sign, and in median nerve motor and sensory conduction time.
RESULTS: Subjects in the yoga groups had significant improvement in grip strength (increased from 162 to 187 mm Hg; P = .009) and pain reduction (decreased from 5.0 to 2.9 mm; P = .02), but changes in grip strength and pain were not significant for control subjects. The yoga group had significantly more improvement in Phalen sign (12 improved vs 2 in control group; P = .008), but no significant differences were found in sleep disturbance, Tinel sign, and median nerve motor and sensory conduction time.
CONCLUSION: In this preliminary study, a yoga-based regimen was more effective than wrist splinting or no treatment in relieving some symptoms and signs of carpal tunnel syndrome.
Low-dose, short-term oral prednisone in the treatment of carpal tunnel syndrome.
We evaluated the effectiveness of low-dose, short-term oral prednisone in ameliorating the pain and other symptoms of carpal tunnel syndrome (CTS) in a randomized, double-blind, placebo-controlled study of patients with mild to moderate CTS. Prednisone, in doses of 20 mg daily for the first week and 10 mg daily for the second week, resulted in significant improvement in global symptom scores. The effect was rapid, but gradually waned over 8 weeks of observation. This approach may provide a treatment alternative in the short-term, conservative management of CTS.
Oral steroid in the treatment of carpal tunnel syndrome.
An innovative hand brace for carpal tunnel syndrome: a randomized controlled trial.
We developed a hand brace and studied its efficacy and tolerability in patients with carpal tunnel syndrome (CTS). We randomized 83 subjects into a treated group, which wore the hand brace at night for 4 weeks, and a control group, which received no treatment. The primary efficacy measure was change in the Boston Carpal Tunnel Questionnaire (BCTQ) score. Secondary measures were Subjects' Global Impression of Change Questionnaire (SGICQ), median distal motor latency, sensory conduction velocity and amplitude, and neurophysiological class of severity. The treated group showed a reduction in BCTQ symptomatic score (from 2.75 to 1.54 at 4 weeks; P < 0.001) and functional score (from 1.89 to 1.48; P < 0.001). There were no significant changes in the control subjects. SGICQ documented improvement in all treated subjects (P = 0.006). No significant difference was found in electrophysiological measurements, but overall neurophysiological classification shifted to less severe classes in the treated group (P < 0.05). Thus, the study demonstrates that this hand brace is highly efficient in relieving symptoms and functional loss in CTS.
Local insulin injection improves median nerve regeneration in NIDDM patients with carpal tunnel syndrome.
It has been suggested that insulin has an effect on nerve regeneration similar to that of nerve growth factor (NGF). Therefore, we aimed to evaluate the effectiveness of local insulin injection on median nerve in patients with non-insulin-dependent diabetes (NIDDM) mellitus who have mild-to-moderate carpal tunnel syndrome (TS). We carried out a prospective, randomized, double-blind, placebo-controlled study in these patients. At the baseline, 20 mg methylprednisolone was injected directly into the carpal tunnel in all patients [n=43 (62 hands)]. A week after prednisolone, the placebo or NPH insulin (12 U) was injected into the carpal tunnel weekly for 7 weeks. The patients were followed up for 23 weeks. A significant improvement in mean median nerve motor distal latency (MNMDL), median nerve sensory velocity (MNSV), and global symptom score (GSS) occurred in both groups (with the exception of mean MNMDL in the placebo group). A more significant improvement in the mean MNMDL, MNSV, and GSS was observed in the insulin group when compared with the placebo group. This study suggests that local insulin treatment may be of great potential benefit in the improvement of nerve functions in NIDDM patients with mild-to-moderate CTS who opt for conservative treatment.
Ultrasound therapy effect in carpal tunnel syndrome.
OBJECTIVE: To investigate the overall effect of repeated ultrasound treatment in carpal tunnel syndrome (CTS).
DESIGN: Patient-blinded, placebo-controlled, before-after treatment trial.
SETTING: University hospital PM&R department outpatient clinic and neurology department electromyography laboratory.
PATIENTS: Eighteen women with diagnosis of CTS in 30 hands.
INTERVENTIONS: Three groups, each with 10 cases of CTS, were randomly established. Continuous ultrasound therapy, with intensities of 1.5W/cm2 (group A), 0.8W/cm2 (group B), and 0.0W/cm2 (group C), was applied to palmar carpal tunnel area for 5 minutes, 5 days a week, for 2 weeks.
OUTCOME MEASURES: Patients were evaluated clinically and electrophysiologically before and after the treatment.
RESULTS: At the end of treatment, statistically significant improvement was obtained in clinical parameters in all groups: pain (p < .05), pain/paresthesia at night/day (p < .05), and frequency of awakening at night (p < .05). Although there was no statistically significant before-after difference in electrophysiologic studies, slightly decreased motor nerve conduction velocity and increased motor distal latency were noted in groups A and B, but not in group C.
CONCLUSION: Ultrasound therapy in CTS was comparable to placebo ultrasound in providing symptomatic relief, and the probability of a negative effect on motor nerve conduction needs to be considered.
Effect of keyboard keyswitch design on hand pain.
This randomized clinical trial evaluated the effects of keyboard keyswitch design on computer users with hand paresthesias. Twenty computer users were matched and randomly assigned to keyboard A (n = 10) or B (n = 10). The keyboards were of conventional layout and differed in keyswitch design. Various outcome measures were assessed during the 12 weeks of use. Subjects assigned keyboard A experienced a decrease in hand pain between weeks 6 and 12 when compared with keyboard B subjects (P = 0.05) and demonstrated an improvement in the Phalen test time (right hand, P = 0.006; left hand, P = 0.06). Keyboard assignment had no significant effect on change in hand function or median nerve latency. We conclude that use of keyboard A for 12 weeks led to a reduction in hand pain and an improved physical examination finding when compared with keyboard B. There was no corresponding improvement in hand function or median nerve latency.
Using pyridoxine to treat carpal tunnel syndrome. Randomized control trial.
In this study, we examined prospectively the effect of pyridoxine on idiopathic carpal tunnel syndrome. Thirty-two patients with the disease were randomized to receive treatment or placebo. No differences in outcome were found in electrophysiologic signs, clinical signs, or significant symptoms. Our findings do not support the use of pyridoxine for treating carpal tunnel syndrome.
Treatment of carpal tunnel syndrome with vitamin B6: a double-blind study.
We undertook a randomized, double-blind, placebo-controlled study to investigate the therapeutic effect of vitamin B6 on carpal tunnel syndrome. After ten weeks in the study, ten of 15 patients improved (this included patients given placebo and those given no treatment). Vitamin B6 seems to have no advantage over conservative therapy for carpal tunnel syndrome. This study also suggests that repeat electrodiagnostic testing is no more useful than clinical symptoms in deciding on surgical intervention after unsuccessful conservative therapy.
An investigation to compare the effectiveness of carpal bone mobilisation and neurodynamic mobilisation as methods of treatment for carpal tunnel syndrome.
Carpal tunnel syndrome is the most common peripheral entrapment neuropathy. There is little literature available that addresses the management of this condition, which may partly explain why physiotherapy is often overlooked as a treatment approach in its management. This study investigated the effects of two manual therapy techniques in the treatment of patients experiencing carpal tunnel syndrome. An experimental different subject design compared three groups of subjects in three different conditions (two treatment interventions and one control group). Each group consisted of seven patients. The objectives of the study were: (1) to investigate differences between treated and untreated groups; (2) to investigate differences in the effectiveness of treatment I (median nerve mobilization) compared with treatment II (carpal bone mobilization). Measurements were taken applying several measurement tools, including active range of wrist movement (ROM flexion and extension), upper limb tension test with a median nerve bias (ULTT2a), three different scales to evaluate pain perception and function, and lastly numbers of patients continuing to surgery in each group were compared. In visual terms a clear trend was demonstrated between subjects who received treatment compared to those who were not treated, in particular the descriptive analysis of results for ULTT2a and numbers of patients continuing to surgery. When analysed statistically, less could be concluded. Only scores on a Pain Relief Scale (P<0.01) demonstrated highly significant differences between the three groups when analyzed using Kruskal-Wallis Test. In exploring the results of the two intervention groups, no statistically significant difference in effectiveness of treatment was demonstrated between carpal bone mobilization and median nerve mobilization.
Effect of four computer keyboards in computer users with upper extremity musculoskeletal disorders.
Eighty computer users with musculoskeletal disorders participated in a 6-month, randomized, placebo-controlled trial evaluating the effects of four computer keyboards on clinical findings, pain severity, functional hand status, and comfort. The alternative geometry keyboards tested were: the Apple Adjustable Keyboard [kb1], Comfort Keyboard System [kb2], Microsoft Natural Keyboard [kb3], and placebo. Compared to placebo, kb3 and to a lesser extent kb1 groups demonstrated an improving trend in pain severity and hand function following 6 months of keyboard use. However, there was no corresponding consistent improvement in clinical findings in the alternative geometry keyboard groups compared to the placebo group. Overall, there was a significant correlation between improvement of pain severity and greater satisfaction with the keyboards. These results provide evidence that keyboard users may experience a reduction in hand pain after several months of use of some alternative geometry keyboards.
Neutral wrist splinting in carpal tunnel syndrome: a comparison of night-only versus full-time wear instructions.
OBJECTIVE: To compare the effects of night-only to full-time splint wear instructions on symptoms, function, and impairment in carpal tunnel syndrome (CTS).
DESIGN: Randomized clinical trial with 6-week follow-up.
SETTING: Veterans Administration Medical Center, outpatient clinic.
SUBJECTS: Outpatients with untreated CTS were consecutively recruited from our electrodiagnostics lab. Twenty-one patients (30 hands) were enrolled, and 17 patients (24 hands) completed the study.
INTERVENTIONS: Thermoplastic, custom-molded, neutral wrist splints with subjects receiving either full-time or night-only wear instructions.
OUTCOME MEASURES: Symptoms and functional deficits were measured by Levine's self-administered questionnaire, and physiologic impairment was measured by median nerve sensory and motor distal latency. COMPLIANCE AND CROSSOVER: Almost all (92%) of the combined sample reported frequent splint use, but their adherence to specific wearing instructions was limited. A majority (73%) of the full-time group reported splint wear less than one half of waking hours, and some (23%) of the night-only group reported occasional daytime wear. Despite this tendency for treatment crossover, the two treatment groups differed in daytime wear as intended (chi2 analysis, p = .004).
RESULTS: The combined sample improved in three of four outcome measures: sensory distal latency (mean = .28msec, standard deviation [SD] = .37, p = .004), symptom severity (mean = .64, SD = .46, p = .0001), and functional deficits (mean = .49, SD = .51, p = .0001). Severity of CTS was a factor only in sensory distal latency improvement (more improvement in severe CTS). Subjects receiving full-time wear instructions showed superior distal latency improvement, both motor (.35 vs -.07msec, p = .04) and sensory (.46 vs . 13msec, p = .05) when compared with subjects receiving night-only wear instructions.
CONCLUSIONS: This study provides added scientific evidence to support the efficacy of neutral wrist splints in CTS and suggests that physiologic improvement is best with full-time splint wear instructions.
Options:
A: Oral steroids, splinting, ultrasound, yoga, and carpal bone mobilisation
B: Diuretics, nonsteroidal anti-inflammatory drugs, vitamin B6, and ergonomic keyboards
C: Magnet therapy, laser acupuncture, exercise, and chiropractic care
D: All non-surgical treatments provide significant short-term benefit | A |
253 | 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 prophylactic and emergency cervical cerclage in preventing pregnancy loss and preterm delivery in women with risk factors? Please answer this question based on the information provided below:
Cervical incompetence prevention randomized cerclage trial (CIPRACT): study design and preliminary results.
OBJECTIVE: The objective of this study was to compare different management strategies for women at risk for cervical incompetence.
STUDY DESIGN: In an ongoing randomized trial patients with a previous preterm delivery at <34 weeks' gestation who met clinical criteria for the diagnosis of cervical incompetence are allocated to receive a prophylactic cerclage (prophylactic cerclage group) or not (observational group) in a proportion of 1:2. Transvaginal ultrasonographic follow-up examination of the cervix is performed in both groups. When a patient of the latter group has a cervical length <25 mm at <27 weeks' gestation, a further random assignment of therapeutic cerclage or no cerclage is performed. The analysis is by intent to treat.
RESULTS: Primary random assignment allocated 23 women to the prophylactic cerclage group and 44 to the observational group. Both groups were comparable with respect to obstetric history. No significant difference was found between the prophylactic cerclage group and the observational group in preterm delivery at <34 weeks' gestation (3/23 vs 6/44, respectively) and neonatal survival (21/23 vs 41/44, respectively). A cervical length <25 mm was found in 18 patients (41%) in the observational group at a mean gestational age of 19.1 +/- 2.9 weeks' gestation. Incidence of preterm delivery at <34 weeks' gestation was significantly higher in the group with short cervical length (6/18 vs 0/26; P =.003). Secondary random assignment of the 18 patients with short cervical length allocated 10 to undergo therapeutic cerclage. Preterm delivery at <34 weeks' gestation was significantly less frequent in the therapeutic cerclage group (1/10 vs 5/8).
CONCLUSION: Transvaginal ultrasonographic serial follow-up examinations of the cervix in women at risk for cervical incompetence, with secondary intervention as indicated, appears to be a safe alternative to the traditional prophylactic cerclage. Transvaginal ultrasonographic follow-up examination of the cervix can save the majority of women from unnecessary intervention. Placement of a therapeutic cerclage may reduce the incidence of preterm delivery at <34 weeks' gestation among high-risk patients.
Final results of the Cervical Incompetence Prevention Randomized Cerclage Trial (CIPRACT): therapeutic cerclage with bed rest versus bed rest alone.
OBJECTIVE: To compare preterm delivery rates (before 34 weeks of gestation) and neonatal morbidity and mortality in patients with risk factors or symptoms of cervical incompetence managed with therapeutic McDonald cerclage and bed rest versus bed rest alone.
STUDY DESIGN: Cervical length was measured in patients with risk factors or symptoms of cervical incompetence. Risk factors for cervical incompetence included previous preterm delivery before 34 weeks of gestation that met clinical criteria for the diagnosis of cervical incompetence, previous preterm premature rupture of membranes before 32 weeks of gestation, history of cold knife conization, diethylstilbestrol exposure, and uterine anomaly. When a cervical length of <25 mm was measured before a gestational age of 27 weeks, a randomization for therapeutic cerclage and bed rest (cerclage group) or bed rest alone (bed rest group) was performed. The analysis is based on intention to treat.
RESULTS: Of the 35 women who met the inclusion criteria, 19 were allocated randomly to the cerclage group and 16 to the bed rest group. Both groups were comparable for mean cervical length and mean gestational age at time of randomization, mean overall 20 mm and 21 weeks. Preterm delivery before 34 weeks was significantly more frequent in the bed rest group than in the cerclage group (7 of 16 vs none, respectively; P =.002). There was no statistically significant difference in neonatal survival between the groups (13 neonates survived in the bed rest group vs all in the cerclage group). The compound neonatal morbidity, defined as admission to the neonatal intensive care unit or neonatal death, was significantly higher in the bed rest group than in the cerclage group (8 of 16 vs 1 of 19, respectively; P =.005; RR = 9.5, 95% CI, 1.3-68.1).
CONCLUSIONS: Therapeutic cerclage with bed rest reduces preterm delivery before 34 weeks of gestation and compound neonatal morbidity in women with risk factors and/or symptoms of cervical incompetence and a cervical length of <25 mm before 27 weeks of gestation.
Cervical incompetence prevention randomized cerclage trial (CIPRACT): study design and preliminary results.
OBJECTIVE: The objective of this study was to compare different management strategies for women at risk for cervical incompetence.
STUDY DESIGN: In an ongoing randomized trial patients with a previous preterm delivery at <34 weeks' gestation who met clinical criteria for the diagnosis of cervical incompetence are allocated to receive a prophylactic cerclage (prophylactic cerclage group) or not (observational group) in a proportion of 1:2. Transvaginal ultrasonographic follow-up examination of the cervix is performed in both groups. When a patient of the latter group has a cervical length <25 mm at <27 weeks' gestation, a further random assignment of therapeutic cerclage or no cerclage is performed. The analysis is by intent to treat.
RESULTS: Primary random assignment allocated 23 women to the prophylactic cerclage group and 44 to the observational group. Both groups were comparable with respect to obstetric history. No significant difference was found between the prophylactic cerclage group and the observational group in preterm delivery at <34 weeks' gestation (3/23 vs 6/44, respectively) and neonatal survival (21/23 vs 41/44, respectively). A cervical length <25 mm was found in 18 patients (41%) in the observational group at a mean gestational age of 19.1 +/- 2.9 weeks' gestation. Incidence of preterm delivery at <34 weeks' gestation was significantly higher in the group with short cervical length (6/18 vs 0/26; P =.003). Secondary random assignment of the 18 patients with short cervical length allocated 10 to undergo therapeutic cerclage. Preterm delivery at <34 weeks' gestation was significantly less frequent in the therapeutic cerclage group (1/10 vs 5/8).
CONCLUSION: Transvaginal ultrasonographic serial follow-up examinations of the cervix in women at risk for cervical incompetence, with secondary intervention as indicated, appears to be a safe alternative to the traditional prophylactic cerclage. Transvaginal ultrasonographic follow-up examination of the cervix can save the majority of women from unnecessary intervention. Placement of a therapeutic cerclage may reduce the incidence of preterm delivery at <34 weeks' gestation among high-risk patients.
Final results of the Cervical Incompetence Prevention Randomized Cerclage Trial (CIPRACT): therapeutic cerclage with bed rest versus bed rest alone.
OBJECTIVE: To compare preterm delivery rates (before 34 weeks of gestation) and neonatal morbidity and mortality in patients with risk factors or symptoms of cervical incompetence managed with therapeutic McDonald cerclage and bed rest versus bed rest alone.
STUDY DESIGN: Cervical length was measured in patients with risk factors or symptoms of cervical incompetence. Risk factors for cervical incompetence included previous preterm delivery before 34 weeks of gestation that met clinical criteria for the diagnosis of cervical incompetence, previous preterm premature rupture of membranes before 32 weeks of gestation, history of cold knife conization, diethylstilbestrol exposure, and uterine anomaly. When a cervical length of <25 mm was measured before a gestational age of 27 weeks, a randomization for therapeutic cerclage and bed rest (cerclage group) or bed rest alone (bed rest group) was performed. The analysis is based on intention to treat.
RESULTS: Of the 35 women who met the inclusion criteria, 19 were allocated randomly to the cerclage group and 16 to the bed rest group. Both groups were comparable for mean cervical length and mean gestational age at time of randomization, mean overall 20 mm and 21 weeks. Preterm delivery before 34 weeks was significantly more frequent in the bed rest group than in the cerclage group (7 of 16 vs none, respectively; P =.002). There was no statistically significant difference in neonatal survival between the groups (13 neonates survived in the bed rest group vs all in the cerclage group). The compound neonatal morbidity, defined as admission to the neonatal intensive care unit or neonatal death, was significantly higher in the bed rest group than in the cerclage group (8 of 16 vs 1 of 19, respectively; P =.005; RR = 9.5, 95% CI, 1.3-68.1).
CONCLUSIONS: Therapeutic cerclage with bed rest reduces preterm delivery before 34 weeks of gestation and compound neonatal morbidity in women with risk factors and/or symptoms of cervical incompetence and a cervical length of <25 mm before 27 weeks of gestation.
Cervical incompetence prevention randomized cerclage trial (CIPRACT): study design and preliminary results.
OBJECTIVE: The objective of this study was to compare different management strategies for women at risk for cervical incompetence.
STUDY DESIGN: In an ongoing randomized trial patients with a previous preterm delivery at <34 weeks' gestation who met clinical criteria for the diagnosis of cervical incompetence are allocated to receive a prophylactic cerclage (prophylactic cerclage group) or not (observational group) in a proportion of 1:2. Transvaginal ultrasonographic follow-up examination of the cervix is performed in both groups. When a patient of the latter group has a cervical length <25 mm at <27 weeks' gestation, a further random assignment of therapeutic cerclage or no cerclage is performed. The analysis is by intent to treat.
RESULTS: Primary random assignment allocated 23 women to the prophylactic cerclage group and 44 to the observational group. Both groups were comparable with respect to obstetric history. No significant difference was found between the prophylactic cerclage group and the observational group in preterm delivery at <34 weeks' gestation (3/23 vs 6/44, respectively) and neonatal survival (21/23 vs 41/44, respectively). A cervical length <25 mm was found in 18 patients (41%) in the observational group at a mean gestational age of 19.1 +/- 2.9 weeks' gestation. Incidence of preterm delivery at <34 weeks' gestation was significantly higher in the group with short cervical length (6/18 vs 0/26; P =.003). Secondary random assignment of the 18 patients with short cervical length allocated 10 to undergo therapeutic cerclage. Preterm delivery at <34 weeks' gestation was significantly less frequent in the therapeutic cerclage group (1/10 vs 5/8).
CONCLUSION: Transvaginal ultrasonographic serial follow-up examinations of the cervix in women at risk for cervical incompetence, with secondary intervention as indicated, appears to be a safe alternative to the traditional prophylactic cerclage. Transvaginal ultrasonographic follow-up examination of the cervix can save the majority of women from unnecessary intervention. Placement of a therapeutic cerclage may reduce the incidence of preterm delivery at <34 weeks' gestation among high-risk patients.
Multicentred controlled trial of cervical cerclage in women at moderate risk of preterm delivery.
A total of 506 women at moderate risk of preterm delivery were randomly allocated to either cervical cerclage or a control group. Significantly more women in the group allocated to cerclage were admitted to hospital for reasons other than the operation and more received oral tocolytic drugs. There were also more caesarean sections and more preterm deliveries in the women allocated to cerclage although the differences between the two groups were small and not statistically significant.
Interim report of the Medical Research Council/Royal College of Obstetricians and Gynaecologists multicentre randomized trial of cervical cerclage. MRC/RCOG Working Party on Cervical Cerclage.
Overall 905 pregnant women whose obstetricians were 'uncertain' whether to recommend cervical cerclage, chiefly because of a history of early delivery or cervical surgery, were randomly allocated to cerclage or no surgery; 92% were treated as allocated. The overall preterm delivery rate was 30%. The results for those allocated cerclage were marginally statistically significant, more favourable in terms of fewer deliveries before 33 weeks [59 (13%) compared with 82 (18%), P = 0.03] and correspondingly for birthweight under 1500 g [48 (11%) compared with 73 (16%), P = 0.01] and for miscarriage, stillbirth or neonatal death [37 (8%) compared with 54 (12%), P = 0.06]. There were similar numbers of deliveries between 33 and 36 weeks [65 (14%) compared with 64 (14%)]. These results suggest that the operation had an important beneficial effect in one in 20 to 25 cases in the trial. But because the observed differences are not strongly statistically significant and because no such benefit has been seen in other randomized trials, there remains uncertainty about how much (if any) of this apparent benefit is real. So, the trial still remains open for randomization of more women whose obstetricians are uncertain about the advisability of cerclage.
Final report of the Medical Research Council/Royal College of Obstetricians and Gynaecologists multicentre randomised trial of cervical cerclage. MRC/RCOG Working Party on Cervical Cerclage.
OBJECTIVE: To assess whether cervical cerclage in women deemed to be at increased risk of cervical incompetence prolongs pregnancy and thereby improves fetal and neonatal outcome.
DESIGN: Multicentre randomised controlled trial.
SETTING: Hospitals in the United Kingdom, France, Hungary, Norway, Italy, Belgium, Zimbabwe, South Africa, Iceland, Ireland, the Netherlands and Canada.
SUBJECTS: One thousand two hundred and ninety-two pregnant women whose obstetricians were uncertain whether to recommend cervical cerclage, most of whom had a history of early delivery or cervical surgery.
INTERVENTIONS: Cervical cerclage was compared with a policy of withholding the operation unless it was considered to be clearly indicated.
MAIN OUTCOME MEASURES: Delivery before 33 completed weeks, preterm delivery (< 37 weeks), and vital status of the baby after completion of the pregnancy.
RESULTS: The overall preterm delivery rate was 28%. There were fewer deliveries before 33 weeks in the cerclage group (83 (13%) compared with 110 (17%), P = 0.03) and this difference reflected deliveries characterised by features of cervical incompetence (painless cervical dilatation and prelabour rupture of the membranes). There was a corresponding difference in very low birthweight deliveries (63 (10%) compared with 86 (13%), P = 0.05). The difference in the overall rate of miscarriage, stillbirth or neonatal death (55 (9%) compared with 68 (11%)) was less marked and was not statistically significant. The use of cervical cerclage was associated with increased medical intervention and a doubling of the risk of puerperal pyrexia.
CONCLUSIONS: These results suggest that the operation had an important beneficial effect in 1 in 25 cases in the trial (95% confidence interval (CI) 1 in 12 to 1 in 300 sutures). Its use is associated with increased medical intervention and puerperal pyrexia. Nevertheless, this trial suggests that, on balance, cervical cerclage should be offered to women at high risk, such as those with a history of three or more pregnancies ending before 37 weeks gestation.
A randomized controlled trial of cervical cerclage in women at high risk of spontaneous preterm delivery.
The effect of cervical suture on pregnancy outcome was studied in 194 women with a high risk (approximately 30%) of having a late abortion or a preterm delivery. The women were randomly allocated either to have a cervical suture inserted (n = 96) or to be managed without a suture (n = 98). There was no evidence that cervical cerclage either prolonged gestation or improved survival. Patients allocated to receive cerclage spent significantly longer in hospital, even when the period of admission for insertion was excluded. The patients in the cerclage group were more likely to receive tocolytic drugs, and more of them experienced puerperal pyrexia, although these differences between the groups were not statistically significant.
A randomized trial of cerclage versus no cerclage among patients with ultrasonographically detected second-trimester preterm dilatation of the internal os.
OBJECTIVE: The aim of this study was to compare perinatal outcomes of patients with second-trimester ultrasonographic evidence of preterm dilatation of the internal os treated with cerclage versus those of patients not treated with cerclage.
STUDY DESIGN: From May 1998 through June 1999 patients with ultrasonographic evidence of preterm dilatation of the internal os between 16 and 24 weeks' gestation were randomly assigned to receive a McDonald cerclage or no cerclage. Before random assignment all patients underwent amniocentesis and urogenital cultures and then received 48 hours of therapy with indomethacin and antibiotics. After treatment each patient was followed up as an outpatient with bed rest and weekly ultrasonographic evaluation.
RESULTS: Of the 61 patients 31 were randomly assigned to cerclage and 30 were randomly assigned to no cerclage. There were no differences between groups with respect to maternal demographic characteristics, risk factors for preterm birth, cervical measurements, rescue procedures, readmission, chorioamnionitis, and abruptio placentae. The mean gestational age at delivery (33.5 +/- 6.3 weeks) and the perinatal death rate (12. 9%) in the cerclage group were similar to the mean gestational age at delivery (34.7 +/- 4.7 weeks; P =.4) and the perinatal death rate (10.0%; P =.9) in the no-cerclage group.
CONCLUSION: Treatment with McDonald cerclage of preterm dilatation of the cervix detected ultrasonographically during the second trimester did not improve perinatal outcomes.
Does cerclage location influence perinatal outcome?
OBJECTIVE: The study was undertaken to measure cerclage location within the cervix and to determine whether placement closer to the internal os is related to perinatal outcome.
STUDY DESIGN: We analyzed data collected during a randomized trial of cervical cerclage versus no cerclage that was conducted at Lehigh Valley Hospital between May 1998 and June 2001 in women with ultrasound findings of short cervix less than 25 mm or funneling between 16 and 24 weeks' gestation. Women who were randomly assigned to the cerclage arm had cervical measurements performed before cerclage, including dilation of the internal os, depth of membrane prolapse into the endocervical canal, cervical length below any funnel (distal length), and total cervical length (including any funnel). Measurements obtained after cerclage placement included the distance from external os to cerclage (A), and a repeat of the same four measurements. The distance from the external os to the cerclage (A) was divided by the total cervical length (B) and a cerclage to cervical length ratio (A/B) was calculated. The relationship between these measurements and gestational age at birth was assessed by linear regression analysis.
RESULTS: Of 150 patients enrolled, 74 received a McDonald cerclage suture. Mean distal cervical length was 1.9+/-0.9 cm before and 2.9+/-1.0 cm after cerclage (P=.001). The mean distance between the cerclage and external os (A) was 1.8+/-0.6 cm; the total cervical length after cerclage (B) was 3.6+/-0.9 cm. The mean cerclage to cervical length ratio (A/B) was 0.5+/-0.1. Linear regression analysis did not demonstrate a correlation between either the cerclage to external os measurement (A) or the cervical length ratio (A/B) and gestational age at birth (R(2)=0.0006 and 0.008, P=.8 and.6, respectively).
CONCLUSION: The length of the cervix below the level of cerclage is not related to duration of pregnancy in women treated with cerclage because of ultrasound evidence of cervical effacement.
A randomized trial of cerclage versus no cerclage among patients with ultrasonographically detected second-trimester preterm dilatation of the internal os.
OBJECTIVE: The aim of this study was to compare perinatal outcomes of patients with second-trimester ultrasonographic evidence of preterm dilatation of the internal os treated with cerclage versus those of patients not treated with cerclage.
STUDY DESIGN: From May 1998 through June 1999 patients with ultrasonographic evidence of preterm dilatation of the internal os between 16 and 24 weeks' gestation were randomly assigned to receive a McDonald cerclage or no cerclage. Before random assignment all patients underwent amniocentesis and urogenital cultures and then received 48 hours of therapy with indomethacin and antibiotics. After treatment each patient was followed up as an outpatient with bed rest and weekly ultrasonographic evaluation.
RESULTS: Of the 61 patients 31 were randomly assigned to cerclage and 30 were randomly assigned to no cerclage. There were no differences between groups with respect to maternal demographic characteristics, risk factors for preterm birth, cervical measurements, rescue procedures, readmission, chorioamnionitis, and abruptio placentae. The mean gestational age at delivery (33.5 +/- 6.3 weeks) and the perinatal death rate (12. 9%) in the cerclage group were similar to the mean gestational age at delivery (34.7 +/- 4.7 weeks; P =.4) and the perinatal death rate (10.0%; P =.9) in the no-cerclage group.
CONCLUSION: Treatment with McDonald cerclage of preterm dilatation of the cervix detected ultrasonographically during the second trimester did not improve perinatal outcomes.
Revisiting the short cervix detected by transvaginal ultrasound in the second trimester: why cerclage therapy may not help.
OBJECTIVE: The purpose of this study was to identify the risk factors that are associated with increased neonatal morbidity in patients who were treated for sonographic evidence of internal os dilation and distal cervical shortening during the second trimester.
STUDY DESIGN: From May 1998 to June 2000 patients between 16 and 24 weeks of gestation with the following sonographic criteria were randomly assigned to McDonald cerclage or no cerclage: internal os dilation and either membrane prolapse into the endocervical canal at least 25% of the total cervical length but not beyond the external os or a shortened distal cervix <2.5 cm. Before randomization, all patients were treated identically with an amniocentesis, multiple urogenital cultures, and therapy with indomethacin and clindamycin for 48 to 72 hours. Except for the cerclage, all patients were treated identically after randomization. Multiple variables of perinatal outcome were analyzed. A regression model with gestational age at delivery as the dependent variable was constructed and repeated with neonatal morbidity as the dependent variable. This model was applied to 3 populations: the cerclage group, the no cerclage group, and both groups combined.
RESULTS: Of the 135 patients, 20 patients declined randomization, and 2 patients were diagnosed with acute chorioamnionitis. Of the 113 patients remaining, 55 patients were randomly assigned to the cerclage group, and 58 patients were randomly assigned to the no cerclage group. There were 8 rescue cerclage procedures (4 in each group). Regression analysis showed that readmission for preterm labor, chorioamnionitis, and abruption were consistently associated with early gestational age at delivery and increased morbidity. Cerclage did not affect perinatal outcome.
CONCLUSION: The sonographic findings of second trimester internal os dilation, membrane prolapse, and distal cervical shortening likely represent a common pathway of several pathophysiologic processes. Use of cerclage does not alter any perinatal outcome variables. Increased neonatal morbidity in these patients appears to be associated with subclinical infection, preterm labor, and abruption.
Options:
A: Prophylactic cerclage significantly reduces overall pregnancy loss and preterm delivery rates.
B: Prophylactic cerclage does not significantly reduce overall pregnancy loss and preterm delivery rates, but may reduce births under 33 weeks' gestation.
C: Emergency cerclage significantly reduces total pregnancy loss and preterm delivery before 28 and 34 weeks.
D: Both prophylactic and emergency cerclage are associated with serious morbidity. | B |
254 | 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 and safety of beta-blocker therapy for the treatment of tremor in patients with Parkinson's disease? Please answer this question based on the information provided below:
Postural tremor of Parkinson's disease.
Previous studies have reported the resting tremor (RT) of Parkinson's disease to occur at frequencies between 3-7 Hz and to be characterised by an alternating pattern of electromyographic (EMG) bursting activity between opposing muscles. A postural tremor (PT), of higher frequency (> 6 Hz) and with a synchronous pattern of EMG activity, has also been previously described in Parkinson's disease. We investigated the electrophysiological and pharmacological properties of both the RT and PT of 11 patients with Parkinson's disease and 10 patients with essential tremor in a double-blind, placebo-controlled study of L-Dopa/benserazide and propranolol. Tremor amplitude and frequency were assessed via bidirectional accelerometry, and the pattern of activation of the antagonist muscles of the forearm was determined with use of surface EMG. In the Parkinson's disease group studied, the frequency, EMG pattern of bursts, and response to L-Dopa were similar for the two tremors (median improvement of RT by 70% and PT by 61%). Despite some overlap between the Parkinson's disease and essential tremor groups in the electrophysiology of the tremor, there was no such dramatic pharmacological response in the latter group. These results suggest that the RT and PT of Parkinson's disease share a common pathophysiology and are distinct from essential tremor.
Letter: Propranolol in Parkinson's disease.
Options:
A: Beta-blocker therapy was found to be highly effective and safe for treating tremor in Parkinson's disease.
B: Beta-blocker therapy showed some efficacy but raised significant safety concerns due to high frequency of bradycardia.
C: There was insufficient evidence to determine the efficacy and safety of beta-blocker therapy for treating tremor in Parkinson's disease.
D: Beta-blocker therapy was found to be ineffective and unsafe for treating tremor in Parkinson's disease. | C |
255 | 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 kava extract for treating anxiety in clinical trials? Please answer this question based on the information provided below:
A placebo-controlled study of Kava kava in generalized anxiety disorder.
We assessed the efficacy and safety of a botanical anxiolytic, Kava kava (Piper methysticum), in treating generalized anxiety disorder (GAD). Thirty-seven adults with DSM-IV GAD were randomly assigned to 4 weeks of double-blind treatment with kava or a matching placebo. Weekly efficacy assessments [Hamilton Anxiety Scale, Hospital Anxiety and Depression Scale (HADS), Self Assessment of Resilience and Anxiety (SARA)] and safety evaluations were conducted. Improvement was observed with both treatments but no differences were found in the principal analysis. Post-hoc analyses revealed significant differences based on baseline anxiety severity, whereby kava was superior on the SARA in low anxiety and placebo was superior on the HADS and SARA in high anxiety. Both treatments were well tolerated. Although kava was not superior to placebo, it would be premature to rule it out as efficacious in GAD.
Treatment of anxiety, tension and restlessness states with Kava special extract WS 1490 in general practice: a randomized placebo-controlled double-blind multicenter trial.
The efficacy and tolerability of 150 mg/d Kava special extract WS 1490 were investigated in a randomized, placebo-controlled, double-blind multicenter study in patients suffering from neurotic anxiety (DSM-III-R diagnoses 300.02, 300.22, 300.23, 300.29, or 309.24). 141 adult, male and female out-patients received 3 x 1 capsule of 50 mg/d WS 1490 or placebo for four weeks, followed by two weeks of observation without study-specific treatment. During randomized treatment the total score of the Anxiety Status Inventory (ASI) observer rating scale showed more pronounced decreases in the WS 1490 group than in the placebo group. Although a treatment group comparison of the post-treatment ASI scores was not significant (p > 0.05), an exploratory analysis of variance across the differences between treatment end and baseline, with center as a second factor, showed superiority of the herbal extract over placebo (p < 0.01, two-sided). 73% of the patients treated with WS 1490 exhibited ASI score decreases > 5 points versus baseline, compared to 56% for placebo. Significant advantages for WS 1490 were also evident in a structured well-being self-rating scale (Bf-S) and the Clinical Global Impressions (CGI), while the Erlangen Anxiety, Tension and Aggression Scale (EAAS) and the Brief Test of Personality Structure (KEPS) showed only minor treatment group differences. Although the results show consistent advantages for WS 1490 over placebo in several psychiatric scales and indicate significant improvements in the patients' general well-being, the differences versus placebo were not as large as in previous trials which employed 300 mg/d of the same extract. WS 1490 was well tolerated, with no influence on liver function tests and only one trivial adverse event (tiredness) attributable to the study drug.
Kava treatment in patients with anxiety.
In several clinical trials, mainly conducted with a dose of 300 mg kava extract per day, kava has been employed successfully for the treatment of anxiety disorders. The goal of the placebo-controlled double-blind outpatient trial was to obtain more information on the dosage range and efficacy of a kava special extract WS 1490 in patients with non-psychotic anxiety. 50 patients were treated with a daily dose of 3 x 50 mg WS 1490 during a 4-week treatment period followed by a 2-week safety observation phase. In the active treatment group, the total score of the Hamilton anxiety scale (primary efficacy variable), showed a therapeutically relevant reduction in anxiety versus placebo (more than 4 points). In the secondary variables studied, HAMA 'somatic and psychic anxiety' subscales, the Erlangen anxiety, tension and aggression scale (EAAS), the brief personality structure scale (KEPS), the adjective checklist (EWL 60-S) and clinical global impressions scale (CGI), a trend in favour of the active treatment was detectable. WS 1490 was well tolerated and showed a safety profile with no drug-related adverse events or post-study withdrawal symptoms. It can be concluded that the applied 150 mg WS 1490 per day is an effective and safe treatment of non-psychotic anxiety syndromes in the described population.
[Effect of a special kava extract in patients with anxiety-, tension-, and excitation states of non-psychotic genesis. Double blind study with placebos over 4 weeks].
Clinical Efficacy of a Kava Extract in Patients with Anxiety Syndrome/Double-blind placebo controlled study over 4 weeks. In a randomized, placebo-controlled double-blind study two groups each containing 29 patients with anxiety syndrome not caused by psychotic disorders were treated for a period of 4 weeks with kava extract WS 1490 (Laitan) 3 x 100 mg/day or a placebo preparation. Therapeutic efficacy was assessed by the Hamilton-Anxiety-Scale (main target variable), the Adjectives-List and the Clinical-Global-Impression-Scale (secondary target variables) after 1, 2 and 4 weeks of treatment. The HAMA overall score of anxiety symptomatology revealed a significant reduction in the drug receiving group already after one week of treatment. This difference between the two groups of patients increased in the course of the study. The results of the secondary target variables were in agreement with the HAMA-score and demonstrate the efficacy of WS 1490 in patients with anxiety disorders. No adverse experiences caused by the medication were noted during the 4 week administration of WS 1490.
Clinical efficacy of kava extract WS 1490 in sleep disturbances associated with anxiety disorders. Results of a multicenter, randomized, placebo-controlled, double-blind clinical trial.
BACKGROUND: The aim of the present trial was to investigate the efficacy and safety of kava special extract WS 1490 in patients with sleep disturbances associated with anxiety, tension and restlessness states of non-psychotic origin.
METHODS: In a multicenter, randomized, double-blind clinical study, 61 patients received daily doses of 200 mg WS 1490 or placebo over a period of 4 weeks. Efficacy was measured by the sleep questionnaire SF-B, the Hamilton Anxiety Scale (HAMA), the Bf-S self-rating scale of well-being and the Clinical Global Impressions (CGI) scale.
RESULTS: The confirmatory analysis of the two primary efficacy variables, the differences of sleep questionnaire SF-B sub-scores 'Quality of sleep' and 'Recuperative effect after sleep' after 4 weeks of double-blind treatment compared to baseline, demonstrated statistically significant group differences in favor of kava extract WS 1490 (P=0.007 and P=0.018, respectively). Superior effects of kava extract were also present in the HAMA psychic anxiety sub-score (P=0.002). More pronounced effects with respect to the self-rating of well-being and the global clinical evaluation also indicated superior therapeutic efficacy of kava extract. Safety and tolerability were good, with no drug-related adverse events or changes in clinical or laboratory parameters.
CONCLUSIONS: We conclude that sleep disturbances associated with non-psychotic anxiety disorders can be effectively and safely treated with kava extract WS 1490.
Efficacy of kava-kava in the treatment of non-psychotic anxiety, following pretreatment with benzodiazepines.
A 5-week randomized, placebo-controlled, double-blind study was carried out to investigate the efficacy of kava-kava special extract WS1490 in non-psychotic nervous anxiety, tension and restlessness states. During the first treatment week, the study dose drug was increased from 50 mg to 300 mg per day and pretreatment with benzodiazepines was tapered off over 2 weeks. These dosage adjustments were followed by 3 weeks of monotherapy with WS1490 or placebo. Outcome measures were the differences between baseline and end of treatment on the Hamilton Anxiety Scale (HAMA) and on a subjective well-being scale (Bf-S), as well as the benzodiazepine withdrawal symptoms. Changes in the Erlanger Anxiety, Tension and Aggression Scale (EAAS) and Clinical Global Impressions (CGI) were analyzed as secondary measures. Treatment safety was checked by interviews, adverse event reports and laboratory investigations. Forty patients (2x20) were included into the study. WS1490 was superior to placebo regarding the HAMA (P=0.01) and Bf-S (P=0.002) total scores and all secondary efficacy measures. The tolerance of WS1490 was not inferior to placebo. The study confirms the anxiolytic efficacy and good tolerance of WS1490 and shows that a further symptom reduction is possible after a change-over from benzodiazepine treatment.
Kava-kava extract WS 1490 versus placebo in anxiety disorders--a randomized placebo-controlled 25-week outpatient trial.
101 outpatients suffering from anxiety of non-psychotic origin (DSM-III-R criteria: agoraphobia, specific phobia, generalized anxiety disorder, and adjustment disorder with anxiety) were included in a 25-week multicenter randomized placebo-controlled double-blind trial with WS 1490, a special extract of kava-kava. In the main outcome criterion, the Hamilton Anxiety Scale (HAMA), there was a significant superiority of the test drug starting from week 8 on. WS 1490 was also found to be superior with respect to the secondary outcome variables. HAMA subscores somatic and psychic anxiety, Clinical Global Impression, Self-Report Symptom Inventory-90 Items revised, and Adjective Mood Scale. Adverse events were rare and distributed evenly in both groups. These results support WS 1490 as a treatment alternative to tricyclic antidepressants and benzodiazepines in anxiety disorders, with proven long-term efficacy and none of the tolerance problems associated with tricyclics and benzodiazepines.
[Psychosomatic dysfunctions in the female climacteric. Clinical effectiveness and tolerance of Kava Extract WS 1490].
Within the framework of a randomized, placebo-controlled double-blind study, two groups each containing 20 patients with climacteric-related symptomatology were treated for a period of 8 weeks with kava WS 1490 extract 3 X 100 mg/day or a placebo preparation. The target variable - the HAMA overall score of anxiety symptomatology - revealed a significant difference in the drug-receiving group vis-à-vis the placebo group already after only 1 week of treatment. The course of such further parameters as depressive mood (DSI), subjective well-being (patient diary), severity of the disease (CGI), and the climacteric symptomatology (Kuppermann Index and Schneider scale) over the overall period of treatment demonstrate a high level of efficacy of kava extract WS 1490 in neurovegetative and psychosomatic dysfunctions in the climacteric, associated with very good tolerance of the preparation.
Options:
A: Kava extract was found to be ineffective in reducing anxiety symptoms compared to placebo.
B: Kava extract was found to be effective in reducing anxiety symptoms compared to placebo, with significant improvements noted.
C: Kava extract was found to be effective in reducing anxiety symptoms compared to placebo, but it was associated with severe and frequent adverse events.
D: Kava extract was found to be effective in reducing anxiety symptoms compared to placebo, but no conclusions could be drawn about its safety. | B |
256 | 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 and safety of amantadine therapy (monotherapy or adjuvant therapy) compared to placebo in treating people with idiopathic Parkinson's disease? Please answer this question based on the information provided below:
Long-term evaluation of amantadine and levodopa combination in parkinsonism by double-blind corssover analyses.
Twenty-three patients with Parkinson's disease participated in long-term, double-blind evaluations of the effectiveness and side effects of amantadine in combination with levodopa therapy. Sixteen patients completed the year-long study, which consisted of randomized crossover of amantadine and placebo before levodopa was begun and again after 5 and 11 months of continuous levodopa therapy. Initially, 16 of 23 patients (70 percent) had a favorable response to amantadine during the first crossover period. After 1 year of levodopa, at least eight of 16 patients (50 percent) responded favorably to amantadine compared with placebo. Some of the amantadine responders previously had been nonresponders, and vice versa. The response to amantadine was quantitatively similar in the responders even after the patients had been receiving levodopa therapy. Amantadine should be tried as a therapeutic agent in addition to levodopa for parkinsonism if more beneficial effect is desired, even if amantadine was previously ineffective in the same patient.
The effect of adding amantadine to optimum L-dopa dosage in Parkinson's syndrome.
Amantadine and a fixed combination of levodopa and carbidopa in the treatment of Parkinson's disease.
Forty-two patients with Parkinson's disease were given amantadine HC1 (Symmetrel) and placebo in an 18 week double-blind cross-over study to determine if amantadine provided additional benefit when combined with levodopa and carbidopa (Sinemet). Analysis of our results showed that amantadine effected a 92% improvement over baseline in symptom scores and a 95% improvement over baseline in activity impairment scores, compared with corresponding values of 4% and 18% for placebo. The difference between amantadine and placebo was statistically significant. Except for one case of mild livedo reticularis and two of blurred vision in the amantadine group, side effects were generally similar for amantadine and placebo in type and frequency. This study provides new evidence of the importance of combinations of antiparkinson drugs to achieve maximum therapeutic benefit.
Double blind study using amantadine hydrochloride in the therapy of Parkinson's disease.
A qualitative and quantitative evaluation of amantadine in the treatment of Parkinson's disease.
Amantadine and levodopa in the treatment of Parkinson's disease.
Options:
A: Amantadine therapy was found to be significantly more effective and safer than placebo.
B: There was insufficient evidence to determine the efficacy and safety of amantadine therapy compared to placebo.
C: Amantadine therapy was found to be less effective and had more side effects than placebo.
D: Amantadine therapy showed some effectiveness but had severe side effects. | B |
257 | 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 options have been evaluated for addressing the physical components of sexual dysfunction in women following pelvic radiotherapy, and what is the strength of the evidence supporting these treatments? Please answer this question based on the information provided below:
Use of topical benzydamine in gynecology.
To evaluate the topical anti-inflammatory activity of benzydamine when used as 0.1% solution for vaginal douche, a double blind, parallel group, randomized clinical trial was carried out on 30 patients with vaginitis following internal radiotherapy for carcinoma of the uterus. The patients were divided into 3 groups, one being treated with 0.1% benzydamine plus tricetol as preservative, one with 0.1% benzydamine alone, and one with placebo. Treatment began 12-24 hours after radiotherapy. Benzydamine was found to be significantly superior to placebo in its overall topical anti-inflammatory activity both after 5 and 15 days of treatment. Tricetol did not interfere with the therapeutic effect of benzydamine.
Prevention of vaginal stenosis in patients following vaginal brachytherapy.
The assessment of patients following intracavitary irradiation administered as part of the treatment of gynaecological malignancy reveals vaginal stenosis in the majority. Vaginal dilators are available for daily insertion in an attempt to prevent the formation of adhesions. However, the design of the dilator neglects the fact that the vagina is the most distensible in the upper third and hence many patients develop stenosis of the upper vagina. Many clinicians have abandoned the use of dilators and instead advise patients to have sexual intercourse to prevent the problem. In 1994, we designed a new vaginal stent, which was given to all patients who had received intracavitary irradiation with full instructions about its use. This stent was designed to suit better the true anatomy of the vagina and hence, with correct use, should prevent vaginal stenosis. A retrospective study was undertaken to look at the incidence of vaginal stenosis and this was compared with the incidence in patients using the new stent. The study revealed that 57% of the patients who were advised to have sexual intercourse had stenosis, whereas 11% of the patients using the stent had evidence of stenosis, which, however, was related to their incorrect use of the stent. In those who used the stent correctly there was no evidence of vaginal stenosis. Details of the design of the stent and the problems relating to those who used the stent incorrectly are presented. The findings of this study strongly support the continued use of this vaginal stent in patients who have undergone intracavitary irradiation as a means of preventing this common complication.
Postirradiation vaginitis. An evaluation of prophylaxis with topical estrogen.
Topical benzydamine in the treatment of vaginal radiomucositis.
Radiotherapy for invasive cervical cancer involves a high risk of local complications. Classically, the critical structures are the rectum, the bladder and the bony ring of the pelvis. However, endocavitary curietherapy is an important component in the radiological treatment since it delivers the highest dose to the vaginal mucosa. The anti-inflammatory efficacy of benzydamine in gynaecology, already well documented, was investigated in our controlled clinical study (benzydamine vs. placebo) involving 32 consecutive unselected patients treated by endocavitary curietherapy with 137caesium sources, alone, after radical surgery, or in association with megavoltage external irradiation. In the group with topical benzydamine, we have observed a statistically significant improvement of subjective symptomatology and colposcopic view. On the contrary in the placebo group a worsening of all the clinical parameters considered became evident.
Options:
A: Topical oestrogens and benzydamine have strong evidence for treating acute radiation vaginal changes, while vaginal dilators have moderate evidence for preventing vaginal stenosis. Hyperbaric oxygen therapy and surgical reconstruction have weak evidence.
B: Topical oestrogens and benzydamine have weak evidence for treating acute radiation vaginal changes, while vaginal dilators have strong evidence for preventing vaginal stenosis. Hyperbaric oxygen therapy and surgical reconstruction have moderate evidence.
C: Topical oestrogens and benzydamine have moderate evidence for treating acute radiation vaginal changes, while vaginal dilators have weak evidence for preventing vaginal stenosis. Hyperbaric oxygen therapy and surgical reconstruction have strong evidence.
D: Topical oestrogens and benzydamine have weak evidence for treating acute radiation vaginal changes, while vaginal dilators have moderate evidence for preventing vaginal stenosis. Hyperbaric oxygen therapy and surgical reconstruction have strong evidence. | A |
258 | 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 relative effectiveness of different methods of closed reduction for treating displaced fractures of the distal radius in adults? Please answer this question based on the information provided below:
Closed reduction of colles fractures: comparison of manual manipulation and finger-trap traction: a prospective, randomized study.
BACKGROUND: An optimal outcome of closed treatment of a Colles fracture may depend on accurate reduction and adequate immobilization. It has been suggested that the use of finger-trap traction results in a better reduction and a lower rate of redisplacement than manual manipulation does, but to our knowledge these concepts have never been evaluated scientifically. We compared these two methods in a prospective, randomized controlled trial.
METHODS: Two hundred and twenty-three patients with 225 displaced Colles-type fractures were randomized to treatment with closed reduction with either finger-trap traction (112 patients) or manual manipulation (111 patients). The fractures were assessed radiographically by measurement of the radial angle, dorsal tilt, and radial shortening before reduction, immediately after reduction, and at one and five weeks after reduction.
RESULTS: The groups were comparable with regard to age, sex, side of injury, fracture grade, and amount of displacement at presentation. No significant differences were found between the alignment of the fractures in the two treatment groups at any time. With dorsal tilt of <10 degrees and radial shortening of <5 mm considered acceptable, the two techniques both produced an 87% rate of satisfactory reductions. However, the percentages of fractures in an acceptable alignment were only 57% and 50% at one week after finger-trap traction and manual manipulation, respectively, and only 27% and 32% at five weeks. The failure rates did not differ significantly between the two groups.
CONCLUSIONS: The two methods of fracture reduction did not differ with regard to the eventual position of the fracture or the rate of failure. Although closed reduction was successful for the majority of fractures, most redisplaced substantially during the period of cast immobilization.
[Reposition of Colles' fracture--a new, more rapid, simpler and cheaper method].
Neurological complications of dynamic reduction of Colles' fractures without anesthesia compared with traditional manipulation after local infiltration anesthesia.
To investigate whether or not injection of local anesthetic into the fracture hematoma on reduction of a Colles' fracture increases the risk of neurological complications, a prospective randomized trial was conducted. The outcome in 62 patients whose Colles' fractures were reduced in a new bone-alignment device without anesthesia was compared with that in 54 patients with Colles' fractures that were reduced manually after injection of local anesthetic. At follow-up, any symptoms and signs of nerve damage were recorded. Four cases of such damage were noted in the group treated without local anesthesia, as opposed to 14 in the group in which a local anesthetic was used. The difference is significant (p less than 0.01). The authors have previously shown that injection of local anesthetic into the hematoma of Colles' fractures increases the carpal tunnel pressure. Neurological complications after the use of local anesthesia in reducing Colles' fractures is considered to be secondary to the scarring and fibrosis caused by this increase in pressure.
Reduction of Colles' fractures without anaesthesia using a new dynamic bone alignment system.
Two techniques for reduction of Colles' fractures were compared in a prospective, randomized study. With use of a newly designed dynamic bone alignment device, reduction manoeuvres were performed on 62 patients with Colles' fractures (group A) without any form of anaesthesia. In a control group of 54 patients (group B) Colles' fractures were reduced manually in the traditional way using local infiltration anaesthesia. In each group the pain experienced by the patients was recorded. Severe pain during the reduction was reported by 8 per cent of the patients in group A and by 35 per cent of those in group B. No complications occurred during or after dynamic reduction without anaesthesia. This method of treatment seems to be a very gentle one for the patients, with the advantage of causing less pain than treatment under local anaesthesia.
Options:
A: Mechanical reduction using finger trap traction is significantly more effective than manual reduction in anatomical outcomes.
B: Manual reduction under intravenous regional anaesthesia is significantly more effective than a novel method of manual reduction where the patient actively provides counter-traction.
C: There is insufficient evidence to establish the relative effectiveness of different methods of closed reduction.
D: Mechanical reduction involving a special device without anaesthesia is significantly more effective than manual reduction under haematoma block. | C |
259 | 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 splints/orthoses in the treatment of rheumatoid arthritis on pain, grip strength, and function? Please answer this question based on the information provided below:
Can foot orthoses prevent hallux valgus deformity in rheumatoid arthritis? A randomized clinical trial.
Hallux valgus deformity is the most commonly observed forefoot deformity in patients with rheumatoid arthritis. This 5-year, double-blind, randomized clinical trial compared treatment orthoses with placebo orthoses for the prevention of hallux valgus deformity in the rheumatoid arthritic foot.One hundred and two subjects with active rheumatoid arthritis and with foot pain and minimal radiographic changes of the feet participated in the study. They were recruited from five arthritis clinics in the Chicago metropolitan area that are affiliated with or are teaching clinics of area medical schools. Patients were followed for 3 years.Eighty-one subjects completed the study. In a logistic regression analysis, the treatment group was 73% less likely to develop hallux valgus deformity compared with the control group (adjusted odds ratio 0.27, 95% confidence interval 0.078, 0.916 p = .04). These findings suggest that foot orthoses can prevent or slow the progression of hallux valgus deformity.
Soft versus hard resting hand splints in rheumatoid arthritis: pain relief, preference, and compliance.
OBJECTIVES: This study compared soft versus hard resting hand splints on pain and hand function in 39 persons with rheumatoid arthritis. Splint preference was also evaluated to determine its effects on splint wear compliance.
METHOD: A repeated measures research design was used to compare the two experimental conditions, wearing a soft splint versus a hard splint on the dominant hand for 28 days at night only, and an unsplinted control period of 28 days.
RESULTS: Arthritis pain was considerably less during both splinted periods when compared with the pretest. Subjects identified fewer joints as being painful during the soft splint condition than during the unsplinted condition. There were no significant differences among conditions on hand function measures. Splint preference was 57% for the soft splint, 33% for the hard splint, and 10% for no splint. Splint wear compliance was significantly better with the soft splint (82%) than with the hard splint (67%).
CONCLUSION: The findings indicate that resting hand splints are effective for pain relief and that persons with rheumatoid arthritis are more likely to prefer and comply with soft splint use for this purpose. Individualized splint prescription that focuses on client comfort and preference may enhance splint wear compliance.
Metatarsalgia and rheumatoid arthritis--a randomized, single blind, sequential trial comparing 2 types of foot orthoses and supportive shoes.
OBJECTIVE: To compare the effects of semi-rigid and soft orthoses worn in supportive shoes, and supportive shoes worn alone, on metatarsal phalangeal (MTP) joint pain. MTP joint synovitis, and lower extremity function in patients with rheumatoid arthritis.
METHODS: Twenty-eight subjects referred to occupational therapy received in random order 3 interventions for 12 week trials, separated by 2 week washouts. A crossover design compared effectiveness of interventions.
RESULTS: Twenty-four subjects completed the study. A reduction in mean pain scores from baseline to final visits showed that semi-rigid orthoses had a highly significant effect on pain. Soft orthoses did not show a significant effect on pain from baseline to final visit, nor did shoes worn alone. None of the interventions had a significant effect on synovitis or function.
CONCLUSION: Semi-rigid orthoses worn in supportive shoes were an effective treatment for metatarsalgia. Supportive shoes worn alone or worn with soft orthoses did not provide pain relief for metatarsalgia.
Impacts of foot orthoses on pain and disability in rheumatoid arthritics.
Rheumatoid arthritis (RA) frequently causes foot pain and swelling that affect ambulation. Pharmaceutical management of pain and disability is standard in clinical practice. The use of functional posted foot orthoses, as an adjunct to pharmaceutical treatment, is a promising treatment for managing foot pain and disability in RA. Its effectiveness, however, has not been rigorously evaluated. We performed a double-blind clinical trial using foot orthoses vs. placebo orthoses in the management of the rheumatoid arthritic foot, while subjects continued customary treatment. On the basis of findings of no effect on disability and pain measures, this study indicates no benefit of functional posted foot orthoses over placebos.
Use of resting splints by patients with rheumatoid arthritis.
A follow-up evaluation of 50 patients with rheumatoid arthritis who were fitted with full bilateral wrist and hand resting splints revealed that 62 percent wore them most or all of the prescribed time. Patients deviated from the prescribed splint program when their symptoms remitted or diminished, and adhered more closely to the program when they experienced persistent inflammation. Patients splinted during a hospital stay were somewhat more compliant than those splinted as outpatients. Patients judged to be noncompliant discontinued splint usage because of a decrease of joint pain or stiffness, or both. Their decision did not appear detrimental, since, during the course of the study, there was no significant difference between compliant and noncompliant patients in range of motion of hand or wrist joints at followup evaluation and, when range of motion at the time of initial evaluation was compared with that at the follow-up examination, a higher proportion of noncompliant (37%) than compliant patients (16%) showed improvement.
Effect of the arthritis health professional on compliance with use of resting hand splints by patients with rheumatoid arthritis.
This study examined the effects of an occupational therapist's approach during the initial splinting session on the subsequent use of resting hand splints by patients with rheumatoid arthritis. Forty subjects were randomly assigned either to a standard treatment (control) group or to a compliance-enhancement (experimental) group, for whom the use of learning principles, sharing of expectations, use of a positive affective tone and behaviors by the therapist, and the assumption of responsibility by the patient were emphasized. During the 28-day period after splinting, patients in the experimental and control groups wore their splints an average of 23.3 and 18.1 days, respectively (p = 0.056). Nine subjects in the experimental group, but only four in the control group used their splints every day (p = 0.035). Knowledge of splint use correlated with actual use, regardless of the group assignment (p = 0.035). Change in the amount of wrist and hand pain was not significant in either group; however, the experimental group experienced a decrease in the duration of morning stiffness (p = 0.013). This intervention provides health professionals with a pragmatic and effective method to enhance compliance.
Off-the-shelf orthopedic footwear for people with rheumatoid arthritis.
OBJECTIVES: To assess the effectiveness of off-the-shelf orthopedic footwear for people with rheumatoid arthritis (RA) reporting chronic foot pain, in terms of self-reported pain and physical function, as well as objectively measured gait variables using an electric footswitch walkway.
METHODS: A small, randomized, controlled trial followed by a larger repeated measures analysis was used.
RESULTS: The control group (n = 15) demonstrated no significant changes over a 2-month period in pain, physical function, or gait scores. In contrast, after supply of the footwear both the original footwear group (n = 15) and the control group demonstrated significant improvements, with small to large effect sizes, in weight-bearing pain scores, physical function, gait velocity, and gait stride length without increases in use of arthritis medications or walking aids.
CONCLUSION: These data suggest that off-the-shelf orthopedic footwear is beneficial for people with RA even when subjects were unselected on basis of age, sex, disease duration, or disability as measured by the Stanford Health Assessment Questionnaire.
Use of commercially produced elastic wrist orthoses in chronic arthritis: a controlled study.
OBJECTIVE: To examine the efficacy of wrist orthoses on pain, motion, and function of the wrist.
METHODS: Consecutive patients were randomized to a treatment group using wrist orthoses or to a control group using no wrist orthoses, in a prospective, controlled, 6-month study.
RESULTS: Changes in wrist joint variables and general disease activity variables were not statistically different between the orthosis group (n = 36) and the control group (n = 33). Patients in the orthosis group had 25% and 12% improvements in grip strength and pinch grip and 50% reduction in pain while using the wrist orthosis.
CONCLUSION: Use of wrist orthoses improves function and reduces pain, but has no effects after 6 months, compared to a control group, on measures of local or general disease activity.
Elastic wrist orthoses. Reduction of pain and increase in grip force for women with rheumatoid arthritis.
The aim of this study was to investigate effects of elastic wrist orthoses on pain, grip strength, and function. Twenty-two women with seropositive rheumatoid arthritis (mean age, 53 years) registered their pain on a visual analogue scale both with and without orthosis on the wrist of the dominant hand in three standardized activities of daily living (ADL) situations. Grip force at onset of pain was measured on an electronic instrument (Grippit) with three different grips. Pain was decreased by 39%, 42%, and 52% when using an orthosis in the three ADL situations. Anecdotally, the women noted that the splints provided support and decreased pain both in home, at work, and during leisure activities. Orthoses improved grip force at onset of pain by 26%, 22%, and 29%. All subjects showed reduced strength (20%-25%) when compared to grip strength in a group of women without rheumatoid arthritis.
The effect of a static wrist orthosis on hand function in individuals with rheumatoid arthritis.
OBJECTIVE: To determine the effect of a wrist orthosis on work performance, hand dexterity, and pain during task performance, 40 individuals with rheumatoid arthritis were studied using a 2 period, crossover design.
METHODS: Each patient was fitted with a Futuro wrist orthosis. Dexterity was measured with and without the orthosis using the Jebsen Hand Function Test. Work performance was assessed using 2 tasks (one simulating the use of shears, the other the use of a screwdriver) on a work simulator. All tasks were performed both with and without the orthosis, with the order of orthosis versus no orthosis randomly assigned. Pain before and after performing tasks was assessed using a 10 cm horizontal visual analog scale.
RESULTS: While on the screwdriver task work performance was less with the orthosis (p = 0.0002); on the shears task there was no significant difference in work performance with and without the orthosis. The average pain after performing both tasks was significantly less with the orthosis on. A 2 factor analysis of variance model with repeated measures suggested that taking into account the reduced work performance during splint wear, pain was still significantly reduced with splint wear. The average time to complete all 7 tasks on the Jebsen Hand Function Test was longer when the subjects wore the splint compared to when they did not (62.0 vs 57.6 s, respectively; p = 0.0086).
CONCLUSION: The results suggest that the effect of splint wear on work performance is highly task specific, and thus the ergonomic demands of the individual's daily life must be considered if a splint is to provide maximal effectiveness.
Evaluation of the effectiveness of a metacarpophalangeal ulnar deviation orthosis.
Rheumatoid arthritis (RA) causes structural damage that precipitates joint deformity, including metacarpophalangeal (MCP) joint ulnar drift (UD). Orthoses have been designed in order to maintain hand function by improving joint alignment, restoring biomechanical balance and reducing stress on supporting diseased tissues. This study investigated the impact an MCP UD (MUD) splint had on: pain, hand function, grip strength, and passive correction of UD when worn for function by RA patients. Twenty seven hands (26 subjects) were evaluated and performances compared with and without the splint. Results showed anatomic alignment improved significantly in all except the index finger. The mean difference for all fingers combined was 10 degrees. Observable correction of subluxation was identified from x-ray film and noted in 14.8% of index fingers, 18.5% of middle fingers, 33.3% of ring fingers, and 48.1% of little fingers. Three point pinch showed a statistically significant change, the mean difference being an improvement of 15% while wearing the splint. There was no significant change in hand function score, pain score, gross grip strength, and lateral pinch. Subjects' perceptions of the MUD splint gained from a questionnaire showed a high acceptance: 79.2% reporting minimal interference in ADL, 95.8% satisfied with cosmesis, 87.5% satisfied with comfort, and 95.8% reported continued use of the orthosis.
Immediate and short-term effects of three commercial wrist extensor orthoses on grip strength and function in patients with rheumatoid arthritis.
OBJECTIVE: To investigate the immediate and short-term effects of 3 commercial wrist orthoses on grip strength and function.
METHODS: Thirty-six patients with definite rheumatoid arthritis participated in the randomized, controlled, cross-over design study of 3 commercial wrist extensor orthoses. Dominant-hand dynamometric grip strength was assessed at both initial and followup sessions while splinted and nonsplinted. Functional impact was assessed using a written questionnaire.
RESULTS: All 3 commercial orthoses reduced grip strength when first donned. After a 1-week adjustment period, one orthosis, the Smith and Nephew Roylan D-Ring (Roylan), afforded splinted grip strength equal to that of the nonsplinted grip strength. The other 2 orthoses continued to reduce grip strength, and afforded splinted grip strength significantly below that of the Roylan. The Roylan was deemed comfortable by more subjects than the other orthoses.
CONCLUSIONS: The belief that commercial orthotic use increases grip strength, either immediately or after 1 week, is not supported by this study's data. Different styles of commercial wrist orthoses appear to have differing influence on splinted grip strength.
Finger dexterity and hand function: effect of three commercial wrist extensor orthoses on patients with rheumatoid arthritis.
OBJECTIVE: To investigate the effect of 3 commercial wrist orthoses on finger dexterity and hand function of patients with rheumatoid arthritis (RA).
METHODS: Forty-two patients with definite RA participated in the cross-over study comparing 3 styles of commercial wrist orthoses. Finger dexterity and hand function of the dominant hand were assessed while splinted and unsplinted, at the initial session and after 1 week of intermittent orthosis use. Finger dexterity was assessed using two subtests from the Purdue Pegboard Test (Purdue) and hand function was assessed using the Jebsen-Taylor Hand Function Test (Jebsen-Taylor).
RESULTS: Both finger dexterity and hand function were reduced by splinting; men and women were affected similarly. There was no difference in finger dexterity or hand function afforded by the 3 orthoses. Results on both the Purdue and Jebsen-Taylor tests showed a significant learning effect across time.
CONCLUSIONS: The 3 commercial wrist orthoses studied reduce dexterity similarly and significantly. When commercial wrist orthoses are to be used during tasks that require maximum dexterity, this reduction should be weighed against the known benefits of splinting.
Commercial wrist extensor orthoses: a descriptive study of use and preference in patients with rheumatoid arthritis.
OBJECTIVE: To describe patients' functional uses of 3 commercial wrist orthoses, to describe patients' preference patterns for the orthoses, and to clarify orthotic attributes that are viewed positively and negatively.
METHODS: Using a cross-over design, 42 patients with definite rheumatoid arthritis used each of 3 commercial orthoses for one week. There was a one-week wash-out between each week of use. At the end of the study, private semi-structured interviews were conducted with each participant. Data from close-ended questions were tabulated. Open-ended data were analyzed using qualitative methods.
RESULTS: Patients reported that the 3 commercial wrist orthoses reduced wrist pain similarly, but that comfort and a sense of security during functional tasks were only found if the orthoses were comfortable and well-fitting. Most subjects preferred the padded, short forearm orthosis, though a small number found it uncomfortably warm, and many complained that it was difficult to use when wearing long-sleeved garments. Common complaints about the two elastic orthoses included chafing at the thumb webspace and chafing at the proximal closures. Longer forearm length was often perceived as providing unnecessarily high levels of wrist support.
CONCLUSIONS: No single orthosis suited all subjects. Satisfaction with an orthosis appears to be based not only on its therapeutic effect, but also the comfort and ease of its use. To maximize patient satisfaction and improve the likelihood of appropriate fit and comfort, several styles of commercial orthoses should be available. The current trend toward restricted clinic stocks appears contrary to both therapeutic goals and patient satisfaction.
Splinting in the treatment of arthritis of the first carpometacarpal joint.
Although much has been written about surgical treatment of arthritis of the first carpometacarpal joint, no literature exists on splinting as a conservative treatment. One hundred fourteen patients (130 thumbs) were retrospectively reviewed to determine the efficacy of splinting. Patients were grouped according to their stage of disease and whether they had carpometacarpal joint surgery. Seventy-six percent of patients with stage I and II disease and 54% of patients with stage III and IV disease had improvement in their symptoms with splinting. There was no significant difference in the degree of improvement between the 2 groups. All patients who had initial improvement in their symptoms with splinting had between 54% and 61% average improvement in symptom severity 6 months after splinting. All groups were found to be equally tolerant of the splinting protocol and no group had a significantly higher rate of activity modification. Overall, splinting was found to be a well-tolerated and effective conservative treatment to diminish, but not completely eliminate, the symptoms of carpometacarpal joint arthritis and inflammation.
A comparison of the Futuro wrist orthosis with a synthetic ThermoLyn orthosis: utility and clinical effectiveness.
OBJECTIVE: To compare the short-term utility and clinical effectiveness of the commercial-made Futuro wrist orthosis with a newly developed, custom-made ThermoLyn wrist orthosis.
METHODS: Using a randomized cross-over trial, 10 patients with rheumatoid arthritis used each of the two orthoses for two weeks. Outcome measures were patients' judgments with respect to different statements about utility and clinical assessments including pain and swelling of the wrist and finger joints, range of motion of the wrist, and grip strength. At the end of the study the patients were asked which of the two orthoses they preferred and why.
RESULTS: Patients tended to favor the Futuro wrist orthosis with respect to pain relief and to handling the orthosis. The visual analog scale score of the appearance of the ThermoLyn wrist orthosis was a little higher than that of the Futuro wrist orthosis, but the difference was not statistically significant. Clinical parameters such as pain in the wrist, swelling of the wrist and finger joints, and movements of the wrist showed that the Futuro orthosis tended to be more effective than the ThermoLyn orthosis. None of the differences reached statistical significance. At the end of the study, 5 patients preferred the Futuro and 5 patients the ThermoLyn wrist orthosis. Arguments in favor of the ThermoLyn orthosis were better hygiene, stability, and no need to remove the orthosis during dirty and wet conditions. Arguments in favor of the Futuro orthosis were greater suppleness and freedom of movement.
CONCLUSIONS: The ready-made fabric Futuro wrist orthosis appears to be as good as the more expensive individually made synthetic ThermoLyn wrist orthosis with respect to short-term utility and clinical effectiveness. The conditions under which the orthosis will be worn will help to decide which orthosis is the best for the patient. In the event that the patient wants to use the orthosis in wet and dirty conditions, the ThermoLyn wrist orthosis is a good alternative to the Futuro wrist orthosis.
Options:
A: Working wrist splints significantly decrease grip strength but do not affect pain or quality of life; resting hand and wrist splints do not change pain or grip strength but are preferred by patients; extra-depth shoes and insoles decrease pain on weight-bearing activities.
B: Working wrist splints significantly increase grip strength and reduce pain; resting hand and wrist splints significantly reduce pain and improve grip strength; extra-depth shoes and insoles have no effect on pain.
C: Working wrist splints have no effect on grip strength or pain; resting hand and wrist splints significantly reduce pain and improve grip strength; extra-depth shoes and insoles increase pain on weight-bearing activities.
D: Working wrist splints significantly decrease grip strength and increase pain; resting hand and wrist splints significantly increase pain and reduce grip strength; extra-depth shoes and insoles have no effect on pain. | A |
260 | 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 outcomes of early treatment versus deferred treatment in patients with early stage multiple myeloma? Please answer this question based on the information provided below:
Initial versus deferred melphalan-prednisone therapy for asymptomatic multiple myeloma stage I--a randomized study. Myeloma Group of Western Sweden.
From October 1983 until December 1988, 50 patients with asymptomatic multiple myeloma stage I were included in a prospective randomized multi-centre study comparing melphalan-prednisone (MP) therapy started at the time of diagnosis with deferred therapy where MP was started at the time of disease progression. Twenty-five patients were randomized to each group. The median time from diagnosis to start of therapy in the group with deferred therapy was 12 months. The reasons for starting therapy were increasing M-protein in 8 cases, symptomatic bone disease in 9 and anaemia in 5. In 2 cases, disease progression was complicated by vertebral fractures necessitating radiotherapy. Two patients in the group in which MP was started at the time of diagnosis developed acute leukaemia. No differences in response rate, response duration or survival were observed between the treatment groups. We conclude that in asymptomatic myeloma deferral of chemotherapy is feasible in well-informed and well-controlled patients but conveys no advantage in survival. In clinical practice the benefits of treatment deferral are to some extent outweighed by disease progression before start of treatment.
Treatment of multiple myeloma according to the extension of the disease: a prospective, randomised study comparing a less with a more aggressive cystostatic policy. Cooperative Group of Study and Treatment of Multiple Myeloma.
The purpose of the study was to ascertain whether the prognostic significance of staging in multiple myeloma (MM) is influenced by the aggressiveness of effective induction treatment and/or by continuing or discontinuing maintenance chemotherapy. Patients with untreated stage I MM (defined according to Durie and Salmon) were randomised between being followed without cytostatics until the disease progressed and receiving six courses of melphalan and prednisone (MP-P) just after diagnosis; stage II patients were uniformly treated with MPH-P and stage III patients were randomised between MPH-P and four courses of combination chemotherapy with Peptichemio, vincristine and prednisone (PTC-VCR-P). Within each stage, responsive patients were randomised between receiving additional therapy only until maximal tumour reduction was reached (plateau phase) and continuing induction therapy indefinitely until relapse. With resistant, progressive or relapsing disease, patients originally treated with MPH-P for induction received combination chemotherapy and vice versa. The overall first response rate was 43.8% (42.2% in 206 stage I, II and III patients treated with MPH-P and 48.0% in 75 stage III patients treated with combination chemotherapy, P = NS). Combination chemotherapy was more myelotoxic than MPH-P and, in particular, caused more non-haematological side-effects. Both the less and the more aggressive induction policies gave the same disease control. Progression of disease was statistically similar in stage I patients who were initially left untreated and in t hose who received MPH-P just after diagnosis; median duration of first response was similar in stage III patients receiving MPH-P and in those on combination chemotherapy. In all stages, discontinuing or continuing maintenance did not alter the median duration of first response. The overall second response rate was 28.5% (34.0% to MPH-P and 25.3% to combination chemotherapy, P = NS). Median survival was greater than 78 months in stage I, was 46.3 months in stage II and was 24.3 months in stage III patients, still independent of both induction and post-induction policies. In MM, the significance of staging for survival is independent of both the aggressiveness of induction and of continuing or discontinuing maintenance chemotherapy after the maximal tumor reduction has been achieved. Both MPH-P and and the association of PTC, VCR and P are effective in inducing first response and also second response in patients failing on the alternative regimen, but PTC-VCR-P causes more side effects. Thus, the overwhelming majority of patients with MM can safely be given MPH-P as first therapy, and this treatment may be delayed in early diseases.
Long-term survival of stage I multiple myeloma given chemotherapy just after diagnosis or at progression of the disease: a multicentre randomized study. Cooperative Group of Study and Treatment of Multiple Myeloma.
We conducted a randomized trial to evaluate whether melphalan-prednisone (MPH-P) treatment administered just after diagnosis improves survival of stage I multiple myeloma (MM). Between January 1987 and March 1993, 145 consecutive previously untreated patients with stage I MM were randomized between treatment with MPH-P (administered for 4 days every 6 weeks) just after diagnosis and treatment only at disease progression. Survival was not influenced by MPH-P treatment either administered just after diagnosis or at disease progression (64 vs 71 months respectively). Comparing the first with the second group the odds ratio of death is 1.17 (95% confidence interval 0.57-2.42; P = 0.64). Disease progression occurred within a year in about 50% of patients who were initially untreated. Response rate was similar in both groups, but duration of response was shorter in patients who were treated at disease progression (48 vs 79 months, P = 0.044). Patients actually treated at disease progression (34/70) survived shorter than those who had neither disease progression nor treatment (56 vs > 92 months; P = 0.005). Starting MPH-P just after diagnosis does not improve survival and response rate in stage I MM, with respect to deferring therapy until disease progression. However, patients with stage I MM randomized to have treatment delayed and who actually progressed and were treated had shorter survival than those with stable disease and no treatment. Biologic or other disease features could identify these subgroups of patients.
Options:
A: Early treatment significantly reduces mortality compared to deferred treatment.
B: Early treatment significantly delays disease progression compared to deferred treatment.
C: Early treatment significantly improves response rate compared to deferred treatment.
D: Early treatment significantly reduces the risk of acute leukemia compared to deferred treatment. | B |
261 | 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 has been found to be most effective for severe ocular mucous membrane pemphigoid based on limited evidence from small trials? Please answer this question based on the information provided below:
Cicatricial pemphigoid.
Cicatricial pemphigoid.
Options:
A: Prednisone
B: Dapsone
C: Cyclophosphamide
D: No treatment has been found to be effective | C |
262 | 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 asthma self-management education programs for adults? Please answer this question based on the information provided below:
A randomized trial of peak-flow and symptom-based action plans in adults with moderate-to-severe asthma.
OBJECTIVE: Peak flow meters (PFM) continue to be recommended as an important part of asthma self-management plans. It remains unclear if there is an advantage in using PFM in people with moderate-to severe asthma who are not poor perceivers of bronchoconstriction.
METHODOLOGY: Prospective, randomized controlled trial of 134 adults with moderate-to-severe asthma who did not have evidence of poor perception of bronchoconstriction on histamine challenge testing, who were recruited from inpatients and outpatients of a university teaching hospital. Comparison was made over 12 months of the effectiveness of written action plans using either peak flow monitoring or symptoms to guide management. Subjects were contacted at monthly intervals by telephone for reinforcement and evaluation of use of the action plans, and to provide ongoing education. Spirometry and PD20 histamine were measured at 3-monthly intervals. Measures of health care utilization and morbidity (asthma exacerbations; hospitalizations; emergency department (ED) visits; days absent from work or school due to asthma; medication use and a self-rating of asthma severity) were made monthly. A psychosocial questionnaire (attitudes and beliefs, state-trait anxiety, denial) was given at entry and at 12-months or at withdrawal from the study.
RESULTS: There were significant improvements for both groups for hospitalizations, ED visits, days off from school or work, and PD20 histamine, but no between-group differences. Appropriate use of action plans was 85% in the symptoms group and 86% in the PFM group. For all subjects, those who subsequently had an ED visit had significantly higher levels of denial (P=0.04) and lower scores for self-confidence (P=0.04), compared to those who did not have an ED visit.
CONCLUSIONS: Use of written action plans, combined with regular contact to reinforce self-management, improved airway reactivity and reduced health care utilization. However, use of PFM was not superior to symptom-based plans.
A controlled assessment of an asthma self-management plan involving a budesonide dose regimen. OPTIONS Research Group.
Our aim was to assess the efficacy of budesonide (Pulmicort Turbohaler Astra) used as part of a self-management plan in a group of patients with chronic asthma. One hundred and twenty five patients with nocturnal asthma symptoms, despite the use of inhaled prophylactic and beta 2-agonist therapy, were randomized to inhaled budesonide 200, 400 or 800 micrograms b.i.d. either with dose adjustments made by the physician, i.e. doctor-managed (DM; n = 64), or as part of a self-management plan (SM; n = 61). The SM group were allowed to adjust their dose according to written guidelines based on morning peak flow. At the end of the 6 month treatment period, there were no significant differences detected between the DM and the SM groups either from the clinic or diary card data. Both groups demonstrated a significant reduction in the number of sleep-disturbed nights, by 75% in the DM group and 77% in the SM group, at the end of the study. In conclusion, for patients with mild-to-moderate asthma, either a doctor-adjusted dose regimen or a peak flow based self-management plan involving budesonide is equally efficacious. For some patients, a simple regimen, adjusted by the physician at clinic visits, may be easier to follow.
Evaluation of peak flow and symptoms only self management plans for control of asthma in general practice.
OBJECTIVE: To compare a peak flow self management plan for asthma with a symptoms only plan.
DESIGN: Randomisation to one of the self management plans and follow up for a year.
SETTING: Four partner, rural training practice in Norfolk.
SUBJECTS: 115 Patients (46 children and 69 adults) with asthma who were having prophylactic treatment for asthma and attending a nurse run asthma clinic.
MAIN OUTCOME MEASURES: The number of doctor consultations, courses of oral steroids, and short term nebulised salbutamol treatments and the number of patients who required doctor consultations, courses of oral steroids, and short term nebulised salbutamol.
RESULTS: Both self management plans produced significant reductions in the outcome measures but there were no significant differences in the degree of improvement between the groups. The results were similar for children and adults. The proportions of patients requiring a doctor consultation fell from 98% (50/51) to 66% (34/51) in the peak flow group and from 97% (62/64) to 53% (34/64) in the symptoms only group and the proportions requiring oral steroids from 73% (34/46) to 47% (21/46) and 52% (31/60) to 12% (7/60). The median number of doctor consultations was reduced from 8.0 to 2.0 in the peak flow group and from 4.5 to 1.0 in the symptoms only group.
CONCLUSIONS: The peak flow meter was not the crucial ingredient in the improved illness of the two groups. Teaching patients the importance of their symptoms and the appropriate action to take when their asthma deteriorates is the key to effective management of asthma. Simply prescribing peak flow meters without a system of self management and regular review will be unlikely to improve patient care.
Influence on asthma morbidity of asthma education programs based on self-management plans following treatment optimization.
The objective of this study was to evaluate the effectiveness of an asthma education program on morbidity, knowledge, and compliance with inhaled corticosteroid treatment using a prospective, randomized, controlled, one-year-before/one-year-after protocol. After rigorous optimization of asthma therapy under the care of respirologists, patients were assigned to one of three groups: Group C (control group: no formal education), Group P (education and action plan based on peak-flow monitoring), and Group S (education with action plan based on monitoring of asthma symptoms). A total of 188 subjects with moderate to severe asthma were enrolled and 149 completed the study. Asthma morbidity decreased significantly in all groups (p = 0.001). Mean values one-year-before/one-year-after in Groups C, P, and S were: unscheduled medical visits, 2.4/0.8, 2.3/0.7, and 1.9/ 0.7; hospitalizations, 0.21/0.04, 0.24/0.04, and 0.40/0.09; oral steroid treatments; 1.3/0.5, 1.2/0.7, and 1.3/0.9; absenteeism from work/school, 9.6/5.2, 8.8/2.2, and 6.3/2.9. Between-group differences did not reach statistical significance (p > 0.05). Asthma knowledge increased in both educated groups compared with the control group (p < 0.001) as did short-term compliance with inhaled corticosteroids. These results confirm that treatment optimization coupled with sustained high quality care in motivated patients can lead to a significant decrease in asthma morbidity. In such clinical settings, structured asthma education significantly improved short-term compliance with treatment and knowledge about asthma, although it could not add extra benefit with regard to morbidity. Nevertheless, this study does not refute the potential benefit of educational interventions aimed at improving asthma-related morbidity over a longer time period or in patients with less optimal care or with high-risk factors.
Influence of asthma education on asthma severity, quality of life and environmental control.
BACKGROUND: Several studies have examined the influence of asthma education, focusing mainly on the use of health services.
OBJECTIVES: To assess the influence of an asthma education program (AEP) on airway responsiveness, asthma symptoms, patient quality of life (QOL) and environmental control.
DESIGN: A prospective, randomized, controlled study with parallel groups.
SETTING: Three tertiary care hospitals in Quebec.
POPULATION: One hundred and eighty-eight patients with moderate to severe asthma.
INTERVENTION: After optimization of asthma treatment with inhaled corticosteroids, patients were randomly assigned to receive either an education program based on self-management (group E) or usual care (control group C).
RESULTS: One year after an AEP, there was a significant decrease in the number of days per month without daytime asthma symptoms in group E only (P=0.03). Asthma daily symptom scores decreased significantly in group E in comparison with group C (P=0. 006). QOL scores improved markedly in both groups after treatment optimization during the run-in period (P<0.01). After an AEP, the QOL score increased further in group E patients in comparison with group C patients (P=0.04). The concentration of methacholine that induces a 20% fall in forced expiratory volume in 1 s (PC20) improved significantly in both groups (group E 1.2+/-1.1 to 2.4+/-0. 2, group C 1.5+/-1.2 to 2.4+/-1.3, P<0.01). After one year, 26 of 37 patients from group E sensitized to house dust mites (HDM) adopted the specific measures recommended to reduce their exposure to HDM, while none of the 21 subjects from group C did (P<0.001). Among the patients sensitized to cats or dogs, 15% of patients from group E and 23% of patients in group C no longer had a pet at home at the final visit (P>0.5).
CONCLUSIONS: One year after the educational intervention, it was observed that the program had added value over and above that of optimization of medication and regular clinical follow-ups. The education program was highly effective in promoting HDM avoidance measures but minimally effective for removing domestic animals, suggesting that more efficient strategies need to be developed for the latter.
Evaluation of two different educational interventions for adult patients consulting with an acute asthma exacerbation.
Asthma education decreases the number of emergency visits in specific subgroups of patients with asthma. However, it remains unknown whether this improvement is related only to the use of an action plan alone or to other components of the educational intervention. A total of 126 patients consulting urgently for an acute asthma exacerbation were recruited; 98 completed the study. The first 45 patients were assigned to Group C (control; usual treatment). Thereafter, patients were randomized to either Group LE (limited education; teaching of the inhaler technique plus self- action plan given by the on call physician) or Group SE (same as group LE plus a structured educational program emphasizing self-capacity to manage asthma exacerbations). At baseline, there was no difference between groups in asthma morbidity, medication needs, or pulmonary function. After 12 mo, only Group SE showed a significant improvement in knowledge, willingness to adjust medications, quality of life scores, and peak expiratory flows. In the last 6 mo, the number of unscheduled medical visits for asthma was significantly lower in Group SE in comparison with groups C and LE (p = 0.03). The number (%) of patients with unscheduled medical visits also decreased significantly in Group SE compared with Groups C and LE (p = 0.02). We conclude that a structured educational intervention emphasizing self-management improves patient outcomes significantly more than a limited intervention or conventional treatment.
The effect of a peak flow-based action plan in the prevention of exacerbations of asthma.
STUDY OBJECTIVE: To determine the effect of a symptom-based and a peak flow-based action plan in preventing acute exacerbations in subjects with poorly controlled asthma.
DESIGN: A randomized controlled trial in which subjects who had required urgent treatment for their asthma were allocated to receive no action plan, a symptom-based plan, or a peak flow-based action plan.
SETTING: A university hospital asthma clinic.
POPULATION: One hundred fifty subjects were recruited after attending an emergency department or a clinic for urgent treatment of asthma.
INTERVENTIONS: All subjects received evaluation and education for asthma before being randomly allocated to receive no action plan, a symptom-based action plan, or a peak flowmeter and a peak flow-based action plan.
MEASUREMENTS: Subjects were assessed by questionnaire at 3 and 6 months after enrollment with questions relating to their asthma control and their need for urgent treatment or hospital admission for asthma.
RESULTS: At 6 months after enrollment, although all three intervention groups experienced improvement in their asthma control, there was a striking reduction in emergency department visits for asthma only in the peak flow-based action plan group (p=0.006). No significant difference in emergency visits was apparent between the symptom-based action plan and no action plan groups.
CONCLUSIONS: We conclude that a peak flow-based action plan is effective, at least in the short term, in protecting patients with asthma against severe exacerbations of their disease.
Effectiveness of routine self monitoring of peak flow in patients with asthma. Grampian Asthma Study of Integrated Care (GRASSIC).
OBJECTIVE: To evaluate the effectiveness of routine self monitoring of peak flow for asthma outpatients.
DESIGN: Pragmatic randomised trial.
SETTING: Hospital outpatient clinics and general practices in north east Scotland.
MAIN OUTCOME MEASURES: Use of bronchodilators and inhaled and oral steroids; number of general practice consultations and hospital admissions for asthma; sleep disturbance and other restrictions on normal activity; psychological aspects of health including perceived control of asthma.
RESULTS: After one year there were no significant differences between patients randomised between self monitoring of peak flow and conventional monitoring. However, those given a peak flow meter recorded an increase in general practice consultations that was nearly significant. Among patients whose asthma was judged on entry to be more severe, those allocated to self monitoring used more than twice as many oral steroids (2.2; 95% confidence interval 1.1 to 4.6). Patients who already possessed a peak flow meter at the start of the study recorded higher morbidity over the course of the year than those eligible for randomisation.
CONCLUSION: Prescribing peak flow meters and giving self management guidelines to all asthma patients is unlikely to improve mortality or morbidity. Patients whose asthma is severe may benefit from such an intervention.
Peak flow based asthma self-management: a randomised controlled study in general practice. British Thoracic Society Research Committee.
BACKGROUND: Peak flow based asthma self-management plans have been strongly advocated in consensus statements, but convincing evidence for the effectiveness of this approach has been largely lacking.
METHODS: A randomised controlled trial was conducted in 25 general practices comparing an asthma self-management programme based on home peak flow monitoring and surgery review by a general practitioner or practice nurse with a programme of planned visits for surgery review only over a six month period.
RESULTS: Seventy two subjects (33 in the self-management group and 39 in the planned visit group) completed the study protocol, but diary card data for at least three months were available on a total of 84 (39 in the self-management group and 45 in the planned visit group). Teaching self-management took longer than the planned visit review. In the self-management group home peak flow monitoring was felt to be useful by doctors and patients in 28 (85%) and 27 (82%) cases, respectively. There were no between group differences during the study period in terms of lung function, symptoms, quality of life, and prescribing costs. Only within the self-management group were improvements noted in disturbance of daily activities and quality of life. Possible explanations for these negative results include small numbers of subjects, the mild nature of their asthma, and inappropriate self-management strategies for such patients.
CONCLUSIONS: Rigid adherence to long term daily peak flow measurement in the management of mild asthma in general practice does not appear to produce large changes in outcomes. Self-management and the use of prescribed peak flow meters need to be tailored to individual circumstances.
Long-term (3-year) economic evaluation of intensive patient education for self-management during the first year in new asthmatics.
Patient education and self-management programmes have proved effective in many studies with short follow-up periods. We studied the 3-year cost-effectiveness of an intensive programme of patient education and supervision for self-management. The study consisted of 162 consecutive newly diagnosed asthmatics who were randomized either into an intervention group (IG) receiving intensive patient education and supervision for self-management at an outpatient clinic during the first year, or a control group (CG) receiving conventional education at the baseline visits only. Both groups had 2 additional years of follow-up. Lung functions and health-related quality of life (HRQOL) were measured. Extra direct and indirect costs were recorded. At 3 years the differences in forced expiratory volume in 1 s (FEV1) and in peak expiratory flow (PEF) were significantly better in the IG being in (% predicted) respectively 5.3 (95% CI 0.6-10.0) and 4.4 (95% CI 0.1-8.7), (P < 0.05). The airway responsiveness (PD15) did not differ significantly, but the improvement from baseline to 3 years was significantly greater in the IG, being 0.40 dose steps (95% CI 0.05-0.75) (P < 0.05). HRQOL scores did not differ significantly. The risk for sickness day was less in the IG with a RR of 0.6 (95% CI 0.50-0.69) (P = 0.000) and among patients who used the PEF meter. The compliance was similar in both groups when measured by the PEF-based self-management. There was no statistically significant difference in costs, although there was a consistent tendency for lower costs in the intensive programme. The intensive programme was more effective in terms of FEV1, PEF and improvement in PD15 and equally effective in terms of other lung functions and HRQOL, but there was no clear difference in the costs.
One-year economic evaluation of intensive vs conventional patient education and supervision for self-management of new asthmatic patients.
The purpose was to compare the short-term cost-effectiveness of intensive vs conventional education and supervision for the self-management of mild asthmatic patients. Consecutive newly diagnosed asthmatic patients (n = 162) were randomized into an intervention group (IG) and a control group (CG) with 1 yr of treatment and follow-up. Intensive education was given to 77 patients at visits every third month in the outpatient clinic. Eighty CG patients received conventional education and advice at the baseline visit only. All patients received similar inhaled anti-inflammatory treatment. At baseline and at 12 months standard clinical lung functions and health-related quality of life (HRQOL) were measured, the latter by the disease-specific St George's Respiratory Questionnaire and the generic 15D. Furthermore, the use of extra health care services, medication and sickness days were recorded. The IG experienced a significant improvement in all clinical and HRQOL outcome variables. The same applied to the CG except spirometric values. The groups differed significantly only in terms of FEV1 (P < 0.05) in favour of the IG. There was a significant difference between the groups in extra costs. The mean cost was FIM 2351 per patient (294 Pounds sterling) in the CG and FIM 2757 per patient (345 Pounds) in the IG, of which the intervention cost was FIM 1978 per patient (247 Pounds). In 1 yr follow-up the intensive education programme did not prove to be cost effective but was dominated by the conventional one regardless of what effectiveness measure was used. Also, a purely monetary cost-benefit calculation showed that the intervention resulted in a negative net benefit (loss) of FIM 406 per patient (51 Pounds). A longer follow-up may be needed before definitive conclusions about the cost-effectiveness of this kind of intervention can be drawn.
Long-term economic evaluation of intensive patient education during the first treatment year in newly diagnosed adult asthma.
The cost-effectiveness of intensive patient education of guided asthma self-management given during the first treatment year was evaluated after 5 years of follow-up. Consecutive, newly-diagnosed asthmatics (n = 162, age 18-76 years) were randomized for intensive (80 patients) vs. conventional patient education. Effectiveness was evaluated in terms of lung functions, airway hyperresponsiveness (PD15), and quality of life as measured by the generic 15D and disease-specific St. George's Respiratory Questionnaire (SGRQ). Total treatment costs were also estimated. All patients had anti-inflammatory treatment from the beginning. Sixty-four intervention group (IG) patients and 70 control group (CG) patients were evaluated after 5 years. Forced expiratory volume in 1 sec (FEV1) improved only in the IG, and only during the first treatment year. However, PD15 improved throughout the follow-up. The unscheduled healthcare costs were significantly higher in the CG than in the IG (P = 0.04) and the relative risk for sickness days due to asthma was lower in the IG than in the CG, odds ratio 0.33 (95% CI 0.28; 0.40). However, because there was no significant difference between the groups in any outcome variable or in total costs at 5 years, the incremental cost-effectiveness ratio could not be calculated. The first year intervention had only a short-term beneficial treatment effect, which the CG could catch up during the two last follow-up years, except in FEV1. The peak expiratory flow (PEF)-based self-management had no advantage over the symptom-based self-management. However, the intervention had a consistent tendency of being less costly in the long-run. It is possible to conclude tentatively that regular effective medical treatment and control visits during the first treatment year is at least as important for the long-term treatment result as intensive patient education.
Benefit from the inclusion of self-treatment guidelines to a self-management programme for adults with asthma.
This study assessed the long-term efficacy of adding self-treatment guidelines to a self-management programme for adults with asthma. In this prospective randomized controlled trial, 245 patients with stable, moderate to severe asthma were included. They were randomized into a self-treatment group (group S) and a control group (group C). Both groups received self-management education. Additionally, group S received self-treatment guidelines based on peak expiratory flow (PEF) and symptoms. Outcome parameters included: asthma symptoms, quality of life, pulmonary function, and exacerbation rate. The 2-yr study was completed by 174 patients. Both groups showed an improvement in the quality of life of 7%. PEF variability decreased by 32% and 29%, and the number of outpatient visits by 25% and 18% in groups S and C, respectively. No significant differences in these parameters were found between the two groups. After 1 yr, patients in both groups perceived better control of asthma and had more self-confidence regarding their asthma. The latter improvements were significantly greater in group S as compared to group C. There were no other differences in outcome parameters between the groups. Individual self-treatment guidelines for exacerbations on top of a general self-management programme does not seem to be of additional benefit in terms of improvements in the clinical outcome of asthma. However, patients in the self-treatment group had better scores in subjective outcome measures such as perceived control of asthma and self-confidence than patients in the control group.
Randomised comparison of cost effectiveness of guided self management and traditional treatment of asthma in Finland.
Randomised comparison of guided self management and traditional treatment of asthma over one year.
OBJECTIVE: To compare the efficacy of self management of asthma with traditional treatment.
DESIGN: 12 month prospective randomised trial.
SETTING: Outpatient clinics in Finland.
SUBJECTS: 115 patients with mild to moderately severe asthma.
INTERVENTIONS: Patient education and adjustment of anti-inflammatory therapy guided by peak flow measurements.
MAIN OUTCOME MEASURES: Unscheduled admissions to hospital and outpatient visits, days off work, courses of antibiotics and prednisolone, lung function, and quality of life.
RESULTS: The mean number of unscheduled visits to ambulatory care facilities (0.5 v 1.0), days off work (2.8 v 4.8), and courses of antibiotics (0.4 v 0.9) and prednisolone (0.4 v 1.0) per patient were lower and the quality of life score (16.6 v 8.4 at 12 months) higher in the self management group than in the traditionally treated group. In both groups admissions for asthma were rare.
CONCLUSIONS: Self management reduces incidents caused by asthma and improves quality of life.
Influence of peak expiratory flow monitoring on an asthma self-management education programme.
We assessed whether peak expiratory flow monitoring added to a self-management education programme reduced morbidity and improved pulmonary function and adherence to treatment in 100 asthma patients (aged 17-65 years) with adequate treatment and regular 1-year follow-up. Patients randomized to the experimental group used peak expiratory flow readings as the basis for their therapeutic plan coupled with educational intervention, whereas patients in the control group received the same educational intervention and used symptoms only to guide self-management. Morbidity parameters, functional status and adherence to medical regimens improved in both groups, although the percentage of patients with satisfactory adherence was significantly better in the group with peak expiratory flow monitoring (83%) than in controls (52%) (P = 0.05). The multivariate analysis showed that severity of asthma (odds ratio 9.28, 95% confidence interval 1.87-45.96, P = 0.006 for moderate asthma) and type of self-management education programme (odds ratio: 6.19; 95% confidence interval: 2.04-18.81; P = 0.001 for the use of peak expiratory flow readings) were the only independent predictors of adherence to treatment. However, a statistically significant association between adherence and use of peak expiratory flow monitoring was only found in patients with moderate asthma (P = 0.0009). We conclude that peak expiratory flow monitorization in optimal conditions (adequate medical regimen, individualized self-management education and regular follow-up) showed a beneficial effect on adherence to prescribed regimens only in patients with moderate asthma.
The effects of a cognitive behavioural intervention in asthmatic patients.
There is evidence that educational programmes may improve patient's compliance with asthma treatment and control symptoms. Whilst medical parameters have been thoroughly studied, few data are available concerning psychological intervention. The aim of our open pilot study was to verify whether any difference in perceived illness and response style to asthma existed in the patients enrolled in an Asthma Rehabilitation Group (ARG) and in a Control Group (CG). Forty consecutive asthmatics were randomly enrolled, all of whom were diagnosed, treated and followed-up according to the International Guidelines. Both groups underwent a psychological assessment at baseline and after one year. A battery of questionnaires was used to obtain data relating to baseline characteristics (anxiety, depression, psychophysiological disorders), emotional reactions to asthma attacks (panic-fear, etc,) and cognitive variables (external control, psychological stigma, internal beliefs, external chance, etc.) involved in the perceived illness. In addition, the Asthma Rehabilitation Group patients underwent an educational programme and a cognitive-behavioural intervention. In both groups, a reduction of anxiety and depression scores was observed, as well as a significant improvement of the medical parameters evaluated. Only the Asthma Rehabilitation Group reported lower scores on the Psychophysiological Questionnaire and on the External Control Subscale after 1 year. The Control Group reported higher score on the External Chance Scale. The data of our study seem to confirm the effectiveness of psychological intervention on the cognitive skills involved in the perception and management of asthma. Larger scale studies on this topic are suggested.
A randomized trial comparing peak expiratory flow and symptom self-management plans for patients with asthma attending a primary care clinic.
Great emphasis is placed on educating asthmatics to use action plans to achieve better control of symptoms. The use of peak flow meters (PFM) has been recommended as an important part of self-management plans. We studied 92 (47 F) adult patients with asthma in a primary care setting to compare the effectiveness of action plans using either peak flow monitoring or symptoms to guide self-management. Each patient was instructed in the use of the action plan in the context of a 6-mo asthma education program taught by a nurse. Patients were already using inhaled corticosteroids or were newly prescribed corticosteroids by their family physician. Forty-four patients were randomized to the PFM group and 48 to the symptoms group. Spirometry, symptom scores, quality of life, medication use, and measures of health care utilization and morbidity (emergency department visits, hospitalizations, unscheduled doctor visits, and days lost from work or school) were recorded at baseline and throughout the study period. PC20 methacholine was measured at the first and at the final visits. There were significant improvements within groups for FEV1, symptoms score, PC20 methacholine, and quality of life, but no between-group differences. A significant shift from higher to lower daily use of beta-agonists (p < 0.008 for both groups) and significant shifts to higher daily doses of inhaled steroids (p < 0.001) occurred in each group. Adherence to the self-management plans was only 65% in the PFM group and 52% in the symptoms group. Outcomes for health care utilization were similar except for fewer patients making unscheduled doctor visits within the PFM group. Our findings show that education, regular follow-up, and an action plan are effective in improving asthma control and quality of life, but the routine use of PFM to guide interventions is not the only way to accomplish these objectives.
Options:
A: Self-management with individualised written action plans based on peak expiratory flow is more effective than those based on symptoms.
B: Self-management with individualised written action plans is as effective as regular medical review for adjusting medications.
C: Reducing the intensity of self-management education does not affect the number of unscheduled doctor visits.
D: Verbal instruction is significantly more effective than written action plans for asthma self-management. | B |
263 | 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 oxatomide in managing stable asthma in adults and children? Please answer this question based on the information provided below:
A clinical trial of oxatomide in asthma.
A controlled trial of oxatomide in the treatment of asthma with or without perennial rhinitis. Brompton Hospital/Medical Research Council Collaborative Trial.
A double-blind study comparing oxatomide, a new oral drug with anti-allergic properties, with placebo in the treatment of patients with asthma with or without perennial rhinitis has been undertaken. Sixty-two patients were followed up to 28 weeks and fifty-two to 52 weeks. On admission to the study the great majority of the patients were receiving inhaled steroids and about a third sodium cromoglycate for their asthma. The results of the study suggest that oxatomide has some activity but have failed to show that it is substantially better than placebo in this group of patients. For the first time weight-gain is reported as a side effect of oxatomide.
Double-blind placebo-controlled study of oxatomide in the treatment of childhood asthma.
Oxatomide is an orally active H1-histamine receptor antagonist. It has been demonstrated to have therapeutic efficacy in the treatment of allergic diseases in adults. The aim of this study was to evaluate the efficacy and safety of oxatomide in the treatment of asthma in children. Sixty-four asthmatic children of both sexes, aged between 5 and 16 years, were enrolled in this double-blind, placebo-controlled trial with a duration of 4 months. Patients were randomized chosen to receive either oxatomide with a daily dose of 1 to 2 mg/kg body weight or a placebo twice daily. Clinical evaluations including pulmonary function tests and immunological studies. The patients' impression on the effect of treatment also were recorded during the study. The effects of bronchodilatation and normalizing pulmonary function were observed 2 months after oxatomide treatment. The levels of eosinophil cationic protein and total asthma symptom scores were significantly reduced during treatment with oxatomide. There was no significant change in total IgE or IgG4 before or after treatment in either the treatment or control groups. During the study, two (5.8%) oxatomide treated patients reported slight drowsiness and one (2.9%) reported body weight gain. Routine laboratory tests showed no significant alterations. In conclusion, oxatomide was generally well tolerated in this study and may have the potential of being an effective treatment for childhood asthma.
[Protective effect of oxatomide in infantile bronchial asthma. Double-blind study vs placebo].
BACKGROUND: This study has been designed to assess the protective effect of oxatomide in allergic bronchial asthma of the seasonal type in young children.
METHODS: The study was carried out in a paediatric clinic; sixteen children divided into two balanced groups took oxatomide in an oral suspension at the dosage of 1 mg/kg/day, or placebo for a period of 2 months. Eight patients (7 males, 1 female), aged 22 months +/- 2.83 (mean +/- SD) took oxatomide in an oral suspension at the dosage of 1 mg/kg/day, while the other eight (3 males, 5 females; 22.13 months +/- 3.48) took placebo. Efficacy was assessed by monitoring cough, dyspnea at rest, dyspnea following exercise, wheezing, sleep disorders at baseline and after 15, 30 and 60 days of treatment, on the basis of a semiquantitative scale. All side effects were recorded.
RESULTS: Persistent coughing was significantly reduced (p < 0.05) after two weeks' treatment with oxatomide. Sleep disorders and other symptoms remarkably improved. Dyspnea at rest and following exercise disappeared after 15 days' therapy, while the intensity of wheezing decreased after 30 days' active treatment. In all parameters examined, oxatomide was significantly more active than placebo at the first examination (p < 0.05 and p < 0.01). Oxatomide was well tolerated and only 2 patients complained of drowsiness which required a reduction in dosage.
CONCLUSIONS: Oxatomide, at the dose of 1 mg/kg/day, obtained a good control of respiratory symptoms.
Options:
A: Oxatomide significantly improved lung function and asthma symptoms without any notable adverse events.
B: Oxatomide showed no significant effect on asthma control, with inconsistent improvements in lung function and a higher risk of adverse events, including drowsiness.
C: Oxatomide was found to be more effective than placebo in reducing the use of inhaled corticosteroids and bronchodilators, with minimal adverse events.
D: Oxatomide had a uniform positive effect on symptom scores and was well-tolerated with no significant adverse events. | B |
264 | 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 recommended initial treatment for women with metastatic breast cancer and hormone receptor presence, considering the effects on survival, response rate, toxicity, and quality of life? Please answer this question based on the information provided below:
Effects of medroxyprogesterone acetate therapy on advanced or recurrent breast cancer and its influences on blood coagulation and the fibrinolytic system.
The effects of medroxyprogesterone acetate (MPA) therapy on advanced or recurrent breast cancer and its influence on blood coagulation and the fibrinolytic system were compared among three different therapy regimens consisting of cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) + MPA and CAF or MPA alone. A clinical response was observed in 42.9% (9/21) of the patients for CAF + MPA, 36.4% (8/22) for CAF and 23.8% (5/21) for MPA alone. No marked thrombosis or its prodromal condition was observed in any group. The effects on the test values for blood coagulation and the fibrinolytic system did not significantly change in the CAF group. However, both AT-III and protein C significantly increased above the normal ranges in the CAF+MPA and MPA groups. Increases in factor X, plasminogen, and alpha 2-plasmin inhibitor/plasmin complex (PIC) and decreases in fibrinogen, tissue plasminogen activator, and D-dimer, were all observed in the MPA and CAF + MPA groups, especially in the MPA group, although these changes remained within the normal ranges. The data indicated that MPA has various influences on blood coagulation and the fibrinolytic system, but these changes did not suggest activation of the blood coagulation system.
A randomized trial in postmenopausal patients with advanced breast cancer comparing endocrine and cytotoxic therapy given sequentially or in combination. The Australian and New Zealand Breast Cancer Trials Group, Clinical Oncological Society of Australia.
A prospective randomized clinical trial was performed in 339 postmenopausal patients with advanced breast cancer. Two single modality treatment sequences, doxorubicin plus cyclophosphamide (AC) followed on failure by tamoxifen (TAM), and TAM followed by AC, were compared with combined modality chemo-endocrine therapy (TAM plus AC). The response rate to initial TAM (22.1%) was inferior to that for AC (45.1%), and for TAM plus AC (51.3%). However, patients randomized to the sequence TAM followed by AC showed a 42.5% overall tumor response to sequential protocol therapy, similar to the 46.9% for those randomized to AC followed by TAM. Furthermore, survival in all three arms was almost identical. Adverse prognostic factors for survival were liver metastases, short disease-free interval, poor performance status, and prior adjuvant chemotherapy. In no subgroup was significantly better survival associated with initial cytotoxic therapy. Endocrine therapy followed on failure by cytotoxics is appropriate for postmenopausal patients with advanced breast cancer.
[Management of advanced breast cancer in post-menopausal women. A comparative trial of hormonal therapy, chemotherapy, and a combination of both].
A randomized trial was done in 98 post-menopausal women with breast cancer. Hormonal receptors had not been assayed in any patient. Patients were given hormonal therapy with tamoxifen and drostanolone propionate (n = 34), or chemotherapy with the CMF protocol (n = 30), or a combination of both (n = 34). The results are in favour of hormonal therapy alone, which gave the best immediate objective responses, the least adverse side-effects, and possibly improved survival rates.
A randomised trial of second-line hormone vs single agent chemotherapy in tamoxifen resistant advanced breast cancer.
Sixty patients with advanced breast cancer unresponsive to tamoxifen have been randomised to receive four course of mitozantrone, 14 mg m-2 (n = 30) intravenously every 3 weeks (9 weeks total) or megesterol acetate, 160 mg bd (n = 30). One in three patients (11 from each group) had substantial disease control for a minimum period of 6 months i.e., lack of progression; seven patients (23%) showed objective response to mitozantrone compared to four (13%) receiving megesterol. Non-progressive disease occurred in all sites, including visceral metastases and receptor negative patients. There were no significant differences between treatment groups in the median time (5 months each) to disease progression response duration or survival (13 months megesterol, 11 months mitozantrone) from commencing second-line therapy. Toxicity was considerably higher in the mitozantrone group. Second-line hormonal therapies can produce similar therapeutic results as those achieved from a short course of a 'short option' single agent cytotoxic in patients who were previously thought hormone insensitive. Provided that the patient does not have life threatening disease a trial of megesterol acetate is worth consideration in that it does not prejudice subsequent response to combination cytotoxic chemotherapy.
Continuous chemotherapy in responsive metastatic breast cancer: a role for tumour markers?
A biochemical response index comprising ESR, CEA and CA 15.3 was evaluated in 67 patients with systemic breast cancer treated by chemotherapy; 55 were assessable by UICC criteria and the response index (96% of all UICC assessable patients). Marker changes at 2 and 4 months showed a highly significant correlation with the UICC assessed response at 3 and 6 months (P < 0.001); sensitivity 100%, specificity 87%; positive predictive value 85%; negative predictive value 100%. This index was then used to select out truly responsive patients and to prospectively direct their chemotherapy. Twenty-six responding (biochemical/clinical) patients were randomised to discontinue cytotoxics after 6 months and move to maintenance hormones (n = 13) or continue chemotherapy whilst the biochemical markers kept falling or remained within the normal range. Biochemical progression prompted a change of chemotherapy. Continuous chemotherapy in biochemically defined responders was associated with a significant lengthening of remission duration and an improved quality of life and survival. We are now using the index to routinely direct chemotherapy and select out true responders for maintenance chemotherapy.
Combined androgen and antimetabolite therapy of advanced female breast cancer. A report of the cooperative breast cancer group.
A clinical trial of androgen and antimetabolite therapy of advanced female breast cancer was conducted in 110 patients by the Cooperative Breast Cancer Group. An objective regression rate of 20% was achieved in women receiving oral testolactone, 6% in patients given intravenous fluorouracil alone, and 14% when the androgen and antimetabolite were administered together. This randomized trial according to the CBCG protocol did not produce the high regression rate noted previously in a nonrandomized, nonprotocol evaluation of these drugs.
Comparative trial of endocrine versus cytotoxic treatment in advanced breast cancer.
Ninety-two women with advanced breast cancer were allocated at random to receive either cytotoxic or endocrine treatment. Out of 45 women included in the cytotoxic treatment group, 22 (49%) achieved complete or partial remission of their disease, whereas of the 47 included in the endocrine treatment group, only 10 (21%) achieved such remission. Significantly longer survival times in the cytotoxic treatment group were most apparent among premenopausal women, 75% of such patients responding to cytotoxic drugs (median survival 46 weeks) compared with only 11% benefiting from ovarian ablation (median survival 12 weeks). In postmenopausal women with predominantly soft-tissue disease, however, additive hormonal treatment with tamoxifen produced remission rates and survival times equivalent to those produced by cytotoxic drugs.
Treatment and survival on advanced breast cancer.
The final results of a clinical trial comparing endocrine with cytotoxic drug treatment for advanced breast cancer were analysed. Although cytotoxic treatment gave a significantly higher response rate with a remission duration comparable to that obtained with endocrine treatment, the sequence in which the two treatments were given did not appear to influence survival--except possibly in women with rapidly progressing disease, when cytotoxic treatment is preferred.
Effect of treatment on the immunological status of women with advanced breast cancer.
An immunological profile has been serially studied in 72 patients with advanced breast cancer during the course of a randomized trial of chemotherapy and hormonal manipulation. DNCB+ patients were more likely to respond to either therapy, but no other test was predictive of response. In the follow-up period all chemotherapy patients had a reduction in white-cell count which was significantly greater in those responding to treatment. None of the other tests (phytohaemagglutinin response, immunoglobulins G, A and M, or Mantoux test) demonstrated changes that could be related to treatment or response, but there was a gradual unexplained fall in IgM levels in all groups the study progressed. It is concluded that the chemotherapeutic regimen (cyclophosphamide, vincristine, adriamycin and 5-fluorouracil) is relatively non-immunosuppressive, and that hormonal therapy (oophorectomy, tamoxifen or androgens) had no detectable effect on the immune response.
[A randomized trial of endocrine therapy, chemotherapy, and chemo-endocrine therapy in advanced breast cancer].
A randomized trial of endocrine therapy (adreno-oophorectomy, H), chemotherapy (FAC, C), chemoendocrine therapy (FAC + tamoxifen, H'C, or FAC + adreno-oophorectomy, HC) was performed in 114 advanced breast cancer patients from September, 1979 to December, 1983, and 106 were evaluable. The response to H, C, H'C, and HC was shown to be 33% (10/30), 54% (14/26), 59% (17/29), and 76% (16/21), respectively. There was a significantly higher response rate in HC group than H group. Higher but not significantly different response was obtained by H'C as compared with H. There were no significant differences in the overall survival among the treatment arms. However, patients treated with H survived longer (greater than 5 years). These results suggest that higher response obtained by chemotherapy, alone or in combination with endocrine therapy does not seem to contribute to the prolongation of survival of the patients.
Combination chemotherapy compared to tamoxifen as initial therapy for stage IV breast cancer in elderly women.
In a randomized crossover study, 181 patients over the age of 65 with recurrent breast cancer received either tamoxifen or cyclophosphamide, methotrexate, and fluorouracil (CMF). After progression on tamoxifen, a hormone withdrawal period was required. Because of altered pharmacokinetics with aging, creatinine clearance was used in calculating the dose of CMF. Response rates were 45% on tamoxifen and 38% on CMF, with median durations of 10.4 and 7.9 months, respectively. Survival rates tended to favor tamoxifen as the initial treatment even in estrogen-receptor-negative patients. Additional disease control with hormone withdrawal occurred in 23% of patients, and this benefit was highly correlated with prior hormone response. We conclude that initiation of hormone therapy rather than CMF chemotherapy is justified in almost all situations in elderly patients, and combination chemotherapy, is safe and useful after hormone failure if modified on the basis of renal dysfunction.
Options:
A: Chemotherapy alone
B: Endocrine therapy alone
C: Combination of chemotherapy and endocrine therapy
D: No treatment | B |
265 | 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 systemic corticosteroids for children admitted to the hospital with acute asthma? Please answer this question based on the information provided below:
Prednisolone and salbutamol in the hospital treatment of acute asthma.
The use of oral prednisolone (2 mg/kg) to treat children admitted to hospital with acute asthma was assessed in a placebo controlled study. Children were further randomised to receive either 0.15 mg/kg salbutamol every 30 minutes for the first three hours of admission, or 5 mg salbutamol every one to four hours as needed. Treatment was double blind and the assessor was unaware of the nebuliser regimen given. Children were examined before and after treatment with salbutamol on arrival and reassessed four hours after admission. Seventy children completed the study. Seventeen (46%) of 37 children receiving prednisolone and six (9%) of 33 receiving placebo were fit for discharge after four hours of treatment. There was no significant difference between the two nebuliser regimens. Clinical parameters indicative of asthma severity were improved in all groups. Between group comparisons at reassessment showed higher peak flows in those receiving prednisolone and nebulisers every 30 minutes but differences were not significant for other parameters. Objective parameters indicating steroid efficacy over placebo were minimal. Despite this, those receiving prednisolone were more readily identifiable as being fit for discharge within four hours of treatment.
Placebo controlled trial of systemic corticosteroids in acute childhood asthma.
In a randomised controlled trial 38 asthmatic children aged 2-11 yr who had not received regular oral or inhaled steroids during the previous year, were treated with a standard regime of nebulised salbutamol and intravenous aminophylline plus either hydrocortisone and oral prednisolone for 5 days, or placebo. The children were observed throughout their hospital stay and for 3 months afterwards. There was a greater fall in heart rates in the steroid treated group on the second day of treatment (mean diff. 16 beats/min) and at discharge (mean diff. 13 beats/min); p less than 0.025. Peak Expiratory Flow Rates recorded in 26 children, 13 in each group, showed more improvement on day 2 in those given steroids (mean diff 16% predicted); p less than 0.05. This difference was not apparent at discharge but 9 children treated with steroids were clinically wheeze-free when they left hospital compared with 3 in the placebo group, p less than 0.05. There were no differences in respiratory rate, pulsus paradoxus and arterial oxygen saturation. Trends in duration of hospital stay and relapse rate during the succeeding 3 months favoured active treatment. These findings support the use of systemic corticosteroids in addition to high dose bronchodilators to treat 'non steroid dependent' children hospitalised with acute severe asthma.
Lack of efficacy of single-dose prednisolone in moderately severe asthma.
OBJECTIVE: To assess the effectiveness of single-dose prednisolone in reducing the length of illness and hospital stay in children admitted with moderately severe asthma.
DESIGN: A randomised, double-blind, controlled trial of a single dose of prednisolone in 64 children presenting with an acute attack of asthma with arterial oxygen saturation less than 93%.
RESULTS: No significant differences in the rate of recovery of oxygen saturation, lung function measurements or duration of hospital stay were found.
CONCLUSIONS: This study failed to confirm the benefit of a single dose of prednisolone in the management of children with acute severe asthma.
Corticosteroids in status asthmaticus.
Nineteen children who were not steroid dependent and were hospitalized in status asthmaticus were studied to evaluate the effect of corticosteroids. They were randomized into two groups. Each group received salbutamol inhalations and intravenous aminophylline therapy. One group received 7 mg/kg hydrocortisone intravenously every six hours; the other group served as a control. Each group showed significant improvement in clinical score and peak expiratory flow rate after 36 hours; there was no statistical difference in the degree of improvement. Six of ten steroid-treated children and six of nine controls achieved a PEFR of 50% predicted by 36 hours. The response to inhaled salbutamol was similar in each group. The results show that in the first 36 hours of therapy, corticosteroids have no additive effect on the bronchodilator response of aminophylline and salbutamol and do not hasten the recovery of nonsteroid-dependent children in status asthmaticus. Although the results show that an inhaled sympathomimetic drug is beneficial in status asthmaticus, corticosteroid therapy does not increase the responsiveness of the airways to these agents.
Nebulized budesonide versus oral steroid in severe exacerbations of childhood asthma.
The aim of this study was to assess whether nebulized budesonide may substitute for oral prednisolone in the management of children whose asthma is severe enough to warrant hospital admission, but who have no life threatening features. In a prospective, double-blind, randomized study nebulized budesonide (2 mg 8 hourly) was compared with oral prednisolone (2 mg/kg at entry and again at 24 h) in 46 children admitted to hospital with severe asthma exacerbations. Efficacy variables (including lung function measurements such as the primary outcome variable, Forced Expiratory Volume in 1 second (FEV1) and symptoms) were measured 24 h after treatment initiation. FEV1 improved significantly compared to baseline in patients who received nebulized budesonide compared to the prednislone group. The data show nebulized budesonide to be at least as effective as oral steroid in improving lung function and symptom severity in severe exacerbations of childhood asthma.
Effect of a single oral dose of prednisolone in acute childhood asthma.
140 children of 184 with acute asthma entered a randomised double-blind trial of oral prednisolone (n = 67) compared with placebo (n = 73) administered soon after admission. The dose of prednisolone was 30 mg in children under 5, otherwise 60 mg. All children also received salbutamol. All had moderate or severe dyspnoea. Initial evaluation was similar for both groups. On reassessment after a few hours 20 children in the prednisolone group were fit for discharge compared with only 2 in the placebo group. There were no early reattendances. Children remaining in hospital had a shorter median duration of stay and were less likely to require further steroid therapy if they had initially received prednisolone. In acute asthma the prompt use of a single dose of oral prednisolone can reduce morbidity and the need for hospital care.
Intravenous methylprednisolone efficacy in status asthmaticus of childhood.
Forty-nine nonsteroid-dependent children hospitalized with status asthmaticus were randomized to receive IV placebo or methylprednisolone treatment (1 mg/kg every six hours). All patients received nebulized isoetharine inhalations and continuous IV aminophylline infusion. Twenty-four hours after admission, the methylprednisolone-treated patients demonstrated a greater rate of improvement in their clinical scoring index than did placebo-treated children. However, the duration of hospital stay was not significantly shortened. Twenty-eight of the patients performed serial bedside spirometry at 0, 12, 24, and 36 hours after admission. The methyl-prednisolone-treated patients experienced a more rapid recovery from peripheral airway obstruction as measured by forced expiratory flow rate during 25% to 75% of forced vital capacity (FEF25-75). The magnitude and rate of improvement in FEF25-75 was significantly greater at 36 hours (P less than .05) and independent of changes in peak expiratory flow rate, forced vital capacity, or forced expiratory volume in the first second of forced vital capacity. Placebo-treated patients had a higher incidence of asthma relapse within 4 weeks of discharge (eight v two relapses, P less than .05). Findings of this study indicate that IV corticosteroid therapy is beneficial in treating pediatric status asthmaticus.
Options:
A: Earlier discharge from the hospital and fewer relapses within one to three months.
B: Improved pulmonary function and oxygen saturation measurements.
C: No significant difference in outcomes compared to placebo.
D: Increased risk of adverse effects and longer hospital stays. | A |
266 | 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 most effective smoking cessation intervention for individuals with chronic obstructive pulmonary disease (COPD) according to the systematic review? Please answer this question based on the information provided below:
Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1. The Lung Health Study.
OBJECTIVE: To determine whether a program incorporating smoking intervention and use of an inhaled bronchodilator can slow the rate of decline in forced expiratory volume in 1 second (FEV1) in smokers aged 35 to 60 years who have mild obstructive pulmonary disease.
DESIGN: Randomized clinical trial. Participants randomized with equal probability to one of the following groups: (1) smoking intervention plus bronchodilator, (2) smoking intervention plus placebo, or (3) no intervention.
SETTING: Ten clinical centers in the United States and Canada.
PARTICIPANTS: A total of 5887 male and female smokers, aged 35 to 60 years, with spirometric signs of early chronic obstructive pulmonary disease.
INTERVENTIONS: Smoking intervention: intensive 12-session smoking cessation program combining behavior modification and use of nicotine gum, with continuing 5-year maintenance program to minimize relapse. Bronchodilator: ipratropium bromide prescribed three times daily (two puffs per time) from a metered-dose inhaler.
MAIN OUTCOME MEASURES: Rate of change and cumulative change in FEV1 over a 5-year period.
RESULTS: Participants in the two smoking intervention groups showed significantly smaller declines in FEV1 than did those in the control group. Most of this difference occurred during the first year following entry into the study and was attributable to smoking cessation, with those who achieved sustained smoking cessation experiencing the largest benefit. The small noncumulative benefit associated with use of the active bronchodilator vanished after the bronchodilator was discontinued at the end of the study.
CONCLUSIONS: An aggressive smoking intervention program significantly reduces the age-related decline in FEV1 in middle-aged smokers with mild airways obstruction. Use of an inhaled anticholinergic bronchodilator results in a relatively small improvement in FEV1 that appears to be reversed after the drug is discontinued. Use of the bronchodilator did not influence the long-term decline of FEV1.
The US Lung Health Study.
The US Lung Health Study was a randomized clinical trial carried out in 10 clinical centres in the United States of America and Canada that enrolled 5887 male and female smokers age 35-60 years with early chronic obstructive pulmonary disease (COPD). Its purpose was to determine whether a programme incorporating smoking intervention and use of an inhaled bronchodilator (ipratropium bromide) can slow the rate of decline in the forced expiratory volume in one second (FEV1) in middle aged smokers with early COPD. Participants were randomized with equal probability into three groups: (i) smoking intervention plus bronchodilator; (ii) smoking intervention plus placebo; or (iii) no intervention. The primary outcome was rate of change and cumulative change in FEV1 over a 5 year period. The primary finding was that the use of the bronchodilator did not influence the long-term decline in FEV1. However, the aggressive smoking intervention programme significantly reduced the age-related decline in FEV1.
Chronic Obstructive Pulmonary Disease Early Intervention Trial (Lung Health Study). Baseline characteristics of randomized participants.
The Chronic Obstructive Pulmonary Disease Early Intervention Trial, or Lung Health Study, is a multicenter randomized clinical trial sponsored by the Division of Lung Diseases of the National Heart, Lung, and Blood Institute. The hypothesis being tested is that over a 5-year period, a comprehensive intervention program can reduce both the rate of decline in pulmonary function and the rates of respiratory morbidity and mortality in middle-aged smokers with mild to moderate airflow obstruction. The primary outcome variable of the trial is the annual rate of decline of maximum postbronchodilator FEV1. Secondary outcomes are the development of respiratory and nonrespiratory morbidity and mortality. After screening 73,694 cigarette smokers, aged 35 to 60 years, 5,887 participants were randomized into three equal groups: usual care, smoking intervention with daily use of a metered-dose inhaler with ipratropium bromide, and smoking intervention with inhalation of placebo. Eligible participants had a ratio of FEV1 to forced vital capacity (FVC) of 70 percent or less, were free of known life-limiting conditions, expressed willingness to enter the intervention program if so randomized, and gave written informed consent prior to entry into the trial. Spirometry, methacholine challenge, and questionnaires were strictly standardized within and across centers. The purpose of this report is to describe the characteristics of randomized participants at the time of entry into the study. For both sexes, three measures of lung function--average cross-sectional FEV1/FVC ratio, FEV1, and FEV1 percentage of predicted normal--showed slight downward trends for each successively older 5-year age cohort. The increase in FEV1 after isoproterenol was 15 percent or more in only 2.4 percent of men and 2.8 percent of women. A positive response to methacholine (defined as a fall in FEV1 of > 20 percent from baseline at concentrations up to 25 mg/ml) occurred in 63 percent of men and 87 percent of women. The cross-sectional prevalences of cough, phlegm, wheeze on most days or nights, and shortness of breath were 49 percent, 43 percent, 32 percent, and 43 percent, respectively. Respiratory symptoms were reported by a higher proportion of participants in the younger age groups than in the older age groups. Participants who reported cough, phlegm, and/or wheeze averaged lower FEV1 percent predicted and higher probability of positive response to methacholine than participants who did not. Shortness of breath appeared to be significantly associated with lower lung function and higher reactivity in men but not in women.(ABSTRACT TRUNCATED AT 400 WORDS)
Recruitment of participants in the Lung Health Study, II: Assessment of recruiting strategies.
The Lung Health Study (LHS), a multicenter randomized clinical trial of treatment to prevent chronic obstructive pulmonary disease (COPD), recruited, over a 28-month period, 5887 smokers aged 35-60 who had evidence of mild airflow obstruction on pulmonary function testing. The LHS participants were identified from a pool of over 73,000 age-eligible smokers who underwent the initial pulmonary function screening tests. Methods of recruitment in the 10 centers are here classified into five general strategies: worksites, public sites, mail/phone, media, and other. This paper deals with the results of each of these general methods and their effectiveness in producing participants eligible for the study. The most effective strategies proved to be mail/phone and media. Ongoing monitoring and a flexible approach to recruitment characterized the most successful clinics. Over the recruitment period, LHS clinics shifted their emphasis away from worksite and public site strategies and tended to focus on variations of the mail/phone strategy. Female screenees who passed first-screen eligibility criteria were more likely than males to refuse further participation.
Design of the Lung Health Study: a randomized clinical trial of early intervention for chronic obstructive pulmonary disease.
The Lung Health Study is a multicenter randomized clinical trial. Participants are smokers aged 35-60 with spirometric evidence of moderate lung function impairment. The objective of the trial is to determine whether a program of smoking intervention and use of an inhaled bronchodilator can slow the rate of decline in pulmonary function over a 5-year follow-up period. This paper describes the background, design, sample size (approximately 6000 participants), and power estimates for the trial, as well as the treatment program and the rationale for the choice of inhaled bronchodilator. Plans for analysis of changes in pulmonary function parameters and for analysis of participants' survival and smoking-related morbidity are also discussed.
Early intervention in chronic obstructive pulmonary disease. A review of the Lung Health Study results.
The major findings of the LHS that have been reported thus far are that an effective smoking cessation program can be developed that can produce more than a 20% success rate in getting smokers to give up the habit permanently, and that by stopping smoking, individuals with early COPD benefit by having an initial improvement in lung function and a slowing of the annual loss of their FEV1. The use of a bronchodilator has a short-term effect in improving the FEV1, but it does not affect long-term changes in lung function. AHR is common in patients with mild-to-moderate COPD. The reward for a smoker to give up the habit is an initial gain in FEV1 and a subsequent close to normal annual rate of decline of this pulmonary function parameter. These results should provide a positive incentive for smokers to quit and thereby decrease the morbidity and mortality caused by the use of tobacco.
Effects of randomized assignment to a smoking cessation intervention and changes in smoking habits on respiratory symptoms in smokers with early chronic obstructive pulmonary disease: the Lung Health Study.
PURPOSE: To evaluate the effects of randomly assigning smokers who have early chronic obstructive pulmonary disease (COPD) to a smoking-cessation intervention on the symptoms of chronic cough, chronic phlegm production, wheezing and shortness of breath, and to determine the effects of quitting smoking on these symptoms.
SUBJECTS AND METHODS: A total of 5,887 male and female smokers 35 to 60 years of age with early COPD [defined as a forced expiratory volume in the first second (FEV1) of 55% to 90% of predicted and FEV1/forced vital capacity (FVC) <0.70] were enrolled in a 5-year clinical trial. Two-thirds of participants were randomly assigned to smoking-intervention groups and one-third to a usual-care group. The intervention groups attended 12 intensive smoking-cessation sessions that included behavior modification techniques and the use of nicotine chewing gum. One intervention group was treated with ipratropium bromide by inhaler; the other intervention group received placebo inhalers. The usual-care group was advised to stop smoking. All participants were followed annually. Smoking status was biochemically validated by salivary cotinine measurements or exhaled carbon monoxide values.
RESULTS: Validated 5-year sustained smoking cessation occurred in 22% of participants in the intervention compared with only 5% of participants in the usual-care group. At the end of the study, the prevalence of each of the four symptoms in the two intervention groups was significantly less than in the usual-care group (P <0.0001). For example, among participants who did not report cough at baseline, 15% of those in the intervention groups had cough at least 3 months during the year, compared with 23% of those in usual care. Sustained quitters had the lowest prevalence of all four symptoms, whereas continuous smokers had the greatest prevalence of these symptoms. Changes in symptoms occurred primarily in the first year after smoking cessation. Respiratory symptoms were associated with greater declines in FEV1 during the study (P <0.001). Ipratropium bromide had no long-term effects on respiratory symptoms.
CONCLUSIONS: In this prospective randomized trial using an intention-to-treat analysis, smokers with early COPD who were assigned to a smoking-cessation intervention had fewer respiratory symptoms after 5 years of follow-up.
Effects of multiple attempts to quit smoking and relapses to smoking on pulmonary function. Lung Health Study Research Group.
The effect of intermittent smoking on pulmonary function was assessed among participants in the Lung Health Study, 5887 adult smokers with evidence of early chronic obstructive pulmonary disease (COPD), followed up for 5 years. The mean annual rate of loss in FEV1% of predicted after year 1 was smallest for those who quit at some point during the first year of the study and stayed quit (-0.33%/year, +/-0.05%), intermediate for those who smoked intermittently during the study (-0.58%/year, +/-0.05%) and greatest for those who continued to smoke throughout the study (-1.18%/year, +/-0.03%). Surprisingly, those who made several attempts to quit smoking had less loss of lung function at comparable cumulative doses of cigarettes than those who continued to smoke. Quitting smoking for an interval followed by relapse to smoking appeared to provide a measurable and lasting benefit in comparison to continuous smoking. In this early COPD population, not only quitting smoking but attempts to quit smoking can prevent some loss of lung function. These results provide some encouragement to exsmokers who relapse on their way to complete cessation.
Characteristics of participants who stop smoking and sustain abstinence for 1 and 5 years in the Lung Health Study.
BACKGROUND: This study describes baseline and Year 1 predictors of abstinence from smoking for the 3,523 intervention participants who had complete annual 5-year follow-up data in the Lung Health Study (LHS).
METHODS: The LHS enrolled 5,887 smokers, aged 35 to 60 years, of whom 3,923 were offered a cessation intervention. Of these, 22% achieved biochemically verified abstinence for 5 years. Logistic regressions were performed. The first outcome variable was abstinence from smoking at 1 year. Then for those who were quit at 1 year, the outcome variable was 5 years of sustained abstinence.
RESULTS: All participants who were not using nicotine gum after 1 year in the study were more likely to sustain cessation over 5 years than were gum users at year 1 (OR ranged from 0.31 to 0.44 for four age- and sex-specific groups). Baseline number of previous quit attempts was negatively associated with 5-year quitting success among younger and older men (OR = 0.82 and 0.83). Older participants who were less likely to associate smoking with emotional coping had higher abstinence rates at 5 years of follow-up (OR = 0.89 and 0.84).
CONCLUSIONS: Different mechanisms may be responsible for achieving cessation in age/gender groups. These results have implications for planning successful interventions.
Early and late weight gain following smoking cessation in the Lung Health Study.
The authors examine weight gains associated with smoking cessation in the Lung Health Study (1986-1994) over a 5-year follow-up period. A cohort of 5,887 male and female smokers in the United States and Canada, aged 35-60 years, were randomized to either smoking intervention or usual care. Among participants who achieved sustained quitting for 5 years, women gained a mean of 5.2 (standard error, 5.0) kg in year 1 and a mean of 3.4 (standard error, 5.5) kg in years 1-5. Men gained a mean of 4.9 (standard error, 4.9) kg in year 1 and a mean of 2.6 (standard error, 5.8) kg in years 1-5. In regression analyses, smoking-change variables were the most potent predictors of weight change. Participants going from smoking to quit-smoking in a given year had mean weight gains of 2.95 kg/year (3.61%) in men and 3.09 kg/year (4.69%) in women. Over 5 years, 33% of sustained quitters gained > or = 10 kg compared with 6% of continuing smokers. Also among sustained quitters, 7.6% of men and 19.1% of women gained > or = 20% of baseline weight; 60% of the gain occurred in year 1, although significant weight gains continued through year 5. The average gains and the high proportions of sustained and intermittent quitters who gained excessive weight suggest the need for more effective early interventions that address both smoking cessation and weight control.
Effect of diagnosis of "smoker's lung". RYLUNG Group.
[The diagnosis of "smoker's lung" encourages smoking cessation].
In a controlled randomised trial we analysed whether the use of the term "smoker's lung" (Danish: "rygerlunger") instead of chronic bronchitis when talking to patients with chronic obstructive lung disease (COLD) changed their smoking habits. Fifty-six smoking patients with COLD were allocated to either intervention (n = 25) or control groups (n = 31). In the intervention group the lung disease was designated smoker's lung in all communication with patients about their illness and in the control group traditional terminology was used. All patients were given the same medical treatment and the same encouragement to stop smoking. One week after discharge 57% had stopped smoking in the smoker's lung group vs 26% in the control group (p = 0.028), at three months 50% vs 19% (p = 0.027) and at one year 40% vs 20% (p = 0.148). Referring directly to the cause of a self-inflicted illness may be an effective way of discouraging risk behaviour, at negligible cost.
Behavioral anti-smoking trial in chronic obstructive pulmonary disease patients.
Smoking causes chronic obstructive pulmonary disease (COPD), but few controlled studies have tested anti-smoking treatments in COPD. With procedures likely to attract unmotivated persons we recruited 49 quite-ill, smoking COPD patients. During one or two daily home visits for 85 days, breath carbon monoxide (CO) and self-reports of daily smoking were obtained. Patients, given quit dates and nicotine gum (2-mg pieces, up to 30 per day), were assigned randomly to three groups: Experimentals were reinforced with lottery tickets for CO < 10 ppm. Cigarette Self Report (CSR) patients were reinforced for reporting no smoking that day. Controls received non-contingent payments. Each group's mean CO level fell at the quit date. Thereafter, reinforced patients maintained significantly lower CO levels than Controls. Although many more 24-h abstentions occurred in the intervention period than in baseline, few patients sustained abstinence; the groups did not differ in that regard. Outcome was predicted by decisions to throw away cigarettes when intervention began, but not by motivation scales nor Fagerstrom dependence scores. Pay schedules apparently exaggerated self-reports of reduced smoking. Although results are statistically significant, there is still no proven, practical treatment for smoking in advanced COPD.
The effects of counseling on smoking cessation among patients hospitalized with chronic obstructive pulmonary disease: a randomized clinical trial.
Seventy-four cigarette-smoking patients admitted with COPD to the Chest Unit of a 600-bed teaching hospital served as subjects for a randomized trial of smoking cessation counseling. All patients were advised to quit smoking and smoking in the unit was not allowed. One-half of the patients were, in addition, provided with a self-help manual and three to eight 15- to 20-min counseling sessions on alternate days while in hospital. Self-reports of smoking status were obtained at 3 and 6 months, a sample of which were validated with serum COHb. The results were disappointing. Differences between the counseled group and the controls both in rates of cessation at 6 months (33.3% vs 21.4%) and, for patients still smoking, reductions in amount smoked would have lacked practical significance even if statistical significance had been obtained. Some alternative treatment approaches are suggested for this group of patients.
Smoking cessation in patients with chronic obstructive pulmonary disease: a double-blind, placebo-controlled, randomised trial.
BACKGROUND: Tobacco smoking is associated with chronic obstructive pulmonary disease (COPD) in more than 80% of cases. Our aim was to investigate the effect of sustained-release bupropion (amfebutamone) (SR) in promoting abstinence from smoking in patients with COPD.
METHODS: In a double-blind, randomised, placebo-controlled trial 404 individuals with mild or moderate COPD who smoked 15 or more cigarettes per day, were assigned bupropion SR (150 mg twice daily) or placebo for 12 weeks. All patients received smoking cessation counselling. Study medication was taken for 1 week before patients attempted to stop smoking. The primary efficacy endpoint was the complete and continuous abstinence from smoking from the beginning of week 4 to the end of week 7. Participants were followed up at month 6. Analysis was by intention to treat.
FINDINGS: All patients were chronic smokers with a smoking history of about 51 pack-years. Continuous smoking abstinence rates from week 4 to 7 were significantly higher in participants receiving bupropion SR than in those receiving placebo (28% [57/204] vs 16% [32/200], p=0.003). Continuous abstinence rates from weeks 4 to 12 (18% [36/204] vs 10% [20/200]) and weeks 4 to 26 (16% [32/204] vs 9% [18/200]) were also higher in participants receiving bupropion SR than in those taking placebo (p<0.05). Furthermore, symptoms of tobacco craving and withdrawal were attenuated in those receiving bupropion SR. Seven individuals discontinued study medication because of adverse events.
INTERPRETATION: Bupropion SRis a well-tolerated and effective aid to smoking cessation in people with mild to moderate COPD.
Options:
A: Psychosocial interventions alone
B: Pharmacological interventions alone
C: Combination of psychosocial and pharmacological interventions
D: No treatment | C |
267 | 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 clinical effectiveness of Acetyl-L-carnitine (ALC) in the treatment of people with dementia, based on the review of double-blind, randomized trials? Please answer this question based on the information provided below:
Pharmaco-electroencephalographic and clinical effects of the cholinergic substance--acetyl-L-carnitine--in patients with organic brain syndrome.
In two double-blind, placebo-controlled clinical studies of the nootropic compound acetyl-L-carnitine on the electroencephalogram (EEG) and impaired brain functions of elderly outpatients with mild to moderate cognitive decline of the organic brain syndrome, statistically significant effects could be detected after eight weeks (on the EEG), and after 12 weeks of treatment (on the physician's clinical global impression and the patient-rated level of activities of daily living). Side-effects of acetyl-L-carnitine were generally minor and overall rare. Longer treatment periods and further specifications with regard to the aetiopathology and degree of cognitive impairment are recommended for further clinical studies of this promising compound.
Efficacy and clinical relevance of cognition enhancers.
Changes from the end of 4-week placebo (washout) baselines to the end of 3-month therapy with three chemically different cognition enhancers (CEs) [i.e., piracetam, acetyl-L-carnitine, and nimodipine (NIM)], and parallel changes in placebo controls, were compared to determine the influence of the severity of disease at study entry. Four trials published elsewhere, showing significant treatment differences between active drugs and placebo, were selected according to their (a) sharing at least one global measure for treatment outcome and having shown effects on at least one additional scale or test, and (b) presenting an obvious rank order in the severity of disease. Each study was a standard-controlled clinical phase III trial with greater than 100 psychogeriatric in-or outpatients. The patients' symptoms met the criteria for mild to moderate/severe age-related organic brain syndrome, a core syndrome of senile dementia, either from the primary degenerative, mixed, or multi-infarct type. The extent of changes on placebo was clearly influenced by the mean pretreatment severity of disease. On the whole, the improvements on active drugs reached or exceeded the baseline variability of psychogeriatric scales and tests.
Acetyl-L-carnitine in the treatment of mildly demented elderly patients.
It has been hypothesized that acetyl-L-carnitine has a cholinomimetic action. It is for this reason that it has been used in the therapy of Alzheimer's type senile dementia impairment. In the present controlled double-blind study the authors followed two randomized homogeneous groups of both sexes of 30 patients each, aged over 65 years and suffering from mild mental impairment. One group of patients underwent therapy with acetyl-L-carnitine, 2 g/day for three months, while the other group was treated with a placebo. The statistical evaluation of the results was carried-out using non-parametric methods (Friedman-Nemenyi two-way ANOVA). It was possible to affirm that the acetyl-L-carnitine treated patients showed statistically significant improvement in the behavioural scales, in the memory tests, in the attention barrage test and in the Verbal Fluency test. These satisfactory results confirm the therapeutic importance of acetyl-L-carnitine in the treatment of elderly patients with mental impairment, which could be related principally to acetylcholine defects.
Mental impairment in aging: selection of patients, methods of evaluation and therapeutic possibilities of acetyl-L-carnitine.
The authors carried out a double-blind study in two randomized homogeneous groups of both sexes of 15 patients each, over 65 years of age and suffering from mild mental impairment. One group of patients underwent therapy with acetyl-L-carnitine, 2 g/day for three months, while the other group was treated with a placebo. The statistical evaluation of the results were carried out using nonparametric methods (Friedman-Nemenyi two-way Anova and Mann Whitney U-Test). However, the two groups did not differ significantly in either test at the end of treatment. It is possible to affirm that the acetyl-L-carnitine treated patients showed statistically significant improvement in the behavioural performances (Blessed Dementia Scale p less than 0.02; Stuard Hospital Geriatric Rating Scale p less than 0.01), in the memory tests (Rey short-term p less than 0.02; Rey long-term p less than 0.05; Corsi p less than 0.05), in the attention test (Barrage test p less than 0.01) and in the Verbal Fluency test p less than 0.01).
Double-blind, placebo controlled study of acetyl-l-carnitine in patients with Alzheimer's dementia.
A randomized, double-blind, placebo-controlled, parallel-group clinical trial was carried out to compare 24-week periods of treatment with 1 g acetyl-l-carnitine twice daily and placebo in the treatment of patients with dementia of the Alzheimer type. A total of 36 patients entered the trial, of whom 20 patients (7 active, 13 placebo) completed the full 24 weeks. Whilst several of the efficacy indices showed little change in either group during the trial, there was an apparent trend for more improvement in the acetyl-l-carnitine group in relation to the Names Learning Test and a computerized Digit Recall Test, both related to aspects of short-term memory. Similarly, there was a trend for reaction time in the computerized classification test to show less deterioration in the active treatment group. Changes within groups, and changes between groups, failed to reach statistical significance, at least partially because of the small number of patients available for analysis. Two indices of overall therapeutic benefit showed a trend for less deterioration in the active-treatment group than in the placebo group. Nausea and/or vomiting occurred in 5 patients in the acetyl-l-carnitine group. Laboratory tests revealed no signs of drug toxicity. The results suggest that acetyl-l-carnitine may have a beneficial effect on some clinical features of Alzheimer-type dementia, particularly those related to short-term memory.
Double-blind parallel design pilot study of acetyl levocarnitine in patients with Alzheimer's disease.
Acetyl levocarnitine hydrochloride has been reported to retard dementia in patients with Alzheimer's disease. In a double-blind, parallel design, placebo-controlled pilot study of 30 mild to moderately demented patients with probable Alzheimer's disease, tests of memory, attention, language, visuospatial, and constructional abilities were administered, and the level of acetyl levocarnitine was measured in the cerebrospinal fluid. Patients were then randomly assigned to receive acetyl levocarnitine hydrochloride (2.5 g/d for 3 months followed by 3 g/d for 3 months) or placebo. After 6 months, the acetyl levocarnitine group demonstrated significantly less deterioration in timed cancellation tasks and Digit Span (forward) and a trend toward less deterioration in a timed verbal fluency task. No differences were found in any other neuropsychological test results. A subgroup with the lowest baseline scores, receiving acetyl levocarnitine, had significantly less deterioration on the verbal memory test and a significant increase in cerebrospinal fluid acetyl levocarnitine levels compared with those receiving placebo. These results suggest that acetyl levocarnitine may retard the deterioration in some cognitive areas in patients with Alzheimer's disease and stress the need for a larger study of this drug.
An example of a clinical trial in patients with Alzheimer's disease: some methodological issues.
UNLABELLED: In ten Italian centers--hospitals and geriatric institutions--130 outpatients and inpatients with a diagnosis of Alzheimer's disease were recruited for a randomized, double blind, placebo controlled clinical trial with 1-acetylcarnitine. In planning the trial, we had to deal with some important and largely open issues.
DIAGNOSIS: we decided not to use neuropsychological tests (NPT) in the diagnostic process, both for the unknown risk of false positive and false negative rate and to improve the feasibility of the trial.
FOLLOW-UP: it must be representative of the disease and consequently we chose to follow the patients for one year (assessment at baseline, 3rd, 6th and 12th month) in spite of a possible high rate of drop-outs.
ASSESSMENT: to assess the patients' outcome we used NPT and behavioural scales. However, the validity, reliability and feasibility of these instruments are rarely discussed and their usefulness as indicators of the relevant aspects of the disease needs a careful evaluation.
STATISTICAL ANALYSIS: in this type of trial there is both a high risk of alpha-error, in view of the high number of NPT and behavioural scales used to assess the drug efficacy, and a high risk of beta-error connected with the usually small sample size. Thus, the role of small trials in defining the risk/benefit ratio of a treatment needs to be discussed.
Long-term acetyl-L-carnitine treatment in Alzheimer's disease.
In a double-blind, placebo-controlled, parallel-group, randomized clinical trial, we studied the efficacy of long-term (1-year) oral treatment with acetyl-L-carnitine in 130 patients with a clinical diagnosis of Alzheimer's disease. We employed 14 outcome measures to assess functional and cognitive impairment. After 1 year, both the treated and placebo groups worsened, but the treated group showed a slower rate of deterioration in 13 of the 14 outcome measures, reaching statistical significance for the Blessed Dementia Scale, logical intelligence, ideomotor and buccofacial apraxia, and selective attention. Adjusting for initial scores with analysis of covariance, the treated group showed better scores on all outcome measures, reaching statistical significance for the Blessed Dementia Scale, logical intelligence, verbal critical abilities, long-term verbal memory, and selective attention. The analysis for patients with good treatment compliance showed a greater drug benefit than for the overall sample. Reported adverse events were relatively mild, and there was no significant difference between the treated and placebo groups either in incidence or severity.
Acetyl L-carnitine slows decline in younger patients with Alzheimer's disease: a reanalysis of a double-blind, placebo-controlled study using the trilinear approach.
OBJECTIVES: To assess the longitudinal effects of acety-L-carnitine (ALC) on patients diagnosed with Alzheimer's disease.
DESIGN: Longitudinal, double-blind, parallel-group, placebo-controlled.
SETTING: Twenty-four outpatient sites across the United States.
PARTICIPANTS: A total of 334 subjects diagnosed with probable Alzheimer's disease by NINCDS-ADRDA criteria. These data were originally reported by Thal and colleagues (1996).
MEASUREMENTS: Cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS) given every 3 months for 1 year.
RESULTS: The average rate of change was estimated using the trilinear approach, which allows for periods of both change and stability. Both the ALC group and the placebo group exhibited the same mean rate of change on the ADAS (0.68 points/month). However, a multiple regression analysis revealed a statistically significant Age x Drug interaction characterized by younger subjects benefiting more from ALC, significant, cutpoint for ALC benefit was 61 years of age.
CONCLUSIONS: ALC slows the progression of Alzheimer's disease in younger subjects, and the use of the trilinear approach to estimate the average rate of change may prove valuable in pharmacological trials.
A 1-year multicenter placebo-controlled study of acetyl-L-carnitine in patients with Alzheimer's disease.
A 1-year, double-blind, placebo-controlled, randomized, parallel-group study compared the efficacy and safety of acetyl-L-carnitine hydrochloride (ALCAR) with placebo in patients with probable Alzheimer's disease (AD). Subjects with mild to moderate probable AD, aged 50 or older, were treated with 3 g/day of ALCAR or placebo (1 g tid) for 12 months. Four hundred thirty-one patients entered the study, and 83% completed 1 year of treatment. The Alzheimer's Disease Assessment Scale cognitive component and the Clinical Dementia Rating Scale were the primary outcome measures. Overall, both ALCAR- and placebo-treated patients declined at the same rate on all primary and most secondary measures during the trial. In a subanalysis by age that compared early-onset patients (aged 65 years or younger at study entry) with late-onset patients (older than 66 at study entry), we found a trend for early-onset patients on ALCAR to decline more slowly than early-onset AD patients on placebo on both primary endpoints. In addition, early-onset patients tended to decline more rapidly than older patients in the placebo groups. Conversely, late-onset AD patients on ALCAR tended to progress more rapidly than similarly treated early-onset patients. The drug was very well tolerated during the trial. The study suggests that a subgroup of AD patients aged 65 or younger may benefit from treatment with ALCAR whereas older individuals might do more poorly. However, these preliminary findings are based on past hoc analyses. A prospective trial of ALCAR in younger patients is underway to test the hypothesis that young, rapidly progressing subjects will benefit from ALCAR treatment.
A 1-year controlled trial of acetyl-L-carnitine in early-onset AD.
A 1-year controlled trial of acetyl-l-carnitine in early-onset AD.
OBJECTIVE: To determine the efficacy of acetyl-l-carnitine (ALCAR) on the rate of decline in early-onset AD patients.
METHODS: A 1-year, multicenter, double-blind, placebo-controlled, randomized trial was conducted. Subjects were 45 to 65 years old, with a diagnosis of probable AD according to National Institute of Neurological Communicative Disorders-Alzheimer's Disease and Related Disorders Association criteria and had a Mini-Mental State Examination (MMSE) score between 12 and 26. They were treated with ALCAR (1 g tid) or placebo. Primary outcome measures were the Alzheimer's Disease Assessment Scale-Cognitive Component and the Clinical Dementia Rating Scale. Secondary measures included the ADAS Non-Cognitive Subscale, the MMSE, an Activities of Daily Living Scale (ADL), and a Clinician-Based Impression of Change (CIBIC).
RESULTS: Two-hundred twenty-nine patients were enrolled and randomized to drug treatment, with 117 taking placebo and 112 taking ALCAR. There were no significant differences between the two groups at baseline. For the primary outcome measures, there were no significant differences between the treatment groups on the change from baseline to endpoint in the intent-to-treat analysis. In the completer sample only, there was less deterioration in the MMSE for the ALCAR-treated subjects. There was no difference in rate of decline on the CIBIC and the ADL scale. There were no significant differences in the incidence of adverse events by treatment arm.
CONCLUSION: Overall, in a prospectively performed study in young-onset AD patients, ALCAR failed to slow decline. Less decline was seen on the MMSE in the completer sample only, with the difference being mediated by reducing decline in attention. A combination of ALCAR and a cholinesterase inhibitor should be tested for additivity.
Options:
A: ALC showed significant improvement in cognitive function, severity of dementia, and functional ability.
B: ALC demonstrated statistically significant improvement in Clinical Global Impression at 12 and 24 weeks, but not at 52 weeks, with no evidence of benefit in other areas.
C: ALC was found to be highly effective across all measured outcomes, including cognition, severity of dementia, and functional ability.
D: ALC showed no statistically significant differences in any measured outcomes compared to placebo. | B |
268 | 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 involving diabetes specialist nurses or nurse case managers on the metabolic control and overall outcomes for patients with type 1 and type 2 diabetes mellitus compared to usual care without specialist nurse input? Please answer this question based on the information provided below:
Failure to maintain the benefits of home-based intervention in adolescents with poorly controlled type 1 diabetes.
OBJECTIVE: To determine whether a 6-month home-based intervention program in adolescents with poorly controlled diabetes improves metabolic control and whether benefits are maintained after the intervention.
RESEARCH DESIGN AND METHODS: Adolescents with a mean HbA1c of > 9.0% over the preceding 12 months received either routine care in a diabetes clinic and an ambulatory intervention for 6 months (n = 37) or routine care only (n = 32). A diabetes educator provided monthly home visits and weekly phone contact to educate and support the adolescents in setting goals for insulin adjustment, blood glucose monitoring, and target blood glucose range. There was no systematic change in the frequency of insulin injections. After the intervention, there was a 12-month follow-up when the intervention and control groups both received only routine care. Outcome measures were HbA1c and Diabetes Knowledge Assessment (DKN).
RESULTS: During the intervention, mean HbA1c fell (baseline: 11.1 +/- 1.3%, 6 months: 9.7 +/- 1.6%; P = 0.0001) and mean knowledge scores increased (P = 0.0001) in the intervention group but not in control subjects. However, this improvement in HbA1c and increase in knowledge was not maintained in the intervention group at 12- and 18-month follow-up assessments. Parents' knowledge scores also improved significantly from baseline levels in the intervention group at 6 and 12 months (P = 0.001, P = 0.005, respectively).
CONCLUSIONS: An ambulatory program improves metabolic control and knowledge in adolescents with poorly controlled type 1 diabetes; however, it is effective only while the intervention is maintained.
Using telecommunication technology to manage children with diabetes: the Computer-Linked Outpatient Clinic (CLOC) Study.
The purpose of this study was to evaluate the efficacy of using a telecommunication system to assist in the outpatient management of pediatric patients with insulin-dependent diabetes. Metabolic control, patients' psychosocial status, family functioning, perceived quality of life, patterns of parental/child responsibility for daily diabetes maintenance, and nursing time-on-task were evaluated. One hundred six pediatric patients (mean age = 13.3 years) were randomly assigned to an experimental or control outpatient clinic for 1 year. Experimental subjects transmitted self-monitoring blood glucose data by modem to the hospital every 2 weeks. Transmitted data were reviewed by nurse practitioners who telephoned subjects to discuss regimen adjustments. Control subjects received standard care with regimen adjustments made by physicians. There were no significant between-group differences for metabolic control, rates of hospitalization or emergency-room visits, psychological status, general family functioning, quality of life, or parent-child responsibility. A significant decrease was noted in nursing time-on-task for experimental subjects.
Do automated calls with nurse follow-up improve self-care and glycemic control among vulnerable patients with diabetes?
PURPOSE: We sought to evaluate the effect of automated telephone assessment and self-care education calls with nurse follow-up on the management of diabetes.
SUBJECTS AND METHODS: We enrolled 280 English- or Spanish-speaking adults with diabetes who were using hypoglycemic medications and who were treated in a county health care system. Patients were randomly assigned to usual care or to receive an intervention that consisted of usual care plus bi-weekly automated assessment and self-care education calls with telephone follow-up by a nurse educator. Outcomes measured at 12 months included survey-reported self-care, perceived glycemic control, and symptoms, as well as glycosylated hemoglobin (Hb A1c) and serum glucose levels.
RESULTS: We collected follow-up data for 89% of enrollees (248 patients). Compared with usual care patients, intervention patients reported more frequent glucose monitoring, foot inspection, and weight monitoring, and fewer problems with medication adherence (all P -0.03). Follow-up Hb A,, levels were 0.3% lower in the intervention group (P = 0.1), and about twice as many intervention patients had Hb A1c levels within the normal range (P = 0.04). Serum glucose levels were 41 mg/dL lower among intervention patients than usual care patients (P = 0.002). Intervention patients also reported better glycemic control (P = 0.005) and fewer diabetic symptoms (P <0.0001 ), including fewer symptoms of hyperglycemia and hypoglycemia.
CONCLUSIONS: Automated calls with telephone nurse follow-up may be an effective strategy for improving self-care behavior and glycemic control, and for decreasing symptoms among vulnerable patients with diabetes.
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.
Insulin adjustment by a diabetes nurse educator improves glucose control in insulin-requiring diabetic patients: a randomized trial.
BACKGROUND: Diabetic patients taking insulin often have suboptimal glucose control, and standard methods of health care delivery are ineffective in improving such control. This study was undertaken to determine if insulin adjustment according to advice provided by telephone by a diabetes nurse educator could lead to better glucose control, as indicated by level of glycated hemoglobin (HbA1c).
METHODS: The authors conducted a prospective randomized trial involving 46 insulin-requiring diabetic patients who had poor glucose control (HbA1c of 0.085 or more). Eligible patients were those already taking insulin and receiving endocrinologist-directed care through a diabetes centre and whose most recent HbA1c level was 0.085 or higher. The patients were randomly assigned to receive standard care or to have regular telephone contact with a diabetes nurse educator for advice about adjustment of insulin therapy.
RESULTS: At baseline there was no statistically significant difference between the 2 groups in terms of HbA1c level (mean [and standard deviation] for standard-care group 0.094 [0.008] and for intervention group 0.096 [0.010]), age, sex, type or duration of diabetes, duration of insulin therapy or complications. After 6 months, the mean HbA1c level in the standard-care group was 0.089 (0.010), which was not significantly different from the mean level at baseline. However, the mean HbA1c level in the intervention group had fallen to 0.078 (0.008), which was significantly lower than both the level at baseline for that group (p < 0.001) and the level for the standard-care group at 6 months (p < 0.01).
INTERPRETATION: Insulin adjustment according to advice from a diabetes nurse educator is an effective method of improving glucose control in insulin-requiring diabetic patients.
Options:
A: Specialist nurse involvement significantly improves glycated haemoglobin (HbA1c) levels over a 12-month period.
B: Specialist nurse involvement significantly reduces episodes of hypoglycaemia and hyperglycaemia.
C: Specialist nurse involvement significantly improves quality of life and reduces emergency admissions.
D: Specialist nurse involvement may improve diabetic control over short periods, but long-term effects are not evident, and there are no significant differences in hypoglycaemic episodes, hyperglycaemic incidents, or hospital admissions. | D |
269 | 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 regular breast self-examination in reducing breast cancer mortality and morbidity? Please answer this question based on the information provided below:
Outcome of screening by clinical examination of the breast in a trial in the Philippines.
The value of screening by Clinical Examination of the Breast (CBE) as a means of reducing mortality from breast cancer (BC) is not established. The issue is relevant, as CBE may be a suitable option for countries in economic transition, where incidence rates are on the increase but limited resources do not permit screening by mammography. Our aims were to assess whether mass screening by CBE carried out by trained para-medical personnel is feasible in an urban population of a low-income country, and its efficacy in reducing BC mortality. Our study was designed as a randomised controlled trial of the effect on BC mortality of 5 annual CBE carried out by trained nurses. The target population was women aged 35-64 years, resident in 12 municipalities of the National Capital Region of Manila, Philippines. The units of randomization were the 202 health centres (HC) within the selected municipalities. During 1995 nurses and midwives were recruited and trained in performing CBE. The first round of screening took place in 1996-1997. The intervention however showed a refractory attitude of the population with respect to clinical follow-up and was discontinued after the completion of the first screening round. Cases of breast cancer occurring in the study population during 1996-1999 were identified by the 2 local population-based registries. In the single screening round 151,168 women were interviewed and offered CBE, 92% accepted (138,392), 3,479 were detected positive for a lump and referred for diagnosis. Of these only 1220 women (35%) completed diagnostic follow-up, whereas 42.4% actively refused further investigation even with home visits, and 22.5% were not traced. Of 53 cases that occurred among screen-positive women in the 2 years after CBE only 34 were diagnosed through the intervention. Eighty cases occurred among screen-negative women. The test sensitivity for CBE repeated annually was 53.2%. The actual sensitivity of the programme was 25.6% and positive predictive value 1%. Screen-detected cases were non-significantly less advanced than the others. Previous studies have shown that most breast cancer cases in the Philippines present at advanced stages and have an unfavourable outcome. Although CBE undertaken by health workers seems to offer a cost-effective approach to reducing mortality, the sensitivity of the screening programme in the real context was low. Moreover, in this relatively well-educated population, cultural and logistic barriers to seeking diagnosis and treatment persist and need to be addressed before any screening programme is introduced.
[Results of a prospective randomized investigation [Russia (St.Petersburg)/WHO] to evaluate the significance of self-examination for the early detection of breast cancer].
Indications for puncture or excision biopsy were significantly higher in the study group (7.5%) as compared with control (3.5%) (p < 0.01) in a randomized prospective controlled trial of a comprehensive breast cancer screening (123,748) carried out in the framework of a self-examination education program. In the self-examination group, detection rates were higher both for benign (1.1%) and malignant (0.85%) tumors than in control (0.5% and 0.69%, respectively) (p < 0.05). Early stage (T1NOMO, Tis) distribution difference in the study group and controls was insignificant--23 and 17.6%, respectively. Compliance with the program requirements including monthly or bimonthly self-examination was followed by higher 15-year survival rates (53.2%) in 70-75% as compared with controls(45.8%) (p = 0.05105): yet it did not affect mortality.
Breast self-examination for the early detection of breast cancer: a USSR/WHO controlled trial in Leningrad.
Breast self-examination (BSE) is of great potential value for the early detection of breast cancer, especially in areas where mammography and regular examinations by physicians are not practicable. However, BSE cannot be recommended for routine public health practice until there is good evidence that it is effective in reducing mortality from breast cancer. Prospective controlled trials of BSE were therefore initiated in 1985 in Leningrad and Moscow, under the auspices of WHO, in order to establish the value of this potentially cost-effective technique. More than 62 000 women aged 40-64 years have been enrolled in the BSE and control groups in Leningrad and another 88 000 will be added in the next three years. This paper presents the results of the study in Leningrad after the first 15 months.
[Work experience of the WHO International Reference Center in assessing the effectiveness of self-examination for the early diagnosis of breast cancer (results of 2 years' research)].
A prospective controlled study of the effectiveness of self-examination for early detection of breast cancer has been conducted in Leningrad since 1985. The study was carried out in a cohort of 90,000 females at 28 in- and outpatient clinics within 24 months. As a result, breast cancer was identified in 82 cases. Mean size of primary tumor proved 1.0 cm less and tumor detected 4.8 months earlier than those with standard diagnostic procedures. The cohort is planned to expand to 150,000 by the end of 1988. Data on correlation between application of self-examination and breast cancer mortality are expected by 1994.
[Interim results of a prospective randomized study of self-examination for early detection of breast cancer (Russia/St.Petersburg/WHO)].
Training in breast self-examination (BSE) technique involved 57,712 women, aged 40-64, at 14 out of randomly selected out-patient hospitals in St. Petersburg (1985-1989). Another 64,759 women selected at another 14 out-patient hospitals were in control. All patients with detected tumor pathology of the breast were biopsied and treated at the Institute's Clinic. The study focused on breast cancer incidence, survival and mortality. More women in the BSE group sought medical advice for suspected pathology (4,300) than those in control (2,438; p < 0.05). There were 493 cases of breast cancer in the BSE group with 157 fatalities, 446 cases of breast cancer with 167 fatalities in the control group. There was no significant difference in tumor stage. Nine-year survival (after Kaplan-Meyer) from the time of tumor detection was 65% in the study group and 55% in control (log rank 0.774; p > 0.05). There has been no significant difference in death rates in both groups for the past ten years. The study is to continue until the year 2001.
[Preliminary results of the Russia (St.Petersburg)/WHO program for the evaluation of the effectiveness of breast self-examination].
Although an absolute difference of 10% (65,4 vs. 54,9%) in 5- and 9-year survival in breast cancer patients was recorded between the self-examination and control groups a large-scale randomized population-controlled study of 122,471 females has failed to provide significant differences (Log-rank - 0,774, p > 0.05). No significant decrease in mortality was observed in the self-examination group as compared with the untrained controls. As a result of providing more information to the population on risk factors. twice as many of the trained females consulted oncologists. Also, the number of early detection of breast tumor (T1-2NOMO) in both groups was 1,5-2,5 times that recorded elsewhere. Since 3,55 per 1,000 patients with breast tumors per year, aged 50-59, died of cardio-vascular disease, i.e. 3,1 times the expected 1,16 per 1,000, more attention should be focused on timely diagnosis and treatment of concomitant cardio-vascular pathology.
[Results of phase I study of the effectiveness of self-examination in a program of early detection of breast cancer].
The paper deals with the results of the first phase of a WHO-sponsored study concerned with evaluation of the effectiveness of breast self-examination and carried out in Leningrad. The study was part of a program for early breast cancer diagnosis. 8,000 females were taught the procedure of self-examination. A randomized survey of a representative group of 400 females was conducted during the first 12 months using a special questionnaire. It was intended for evaluating the subjects' comprehension of the aims of the program, their attitude to it and their knowledge on cancer. Due to training as well as regular reminding, the percentage of women who practiced self-examination was as high as 75.1. The results of an analysis of refusals to carry out self-examination are presented.
Current evaluation of the contribution of self-examination to secondary prevention of breast cancer.
The "state of art" in the problem of BSE and its role in breast cancer early diagnoses in analysed. Advantages and disadvantages of this method and a complex of socio-psychologic problems arising in healthy population due to its introduction are discussed. The absence of scientifically grounded data on the importance of BSE for early diagnosis of breast cancer suggests the necessity of further investigations in order to identify its efficacy. Such data can be obtained only on the basis of randomized population study with estimation of efficacy by the decrease of breast cancer mortality in population. Under the auspices of the WHO such investigation has been conducted in Leningrad and in Moscow (USSR). Methods or investigation applied are described in short.
The role of breast self-examination in early breast cancer detection (results of the 5-years USSR/WHO randomized study in Leningrad).
A randomized population-based study has been carried out since 1985 in Leningrad in order to evaluate the efficacy of breast self-examination (BSE) in early breast cancer detection. The population under study covers 120,310 women aged 40-64 years with no history of breast cancer. About half of these women were exposed to BSE training (60,221) and 60,098 women constituted the control group. BSE teaching was carried out on a person-to-person basis and each patient received the BSE calendar. BSE education sessions resulted in a higher frequency of visits to specialists with complaints about "pathology" of the breast, a higher rate of referral to a specialized institution for an examination, and a higher number of excision biopsies due to a benign lesion (RR = 1.5; 95% C.I. = 1.1 - 1.9) as compared with the control group. As a result of examination, 190 breast cancer patients in the BSE group and 192 patients in the control group were detected. Comparisons of patients from both groups with regard to the size of primary tumor and the incidence of metastatic lesion in the regional lymph nodes showed no differences. The study is ongoing and all cases of breast cancer in the BSE group will be registered up to 1994 and followed-up to 1999; information will then be available on the impact of BSE upon breast cancer mortality.
[The problem of the participation of women in a program for the early detection of breast cancer using self-examination].
The USSR/WHO program in Leningrad which included 120000 females aged 40-64 years showed the percentage of breast self-examinees to drop from 82.0 to 55.8, and from 52.3 to 17.9% in those who performed monthly self-examination. This is accounted for by the lack of interest in this problem in the mass media.
Study of the role of breast self-examination in the reduction of mortality from breast cancer. The Russian Federation/World Health Organization Study.
The protocol of a study, sponsored by the World Health Organization, of the role of breast self-examination (BSE) in reduction of mortality from breast cancer is presented. The major objective of the study is to determine the effect of a BSE programme on mortality from breast cancer. A population of of over 193,000 women aged 40 to 64 has been defined in Moscow and St Petersburg and randomised to study and control groups. In Moscow the education programme is based on a two-way communication principle allowing efficient person-to-person education in groups of up to 20 individuals and feedback information through specially designed personal calendars. In St Petersburg, class and individual instruction is carried out. After a 1-year feasibility study the project is planned to last for 15 years. It consists of an aggressive education programme, during and following which, all newly diagnosed breast cancers will be registered and treated, and followed up for 3 to 15 years. A key issue of the study is compliance of the population with BSE. The frequency and competence of BSE practice has been defined in subsamples of 400 randomly selected women by means of surveys at 6 months, 1, 2 and 3 years after the start of the project. The study is expected to result in the accrual of more than 1470 new breast cancer cases and 778 deaths from breast cancer. The power of the study is expected to permit detection of a 30% reduction in cumulative breast cancer mortality, assuming that 50-70% of the women in the study group practise BSE.
[Evaluation on the effect of intervention regarding breast self-examination for decreasing breast cancer mortality].
OBJECTIVE: A randomized trial of breast self-examination (BSE) Program was carried out to evaluate whether the intensive BSE could reduce the number of deaths among women from breast cancer.
METHODS: This study was a randomized controlled trial (RCT). A total of 266 064 women (age of 30 to 64 years) associated with 519 textile factories in Shanghai had been randomly assigned to a BSE group (132 979 women) or a control group (133 085 women) since 1989. Initial instruction in BSE group would include demonstration of proper palpation techniques and was followed by 2 reinforcement sessions during the subsequent 4 years including video shows, BSE instruction sessions and BSE practice under medical supervision. These activities were continued for 5 years. Attendance at all events was recorded. The cohort was followed through July 2000 for development of breast diseases, and the breast cancer cases were followed through 2001 for vital status. Data analysis methods used would include Kaplan-Meier plots, log-rank test and Cox modeling.
RESULTS: Among women under instruction, 864 breast cancers detected and 133 breast cancer deaths occurred while 896 breast cancers were detected and 130 deaths recorded in the control group. The tumor size (P = 0.07), TNM stage (P = 0.39) and cumulative breast cancer mortality rate (P = 0.72) were not significantly different between the 2 groups. However, more and smaller fibroadenomas were detected in the instruction group than in the control group (P< 0.01).
CONCLUSION: Intensive instruction in BSE did not seem to have reduced the mortality rate of breast cancer, but more and smaller benign breast lumps could be detected.
[Randomized trial of breast self-examination in 266,064 women in Shanghai].
OBJECTIVE: A randomized trial of breast self-examination (BSE) program was carried out to evaluate whether the intensive BSE can reduce the death number of women from breast cancer.
METHODS: A total of 266,064 women (age of 30 to 64 years) associated with 519 textile factories in Shanghai had been randomly assigned to a BSE instruction group (132,979 women) or a control group (133,085 women) since 1989. Initial instruction in BSE group included demonstration of proper palpation techniques. It was followed by 2 reinforcement sessions during the subsequent 4 years including video shows, BSE instruction sessions and BSE practice under medical supervision. These activities were continued for 5 years. Attendance at all events was recorded. The cohort was followed through July 2000 for development of breast diseases, and the breast cancer cases were followed up through 2001 for vital status. The data analysis methods used included Kaplan-Meier plots, Log-rank test and Cox modeling.
RESULTS: Among women under instruction, 864 breast cancers were detected and 133 breast cancer deaths occurred, and 896 breast cancers were detected and 130 deaths recorded in the control group. The tumor size (P = 0.07), TNM stage (P = 0.39) and cumulative breast cancer mortality rate (P = 0.72) were not significantly different between the 2 groups. However, more and smaller fibroadenomas were detected in the instruction group than in the control group (P < 0.01).
CONCLUSION: Intensive instruction in BSE can not reduce mortality rate of breast cancer, but more and smaller benign breast lumps can be detected.
Randomized trial of breast self-examination in Shanghai: final results.
BACKGROUND: Among women who practice breast self-examination (BSE), breast cancers may be detected when they are at an earlier stage and are smaller than in women who do not practice BSE. However, the efficacy of breast self-examination for decreasing breast cancer mortality is unproven. This study was conducted to determine whether an intensive program of BSE instruction will reduce the number of women dying of breast cancer.
METHODS: From October 1989 through October 1991, 266,064 women associated with 519 factories in Shanghai were randomly assigned to a BSE instruction group (132,979 women) or a control group (133,085 women). Initial instruction in BSE was followed by reinforcement sessions 1 and 3 years later, by BSE practice under medical supervision at least every 6 months for 5 years, and by ongoing reminders to practice BSE monthly. The women were followed through December 2000 for mortality from breast cancer. Cumulative risk ratios of dying from breast cancer were estimated using Cox proportional hazards models. All statistical tests were two-sided.
RESULTS: There were 135 (0.10%) breast cancer deaths in the instruction group and 131 (0.10%) in the control group. The cumulative breast cancer mortality rates through 10 to 11 years of follow-up were similar (cumulative risk ratio for women in the instruction group relative to that in the control group = 1.04, 95% confidence interval = 0.82 to 1.33; P =.72). However, more benign breast lesions were diagnosed in the instruction group than in the control group.
CONCLUSIONS: Intensive instruction in BSE did not reduce mortality from breast cancer. Programs to encourage BSE in the absence of mammography would be unlikely to reduce mortality from breast cancer. Women who choose to practice BSE should be informed that its efficacy is unproven and that it may increase their chances of having a benign breast biopsy.
Randomized trial of breast self-examination in Shanghai: methodology and preliminary results.
BACKGROUND: The efficacy of breast self-examination in helping to reduce mortality from breast cancer has not been rigorously demonstrated.
PURPOSE: To assess efficacy, a large, randomized trial was initiated in Shanghai, China.
METHODS: From October 1989 to October 1991, 267040 current and retired female employees associated with 520 factories in the Shanghai Textile Industry Bureau were randomly assigned on the basis of factory to either a self-examination instruction group (133375 women) or a control group (133665 women). The women were born within the period from 1925 through 1958. Women in the instruction group were given intensive training in breast self-examination, including the use of silicone breast models and personalized instruction, plus two subsequent reinforcement sessions and multiple reminders to practice the technique. Women in the control group were asked to attend training sessions on the prevention of low back pain. All women have been followed for the development of breast diseases and for death from breast cancer.
RESULTS: A high level of participation during the first 4-5 years of the trial was documented among women in the instruction group. Randomly sampled women in this group demonstrated greater proficiency in detecting lumps in breast models than did randomly sampled women in the control group. Approximately equal numbers of breast cancers were detected in the two groups (331 in the instruction group and 322 in the control group) through 1994, which is the last year for which case-finding efforts have been completed. The breast cancers detected in the instruction group were not diagnosed at an appreciably earlier stage or smaller size than those in the control group. More benign breast lesions were detected in the instruction group than in the control group (1457 versus 623, respectively), suggesting a higher index of suspicion for women who received training. Cumulative breast cancer mortality rates through 5 years from entry into the study were nearly equivalent for the two groups.
CONCLUSIONS: Breast self-examination has not led to a reduction in mortality from breast cancer in this study cohort in the first several years since the trial began. A shift toward the diagnosis of disease at a less advanced stage in women given instruction has also not been demonstrated. Longer follow-up of participants in this trial is required before final assessment can be made of the efficacy of breast self-examination.
IMPLICATIONS: At this time, there is insufficient evidence to recommend for or against the teaching of breast self-examination.
Options:
A: Regular breast self-examination significantly reduced breast cancer mortality.
B: Regular breast self-examination significantly reduced breast cancer morbidity.
C: Regular breast self-examination did not show a statistically significant reduction in breast cancer mortality.
D: Regular breast self-examination showed a significant increase in breast cancer morbidity. | C |
270 | 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 folate as a treatment for depressive disorders? Please answer this question based on the information provided below:
Enhancement of the antidepressant action of fluoxetine by folic acid: a randomised, placebo controlled trial.
BACKGROUND: A consistent finding in major depression has been a low plasma and red cell folate which has also been linked to poor response to antidepressants. The present investigation was designed to investigate whether the co-administration of folic acid would enhance the antidepressant action of fluoxetine.
METHODS: 127 patients were randomly assigned to receive either 500 microg folic acid or an identical looking placebo in addition to 20 mg fluoxetine daily. All patients met the DSM-III-R criteria for major depression and had a baseline Hamilton Rating Scale (17 item version) score for depression of 20 or more. Baseline and 10-week estimations of plasma folate and homocysteine were carried out.
RESULTS: Patients receiving folate showed a significant increase in plasma folate. This was less in men than in women. Plasma homocysteine was significantly decreased in women by 20.6%, but there was no significant change in men. Overall there was a significantly greater improvement in the fluoxetine plus folic acid group. This was confined to women where the mean Hamilton Rating Scale score on completion was 6.8 (S.D. 4. 1) in the fluoxetine plus folate group, as compared to 11.7 (S.D. 6. 7) in the fluoxetine plus placebo group (P<0.001).A percentage of 93. 9 of women, who received the folic acid supplement, showed a good response (>50% reduction in score) as compared to 61.1% of women who received placebo supplement (P<0.005). Eight (12.9%) patients in the fluoxetine plus folic acid group reported symptoms possibly or probably related to medication, whereas in the fluoxetine plus placebo group 19 (29.7%) patients reported such symptoms (P<0.05).
LIMITATIONS AND CONCLUSIONS: Folic acid is a simple method of greatly improving the antidepressant action of fluoxetine and probably other antidepressants. Folic acid should be given in doses sufficient to decrease plasma homocysteine. Men require a higher dose of folic acid to achieve this than women, but more work is required to ascertain the optimum dose of folic acid.
Enhancement of recovery from psychiatric illness by methylfolate.
41 (33%) of 123 patients with acute psychiatric disorders (DSM III diagnosis of major depression or schizophrenia) had borderline or definite folate deficiency (red-cell folate below 200 micrograms/l) and took part in a double-blind, placebo-controlled trial of methylfolate, 15 mg daily, for 6 months in addition to standard psychotropic treatment. Among both depressed and schizophrenic patients methylfolate significantly improved clinical and social recovery. The differences in outcome scores between methylfolate and placebo groups became greater with time. These findings add to the evidence implicating disturbances of methylation in the nervous system in the biology of some forms of mental illness.
Enhancement of recovery from psychiatric illness by methylfolate.
"41 (33%) of 123 patients with acute psychiatric disorders (DSM III diagnosis of major depression or schizophrenia) had borderline or definite folate deficiency (red-cell folate below 200 micrograms/l) and took part in a double-blind, placebo-controlled trial of methylfolate, 15 mg daily, for 6 months in addition to standard psychotropic treatment. Among both depressed and schizophrenic patients methylfolate significantly improved clinical and social recovery. The differences in outcome scores between methylfolate and placebo groups became greater with time. These findings add to the evidence implicating disturbances of methylation in the nervous system in the biology of some forms of mental illness."
Oral 5'-methyltetrahydrofolic acid in senile organic mental disorders with depression: results of a double-blind multicenter study.
5'-Methyltetrahydrofolic acid (5'-MTHF) in addition to standard psychotropic medication significantly improved clinical recovery in depressed patients with borderline or definite folate deficiency, and significantly reduced depressive symptoms in elderly normofolatemic patients after 3 weeks of treatment. In this equivalence study the effect of 5'-MTHF on depressive symptoms and cognitive status was compared to Trazodone (TRZ) in normofolatemic elderly patients with mild to moderate dementia and depression. Ninety-six patients with dementia, scoring 12-23 at the Mini Mental State Examination (MMSE) and > or = 18 at the Hamilton Depression Rating Scale (HDRS) after a 2-week placebo run-in, were randomized to receive either 5'-MTHF (50 mg/day p.o.) (47 patients) or TRZ (100 mg/day p.o.) (49 patients) in a double-blind design for 8 weeks. HDRS was assessed before, after 4 weeks and at the end of treatment; Rey's Verbal Memory (RVM) test for immediate and delayed recall was evaluated before and after treatment. After 4 weeks of treatment HDRS score was reduced from 23 +/- 5 to 20 +/- 6 in the 5'-MTHF (p < 0.05 vs baseline), and from 23 +/- 3 to 21 +/- 4 in the TRZ group (p < 0.05 vs baseline). A further significant decrease to 18 +/- 6 and 19 +/- 5 respectively was obtained at the end of the treatment period (p < 0.05 vs week 4) with 5'-MTHF and TRZ.(ABSTRACT TRUNCATED AT 250 WORDS)
Options:
A: Folate was found to be effective as a standalone treatment for depression, with significant improvements in depression scores.
B: Folate, when used as an adjunctive therapy to other treatments, showed a reduction in depression scores and was found to be safe and acceptable.
C: Folate was found to be ineffective both as a standalone treatment and as an adjunctive therapy for depression.
D: Folate was found to be effective only for individuals with folate deficiency, with no benefits for those with normal folate levels. | B |
271 | 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 and safety of adjuvant amantadine therapy in treating dyskinesia in patients with Parkinson's disease who are already on levodopa? Please answer this question based on the information provided below:
Beneficial effects of amantadine on L-dopa-induced dyskinesias in Parkinson's disease.
L-Dopa-induced dyskinesias constitute a challenge to the management of advanced Parkinson's disease. According to recent reports, treatment with the NMDA receptor antagonist amantadine may significantly diminish L-dopa-induced dyskinesias. In the present study, the effect of amantadine on L-dopa-induced dykinesias was assessed in a 5-week, double-blind crossover trial. Dyskinesia severity as assessed following oral L-dopa challenges and by self-scoring dyskinesia diaries were reduced approximately 50% after amantadine treatment compared with baseline or placebo phases. Similarly, dyskinesia assessments on the Unified Parkinson's Disease Rating Scale, part IV (items 32 and 33) also revealed significant improvement after treatment with amantadine. The magnitude of the L-dopa motor response to oral challenges was not different after amantadine or placebo treatment, and there was no significant reduction of daily off-time when patients received active treatment. These results confirm previous observations concerning the antidyskinetic potential of amantadine.
The effect of amantadine on levodopa-induced dyskinesias in Parkinson's disease: a double-blind, placebo-controlled study.
We performed a double-blind, placebo-controlled, crossover study to assess the effect of amantadine versus placebo on levodopa-induced dyskinesias in Parkinson's disease. We found a 24% reduction in the total dyskinesia score after amantadine administration (p = 0.004). This improvement was achieved without any influence on the severity of "on" period parkinsonism. The results confirm that amantadine reduces levodopa dyskinesias and support the hypothesis that dyskinesias can be reduced by blockade of excitatory pathways in the basal ganglia.
Blockade of glutamatergic transmission as treatment for dyskinesias and motor fluctuations in Parkinson's disease.
In animal models of Parkinson's disease (PD), glutamate antagonists diminish levodopa (LD)-associated motor fluctuations and dyskinesias. We sought to investigate if these preclinical observations can be extended to the human disease, by evaluating the effects of three non-competitive NMDA antagonists (dextrorphan, dextromethorphan and amantadine) on the motor response to LD in patients with advanced PD. In four separate trials, adjuvant therapy with these drugs reduced LD-induced dyskinesias and motor fluctuations. These findings support the view that drugs acting to inhibit glutamatergic transmission at the NMDA receptor can ameliorate LD associated motor response complications.
Amantadine as treatment for dyskinesias and motor fluctuations in Parkinson's disease.
OBJECTIVE: To determine the effects of the N-methyl-D-aspartate (NMDA) antagonist amantadine on levodopa-associated dyskinesias and motor fluctuations in Parkinson's disease (PD).
BACKGROUND: NMDA receptor blockade can ameliorate levodopa-induced dyskinesias in primates and PD patients. Amantadine, a well-tolerated and modestly effective antiparkinsonian agent, was recently found to possess NMDA antagonistic properties.
METHODS: Eighteen patients with advanced PD participated in a double-blind, placebo-controlled, cross-over study. At the end of each 3-week treatment arm, parkinsonian and dyskinesia scores were obtained during a steady-state intravenous levodopa infusion. Motor fluctuations and dyskinesias were also documented with patient-kept diaries and Unified Parkinson's Disease Rating Scale (UPDRS) interviews.
RESULTS: In the 14 patients completing this trial, amantadine reduced dyskinesia severity by 60% (p = 0.001) compared to placebo, without altering the antiparkinsonian effect of levodopa. Motor fluctuations occurring with patients' regular oral levodopa regimen also improved according to UPDRS and patient-kept diaries.
CONCLUSIONS: These findings suggest that amantadine given as adjuvant to levodopa can markedly improve motor response complications and support the view that hyperfunction of NMDA receptors contributes to the pathogenesis of levodopa-associated motor complications.
Options:
A: Amantadine was found to be highly effective and safe in treating dyskinesia.
B: Amantadine showed some efficacy but had significant safety concerns.
C: There was insufficient evidence to determine the efficacy and safety of amantadine.
D: Amantadine was found to be ineffective and unsafe for treating dyskinesia. | C |
272 | 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 supplemental oxygen in preterm or low birth weight infants with prethreshold retinopathy of prematurity (ROP) in terms of progression to threshold ROP, visual outcomes, and adverse effects? Please answer this question based on the information provided below:
Supplemental Therapeutic Oxygen for Prethreshold Retinopathy Of Prematurity (STOP-ROP), a randomized, controlled trial. I: primary outcomes.
OBJECTIVE: To determine the efficacy and safety of supplemental therapeutic oxygen for infants with prethreshold retinopathy of prematurity (ROP) to reduce the probability of progression to threshold ROP and the need for peripheral retinal ablation.
METHODS: Premature infants with confirmed prethreshold ROP in at least 1 eye and median pulse oximetry <94% saturation were randomized to a conventional oxygen arm with pulse oximetry targeted at 89% to 94% saturation or a supplemental arm with pulse oximetry targeted at 96% to 99% saturation, for at least 2 weeks, and until both eyes were at study endpoints. Certified examiners masked to treatment assignment conducted weekly eye examinations until each study eye reached ophthalmic endpoint. An adverse ophthalmic endpoint for an infant was defined as reaching threshold criteria for laser or cryotherapy in at least 1 study eye. A favorable ophthalmic endpoint was regression of the ROP into zone III for at least 2 consecutive weekly examinations or full retinal vascularization. At 3 months after the due date of the infant, ophthalmic findings, pulmonary status, growth, and interim illnesses were again recorded.
RESULTS: Six hundred forty-nine infants (325 conventional and 324 supplemental) were enrolled from 30 centers over 5 years. Five hundred ninety-seven (92.0%) infants attained known ophthalmic endpoints, and 600 (92%) completed the ophthalmic 3-month assessment. The rate of progression to threshold in at least 1 eye was 48% in the conventional arm and 41% in the supplemental arm. After adjustment for baseline ROP severity stratum, plus disease, race, and gestational age, the odds ratio (supplemental vs conventional) for progression was.72 (95% confidence interval:.52, 1.01). Final structural status of all study eyes at 3 months of corrected age showed similar rates of severe sequelae in both treatment arms: retinal detachments or folds (4.4% conventional vs 4.1% supplemental), and macular ectopia (3.9% conventional vs 3.9% supplemental). Within the prespecified ROP severity strata, ROP progression rates were lower with supplemental oxygen than with conventional oxygen, but the differences were not statistically significant. A post hoc subgroup analysis of plus disease (dilated and tortuous vessels in at least 2 quadrants of the posterior pole) suggested that infants without plus disease may be more responsive to supplemental therapy (46% progression in the conventional arm vs 32% in the supplemental arm) than infants with plus disease (52% progression in conventional vs 57% in supplemental). Pneumonia and/or exacerbations of chronic lung disease occurred in more infants in the supplemental arm (8.5% conventional vs 13.2% supplemental). Also, at 50 weeks of postmenstrual age, fewer conventional than supplemental infants remained hospitalized (6.8% vs 12.7%), on oxygen (37.0% vs 46.8%), and on diuretics (24.4% vs 35. 8%). Growth and developmental milestones did not differ between the 2 arms.
CONCLUSIONS: Use of supplemental oxygen at pulse oximetry saturations of 96% to 99% did not cause additional progression of prethreshold ROP but also did not significantly reduce the number of infants requiring peripheral ablative surgery. A subgroup analysis suggested a benefit of supplemental oxygen among infants who have prethreshold ROP without plus disease, but this finding requires additional study. Supplemental oxygen increased the risk of adverse pulmonary events including pneumonia and/or exacerbations of chronic lung disease and the need for oxygen, diuretics, and hospitalization at 3 months of corrected age. Although the relative risk/benefit of supplemental oxygen for each infant must be individually considered, clinicians need no longer be concerned that supplemental oxygen, as used in this study, will exacerbate active prethreshold ROP.
Options:
A: Supplemental oxygen significantly reduced the progression to threshold ROP and improved visual outcomes without any adverse effects.
B: Supplemental oxygen did not significantly reduce the progression to threshold ROP, had no significant effect on visual outcomes, and was associated with increased adverse pulmonary events.
C: Supplemental oxygen significantly reduced the progression to threshold ROP, but had no effect on visual outcomes and was associated with increased adverse pulmonary events.
D: Supplemental oxygen had no effect on the progression to threshold ROP, visual outcomes, or adverse pulmonary events. | B |
273 | 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 and safety of electroconvulsive therapy (ECT) in treating depression in elderly patients? Please answer this question based on the information provided below:
Unilateral and bilateral ECT in elderly patients. A comparative study.
Twenty-nine depressed elderly patients receiving ECT were randomly assigned to a unilateral or bilateral group; post-ictal recovery times, memory changes, and clinical improvement during and after each course were measured by blind and independent observers. All patients but one showed full recovery on testing 3 weeks after treatment. There was no significant difference between the unilateral and bilateral groups either in terms of improvement or the number of treatments needed in each course. A good outcome was predicted by the presence of pathological guilt, impairment of work and interest, agitation, subjectively depressed mood, psychic anxiety and greater overall severity. Longer duration of illness predicted a relatively poor outcome. Memory functions showed uniform impairment before treatment, but during treatment all improved, with some changes reaching high statistical significance; on testing 3 weeks after treatment memory functions in all patients had reached normal values. There was no difference between the two groups. Post-ictal recovery times were significantly longer in the bilateral than in the unilateral group after the first treatment and after the fifth treatment more than three times as long. Recovery time showed a significant decrease during courses of unilateral treatment. There was a very low incidence of side-effects, and all were relatively mild. We conclude that unilateral ECT is a safe and highly effective treatment for selected elderly patients suffering from depression, but that there is nothing to be said for the continued use of bilateral ECT.
Weekly ECT in Geriatric Depression.
Fifteen elderly depressed psychiatric inpatients were randomly assigned to receive either standard three-times-weekly electroconvulsive therapy (ECT) or once-weekly ECT. Outcome measures included cognitive assessment and antidepressant response. Although both groups improved with treatment, the three-times-weekly group improved substantially more quickly. There was no difference in cognitive effect between the two groups. We conclude that the traditional three-times-weekly schedule of ECT may optimally balance speed of antidepressant response and cognitive impairment.
Fixed high-dose electroconvulsive therapy in the elderly with depression: a double-blind, randomized comparison of efficacy and tolerability between unilateral and bilateral electrode placement.
OBJECTIVE: To evaluate efficacy and tolerability of unilateral (RUL) and bilateral (BL) electroconvulsive therapy (ECT) in the elderly with depression.
METHODS: Thirty-nine elderly inpatients with major depression referred to ECT were randomized into RUL or BL ECT, using high, fixed electrical doses. Cognition and depression severity were assessed before, during, and 1 month after treatment. Adverse effects were assessed after each session.
RESULTS: Remission rates for RUL ECT (88.2%) and BL ECT (68.2%) were similar (P = 0.25). Reduction rates of depressive symptoms were also similar. There were no serious adverse events. There were more adverse effects in the BL ECT group (P = 0.05). BL ECT showed more short-term cognitive impairment, whereas improvements in neuropsychological scores were seen in both groups.
CONCLUSION: In elderly depressive subjects, high-dose RUL ECT is as effective as BL ECT yet produces less adverse effects and less cognitive impairment.
Options:
A: ECT was found to be significantly more effective and safer than antidepressants in treating depression in elderly patients.
B: There was insufficient randomised evidence to conclusively determine the efficacy and safety of ECT in treating depression in elderly patients.
C: ECT was found to be less effective than simulated ECT in treating depression in elderly patients.
D: ECT was found to be effective only in elderly patients with concomitant dementia, cerebrovascular disorders, or Parkinson's disease. | B |
274 | 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 tolerability of anticholinergics in the symptomatic treatment of Parkinson's disease compared to placebo or no treatment? Please answer this question based on the information provided below:
A CRITICAL ANALYSIS OF THE EFFECTS OF TRIHEXYPHENIDYL (ARTANE) ON THE COMPONENTS OF THE PARKINSONIAN SYNDROME.
Bornaprine vs placebo in Parkinson disease: double-blind controlled cross-over trial in 30 patients.
The study covers 30 patients with idiopathic Parkinson disease, 13 men and 17 women, aged between 50 and 70, on stabilized L-Dopa and/or bromocriptine, which failed to ensure adequate control of the symptoms, especially tremor. To this regimen was added Bornaprine/placebo in randomized sequence. The patients were tested according to the Webster Rating Scale before, during and after each stage of the treatment. Statistical analysis of the results showed the superiority of Bornaprine over the placebo in reducing tremor (p less than 0.01) and, to a lesser degree, some other parkinsonian symptoms. No noteworthy side effects were found apart from dryness of the mouth, which was more frequent with Bornaprine.
KR 339 in the treatment of Parkinsonian tremor.
A study of the effectiveness of drug therapy in parkinsonism.
Mehixene hydrochloride and parkinsonian tremor.
[Bornaprine in the treatment of parkinsonian tremor].
We report the results of a double-blind placebo controlled study of bornaprine, an anticholinergic drug, in the treatment of Parkinson's disease. We studied 17 patients presenting persistent tremor in spite of a stable long-term L-Dopa therapy. The bornaprine, in doses of 8 mg/die, compared with placebo significantly improves tremor. Only mild side effects occurred. We think the bornaprine may be of value in the treatment of parkinsonian tremor.
Parkinson's disease: Cogentin with Sinemet, a better response.
1. A randomized, placebo controlled, double-blind cross-over study was conducted to evaluate the clinical efficacy of the anticholinergic agent, benztropine mesylate (CogentinR) in 29 patients with mild to moderate, idiopathic Parkinson disease. 2. Patients were maintained on a stable, therapeutically optimal dosage and schedule of levadopa-carbidopa (Sinemet) throughout the study. 3. Both the neurologist's and the patient's global assessments of treatment efficacy indicated that Sinemet plus benztropine mesylate resulted in significantly greater improvement than Sinemet plus placebo. 4. Qualitative and quantitative evaluations of relevant neurologic functions showed small, but statistically significant improvements for rigidity, finger tapping speed and activities of daily living in patients during the Sinemet plus benztropine mesylate treatment period. 5. At the completion of the study 16 patients chose to continue taking benztropine mesylate as an adjuvant to Sinemet. 6. No important adverse side effects occurred during the study.
Levodopa and orphenadrine hydrochloride in Parkinsonism.
Options:
A: Anticholinergics are less effective than placebo in improving motor function in Parkinson's disease.
B: Anticholinergics are more effective than placebo in improving motor function in Parkinson's disease, but they are associated with a higher frequency of neuropsychiatric and cognitive adverse events.
C: Anticholinergics have no significant effect on motor function in Parkinson's disease and have a similar side effect profile to placebo.
D: Anticholinergics are more effective than placebo in improving motor function in Parkinson's disease and have fewer neuropsychiatric and cognitive adverse events. | B |
275 | 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 treatment of asymptomatic patent ductus arteriosus (PDA) with indomethacin in premature infants? Please answer this question based on the information provided below:
Failure of prophylactic indomethacin to improve the outcome of the very low birth weight infant.
Prophylactic closure of the patent ductus arteriosus (PDA) has been recommended as a means of decreasing early respiratory distress, and thereby chronic respiratory sequelae in the very low birth weight (VLBW) neonate. This study was undertaken to evaluate some possible mechanisms for the observed failure of early indomethacin therapy to achieve such improvement. 24 VLBW infants with echocardiographic evidence of PDA were randomized to receive either indomethacin or placebo at 48 h of life; and then they were studied for clinical, metabolic and laboratory signs of ductal constriction and/or reopening. Early indomethacin conferred no improvement in respiratory sequelae. However, this was not secondary to a short-term therapeutic failure. Prophylactic indomethacin, even in the VLBW infant, was successful in decreasing dilator prostaglandin production, and probably in closing the PDA and in decreasing the number of recurrences. The implications are that even with effective ductal constriction, overall morbidity is not affected.
The silent ductus: its precursors and its aftermath.
Prophylactic closure of the patent ductus arteriosus has been recommended as a means of decreasing the morbidity of the very low birth weight neonate. This study was undertaken in order to determine potential risk factors involved in the development of the silent ductus, its impact upon both the early cardiorespiratory symptomatology and the subsequent morbidity of the premature neonate, and finally the potential benefit to be derived from prophylactic closure in this presymptomatic stage. Infants with birth weights of 1000 g or less were studied on days 2-3 of life echocardiographically, clinically, and with determination of plasma dilator prostaglandin levels. On entry to the study, those infants with early evidence of silent left-to-right patent ductus arteriosus (PDA) shunting were randomized to receive either prophylactic indomethacin or placebo therapy. Those infants with no evidence of ductal shunting were not treated at all. Infants with silent PDAs had elevated levels of the dilator prostaglandin metabolite 6-keto PGF1 alpha on admission, although they had no echocardiographic abnormalities. No other risk factors for PDA development could be identified. Silent PDA infants had an increased incidence of subsequent symptomatic PDAs, and overall morbidity and mortality when compared with those with no evidence of PDA (silent or symptomatic). Prophylactic ductal closure decreased the incidence of subsequent PDA development, but had no effect on overall morbidity and/or mortality.
Prophylactic indomethacin therapy for patent ductus arteriosus in very-low-birth-weight infants.
We performed a double-blind, controlled study of prophylactic indomethacin therapy in 47 premature infants (less than 1700 g) who had subclinical patent ductus arteriosus. They received either indomethacin or placebo at a mean age of 2.9 days. Among the 25 infants weighing more than 1000 g, a hemodynamically important ductus shunt developed in only four of the 14 given placebo. The incidence of important shunts, the number of surgical ligations, and the duration of oxygen therapy were not appreciably different between the study groups. In contrast, among the 22 infants who weighed 1000 g or less, a major ductus shunt developed in 10 of the 12 given placebo. In the smaller infants indomethacin therapy was associated with a significantly lower incidence of major shunts, fewer surgical ligations, a decreased duration of oxygen therapy, and fewer days necessary to regain birth weight. We conclude that prophylactic indomethacin therapy in infants weighing under 1000 g prevents the later development of large ductus shunts and decreases morbidity.
When to treat the patent ductus arteriosus with indomethacin in very-low-birth-weight infants.
Prophylactic treatment of asymptomatic patent ductus arteriosus in premature infants with respiratory distress syndrome.
Early treatment of premature infants with indomethacin has been proposed as a means of reducing the morbidity associated with respiratory distress syndrome complicated by symptomatic patent ductus arteriosus. We identified 26 infants less than 48 hours old with severe respiratory distress syndrome who had an asymptomatic patent ductus arteriosus. These infants were treated with either indomethacin or placebo. There was a significant difference in the frequency of ductal closure after receiving indomethacin treatment. No significant difference was observed in the time required for mechanical ventilation, time receiving supplemental oxygen, or time in the hospital, and there were no significant differences in the incidence of bronchopulmonary dysplasia, intraventricular hemorrhage, retinopathy of prematurity, or death between the two groups.
Options:
A: Indomethacin significantly reduced the incidence of symptomatic PDA and the duration of supplemental oxygen, but had no effect on mortality, chronic neonatal lung disease (CLD), intraventricular haemorrhage (IVH), retinopathy of prematurity (ROP), or length of ventilation.
B: Indomethacin significantly reduced the incidence of symptomatic PDA, mortality, and chronic neonatal lung disease (CLD), but had no effect on intraventricular haemorrhage (IVH), retinopathy of prematurity (ROP), or length of ventilation.
C: Indomethacin had no significant effect on the incidence of symptomatic PDA, mortality, chronic neonatal lung disease (CLD), intraventricular haemorrhage (IVH), retinopathy of prematurity (ROP), or length of ventilation.
D: Indomethacin significantly reduced the incidence of symptomatic PDA, mortality, chronic neonatal lung disease (CLD), intraventricular haemorrhage (IVH), retinopathy of prematurity (ROP), and length of ventilation. | A |
276 | 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 muscle relaxants in the treatment of non-specific low back pain? Please answer this question based on the information provided below:
Cyclobenzaprine hydrochloride effect on skeletal muscle spasm in the lumbar region and neck: two double-blind controlled clinical and laboratory studies.
A new drug, Cyclobenzaprine hydrochloride (Flexeril), was compared with diazepam (Valium) and placebo in double-blind trials for efficacy in treating spasms and pain in the neck and low back. Complex recording methods involving clinical evaluations (graded), patient self-ratings, goniometry, motion analysis by computer, electromyography of controlled motions and detailed statistical analysis were used. Clinical improvement over two weeks was statistically significant in all treatment groups with a statistically significant preference for Cyclobenzaprine hydrochloride. The most striking improvements recorded were in the electromyographic findings, which showed statistically significant changes for the Cyclobenzaprine group. Clinical muscle spasms are not accompanied by increased myoelectric activity; the reverse is true. With improvement, myoelectric activity in back muscles is augmented during prescribed stressful movements as measured by electromyography and computer analysis combined with complex electrogoniometry.
A multicentre placebo-controlled study in general practice to evaluate the efficacy and safety of tizanidine in acute low-back pain.
Patients (112) with acute low-back pain of recent onset were recruited to this double-blind, randomized, placebo-controlled parallel group study in general practice to evaluate the efficacy and tolerability of the muscle relaxant, tizanidine. They were treated for 7 days with tizanidine (4 mg three times daily) or matching placebo. Aspirin tablets (300 mg) were taken as required as 'rescue' medication. Symptoms were assessed by the patient and doctor before treatment, and after 3 and 7 days. Patients recorded pain and aspirin consumption in a daily diary. Both treatments were effective. In patients who had taken no medication prior to entry, aspirin consumption was almost halved in the first 3 days of taking tizanidine compared with placebo (P = 0.037). Results for pain at rest, pain at night, restriction of movement and pain on movement suggest that tizanidine may give greater improvement, earlier. No serious drug-related adverse events or abnormal biochemistry or haematology were observed in either group. Drowsiness occurred in 22% of patients taking tizanidine although, in patients with severe acute low-back pain, sedation, analgesia and bed rest might be beneficial and desired. Considerably more patients given aspirin/placebo had gastro-intestinal side-effects (P = 0.018). In conclusion, tizanidine may reduce the need for analgesics and be useful in the treatment of acute low-back pain.
Tizanidine and ibuprofen in acute low-back pain: results of a double-blind multicentre study in general practice.
This study reports on 105 patients with acute low-back pain given tizanidine (4 mg three times daily) plus ibuprofen (400 mg three times daily) or placebo plus ibuprofen (400 mg three times daily). Patients assessed their pain using visual analogue scales in a daily diary and the doctor assessed their condition at baseline and on days 3 and 7. Both groups were treated effectively, but earlier improvement occurred in patients given tizanidine/ibuprofen, particularly regarding pain at night and at rest. Doctors assessed the helpfulness of treatment: tizanidine/ibuprofen was significantly better than placebo/ibuprofen at day 3 (P = 0.05). Significant differences between treatments in favour of tizanidine/ibuprofen occurred in patients with moderate and severe pain at night (P less than 0.05), at rest (P less than 0.05) and those with moderate or severe sciatica (P less than 0.05). Significantly more patients given placebo/ibuprofen had gastro-intestinal side-effects compared with tizanidine/ibuprofen (P = 0.002). This supports previous work in animals showing that tizanidine mediates gastric mucosal protection against anti-inflammatory drugs. More patients given tizanidine/ibuprofen suffered drowsiness and other central nervous system effects (P = 0.025). In patients with severe acute low-back pain, however, some sedation and bed rest is advantageous. This study shows that tizanidine/ibuprofen is more effective in the treatment of moderate or severe acute low-back pain than placebo and ibuprofen alone.
Cyclobenzaprine and naproxen versus naproxen alone in the treatment of acute low back pain and muscle spasm.
Two groups of 20 patients each, with mild to moderate acute low back pain with associated muscle spasm of ten days' duration or less, were treated with a combination of cyclobenzaprine and naproxen or naproxen alone in a randomized, 14-day open-label trial. Cyclobenzaprine was added to the naproxen regimen as an adjunct to rest and physical therapy for relief of muscle spasm associated with acute, painful, musculoskeletal conditions. The clinical characteristics of each study group, including the number of worker's compensation patients, were comparable. Combination therapy was associated with less objective muscle spasm and tenderness and greater motion of the lumbosacral spine (P less than 0.05). There were trends toward faster resolution of functional deficits and pain with combined therapy. Combination therapy was associated with more side effects, due primarily to drowsiness from the cyclobenzaprine. The results of this study demonstrated that patients with muscle spasm associated with acute low back strain benefited from the use of combination therapy consisting of a nonsteroidal anti-inflammatory agent (naproxen) and a muscle relaxant (cyclobenzaprine).
Baclofen for the treatment of acute low-back syndrome. A double-blind comparison with placebo.
The efficacy and safety of baclofen (30-80 mg daily) for the treatment of acute low-back syndrome were evaluated in a 14-day, double-blind, randomized study of 200 patients (100 baclofen, 100 placebo). Patients with initially severe or extremely severe symptoms (as opposed to moderate symptoms) benefitted most from treatment with baclofen. The incidence of adverse effects was significantly higher in the baclofen group; however, most were mild to moderate and disappeared in all but two patients who required a reduction in dosage, without reduced drug efficacy. Baclofen was shown to be effective, safe, and well-tolerated for the treatment of patients with acute low-back syndrome.
A new skeletal muscle relaxant (DS 103-282) compared to diazepam in the treatment of muscle spasm of local origin.
The myotonolytic activity of a new muscle-relaxant, DS 103-282, was compared with that of diazepam in a randomized double-blind study on thirty patients suffering from acute muscular spasm due to disorders of the cervical and lumbar segments of the spine. Fifteen patients received 5 mg DS 103-282 and fifteen received 5 mg diazepam on a three times daily regime for 7 days. DS 103-282 was found to alleviate symptoms and improve mobility to a significant degree (p less than or equal to 0.05) in all parameters evaluated and was also significantly superior to diazepam in 5 of these. Onset of action was particularly rapid for DS 103-282. Both medications were well tolerated and there was no significant difference between them. On the basis of these data DS 103-282 may be considered a more powerful and faster-acting myotonolytic agent than diazepam with which it was compared in similar clinical indications.
Comparison of carisoprodol, butabarbital, and placebo in treatment of the low back syndrome.
A double-blind study was carried out to determine the effectiveness of a muscle relaxant, carisoprodol, in the treatment of the low back syndrome, and to test whether this drug would produce any greater effect than an active sedative control. Forty-eight Mexican migrant farm laborers with acute lumbar strain and spasm were given either carisoprodol 350 mg, butabarbital 15 mg, or placebo, four times daily for four days, and then were rated on pertinent symptoms, the degree of limitation of motion (by an objective finger-to-floor test), and overall improvement. In the 43 patients who could be statistically analyzed, carisoprodol was shown to be significantly more effective than butabarbital or placebo in producing improvement of all factors rated. This result suggests that the effects of carisoprodol are not due solely to sedative action, but are also related to its muscle relaxant activity.
Diazepam in backache. A double-blind controlled trial.
Orphenadrin-paracetamol in backache-a double-blind controlled trial.
[Therapy of acute lumbovertebral syndromes through optimal muscle relaxation using diazepam. Results of a double-blind study on 68 cases].
Efficacy and tolerance of repeated oral doses of tolperisone hydrochloride in the treatment of painful reflex muscle spasm: results of a prospective placebo-controlled double-blind trial.
The efficacy and safety of oral tolperisone hydrochloride (Mydocalm) in the treatment of painful reflex muscle spasm was assessed in a prospective, randomized, double-blind, placebo-controlled trial. A total of 138 patients, aged between 20 and 75 years, with painful reflex muscle spasm associated with diseases of the spinal column or proximal joints were enrolled in eight rehabilitation centers. Patients were randomized to receive either 300 mg tolperisone hydrochloride or placebo for a period of 21 days. Both treatment groups recovered during the 3 weeks rehabilitation program. However, tolperisone hydrochloride proved to be significantly superior to placebo: the change score of the pressure pain threshold as the primary target parameter significantly increased during therapy with tolperisone hydrochloride (P = 0.03, valid-case-analysis) compared to the results obtained on placebo treatment. The overall assessment of efficacy by the patient also demonstrated significant differences in favor of tolperisone hydrochloride. Best results were seen in patients aged between 40 and 60 years with a history of complaints shorter than 1 year and with concomitant physical therapy. The evaluation of safety data, i.e., adverse events, biochemical and hematological laboratory parameters, demonstrated no differences between tolperisone hydrochloride and placebo. As a conclusion tolperisone hydrochloride represents an effective and safe treatment of painful reflex muscle spasm without the typical side effects of centrally active muscle relaxants.
Mefenamic acid, chlormezanone-paracetamol, ethoheptazine-aspirin-meprobamate: a comparative study in acute low back pain.
A controlled clinical trial of a muscle relaxant analgesic combination in the treatment of acute lumbago.
Comparison of the effect of diazepam and levomepromazine on pain in patients with acute lumbago-sciatica.
[Flupirtine in comparison with chlormezanone in chronic musculoskeletal back pain. Results of a multicenter randomized double-blind study].
METHOD: The analgesic and muscle-relaxing properties of flupirtine maleate, chlormezanone and placebo were compared in a total of 184 patients. Of these patients, 164 met the criteria of the treatment plan (intention to treat), and the data of 140 patients were finally evaluated in accordance with the test protocol. A positive response was defined as a reduction in pain intensity and muscle tension by 2 categories on the 5-category verbal scale "very severe/severe/moderate/mild/ none" on the seventh day of treatment.
RESULTS: In the per-protocol-analysis the responder rate was 60.9% for flupirtine, 47.8% for chlormezanone, and 43.8% for placebo, the difference between drugs and placebo not being significant. The overall assessment of the physicians involved was very good/ good in 47.8% and satisfactory in 37.0% of the flupirtine group, very good/good in 45.6% and satisfactory in 17.4% of the chlormezanone group, the corresponding figures for the placebo group being 33.4% and 20.6%, respectively. Flupirtine was thus superior to placebo (p = 0.007). The incidence of adverse drug reactions was 14.8% (8/54) for flupirtine, 19.3% (11/57) for chlormezanone, and 7.3% (4/55) for placebo.
Options:
A: Muscle relaxants are ineffective and have no significant adverse effects.
B: Muscle relaxants are effective for short-term pain relief but have a higher incidence of adverse effects.
C: Muscle relaxants are effective for long-term pain relief and have minimal adverse effects.
D: Muscle relaxants are less effective than placebo and have significant adverse effects. | B |
277 | 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 effectiveness and safety of physical cooling methods for managing fever in children? Please answer this question based on the information provided below:
Efficacy of sponging vs acetaminophen for reduction of fever. Sponging Study Group.
Seventy-three children with acute febrile illnesses were enrolled in a study to compare the efficacy of sponging, sponging plus acetaminophen, and acetaminophen alone as methods of lowering body temperature. The greatest temperature reduction was seen in the combined acetaminophen plus sponging group. The smallest temperature reduction was noted in children who received sponging alone. We urge reconsideration of routine sponging of febrile young patients.
Study of antipyretic therapy in current use.
Management of feverish children at home.
OBJECTIVES: To compare the acceptability and effects on temperature of advice to unwrap children and give paracetamol or warm sponging treatments in the management of feverish illness at home.
DESIGN: A randomised, open, parallel group study using factorial design comparison of unwrapping, warm sponging plus unwrapping, paracetamol plus unwrapping, and paracetamol and warm sponging plus unwrapping.
SETTING: Homes of willing families with a feverish child recruited after consulting one of 21 participating general practitioners in Southampton.
SUBJECTS: 52 children aged from 3 months to 5 years with axillary temperatures before treatment of > or = 37.8 degrees C and < 40 degrees C.
MAIN OUTCOME MEASURES: Response to advice assessed over four hours; temperature assessed by continuous data logging from an axillary thermistor; acceptability of treatment to child and parent scored on Likert scales immediately after treatment and on return to health.
RESULTS: Response to treatment advice varied; unwrapping alone had little effect on temperature. Paracetamol increased the time below 37.2 degrees C in four hours by 109 (95% confidence interval 74 to 145) minutes compared with unwrapping; warm sponging caused the fastest reduction in temperature. Parents discriminated between treatments, preferring paracetamol.
CONCLUSION: Advice to give paracetamol is more effective than sponging or unwrapping in controlling temperature in children at home and is more acceptable to parents. Warm sponging has an additive effect and reduces fever more quickly than paracetamol.
Tepid sponging to reduce temperature in febrile children in a tropical climate.
The effectiveness of tepid sponging, in addition to antipyretic medication, in the reduction of temperature in febrile children living in a tropical environment, was assessed in a prospective, randomized, open trial. Seventy-five children aged between 6 and 53 months who attended the casualty department of the Children's Hospital, Bangkok, Thailand, with fever (rectal temperature > or = 38.5 degrees C) of presumed viral origin were randomized to received either tepid sponging and oral paracetamol (sponged group) or paracetamol alone (control group). Rectal temperature and the occurrence of crying, irritability, and shivering were recorded over the following 2 hours. A greater and more rapid fall in mean rectal temperature occurred in the sponged group than in the control group. Temperature fell below 38.5 degrees C sooner in children in the sponged group than in control children (P < 0.001). At 60 minutes, 38 (95.0%) of the controls still had a temperature of 38.5 degrees C or greater, compared with only 15 children (42.9%) in the sponged group (P < 1 x 10(-5). Crying was associated with sponging, but shivering and irritability occurred in only one child who was being sponged. It is concluded that tepid sponging, in addition to antipyretic medication, is clearly more effective than antipyretic medication alone in reducing temperature in febrile children living in a tropical climate.
Evaluation of sponging to reduce body temperature in febrile children.
A study was conducted to evaluate the efficacy of sponging as a way of reducing body temperature in febrile children. Of 130 children 73 received antipyretic medication and sponging and 57 received antipyretic medication alone. No difference in temperature reduction was noted between the two groups. It is therefore suggested that sponging be abandoned as a mode of temperature reduction in febrile children whose increased temperature is due to an infectious process.
The efficacy of tepid sponge bathing to reduce fever in young children.
Tepid sponge baths distress febrile children, and their efficacy at reducing fever has not been established. This study compared fever reduction and with (1) acetaminophen alone and (2) acetaminophen plus a 15-minute tepid sponge bath. Twenty children, ages 5 to 68 months, who presented to the emergency department or urgent care center with fever of > or = 38.9 degrees C were randomized to receive (1) acetaminophen alone or (2) acetaminophen plus a 15-minute tepid sponge bath. All subjects received a 15-mg/kg dose of acetaminophen. Tympanic temperature was monitored every 30 minutes for 2 hours. Subjects were monitored for signs of discomfort (crying, shivering, goosebumps). Sponge-bathed subjects cooled faster during the first hour but there was no significant temperature difference between the groups over the 2-hour study period (P = .871). Subjects in the sponge bath group had significantly higher discomfort scores (P = .009).
Evaluation of sponging and of oral antipyretic therapy to reduce fever.
Options:
A: Physical cooling methods are more effective than drug placebos in reducing fever within one hour.
B: Physical cooling methods, when combined with antipyretic drugs, result in a higher proportion of children without fever at one hour compared to antipyretic drugs alone.
C: Physical cooling methods are associated with a higher incidence of mild adverse events such as shivering and goose pimples.
D: Physical cooling methods are less effective than antipyretic drugs in reducing fever within one hour. | B |
278 | 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 antiplatelet therapy on the risk of stroke and other vascular events in patients after carotid endarterectomy? Please answer this question based on the information provided below:
Controlled trial of aspirin in cerebral ischemia. Part II: surgical group.
Patients (125) who had carotid transient ischemic attacks (TIAs) and one or more accessible carotid lesions visualized angiographically had reconstructive operations of the carotid artery and were then randomly assigned to aspirin or placebo treatment. The were followed to determine the incidence of subsecquent TIAs, death, cerebral infarction, or retinal infarction. Life table analysis (for 24 months follow up) that eliminated deaths which were not stroke-related revealed a significant difference in favor of aspirin. Because of the small number of patients and the short period of follow up, these results should be interpreted only as consistent with those reported in the initial publication but not conclusive of an aspirin effect in preventing cerebral infarction.
Controlled trial of aspirin in cerebral ischemia: an addendum.
Patients (303) who had had carotid territory transient ischemic attacks were randomly assigned to aspirin or placebo treatments. Patients with amaurosis fugax responded as well to aspirin as those with hemisphere events. Patients with lesions of the appropriate carotid artery responded better to aspirin therapy than patients with no lesion or an occlusion. The aspirin effect was the same across all risk-factor groups. Smoking had no effect on clinical outcome.
Danish very-low-dose aspirin after carotid endarterectomy trial.
The effect of very-low-dose aspirin as an antithrombotic agent was evaluated blindly in 301 patients who had recently undergone carotid endarterectomy. After randomization, 150 patients received aspirin and 151 received placebo. The two groups were comparable with regard to age, sex, blood pressure, previous cerebrovascular events, and smoking habits. The effect of the study medication on platelet aggregation was measured twice in each patient during the first 2 months and at each follow-up visit; the dose was individually adjusted. In 76% of the patients receiving aspirin, 50 mg/day gave satisfactory platelet inhibition, 13% needed 60 mg/day, 8% needed 70 mg/day, and 3% needed 100 mg/day. Platelet aggregation was found to be inhibited in only 1.2% of the measurements in the patients receiving placebo. Observation during treatment averaged 21 months; total intention-to-treat follow-up averaged 25 months. For the combined outcome events of transient ischemic attack, stroke, acute myocardial infarction, and vascular death, aspirin reduced risk by 11% (95% confidence limits: -38% to 48%, p greater than 0.1). Thus, there was no significant effect of very-low-dose aspirin in our trial.
Danish very-low-dose aspirin after carotid endarterectomy trial.
The effect of very-low-dose aspirin as an antithrombotic agent was evaluated blindly in 301 patients who had recently undergone carotid endarterectomy. After randomization, 150 patients received aspirin and 151 received placebo. The two groups were comparable with regard to age, sex, blood pressure, previous cerebrovascular events, and smoking habits. The effect of the study medication on platelet aggregation was measured twice in each patient during the first 2 months and at each follow-up visit; the dose was individually adjusted. In 76% of the patients receiving aspirin, 50 mg/day gave satisfactory platelet inhibition, 13% needed 60 mg/day, 8% needed 70 mg/day, and 3% needed 100 mg/day. Platelet aggregation was found to be inhibited in only 1.2% of the measurements in the patients receiving placebo. Observation during treatment averaged 21 months; total intention-to-treat follow-up averaged 25 months. For the combined outcome events of transient ischemic attack, stroke, acute myocardial infarction, and vascular death, aspirin reduced risk by 11% (95% confidence limits: -38% to 48%, p greater than 0.1). Thus, there was no significant effect of very-low-dose aspirin in our trial.
Danish very-low-dose aspirin after carotid endarterectomy trial.
The effect of very-low-dose aspirin as an antithrombotic agent was evaluated blindly in 301 patients who had recently undergone carotid endarterectomy. After randomization, 150 patients received aspirin and 151 received placebo. The two groups were comparable with regard to age, sex, blood pressure, previous cerebrovascular events, and smoking habits. The effect of the study medication on platelet aggregation was measured twice in each patient during the first 2 months and at each follow-up visit; the dose was individually adjusted. In 76% of the patients receiving aspirin, 50 mg/day gave satisfactory platelet inhibition, 13% needed 60 mg/day, 8% needed 70 mg/day, and 3% needed 100 mg/day. Platelet aggregation was found to be inhibited in only 1.2% of the measurements in the patients receiving placebo. Observation during treatment averaged 21 months; total intention-to-treat follow-up averaged 25 months. For the combined outcome events of transient ischemic attack, stroke, acute myocardial infarction, and vascular death, aspirin reduced risk by 11% (95% confidence limits: -38% to 48%, p greater than 0.1). Thus, there was no significant effect of very-low-dose aspirin in our trial.
Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients.
OBJECTIVE: To determine the effects of antiplatelet therapy among patients at high risk of occlusive vascular events.
DESIGN: Collaborative meta-analyses (systematic overviews).
INCLUSION CRITERIA: Randomised trials of an antiplatelet regimen versus control or of one antiplatelet regimen versus another in high risk patients (with acute or previous vascular disease or some other predisposing condition) from which results were available before September 1997. Trials had to use a method of randomisation that precluded prior knowledge of the next treatment to be allocated and comparisons had to be unconfounded-that is, have study groups that differed only in terms of antiplatelet regimen.
STUDIES REVIEWED: 287 studies involving 135 000 patients in comparisons of antiplatelet therapy versus control and 77 000 in comparisons of different antiplatelet regimens.
MAIN OUTCOME MEASURE: "Serious vascular event": non-fatal myocardial infarction, non-fatal stroke, or vascular death.
RESULTS: Overall, among these high risk patients, allocation to antiplatelet therapy reduced the combined outcome of any serious vascular event by about one quarter; non-fatal myocardial infarction was reduced by one third, non-fatal stroke by one quarter, and vascular mortality by one sixth (with no apparent adverse effect on other deaths). Absolute reductions in the risk of having a serious vascular event were 36 (SE 5) per 1000 treated for two years among patients with previous myocardial infarction; 38 (5) per 1000 patients treated for one month among patients with acute myocardial infarction; 36 (6) per 1000 treated for two years among those with previous stroke or transient ischaemic attack; 9 (3) per 1000 treated for three weeks among those with acute stroke; and 22 (3) per 1000 treated for two years among other high risk patients (with separately significant results for those with stable angina (P=0.0005), peripheral arterial disease (P=0.004), and atrial fibrillation (P=0.01)). In each of these high risk categories, the absolute benefits substantially outweighed the absolute risks of major extracranial bleeding. Aspirin was the most widely studied antiplatelet drug, with doses of 75-150 mg daily at least as effective as higher daily doses. The effects of doses lower than 75 mg daily were less certain. Clopidogrel reduced serious vascular events by 10% (4%) compared with aspirin, which was similar to the 12% (7%) reduction observed with its analogue ticlopidine. Addition of dipyridamole to aspirin produced no significant further reduction in vascular events compared with aspirin alone. Among patients at high risk of immediate coronary occlusion, short term addition of an intravenous glycoprotein IIb/IIIa antagonist to aspirin prevented a further 20 (4) vascular events per 1000 (P<0.0001) but caused 23 major (but rarely fatal) extracranial bleeds per 1000.
CONCLUSIONS: Aspirin (or another oral antiplatelet drug) is protective in most types of patient at increased risk of occlusive vascular events, including those with an acute myocardial infarction or ischaemic stroke, unstable or stable angina, previous myocardial infarction, stroke or cerebral ischaemia, peripheral arterial disease, or atrial fibrillation. Low dose aspirin (75-150 mg daily) is an effective antiplatelet regimen for long term use, but in acute settings an initial loading dose of at least 150 mg aspirin may be required. Adding a second antiplatelet drug to aspirin may produce additional benefits in some clinical circumstances, but more research into this strategy is needed.
Failure of aspirin plus dipyridamole to prevent restenosis after carotid endarterectomy.
OBJECTIVE: To evaluate therapy with aspirin plus dipyridamole in reducing restenosis after carotid endarterectomy.
PATIENTS: A total of 163 patients having 175 surgical carotid endarterectomies.
INTERVENTION: Eighty-three patients (90 endarterectomies) were randomly assigned to receive oral aspirin, 325 mg, plus dipyridamole, 75 mg, beginning 12 hours preoperatively, followed by a second dose administered within 8 hours after the operation, and given three times daily thereafter for 1 year. Eighty patients (85 endarterectomies) received placebo medication that was identical in appearance to the study drugs.
MEASUREMENTS: After the adequacy of the surgical procedure was confirmed by intraoperative angiography, restenosis at the endarterectomy sites was evaluated using serial duplex ultrasound studies before hospital discharge and at 3-month intervals postoperatively for 1 year.
RESULTS: Based on the time for developing identifiable restenosis and on efficacy analysis, greater than 50% restenosis developed in 11 operated vessels (16%) in the treated group and in 10 arteries (14%) in the placebo group, yielding an observed risk increase of 14% (95% CI, -52% to 167%; P greater than 0.2). By intention-to-treat analysis, greater than 50% restenosis developed in 16 of 90 operated vessels in treated patients and in 10 of 85 arteries in patients receiving placebo (26% for the treated group and 12% for the placebo group; P = 0.18, Mantel-Haenszel statistic), representing an observed risk increase of 110% (CI, -5% to 365%). Similar differences were observed for greater than 20% restenosis and for the comparison of patients rather than operated vessels by either intention-to-treat or efficacy analyses.
CONCLUSIONS: Because therapy not only failed to reduce carotid restenosis but may have actually increased its frequency, treatment with aspirin plus dipyridamole probably has no clinically important benefit on restenosis in patients having carotid endarterectomy.
Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients.
OBJECTIVE: To determine the effects of antiplatelet therapy among patients at high risk of occlusive vascular events.
DESIGN: Collaborative meta-analyses (systematic overviews).
INCLUSION CRITERIA: Randomised trials of an antiplatelet regimen versus control or of one antiplatelet regimen versus another in high risk patients (with acute or previous vascular disease or some other predisposing condition) from which results were available before September 1997. Trials had to use a method of randomisation that precluded prior knowledge of the next treatment to be allocated and comparisons had to be unconfounded-that is, have study groups that differed only in terms of antiplatelet regimen.
STUDIES REVIEWED: 287 studies involving 135 000 patients in comparisons of antiplatelet therapy versus control and 77 000 in comparisons of different antiplatelet regimens.
MAIN OUTCOME MEASURE: "Serious vascular event": non-fatal myocardial infarction, non-fatal stroke, or vascular death.
RESULTS: Overall, among these high risk patients, allocation to antiplatelet therapy reduced the combined outcome of any serious vascular event by about one quarter; non-fatal myocardial infarction was reduced by one third, non-fatal stroke by one quarter, and vascular mortality by one sixth (with no apparent adverse effect on other deaths). Absolute reductions in the risk of having a serious vascular event were 36 (SE 5) per 1000 treated for two years among patients with previous myocardial infarction; 38 (5) per 1000 patients treated for one month among patients with acute myocardial infarction; 36 (6) per 1000 treated for two years among those with previous stroke or transient ischaemic attack; 9 (3) per 1000 treated for three weeks among those with acute stroke; and 22 (3) per 1000 treated for two years among other high risk patients (with separately significant results for those with stable angina (P=0.0005), peripheral arterial disease (P=0.004), and atrial fibrillation (P=0.01)). In each of these high risk categories, the absolute benefits substantially outweighed the absolute risks of major extracranial bleeding. Aspirin was the most widely studied antiplatelet drug, with doses of 75-150 mg daily at least as effective as higher daily doses. The effects of doses lower than 75 mg daily were less certain. Clopidogrel reduced serious vascular events by 10% (4%) compared with aspirin, which was similar to the 12% (7%) reduction observed with its analogue ticlopidine. Addition of dipyridamole to aspirin produced no significant further reduction in vascular events compared with aspirin alone. Among patients at high risk of immediate coronary occlusion, short term addition of an intravenous glycoprotein IIb/IIIa antagonist to aspirin prevented a further 20 (4) vascular events per 1000 (P<0.0001) but caused 23 major (but rarely fatal) extracranial bleeds per 1000.
CONCLUSIONS: Aspirin (or another oral antiplatelet drug) is protective in most types of patient at increased risk of occlusive vascular events, including those with an acute myocardial infarction or ischaemic stroke, unstable or stable angina, previous myocardial infarction, stroke or cerebral ischaemia, peripheral arterial disease, or atrial fibrillation. Low dose aspirin (75-150 mg daily) is an effective antiplatelet regimen for long term use, but in acute settings an initial loading dose of at least 150 mg aspirin may be required. Adding a second antiplatelet drug to aspirin may produce additional benefits in some clinical circumstances, but more research into this strategy is needed.
Anticoagulants, antiaggregants or nothing following carotid endarterectomy?
Carotid endarterectomy (TEA) has proven to be beneficial for symptomatic patients. Anticoagulation (AC) and antiplatelet therapy (ASA) have been shown to prolong life following vascular surgery in patients with occlusive arterial disease (PAOD). To determine whether ASA or AC prolong life after TEA, retrospective analysis was undertaken, since cerebral haemorrhage is associated with the use of both drugs, especially AC. Between 1979-1986, 328 patients with stenotic lesions of the carotid bifurcation were operated upon electively. Patient survival and causes of death were the primary end points of the analysis. Recent data were obtained from the Austrian Central Bureau of Statistics. Cumulative survival rates were calculated by Kaplan-Meier estimation and differences determined by Breslow and Mantel tests. 36 patients were on AC, 157 on ASA and 135 remained without medication (0-group). Since the common risk factors in PAOD were unevenly distributed between groups, a stepwise Cox regression model was applied which revealed age (p < 0.01), cardiac pathology (p < 0.01) and diabetes (p < 0.05) as relevant for survival. Therefore, ASA patients and 0-group patients were selected and matched, employing the aforementioned prognostic criteria, and compared to the patients on long-term AC for various indications (vein bypass surgery, myocardial infarction, pulmonary embolism; i.e. data-matching). The median postoperative survival was 7.72 years for ASA and 8.48 years for AC, compared to 6.07 years for the 0-group (p = 0.0095 Breslow, p = 0.477 Mantel). There was no significant difference between AC and ASA treated patients. Irrespective of medication, the causes of death were well balanced, and no higher incidence of intracerebral haemorrhage was detected.(ABSTRACT TRUNCATED AT 250 WORDS)
Antiplatelet treatment prolongs survival after carotid bifurcation endarterectomy. Analysis of the clinical series followed by a controlled trial.
To examine the role of antiplatelet drugs in the secondary prevention of arteriosclerotic arterial disease following carotid endarterectomy, a clinical series (n = 252) was analyzed. Based on these results a prospective randomized trial was initiated, comparing the effect of antiplatelet drugs (acetyl-salicylic acid [ASA] 1000 mg/day) versus untreated controls. In both investigations patient survival was the primary end point. A cardiac risk (n = 91) implied a significant reduction in patient survival (p less than 0.019 Breslow, p less than 0.052 Mantel). Antiaggregating drugs prolonged survival in the collective series (p less than 0.0001 Breslow, p less than 0.0002 Mantel) and in the subgroup of patients with cardiac risk (p less than 0.014 Breslow, p less than 0.020 Mantel) as well. In the prospective trial 66 patients were recruited, receiving ASA (n = 32) versus no therapy (n = 34). During follow-up 15 patients died, 4 in the treatment, and 11 in the control group. Between both groups there was a significant difference in the probability of survival (p less than 0.021 Breslow, p less than 0.048 Mantel).
Antiplatelet therapy following carotid bifurcation endarterectomy. Evaluation of a controlled clinical trial. Prognostic significance of histologic plaque examination on behalf of survival.
To determine whether antiplatelet therapy following carotid bifurcation endarterectomy influences postoperative survival and whether signs of progression in the plaques harvested at the time of surgery might be a prognostic indicator, a controlled clinical trial was undertaken. During 1982 to 1985, 66 patients were recruited, operated on (carotid endarterectomy) and assigned, using the method of adaptive randomisation to the therapy group (n = 32) receiving 1.0 g acetylsalicylic acid (ASA) per day, starting day two prior to surgery, or to the control group (n = 34), which remained without antiplatelet medication. The plaques harvested at the time of surgery were processed using standard histopathological methods and examined "blindly" by light microscopy for signs of arterio-sclerotic progression. The final endpoint was patient survival. The last assessment of the participants survival status was done by June 1989. During follow-up, 20 patients died, six in the treatment group and 14 in the untreated group, the difference being statistically significant (P less than 0.013 Breslow, P less than 0.029 Mantel). In 27 instances the histo-pathological examination showed signs of progression. In this subgroup ASA yielded a significant prolongation of patient survival (P less than 0.017 Breslow, P less than 0.048 Mantel). In the remaining patients no signs of cellular infiltration were evident and no influence of ASA on patient survival was demonstrable (P less than 0.503 Breslow, P less than 0.390 Mantel).
Can recurrent stenosis after carotid endarterectomy be prevented by low-dose acetylsalicylic acid? A double-blind, randomised and placebo-controlled study.
Recurrent stenosis (> 50%) after carotid endarterectomy is reported with a frequency ranging from 7-20%. 232 patients undergoing carotid endarterectomy were randomised to low-dose acetylsalicylic acid (ASA, 75 mg daily) or placebo (identical tablets). The treatment was started the day before surgery and continued for 6 months. All patients were followed clinically for 1 year. Doppler examination was performed preoperatively (n = 230) and postoperatively (n = 228) and at follow-up at 2 (n = 220) and at 6 months (n = 174) after surgery. The degree of stenosis was estimated from the maximum Doppler frequency shift in the internal carotid artery. Recurrent stenosis of 30% or more was detected in 85 of the 220 patients (38.6%) at 2 months, and at 6 months in 73 of the 174 examined patients (42.0%). Stenosis > 50% was seen in 16 patients (9.2%) and occlusion was found in four patients (1.8%) at 6 months. No difference between the low-dose ASA-treated group (n = 112) compared to the placebo group (n = 108) was seen regarding recurrent stenosis. Women had an increased risk of recurrent stenosis (p < 0.001), whereas other factors such as age, hyperlipidaemia, diabetes and smoking were not associated with increased risk. Importantly, the number of neurological events did not differ between those with or without restenosis. Therefore, the indications for surgery of asymptomatic recurrent stenosis are questionable. The progress of arteriosclerosis in the contralateral carotid artery did not differ between the treatment groups.
Does low-dose acetylsalicylic acid prevent stroke after carotid surgery? A double-blind, placebo-controlled randomized trial.
BACKGROUND AND PURPOSE: The aim of this randomized double-blind, placebo-controlled trial was to evaluate whether neurological deficits could be prevented with low-dose acetylsalicylic acid (ASA) as an adjunct to carotid endarterectomy.
METHODS: A total of 232 patients were randomized to two groups, 75 mg/d ASA starting preoperatively and continued for 6 months (n = 117) or placebo (identical tablets) (n = 115). The patients were followed up regularly for 1 year.
RESULTS: The groups were well matched regarding laboratory data and indication for operation. The number of patients with intraoperative or postoperative stroke without complete recovery within 1 week were 0 and 2 at 30 days and 6 months, respectively, in the ASA group, compared with 7 and 11 in the placebo group (P = .01). Including all neurological events within 6 months, this was found in 15 patients in the ASA group compared with 24 in the placebo group (P = .12). Mortality was 0.8% and 3.4% at 30 days and 6 months, respectively, in the ASA group. In the placebo group, the corresponding figures were 4.3% and 6.0%, respectively (P = .12). The intraoperative bleeding did not differ between the groups nor did the number of reoperations due to bleeding or other complications related to pharmacology.
CONCLUSIONS: This study indicates that low-dose ASA (75 mg/d) reduces the number of postoperative strokes without complete recovery within 1 week. Overall neurological events are insignificantly reduced, as also mortality. The use of low-dose ASA (75 mg) seems safe and effective in reducing cerebrovascular events after carotid endarterectomy.
Indobufen versus placebo in the prevention of restenosis after carotid endarterectomy: a double-blind pilot study.
A randomized clinical trial was undertaken to assess the efficacy of indobufen in inhibiting platelet adhesiveness in carotid thromboendarterectomy. The patients were treated under double-blind conditions with indobufen and with placebo, and were then assessed by means of scintigraphy with labelled platelets, ultrasonic tomography and angiography for a minimum follow-up period of 6 months. Haematological and clinical assessments were also performed. The results of the study suggest that platelet accumulation in carotid endarterectomy may be an early sign of restenosis; anti-aggregant treatment with indobufen carried out at an early stage prior to surgery inhibited platelet accumulation. The final result showed that anti-aggregant treatment had a positive influence on the short- and medium-term outcome of carotid endarterectomy.
Options:
A: Antiplatelet therapy significantly reduces the risk of death from all causes.
B: Antiplatelet therapy significantly reduces the risk of stroke of any cause.
C: Antiplatelet therapy significantly increases the risk of myocardial infarction.
D: Antiplatelet therapy significantly increases the risk of major extracranial haemorrhage. | B |
279 | 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 use of granulocyte colony stimulating factor (G-CSF) or granulocyte-macrophage colony stimulating factor (GM-CSF) in neonatal practice for treating or preventing systemic infections? Please answer this question based on the information provided below:
Comparison of recombinant granulocyte colony-stimulating factor, recombinant human granulocyte-macrophage colony-stimulating factor and placebo for treatment of septic preterm infants.
BACKGROUND: To reduce morbidity and mortality adjuvant cytokine therapy was administered to septic neonates with variable results. The objective of this case series was to compare the effectiveness of recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) and recombinant granulocyte colony-stimulating factor (rG-CSF) with that of placebo in correcting neutropenia induced by sepsis.
METHODS: Symptomatic, septic premature neonates with or without a positive blood culture were eligible. Twenty-eight patients were randomized: 10 received rG-CSF (5 microg/kg/dose i.v. twice a day); 10 received rhuGM-CSF (4 microg/kg/dose i.v. twice a day) and 8 received placebo for a maximum of 7 days, or until an absolute neutrophil count (ANC) of 10,000 cells/mm was reached.
RESULTS: A significant increase in the ANC above the baseline was present on Day 2 in the rG-CSF group (P = 0.015) and on Day 5 in the rhuGM-CSF (P = 0.002) and placebo (P = 0.027) groups. The ANC of the rG-CSF group was significantly above that in the rhuGM-CSF and placebo groups on Day 7 (P = 0.03). Mortality and neonatal intensive care unit morbidity was not significantly different between the groups.
CONCLUSION: The neutrophil count in the rG-CSF-treated group increased significantly faster than that in the placebo or rhuGM-CSF group.
A trial of recombinant human granulocyte colony stimulating factor for the treatment of very low birthweight infants with presumed sepsis and neutropenia.
OBJECTIVES: The primary objective was to investigate the safety of recombinant human granulocyte colony stimulating factor (rhG-CSF) for the treatment of very low birthweight infants (VLBW) with sepsis and relative neutropenia, specifically with regard to worsening of respiratory distress and thrombocytopenia and all cause mortality. Secondary objectives were to evaluate duration of ventilation, intensive care, and antibiotic use as markers of efficacy.
DESIGN: Neonates (< or = 28 days) in intensive care, with birth weights of 500-1500 g, absolute neutrophil count (ANC) of < or = 5 x 10(9)/l, and clinical evidence of sepsis, were randomly assigned to receive either rhG-CSF (10 microg/kg/day) administered intravenously (n = 13), or placebo (n = 15) for a maximum of 14 days, in addition to standard treatment and antibiotics. All adverse events, oxygenation index, incidence of thrombocytopenia, all cause mortality, duration of ventilation, intensive care and antibiotic treatment, and ANC recovery were compared between the two groups.
RESULTS: Adverse events and oxygenation index were not increased by, and thrombocytopenia was not attributable to, treatment with rhG-CSF. At 6 and 12 months postmenstrual age, there were significantly fewer deaths in the group receiving rhG-CSF (1/13 v 7/15; p < or = 0.038). There was a non-significant trend towards a reduction in duration of ventilation, intensive care, and antibiotic use in the rhG-CSF group. There was a significantly more rapid increase in ANC in the rhG-CSF treated babies (p < 0.001).
CONCLUSIONS: In a small randomised placebo controlled trial in a highly selected group of neonates, adjuvant treatment with rhG-CSF increased ANC rapidly, and no treatment related adverse events were identified. Mortality at 6 and 12 months postmenstrual age was significantly lower in the treatment group. A large trial investigating efficacy in a similar group of neonates is warranted.
A randomized trial of granulocyte-macrophage colony-stimulating factor in neonates with sepsis and neutropenia.
OBJECTIVES: To determine whether adjunctive therapy with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) could reverse sepsis-associated neonatal neutropenia and improve neonatal survival and to assess its safety compared with conventional therapy in a control group.
STUDY DESIGN: This prospective, randomized, controlled trial was performed in 60 infants with neutropenia and clinical signs of sepsis. A subcutaneous injection of rhGM-CSF (5 microgram/kg/day) was administered to 30 of the patients for 7 consecutive days. Hematologic parameters (absolute neutrophil, eosinophil, monocyte, lymphocyte counts, and platelet number) and outcome were compared with 30 conventionally treated (control) patients.
RESULTS: Twenty-five patients from the GM-CSF-treated group and 24 from the conventionally treated group had early-onset sepsis (</=3 days' postnatal age), and the other 11 patients had late-onset sepsis (>3 days' postnatal age). There was no difference between groups in terms of birth weight; gestational age; gender; maturity; maternal age; and incidence of prolonged rupture of membranes, maternal hypertension, or severity of sepsis. All neonates tolerated GM-CSF well with no adverse reactions. The absolute neutrophil count on day 7 was significantly increased in the GM-CSF-treated group compared with the conventionally treated group: 8088 +/- 2822/mm(3) versus 2757 +/- 823/mm(3). The mean platelet count was significantly higher on days 14 in the GM-CSF-treated group compared with conventionally treated group: 266 867 +/- 55 102/mm(3) versus 229 200 +/- 52 317/mm(3). Hematologic parameters were otherwise similar between groups before treatment and on day 28. Twenty-seven neonates in the rh-GMCSF group and 21 in the control group survived to hospital discharge. The mortality rate in the rhGM-CSF group (10%) was significantly lower than in the conventionally treated group (30%).
CONCLUSION: Treatment with rhGM-CSF is associated with an increase in absolute neutrophil, eosinophil, monocyte, lymphocyte, and platelet counts and decreased mortality in critically ill septic neutropenic neonates. These results suggest that rhGM-CSF may be effective in the treatment of neonatal sepsis with neutropenia, and further randomized trials are needed to confirm its beneficial effects.
Results of a phase I/II trial of recombinant human granulocyte-macrophage colony-stimulating factor in very low birthweight neonates: significant induction of circulatory neutrophils, monocytes, platelets, and bone marrow neutrophils.
Neonates, especially those of very low birthweight (VLBW), have an increased risk of nosocomial infections secondary to deficiencies in development. We previously demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) production and mRNA expression from stimulated neonatal mononuclear cells are significantly less than that from adult cells. Recombinant murine GM-CSF administration to neonatal rats has resulted in neutrophilia, increased neutrophil production, and increased survival of pups during experimental Staphylococcus aureus sepsis. In the present study, we sought to determine the safety and biologic response of recombinant human (rhu) GM-CSF in VLBW neonates. Twenty VLBW neonates (500 to 1,500 g), aged < 72 hours, were randomized to receive either placebo (n = 5) or rhuGM-CSF at 5.0 micrograms/kg once per day (n = 5), 5.0 micrograms/kg twice per day (n = 5), or 10 micrograms/kg once per day (n = 5) given via 2-hour intravenous infusion for 7 days. Complete blood counts, differential, and platelet counts were obtained, and tibial bone marrow aspirate was performed on day 8. Neutrophil C3bi receptor expression was measured at 0 and 24 hours. GM-CSF levels were measured by a sandwich enzyme-linked immunosorbent assay at 2, 4, 6, 12, and 24 hours after the first dose of rhuGM-CSF. At all doses, rhuGM-CSF was well tolerated, and there was no evidence of grade III or IV toxicity. Within 48 hours of administration, there was a significant increase in the circulating absolute neutrophil count (ANC) at 5.0 micrograms/kg twice per day and 10.0 micrograms/kg once per day, which continued for at least 24 hours after discontinuation of rhuGM-CSF. When the ANC was normalized for each patient's first ANC, there was a significant increase in the ANC on days 6 and 7 at each dose level. By day 7, all tested doses of rhuGM-CSF resulted in an increase in the absolute monocyte count (AMC) compared with placebo-treated neonates. In those receiving rhuGM-CSF 5.0 micrograms/kg twice per day, there was additionally a significant increase in the day 7 and 8 platelet count. Tibial bone marrow aspirates demonstrated a significant increase in the bone marrow neutrophil storage pool (BM NSP) at 5.0 micrograms/kg twice per day and 10.0 micrograms/kg once per day. Neutrophil C3bi receptor expression was significantly increased 24 hours after the first dose of rhuGM-CSF at 5.0 micrograms/kg once per day. The elimination half-life (T1/2) of rhuGM-CSF was 1.4 +/- 0.8 to 3.9 +/- 2.8 hours.(ABSTRACT TRUNCATED AT 400 WORDS)
A randomized, double-blind, placebo-controlled trial of prophylactic recombinant human granulocyte-macrophage colony-stimulating factor to reduce nosocomial infections in very low birth weight neonates.
OBJECTIVE: We carried out a randomized placebo-controlled trial in very low birth weight neonates (VLBWNs), comparing the incidence of nosocomial infections after the prophylactic use of recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) versus placebo in VLBWNs.
STUDY DESIGN: VLBWNs (n = 264), weighing 501 to 1000 g, </=72 hours of age were randomly assigned to receive rhu GM-CSF (8 microg/kg/d), administered intravenously (n = 134) over 2 hours daily x 7 days and every other day for 21 days, or placebo (n = 130). The safety, incidence of nosocomial infections, days of absolute neutrophil count >/=4000/mm,3 peripheral blood progenitor studies, and 24-hour polymorphonuclear leukocyte C3bi receptor expression were compared between the 2 treatment groups.
RESULTS: No (grade III/IV) toxicity or adverse events were associated with rhu GM-CSF. The absolute neutrophil count and absolute eosinophil count were significantly elevated in the rhu GM-CSF group on days 7 (P =.001), 14 (P =.001), and 21 (P =.007) and on days 7 and 28 (P =.012 and P =.001, respectively). However, there was no difference in the incidence of confirmed nosocomial infections between the 2 treatment groups in this trial (40% vs 39%, rhu GM-CSF vs placebo; P = NS).
CONCLUSION: In a large randomized placebo-controlled trial, prophylactic administration of rhu GM-CSF in VLBWNs does not appear to decrease the incidence of nosocomial infections.
A randomized, controlled trial of prophylactic granulocyte-macrophage colony-stimulating factor in human newborns less than 32 weeks gestation.
OBJECTIVE: Preterm neonates undergoing intensive care have high morbidity from sepsis. These infants also frequently develop neutropenia, and when this is associated with sepsis, mortality is high. This study investigates the potential for granulocyte-macrophage colony-stimulating factor (GM-CSF) to effect a clinically relevant increase in neutrophil number when used prophylactically in high-risk preterm neonates, and assesses its safety in this population.
DESIGN: In an open, randomized, controlled study, 75 neonates (25 small for gestational age) <32 weeks gestation were randomized to receive GM-CSF (10 microg/kg/d) by subcutaneous injection for 5 days from <72 hours after birth, or to a control group. The primary outcome measure was the neutrophil count during 14 days from study entry. The infants were monitored for potential toxicity. Clinical outcomes, sepsis, and mortality, were recorded, but this initial study was not designed to address clinical benefit.
RESULTS: Prophylactic GM-CSF therapy completely abolished neutropenia in treated infants, when both well and septic, throughout the period of study. Neutropenia (</=1.7 x 10(9)/L) developed in 16 of 39 control infants. Five control infants experienced an acute decrease in neutrophil count coincident with the onset of sepsis. There was no evidence of hematologic, respiratory, or gastrointestinal toxicity in treated infants. Treated infants had a trend to fewer symptomatic, blood culture positive septic episodes than controls during 2 weeks from study entry (11/36 vs 18/39).
CONCLUSION: Five-day prophylactic GM-CSF completely abolishes postnatal neutropenia and sepsis-induced neutropenia in preterm neonates at high risk of sepsis, and so removes an important risk factor for sepsis and sepsis-related mortality.GM-CSF, preterm neonates, neutropenia, sepsis.
Administration of recombinant human granulocyte-colony stimulating factor to septic neonates induces neutrophilia and enhances the neutrophil respiratory burst and beta2 integrin expression. Results of a randomized controlled trial.
The objective of this study was to investigate the effect of treatment with recombinant human granulocyte-colony stimulating factor (rhG-CSF) on the neutrophil count and function of preterm neonates with documented sepsis. For this purpose 62 preterm neonates with proven sepsis and 19 healthy preterm ones were studied. Of the 62 patients, 27 septic neonates had an absolute neutrophil count (ANC) > 5000/mm3 (group A) and were scheduled not to receive rhG-CSF and 35/62 had an ANC < 5000/mm3 (n=35) and were randomly assigned either to receive rhG-CSF (group B) or not to receive it (group C). rhG-CSF (10 microg/kg) was administered for 3 consecutive days (0, 1, 2). The ANC, plasma levels of G-CSF (ELISA), neutrophil respiratory burst activity (NRBA) and neutrophil expression of CD11a, CD11b and CD11c (flow cytometry) were measured in all septic neonates on days 0 (onset of sepsis), 1, 3 and 5 and in the healthy neonates once within the first 2 days of life. We found that on day 0, G-CSF levels of all groups of septic neonates were significantly higher than those of the healthy ones. The highest levels were observed in group A. NRBA was diminished only in groups B and C and the expression of CD11a and CD11c was reduced in all groups of septic neonates. Administration of rhG-CSF resulted in a rapid and significant increase in ANC, NRBA and CD11a, CD11b and CD11c expression that persisted throughout the follow up. CONCLUSION; The administration of granulocyte colony stimulating factor to septic neonates significantly increases the absolute granulocyte count and enhances the neutrophil respiratory burst and beta2 integrin expression.
A randomized, placebo-controlled trial of recombinant human granulocyte colony-stimulating factor administration in newborn infants with presumed sepsis: significant induction of peripheral and bone marrow neutrophilia.
Host defenses in the human neonate are limited by immaturity in phagocytic immunity. Such limitations seem to predispose infected newborns to neutropenia from an exhaustion of the neutrophil reserve. Among the critical defects thus far identified in neonatal phagocytic immunity is a specific reduction in the capacity of mononuclear cells to express granulocyte colony-stimulating factor (G-CSF) after stimulation. However, the safety, pharmacokinetics, and biological efficacy of administration of recombinant human (rh)G-CSF to infected human newborns to compensate for this deficiency is unknown. Forty-two newborn infants (26 to 40 weeks of age) with presumed bacterial sepsis within the first 3 days of life were randomized to receive either placebo or varying doses of rhG-CSF (1.0, 5.0 or 10.0 micrograms/kg every 24 hours [36 patients] or 5.0 or 10.0 micrograms/kg every 12 hours [6 patients]) on days 1, 2, and 3. Complete blood counts with differential and platelet counts were obtained at hours 0, 2, 6, 24, 48, 72, and 96. Circulating G-CSF concentrations were determined at hours 0, 2, 6, 12, 14, 16, 18, 24, and 36. Tibial bone marrow aspirates were obtained after 72 hours for quantification of the bone marrow neutrophil storage pool (NSP), neutrophil proliferative pool, granulocyte progenitors, and pluripotent progenitors. Functional activation of neutrophils (C3bi expression) was determined 24 hours after rhG-CSF or placebo administration. Intravenous rhG-CSF was not associated with any recognized acute toxicity. RhG-CSF induced a significant increase in the blood neutrophil concentration 24 hours after the 5 and 10 micrograms/kg doses every 12 and 24 hours and it was sustained as long as 96 hours. A dose-dependent increase in the NSP was seen following rhG-CSF. Neutrophil C3bi expression was significantly increased at 24 hours after 10 micrograms/kg every 24-hour dose of rhG-CSF. The half-life of rhG-CSF was 4.4 +/- 0.4 hours. The rhG-CSF was well tolerated at all gestational ages treated. The rhG-CSF induced a significant increase in the peripheral blood and bone marrow absolute neutrophil concentration and in C3bi expression. Future clinical trials aimed at improving the outcome of overwhelming bacterial sepsis and neutropenia in newborn infants might include the use of rhG-CSF.
A two-year follow-up of neonates with presumed sepsis treated with recombinant human granulocyte colony-stimulating factor during the first week of life.
We have previously reported that recombinant human granulocyte colony-stimulating factor was well tolerated and resulted in sustained neutrophilia and improvement of neutrophil functions in newborn infants with presumed sepsis. We now report a 2-year follow-up on 21 of the initial cohort of 28 patients. Treatment with recombinant human granulocyte colony-stimulating factor in neonates with presumed sepsis was not associated with any long-term adverse hematologic, immunologic, or developmental effects.
A randomized, double-masked, placebo-controlled trial of recombinant granulocyte colony-stimulating factor administration to preterm infants with the clinical diagnosis of early-onset sepsis.
OBJECTIVE: We performed a randomized, double-masked, parallel-groups, placebo-controlled trial of recombinant granulocyte colony-stimulating factor (rG-CSF) administration to 44 preterm neonates who had blood cultures obtained and antibiotics begun because of the clinical diagnosis of early-onset sepsis. Two primary outcome variables were tested 1) mortality and 2) development of nosocomial infections over the 2-week period after dosing.
DESIGN AND METHODS: The treatment group (n = 22) received 10 microgram/kg/day of intravenous rG-CSF once daily for 3 days and the placebo group (n = 22) received the same volume of a visually indistinguishable vehicle. Mortality and culture-proven nosocomial infections were recorded. Immediately before the first, second, and third doses, and again 10 days after the first dose, serum concentrations were determined for tumor necrosis factor-alpha, interleukin 6, granulocyte-macrophage colony stimulating factor, and G-CSF, and blood leukocyte counts, absolute neutrophil counts, immature/total neutrophil ratios, platelet counts, and hemoglobin concentrations were measured.
RESULTS: The treatment and placebo groups were of similar gestational age (29 +/- 3 vs 31 +/- 3 weeks) and birth weight (1376 +/- 491 vs 1404 +/- 508 g), and had similar Apgar scores and 24-hour Score for Neonatal Acute Physiology scores. The mortality rate was not different between treatment and placebo groups. However, the occurrence of a subsequent nosocomial infection was lower in the rG-CSF recipients (relative risk:.19; 95% confidence interval:.05-.78). rG-CSF treatment did not alter the serum concentrations of the cytokines measured (except for G-CSF). Serum G-CSF levels and blood neutrophil counts were higher in the treatment than in the placebo group 24 hours and 48 hours after dosing.
CONCLUSIONS: Administration of 3 daily doses of rG-CSF (10 microgram/kg/day) to premature neonates with the clinical diagnosis of early-onset sepsis did not improve mortality but was associated with acquiring fewer nosocomial infections over the subsequent 2 weeks.
A randomized, placebo-controlled trial of granulocyte colony-stimulating factor administration to newborn infants with neutropenia and clinical signs of early-onset sepsis.
OBJECTIVE: To determine whether recombinant human granulocyte colony-stimulating factor (G-CSF) administration: 1) accelerates production of neutrophils; 2) increases bone marrow stored and precursor neutrophils; and 3) is safe in newborn infants with neutropenia and clinical signs of early-onset sepsis.
STUDY DESIGN: We randomized 20 infants with neutropenia and clinical signs of early-onset sepsis in the first 3 days of life to receive G-CSF (10 microg/kg/d) or placebo for 3 days. Entry criteria included neutropenia as defined by Manroe criteria, an elevated immature to total neutrophil ratio [(I/T) >/=0.25], and a requirement for ventilatory support. Cultures were obtained and antibiotics initiated on all study infants. Circulating absolute neutrophil count (ANC), I/T ratio, bone marrow neutrophil storage pool (NSP) and neutrophil proliferative pool (NPP), and plasma G-CSF concentrations were evaluated. Also, severity of illness as determined using the Score for Neonatal Acute Physiology (SNAP), morbidity, and mortality were recorded.
RESULTS: Circulating ANC increased in both G-CSF and placebo recipients by day 1. Also, the I/T neutrophil ratio decreased in both G-CSF and placebo recipients. There were no significant differences in the ANC or I/T ratio between the two groups during the study period. Similarly, bone marrow NSP and NPP did not differ between G-CSF and placebo recipients at study entry or day 2. No differences were observed in the secondary outcome measures including severity of illness, morbidity, and mortality.
CONCLUSIONS: Administration of recombinant G-CSF to infants with neutropenia and clinical signs of early-onset sepsis did not increase circulating ANC, or bone marrow NSP and NPP compared with placebo. No differences were observed between G-CSF and placebo recipients in severity of illness, morbidity, or mortality. No adverse effects of G-CSF administrations were noted.
Options:
A: G-CSF and GM-CSF significantly reduce mortality in preterm infants with suspected systemic infection.
B: G-CSF and GM-CSF are effective as prophylactic treatments to prevent systemic infections in high-risk neonates.
C: There is insufficient evidence to support the use of G-CSF or GM-CSF in neonatal practice for treating or preventing systemic infections.
D: G-CSF and GM-CSF have been shown to be toxic in neonatal practice. | C |
280 | 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 safety of lumbar epidural analgesia compared to systemic analgesia for postoperative pain relief in patients after elective hip or knee replacement? Please answer this question based on the information provided below:
[Patient-controlled postoperative analgesia in orthopedic surgery: epidural PCA versus intravenous PCA].
OBJECTIVE: To evaluate both effectiveness and incidence of side effects of two techniques of postoperative pain treatment: intravenous and epidural PCA.
DESIGN: Prospective analysis of data from two groups of randomized patients.
SETTINGS: Orthopedic and trauma center.
PATIENTS: Figty ASA class II-III patients undergoing total hip replacement under combined Spinal-Epidural Anesthesia.
METHODS: Patients were divided into 2 groups who received different postoperative pain treatment. One group (group PCA) received a patient-controlled intravenous analgesia with morphine 30 mg and ketorolac 90 mg in 100 ml of saline (back-ground infusion 2-4 ml, according to body weith, bolus 1 ml, lockout 5 min, 4 h dose limit 40 ml). PCEA group received a patient-controlled epidural analgesia with morphine 4 mg and bupivacaine 0.125% 100 ml, (background infusion 3-4 ml, according to patient' height, bolus 1 ml, lockout 10 min, 4 h dose limit 25 ml). Postoperative pain intensity was evaluated, through 24 postoperative hours, by a verbal analogue scale (VPS = 0 to 3) and a total pain score (TOTPAR) was calculated for each patient at 6 and 24 postoperative hours. Side effects were recorded and their incidence was obtained for each group. Statistical data analysis was performed by one-way ANOVA and non-parametric tests for ordinal data. Nominal data were analyzed by chi 2 test. p < 0.05 was considered significant.
RESULTS: Patient receiving PCEA showed a significant (p < 0.005) decrease of incident pain, while VPS at rest was similar in the two groups. TOTPAR VPS was lower (p < 0.05) in PCEA group both at 6 and 24 postoperative hours. Somnolence was observed more often in PCA patients (8% vs 2%; p 0.05), while no significant differences were noted among other side effects incidence.
CONCLUSIONS: Our data show a better control of postoperative pain arising from total hip replacement during PCEA when compared to PCA. It should be emphasized that incident pain is far more decreased by PCEA, so that this technique is particularly indicated when an early postoperative mobilization is required.
Effects of perioperative analgesic technique on the surgical outcome and duration of rehabilitation after major knee surgery.
BACKGROUND: Continuous passive motion after major knee surgery optimizes the functional prognosis but causes severe pain. The authors tested the hypothesis that postoperative analgesic techniques influence surgical outcome and the duration of convalescence.
METHODS: Before standardized general anesthesia, 56 adult scheduled for major knee surgery were randomly assigned to one of three groups, each to receive a different postoperative analgesic technique for 72 h: continuous epidural infusion, continuous femoral block, or intravenous patient-controlled morphine (dose, 1 mg; lockout interval, 7 min; maximum dose, 30 mg/4 h). The first two techniques were performed using a solution of 1% lidocaine, 0.03 mg/ml morphine, and 2 microg/ml clonidine administered at 0.1 ml x kg(-1) x h(-1). Pain was assessed at rest and during continuous passive motion using a visual analog scale. The early postoperative maximal amplitude of knee flexion was measured during continuous passive motion at 24 h and 48 h and compared with the target levels prescribed by the surgeon. To evaluate functional outcome, the maximal amplitudes were measured again on postoperative day 5, at hospital discharge (day 7), and at 1- and 3-month follow-up examinations. When the patients left the surgical ward, they were admitted to a rehabilitation center, where their length of stay depended on prospectively determined discharge criteria
RESULTS: The continuous epidural infusion and continuous femoral block groups showed significantly lower visual analog scale scores at rest and during continuous passive motion compared with the patient-controlled morphine group. The early postoperative knee mobilization levels in both continuous epidural infusion and continuous femoral block groups were significantly closer to the target levels prescribed by the surgeon than in the patient-controlled morphine group. On postoperative day 7, these values were 90 degrees (60-100 degrees)(median and 25th-75th percentiles) in the continuous epidural infusion group, 90 degrees (60-100 degrees) in the continuous femoral block group, and 80 degrees (60-100 degrees) in the patient-controlled morphine group (P < 0.05). The durations of stay in the rehabilitation center were significantly shorter: 37 days (range, 30-45 days) in the continuous epidural infusion group, 40 days (range, 31-60 days) in the continuous femoral block group, and 50 days (range, 30-80 days) in the patient-controlled morphine group (P < 0.05). Side effects were encountered more frequently in the continuous epidural infusion group.
CONCLUSION: Regional analgesic techniques improve early rehabilitation after major knee surgery by effectively controlling pain during continuous passive motion, thereby hastening convalescence.
Reducing perioperative blood loss in patients undergoing total hip arthroplasty.
In this prospective, randomised, double-blind study, we investigated the effect of epidural anaesthesia and an antifibrinolytic agent, Aprotinin (500,000 KIU in bolus before surgery and 500,000 KIU h(-1) in drip form during surgery), on intra and postoperative blood loss and transfusion requirements in total hip arthroplasty. Sixty patients were allocated randomly to four groups (A: epidural + general anesthesia + Aprotinin, B: epidural + general anesthesia + placebo (equal volume), C: general anaesthesia + Aprotinin, D: general anaesthesia + placebo). Postoperative analgesia: epidural analgesia in groups A and B, systemic analgesia with opiates in groups C and D. Blood loss during surgery was monitored and salvaged with the Compact-A Dideco, and postoperative blood loss with the BT 797 Recovery Dideco for the first 24 hours. Perioperative blood loss, frequency and quantity of transfusions were significantly higher in group D (p<0.0001). Total blood loss was reduced by 31.3% by epidural anaesthesia, 20.4% by Aprotinin and 51.4% using a combination of the two techniques.
Extradural and parenteral pethidine as analgesia after total hip replacement: effects and kinetics. A controlled clinical study.
Twenty-one patients who had undergone total hip replacement were randomly assigned to one of three groups in order to compare a single dose of 1 mg/kg of pethidine im (I) and 20 mg (II) or 60 mg of extradural pethidine (III) in a double-blind design. The degree of analgesia, the adverse effects, and the kinetics were studied for 18 h. Pain was monitored using a visual analogue scale (VAS). Supplementary doses of oxycodone if required were given no earlier than 0.75 h after pethidine. Plasma concentrations of pethidine were measured with gas chromatography mass spectrometry (GCMS). Hypoalgesia to pin prick test was evaluated. Low pain scores were observed in the extradural groups between 0.25 and 1.5 h after the dose. A significant difference in pain score compared with the im group was found after the higher extradural dose only between 0.5 and 1 h (p less than 0.05). The area under the curve (AUC) of pain score versus time (0-18 h) was not significantly different between groups. The recorded adverse effects were minor in all three groups. The terminal half-lives and plasma clearances of pethidine, and the time to peak concentration were not different between the groups. Single patients in the extradural groups showed hypoalgesia to pin prick in parallel to the effect. The present study shows that extradural pethidine produces shortlived analgesia, in contrast to the long-lasting effect of morphine found in other studies.
Does morphine premedication influence the pain and consumption of postoperative analgesics after total knee arthroplasty?
Evidence of pre-emptive analgetic effect of opioid would offer great potential benefit to patients with postoperative pain, a better pain relief with less opioid. The aim of this double blind randomised trial was to study the effect of intramuscular morphine premedication on postoperative pain. Forty-one patients undergoing total knee arthroplasty were randomly allocated to four groups. Two groups received epidural morphine, 4 mg immediately after operation and 3 mg ten hours later, and two groups the same volume of saline. All patients had access to intravenous PCA-fentanyl. One epidural morphine and one epidural saline group (PreEpiMo and PreMo, respectively) received morphine, 0.14 mg/kg i.m. as premedication. Pain was measured with a visual analogue scale (VAS). Respiration was monitored by means of pulseoximetry, arterial blood gas analysis and rate of breathing. Morphine premedication reduced postoperative pain in the immediate postoperative period in patients with epidural placebo (PreMo), but the effect was absent in patients with PreEpiMo. Epidural morphine (EpiMo) provided stable analgesia with reduced need of PCA-fentanyl. Two patients (10%) (one in EpiMo and one in PreEpiMo) developed respiratory depression requiring naloxone treatment. The dosage of epidural morphine used in this study was a likely explanation of this depression. Nausea, vomiting, itching and urinary retention were the most frequent side effects without significant differences between the groups. In conclusion, morphine premedication had a temporary rest effect on the postoperative pain. Epidural morphine provides a better analgesia than intravenous PCA-fentanyl.
Ketoprofen for pain after hip and knee arthroplasty.
In a double-blind, randomized study, we have compared the effects of i.v. ketoprofen 200 mg followed by 12.5 mg h-1 over 13 h, with those of extradural morphine 4 mg in 32 patients after hip and knee arthroplasty. A visual analogue scale was used to score pain before analgesic administration (first complaint after operation), 1 h after and every 2 h subsequently. Pain reduction 1 h after the start of analgesia was mean 44% (SEM 17%) in the extradural morphine group and 54% (9%) in the ketoprofen group (ns). There were no significant differences between groups in pain scores, pain reduction and additional analgesia requirement (i.v. paracetamol). Naloxone 5 micrograms kg-1 h-1 was required for hypercapnia exceeding 6.0 kPa in three patients in the extradural morphine group (vs none in the ketoprofen group; ns). There were no differences between groups in side effects, except for urinary retention, which was more frequent in the extradural morphine group (P < 0.05). As there were few differences between i.v. ketoprofen and extradural morphine, we conclude that ketoprofen may be an efficient alternative to extradural morphine after hip and knee arthroplasty.
Antithrombotic efficacy of continuous extradural analgesia after knee replacement.
We have studied the effect of extradural analgesia on postoperative venous thrombosis in patients undergoing knee arthroplasty. Forty-eight patients were allocated randomly to receive either general anaesthesia or extradural analgesia with local anaesthetics for 3 days. All patients wore compressive elastic stockings and no anticoagulant drugs were administered. Bilateral venography was performed 10 days after surgery. Continuous extradural analgesia did not impede mobilization of the patients. One case of nonfatal pulmonary embolism occurred in a patient who received general anaesthesia. The use of continuous extradural analgesia resulted in a significant difference in the total incidence of deep vein thrombosis (18% compared with 59% after general anaesthesia (P = 0.02]. The incidence of calf vein thrombosis was 12% compared with 45% after general anaesthesia (P = 0.05).
Intraarticular, epidural, and intravenous analgesia after total knee arthroplasty.
BACKGROUND: After total knee arthroplasty, patients regularly suffer from severe pain. It is unclear whether epidural or systemic pain therapy is superior in terms of postoperative pain relief, patients' comfort and side effects. A new therapeutic approach, intraarticular opioids, has been suggested with the detection of opioid receptors in inflamed tissue. This method has proven suitable for clinical use in small operations (e.g. knee arthroscopy). In this study, we compared epidural analgesia and intraarticular application of morphine plus "on-demand" intravenous analgesia to "on-demand" intravenous analgesia alone.
METHODS: Thirty-seven patients, scheduled for total knee arthroplasty, were randomly assigned to three treatment groups: in group 1 (EPI) patients received bolus doses of morphine via an epidural catheter; in group 2 (IA) an intraarticular bolus of 1 mg of morphine was applied at the end of the operation with subsequent use of a patient-controlled analgesia (PCA) pump; group 3 (Control), in which only PCA was provided, served as control for both analgesic procedures. Main outcome measures included visual analogue pain scales, total morphine consumption, and stress hormones.
RESULTS: No statistically significant differences in visual analogue pain scales could be detected between the three groups. Application of intraarticular morphine did not reduce the amount of analgesics required for postoperative analgesia as compared to intravenous analgesia alone. Application of epidural morphine significantly suppressed beta-endorphine release, but did not significantly influence other stress hormones as compared to the control group.
CONCLUSION: Epidural and intravenous analgesia after total knee arthroplasty are equivalent methods of pain relief. In major orthopaedic procedures, application of intraarticular morphine does not reduce analgesic requirements.
The effect of balanced analgesia on early convalescence after major orthopaedic surgery.
Forty-two patients scheduled for total knee arthroplasty (n = 20) or hip arthroplasty (n = 22) were randomly allocated to receive either continuous epidural bupivacaine/morphine for 48 h postoperatively plus oral piroxicam, or general anaesthesia followed by a conventional intramuscular opioid and acetaminophen regimen. Patients undergoing knee- or hip arthroplasty treated with epidural analgesia had significantly lower pain scores during mobilization under the 48 h epidural infusion compared with patients receiving conventional treatment, while no important differences were observed after cessation of the epidural regimen. However, the achieved pain relief had no impact on postoperative convalescence parameters, such as ambulation, patient activity including need for nursing care, fatigue or hospital stay. Late postoperative pain, fatigue and conservative attitudes and routines in the postoperative care, were the most important reasons limiting mobilization and activity. We conclude that effective early (48 h) postoperative pain relief with balanced analgesia does not per se lead to important improvements in convalescence and hospital stay.
Epidural infusions of bupivacaine and fentanyl do not improve rehabilitation following one-stage bilateral total knee arthroplasty.
Epidural analgesia with local anaesthetic minimizes the catabolic response to surgery. To determine whether this could enhance the rate of recovery following orthopaedic surgery, 51 patients undergoing bilateral one-stage total knee arthroplasty were allocated to receive infusions of either continuous epidural bupivacaine/fentanyl or continuous intravenous fentanyl to compare the efficacy of these modes of pain relief on postoperative clinical outcomes and rates of rehabilitation. Infusions were maintained for 36 to 48 hours in a post-anaesthesia care unit (PACU). Postoperatively, pain relief (visual analogue scale), attainment of physical therapy goals and cardiopulmonary complications were measured daily for 7 days. Epidural analgesia with a combination of bupivacaine and fentanyl did not result in any measurable improvement in rehabilitation milestones or reduction in postoperative complications following bilateral total knee arthroplasty than with fentanyl infusions alone.
Effects of intravenous patient-controlled analgesia with morphine, continuous epidural analgesia, and continuous three-in-one block on postoperative pain and knee rehabilitation after unilateral total knee arthroplasty.
UNLABELLED: In this study, we assessed the influence of three analgesic techniques on postoperative knee rehabilitation after total knee arthroplasty (TKA). Forty-five patients scheduled for elective TKA under general anesthesia were randomly divided into three groups. Postoperative analgesia was provided with i.v. patient-controlled analgesia (PCA) with morphine in Group A, continuous 3-in-1 block in Group B, and epidural analgesia in Group C. Immediately after surgery, the three groups started identical physical therapy regimens. Pain scores, supplemental analgesia, side effects, degree of maximal knee flexion, day of first walk, and duration of hospital stay were recorded. Patients in Groups B and C reported significantly lower pain scores than those in Group A. Supplemental analgesia was comparable in the three groups. Compared with Groups A and C, a significantly lower incidence of side effects was noted in Group B. Significantly better knee flexion (until 6 wk after surgery), faster ambulation, and shorter hospital stay were noted in Groups B and C. However, these benefits did not affect outcome at 3 mo. We conclude that, after TKA, continuous 3-in-1 block and epidural analgesia provide better pain relief and faster knee rehabilitation than i.v. PCA with morphine. Because it induces fewer side effects, continuous 3-in-1 block should be considered the technique of choice.
IMPLICATIONS: In this study, we determined that, after total knee arthroplasty, loco-regional analgesic techniques (epidural analgesia or continuous 3-in-1 block) provide better pain relief and faster postoperative knee rehabilitation than i.v. patient-controlled analgesia with morphine. Because it causes fewer side effects than epidural analgesia, continuous 3-in-1 block is the technique of choice.
Comparison of epidural and patient-controlled intravenous morphine following joint replacement surgery.
The authors conducted a randomized, prospective study comparing epidural morphine with patient-controlled intravenous (iv) morphine in 30 patients recovering from total hip or total knee arthroplasty. Six, 18, and 24 hr postoperatively, patients used a 10 cm visual-analogue scale to indicate both their current degree of discomfort and the maximum discomfort they had experienced since the previous evaluation. Pain at the time of evaluation did not differ between patients receiving epidural (2.6 +/- 0.4 cm, mean +/- SEM) and patient-controlled iv morphine (3.4 +/- 0.3 cm). However, patients who received epidural morphine recalled less pain during the period preceding evaluation (4.2 +/- 0.5 cm) than did those receiving patient-controlled analgesia (5.5 +/- 0.4 cm, P less than 0.05). Patients receiving epidural morphine were more likely to require treatment for pruritus (4 of 15) than patients who received patient-controlled iv morphine (none of 15, P less than 0.05). Minimum respiratory rates were lower in patients receiving epidural morphine (15.0 +/- 0.3) than in those receiving patient-controlled analgesia (16.5 +/- 0.4, P less than 0.05), but no patients required treatment for respiratory depression. The authors conclude that epidural morphine may provide more consistent analgesia following joint replacement surgery than patient-controlled morphine; however, there is a higher incidence of side-effects with the epidural technique.
Ropivacaine epidural anesthesia and analgesia versus general anesthesia and intravenous patient-controlled analgesia with morphine in the perioperative management of hip replacement. Ropivacaine Hip Replacement Multicenter Study Group.
UNLABELLED: The aim of our study was to compare epidural anesthesia and analgesia (EDA) with ropivacaine versus general anesthesia followed by IV patient-controlled analgesia with morphine (GA/PCA) after hip replacement regarding pain, side effects, and discharge from the postanesthesia care unit. After ethics committee approval, randomization, and informed consent, 90 patients were enrolled. In Group EDA, epidural anesthesia (ropivacaine 10 mg/mL, 15-25 mL) was followed by an epidural infusion (2 mg/mL, 4-6 mL/h for 24 h, plus top-up doses of 6-10 mL for 48 h). GA/PCA patients received general anesthesia (isoflurane/N2O/fentanyl) followed by IV patient-controlled analgesia with morphine postoperatively. Pain was assessed by using visual analog scales (0-100 mm) at rest and during physiotherapy. Pain at rest was less in the EDA (n = 43) group than in the GA/PCA (n = 45) group (at 10 h: 11.8+/-12.9 vs. 28.4+/-17.1 [P< 0.001]; at 24 h: 14.3+/-11.7 vs. 24.0+/-17 [P<0.01]; in 48 h: 14.3+/-9.3 vs. 21.1+/-17.4 [P = 0.1]). Whereas EDA patients were deemed ready for discharge from the postanesthesia care unit earlier than GA/PCA patients (5.6+/-8.9 vs. 39.7+/-41.5 min), the actual discharge time was comparable. The median time for first passage of flatus was shorter in the EDA group than in the GA/PCA group (26 vs. 47 h). Nausea and vomiting were more common in the GA/PCA group than in the EDA group (16% vs. 28% and 11% vs. 22%, respectively), whereas hypotension (11% vs. 4%) and bradycardia (14% vs. 2%) were less frequent. Under the conditions of the present study, EDA with ropivacaine provided pain control after hip replacement superior to that provided by IV patient-controlled analgesia with morphine, particularly during the first 24 h. Both approaches to pain management were equally safe.
IMPLICATIONS: Compared with general anesthesia and postoperative IV patient-controlled analgesia with morphine, epidural anesthesia and analgesia with the new local anesthetic ropivacaine enables patients to be discharged sooner from a postanesthesia care unit and provides superior pain relief during the first 24 h after hip replacement.
Options:
A: Epidural analgesia provides significantly better pain relief at rest and with movement in the first 24 hours post-surgery, with fewer adverse events compared to systemic analgesia.
B: Epidural analgesia provides better pain relief at rest in the first four to six hours post-surgery, but this effect is not statistically significant by 18 to 24 hours. It also results in fewer sedation events but more frequent occurrences of urinary retention, itching, and low blood pressure compared to systemic analgesia.
C: Epidural analgesia provides no significant difference in pain relief at rest or with movement compared to systemic analgesia, and it is associated with a higher frequency of adverse events.
D: Epidural analgesia provides better pain relief at rest and with movement throughout the entire postoperative period, with no significant difference in adverse events compared to systemic analgesia. | B |
281 | 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 effects of routinely administered cotrimoxazole on death and illness episodes in HIV-infected adults, according to the systematic review? Please answer this question based on the information provided below:
Early chemoprophylaxis with trimethoprim-sulphamethoxazole for HIV-1-infected adults in Abidjan, Côte d'Ivoire: a randomised trial. Cotrimo-CI Study Group.
BACKGROUND: In sub-Saharan Africa, various bacterial diseases occur before pneumocystosis or toxoplasmosis in the course of HIV-1 infection, and are major causes of morbidity and mortality. We did a randomised, double blind, placebo-controlled clinical trial at community-health centres in Abidjan, Côte d'Ivoire, to assess the efficacy of trimethoprim-sulphamethoxazole (co-trimoxazole) chemoprophylaxis at early stages of HIV-1 infection.
METHOD: 843 HIV-infected patients were screened and 545 enrolled in the study. Eligible adults (with HIV-1 or HIV-1 and HIV-2 dual seropositivity at stages 2 or 3 of the WHO staging system) received co-trimoxazole chemoprophylaxis (trimethoprim 160 mg, sulphamethoxazole 800 mg) daily or a matching placebo. The primary outcome was the occurrence of severe clinical events, defined as death or hospital admission irrespective of the cause. Analyses were by intention to treat.
FINDINGS: Four of the randomised patients were excluded (positive for HIV-2 only). 120 severe events occurred among 271 patients in the co-trimoxazole group and 198 among 270 in the placebo group. Significantly fewer patients in the co-trimoxazole group than in the placebo group had at least one severe event (84 vs 124); the probability of remaining free of severe events was 63.7% versus 45.8% (hazard ratio 0.57 [95% CI 0.43-0.75], p=0.0001) and the benefit was apparent in all subgroups of initial CD4-cell count. Survival did not differ between the groups (41 vs 46 deaths, p=0.51). Co-trimoxazole was generally well tolerated though moderate neutropenia occurred in 62 patients (vs 26 in the placebo group).
INTERPRETATION: Patients who might benefit from co-trimoxazole could be recruited on clinical criteria in community clinics without knowing the patients CD4-cell count. This affordable measure will enable quick public-health intervention, while monitoring bacterial susceptibility and haematological tolerance.
Safety and efficacy of sulfamethoxazole and trimethoprim chemoprophylaxis for Pneumocystis carinii pneumonia in AIDS.
The safety and efficacy of sulfamethoxazole and trimethoprim in the prevention of Pneumocystis carinii pneumonia associated with the acquired immunodeficiency syndrome (AIDS) were evaluated. Sixty patients with a new diagnosis of Kaposi's sarcoma and no history of opportunistic infections were randomly assigned to receive 800 mg of sulfamethoxazole and 160 mg of trimethoprim twice per day or no therapy. None of the 30 patients receiving sulfamethoxazole and trimethoprim developed P carinii pneumonia. Sixteen of the 30 patients receiving no suppressive therapy developed P carinii pneumonia. Development of P carinii pneumonia was associated with the stage of Kaposi's sarcoma, B subtype disease, and the presence of 0.20 X 10(9)/L (200/mm3) or fewer CD4 cells at study entry. The proportion of patients surviving and the mean length of survival were significantly greater in the treatment group compared with the control group. Adverse reactions occurred in 15 patients (50%).
Primary prevention with cotrimoxazole for HIV-1-infected adults: results of the pilot study in Dakar, Senegal.
OBJECTIVES: To assess the efficacy and tolerance of chemoprophylaxis with cotrimoxazole compared with placebo among HIV-1-infected adults.
DESIGN: Randomized, double-blind, placebo-controlled clinical trial in the urban community of Dakar, Senegal.
METHODS: Eligibility criteria were age greater than 15 years, HIV-1 or HIV-1 and HIV-2 dual seropositivity, CD4 cell count lower than 400 copies/mm3, no progressive infection, no previous history of intolerance to sulphonamide, lack of severe anemia or neutropenia, and renal or hepatic failure. Written informed consent was obtained. Recruited patients received 80 mg of trimethoprim and 400 mg of sulphamethoxazole daily or a matching placebo. The main outcomes were survival and the occurrence of clinical events defined as Pneumocystis carinii pneumonia, cerebral toxoplasmosis, bacterial pneumonia, infectious enteritis, bacterial meningitis, urinary tract infection, bacterial otitis and sinusitis, and pyomyositis.
RESULTS: Between September 1996 and March 1998, 297 patients were screened, and 100 were randomized in the study. Demographic, clinical, and biological characteristics of the two groups were similar as was the mean length of follow-up (7.7 months for the cotrimoxazole group vs. 8.0 months for the placebo group). There was no significant difference between the two groups in survival (hazard ratio = 0.84; 95% confidence interval [CI]: 0.36-1.94) in the probability of severe event occurrence, defined as death or hospital admission (hazard ratio = 1.10; 95% CI: 0.57-2.13), or in the probability of clinical event occurrence (hazard ratio = 1.19; 95% CI: 0.55-2.59). Adjustment for initial CD4 cell count did not change these results. A low dose of cotrimoxazole was tolerated well clinically as well as biologically; only one treatment interruption occurred as the result of a moderate cutaneous eruption (grade 2).
CONCLUSION: Our study does not show a beneficial effect of chemoprophylaxis with low-dose cotrimoxazole on survival or occurrence of opportunistic or nonopportunistic infections for HIV-1-infected patients in Dakar, Senegal.
Efficacy of trimethoprim-sulphamethoxazole prophylaxis to decrease morbidity and mortality in HIV-1-infected patients with tuberculosis in Abidjan, Côte d'Ivoire: a randomised controlled trial.
BACKGROUND: There is a high incidence of opportunistic infection among HIV-1-infected patients with tuberculosis in Africa and, consequently, high mortality. We assessed the safety and efficacy of trimethoprim-sulphamethoxazole 800 mg/160 mg (co-trimoxazole) prophylaxis in prevention of such infections and in decrease of morbidity and mortality.
METHODS: Between October, 1995, and April, 1998, we enrolled 771 HIV-1 seropositive and HIV-1 and HIV-2 dually seroreactive patients who had sputum-smear-positive pulmonary tuberculosis (median age 32 years [range 18-64], median CD4-cell count 317 cells/microL) attending Abidjan's four largest outpatient tuberculosis treatment centres. Patients were randomly assigned one daily tablet of co-trimoxazole (n=386) or placebo (n=385) 1 month after the start of a standard 6-month tuberculosis regimen. We assessed adherence to study drug and tolerance monthly for 5 months and every 3 months thereafter, as well as rates of admission to hospital.
FINDINGS: Rates of laboratory and clinical adverse events were similar in the two groups. 51 patients in the co-trimoxazole group (13.8/100 person-years) and 86 in the placebo group (25.4/100 person-years) died (decrease In risk 46% [95% CI 23-62], p<0.001). 29 patients on co-trimoxazole (8.2/100 person-years) and 47 on placebo (15.0/100 person-years) were admitted to hospital at least once after randomisation (decrease 43% [10-64]), p=0.02). There were significantly fewer admissions for septicaemia and enteritis in the co-trimoxazole group than in the placebo group.
INTERPRETATION: In HIV-1-infected patients with tuberculosis, daily co-trimoxazole prophylaxis was well tolerated and significantly decreased mortality and hospital admission rates. Our findings may have important implications for improvement of clinical care for such patients in Africa.
Options:
A: Cotrimoxazole prophylaxis significantly reduced the risk of death, morbid events, and hospitalisation without a significantly greater risk of adverse effects.
B: Cotrimoxazole prophylaxis had no significant effect on the risk of death, morbid events, or hospitalisation, but increased the risk of adverse effects.
C: Cotrimoxazole prophylaxis significantly increased the risk of death and morbid events, but reduced the risk of hospitalisation.
D: Cotrimoxazole prophylaxis had no significant effect on the risk of death, morbid events, hospitalisation, or adverse effects. | A |
282 | 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 adverse effects of doxorubicin-based combination chemotherapy compared to single-agent doxorubicin in the treatment of adult patients with locally advanced or metastatic soft tissue sarcoma? Please answer this question based on the information provided below:
Randomized comparison of three adriamycin regimens for metastatic soft tissue sarcomas.
This study addressed two major questions regarding therapeutic use of Adriamycin ([Adr] Adria Laboratories, Columbus, OH) in adult soft tissue sarcomas: the influence of dosing schedule and the value of adding imidazole carboxamide (DTIC) to Adr. Patients with objectively measurable metastatic soft tissue sarcomas were randomized to Adr 70 mg/m2 intravenously (IV) day 1 and every 3 weeks (94 patients); Adr 20 mg/m2 IV day 1, 2, and 3, and 15 mg/m2 IV day 8 and weekly thereafter (89 patients); and Adr 60 mg/m2 IV day 1 and DTIC 250 mg/m2 days 1 to 5, repeated every 3 weeks (92 patients). The regimens using Adr as a single agent resulted in an equivalent response frequency (18% and 16%) and survival (median, 8.0 and 8.4 months). DTIC significantly increased (P less than .02) the overall response frequency of Adr to 30%. However, DTIC did not influence survival (median, 8.0 months) or increase the number of complete responses. The toxicities of the two single-agent regimens differed: Adr weekly resulted in more stomatitis (P = .09) and less hematologic toxicity (P less than .05). DTIC resulted in substantially increased toxicity, primarily gastrointestinal (P less than .002); overall, 98% of patients receiving Adr-DTIC experienced moderate or worse toxicity. To decrease the potential for error in interpretation of treatment results, histopathological confirmation of diagnosis was undertaken by a panel of reference pathologists; pathology slides were submitted on 97% of entered patients. The on-study clinical diagnosis was affirmed in 199 of 316 patients (63%) with a final review. In 23% of patients, the panel agreed with the diagnosis of soft tissue sarcoma, but not with the type. In 14%, the panel concluded that a diagnosis of mesenchymal malignancy could not be affirmed. Final treatment results were based on the 275 pathologically confirmed, eligible patients. The most common histological subtype entered was leiomyosarcoma (99 patients). The response to Adr-DTIC of this subtype was higher (44%) than that of any other subtype. However, this difference alone was not responsible for the overall superiority of the combination. This confirmed that the combination of DTIC plus Adr adds to the response rate of Adr alone in soft tissue sarcomas. Whether the increased response frequency, without an impact on survival, is worth the significantly greater toxicity remains a subjective judgement that must be made within the context of the individual patient.
Randomized comparison of doxorubicin and vindesine to doxorubicin for patients with metastatic soft-tissue sarcomas.
Two treatment regimens for metastatic soft-tissue sarcomas were compared in a randomized trial in the cooperative group setting. Histopathologic diagnosis was affirmed by pathology reference panel review in 72% of the 347 patients. In 21% of patients, the reference panel affirmed the diagnosis of soft-tissue sarcoma but disagreed as to type; 7% of patients were ineligible based upon cell type. Of 298 patients evaluable, measurable tumor regression (partial or complete response) occurred in 17% of patients to doxorubicin (70 mg/m2 intravenously) and 18% of patients to doxorubicin (70 mg/m2 intravenously) and vindesine (3 mg/m2 intravenously), each given every 3 weeks. No difference existed in complete response (4% for doxorubicin, 6% for doxorubicin and vindesine) or median survival (9.4 months for doxorubicin, 9.9 months for doxorubicin and vindesine). Overall, 60% of those patients on doxorubicin and vindesine and 46% on doxorubicin experienced a severe or worse toxicity of treatment (P = 0.01). With greater toxicity and lack of any gains in efficacy, the results do not support use of the combination of doxorubicin and vindesine for metastatic soft-tissue sarcomas.
Combination chemotherapy with adriamycin and streptozotocin. I. Clinical results in patients with advanced sarcoma.
In a prospectively randomized study, 17 evaluable patients treated with adriamycin alone, 60 mg/m2 intravenously every 3 wk, were compared with 14 patients treated with adriamycin in the same dose and schedule plus streptozotocin. 500 mg/m2/day intravenously for 5 days every 3 wk. All patients had advanced sarcomas, but none had previously received either adriamycin or streptozotocin. Objective responses were seen in 9 patients on the single drug arm (4 with more than 50% tumor shrinkage and 5 with stabilization of disease), and in 8 patients given the combination drug arm (2 with more than 50% tumor shrinkage and 6 with stabilization of disease). Duration of response and survival from treatment for both treatment groups were similar. Transient hepatic dysfunction, renal function abnormalities, and nausea with vomiting were additive in the combination drug arm, the last two limiting therapy most. Leukopenia, thrombocytopenia, and mucositis appeared to be synergistically increased in patients receiving both adriamycin and streptozotocin. Patients with abnormal pretreatment renal function were able to tolerate the combination therapy without undue incidence of severity of renal toxicity. Patients who developed transient streptozotocin-related renal dysfunction were able to tolerate further doses of streptozotocin after their renal parameters normalized. Adriamycin in combination with streptozotocin did not offer any therapeutic advantage over adriamycin alone.
Randomized comparison of doxorubicin alone versus ifosfamide plus doxorubicin or mitomycin, doxorubicin, and cisplatin against advanced soft tissue sarcomas.
PURPOSE: This three-armed phase III study in adults with advanced soft tissue sarcomas was planned as a comparison of objective regression rates, toxicity, and survival of patients receiving doxorubicin alone, ifosfamide plus doxorubicin, and mitomycin plus doxorubicin plus cisplatin.
PATIENTS AND METHODS: Between December 1987 and July 1990, 279 patients with histologically confirmed sarcomas were enrolled to receive treatment A (doxorubicin 80 mg/m2), treatment B (ifosfamide 7.5 g/m2 plus doxorubicin 60 mg/m2), or treatment C (mitomycin 8 mg/m2 plus doxorubicin 40 mg/m2 plus cisplatin 60 mg/m2).
RESULTS: Of 262 assessable patients, 74 (29%) achieved objective tumor regression. Objective regression occurred in 20% of the 90 patients who received doxorubicin alone (complete remission [CR] rate, 2%), in 34% of the 88 who received ifosfamide plus doxorubicin (CR rate, 3%), and in 32% of the 84 who received mitomycin plus doxorubicin plus cisplatin (CR rate, 7%). With grade 3 or greater myelosuppression in 53% of group A, 80% of group B, and 55% of group C, regimen B was significantly more myelosuppressive than either regimen A or C (P = .01) with two, three, and one treatment-related deaths, respectively. Synovial sarcomas were responsive to ifosfamide plus doxorubicin, especially among patients younger than 40 years of age.
CONCLUSION: Ifosfamide plus doxorubicin produced a significantly higher regression rate (P = .03) than did doxorubicin alone; however, this was achieved at a level of myelosuppression significantly more intense than that produced by the single agent or by the three-drug combination. Mitomycin, doxorubicin, and cisplatin also appeared to be more active than the single agent; however, at a myelosuppression level similar to that of doxorubicin alone, this trend (P = .07) did not attain the usual level for significance. No significant survival differences were observed.
Treatment of recurrent or advanced uterine sarcoma. A randomized trial of doxorubicin versus doxorubicin and cyclophosphamide (a phase III trial of the Gynecologic Oncology Group).
Recurrent or metastatic uterine sarcoma represents an ominous and aggressive form of malignant disease. In an attempt to define a beneficial treatment program, we compared treatment with doxorubicin (A) 60 mg/m2 versus a combination of doxorubicin 60 mg/m2 and cyclophosphamide 500 mg/m (CA), each regimen given every 3 weeks. Of 132 patients entered on study, 104 were eligible; 50 received A and 54 CA. Pretreatment characteristics were similar, and no patient had received prior chemotherapy. The proportion of complete responses (CR) + partial responses (PR) for measurable disease patients was 5 of 26 (19%) for both A and CA. Multivariate analysis done on progression-free interval (PFI) and survival (S) showed CA to be of no benefit over A (PFI, P = 0.22; S, P = 0.55). For both A and CA patients, measurable disease (PFI, P = 0.002; S, P = 0.02, respectively), performance status (PFI, P = 0.004; S, P = 0.0002; respectively), and sites of residual disease (PFI, P = 0.008; S, P = 0.003, respectively) were detected as prognostic variables. Conversely, histologic type, age, and recurrence status (primary versus recurrent at entry) were not prognostic indicators. These data indicate no significant benefit of CA versus A alone in patients with uterine sarcoma.
A randomized study of adriamycin with and without dimethyl triazenoimidazole carboxamide in advanced uterine sarcomas.
Various drug combinations including Adriamycin have been tested in soft tissue sarcomas, but optimal treatment remains unclear. We have evaluated Adriamycin with and without dimethyl-triazeno-imidazole-carboxamide (DTIC) in the treatment of Stage III or IV and recurrent sarcomas of the uterus. Two hundred and forty cases of these rare tumors were evaluable. Of 146 evaluable patients with measurable disease, 13/80 (16.3%) of Adriamycin-treated patients and 16/66 (24.2%) of patients receiving the combination showed an objective response (P greater than 0.05). Lung metastases responded more frequently (P equal to 0.04) to combination therapy, but there was no survival advantage. For patients with nonmeasurable disease the progression-free interval was similar (10.0 months for Adriamycin and 8.0 months for the combination). Leiomyosarcomas had a significantly longer survival than other cell types (12.1 versus 6.0 months, P less than 0.001) but there was no advantage for either regimen. There was a suggestion that heterologous mixed mesodermal sarcomas were more responsive to the combination (27.3 versus 8.7%). The addition of DTIC produced significantly more hematologic and gastrointestinal toxicity. Other Adriamycin combinations should be evaluated in uterine sarcomas.
Doxorubicin versus CYVADIC versus doxorubicin plus ifosfamide in first-line treatment of advanced soft tissue sarcomas: a randomized study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group.
PURPOSE: The aim of this trial was to compare the activity and toxicity of single-agent doxorubicin with that of two multidrug regimens in the treatment of patients with adult advanced soft tissue sarcomas.
PATIENTS AND METHODS: This was a prospective randomized phase III trial performed by 35 cancer centers within the Soft Tissue and Bone Sarcoma Group of the European Organization for Research and Treatment of Cancer (EORTC). Six hundred sixty-three eligible patients were randomly allocated to receive either doxorubicin 75 mg/m2 (arm A), cyclophosphamide, vincristine, doxorubicin, and dacarbazine (CYVADIC) (arm B), or ifosfamide 5 g/m2 plus doxorubicin 50 mg/m2 (arm C).
RESULTS: The overall response rate was 24% (95% confidence interval, 20.7% to 27.3%) among eligible patients and 26% among assessable patients. No statistically significant difference was detected among the three study arms in terms of response rate (arm A, 23.3%; arm B, 28.4%; and arm C, 28.1%), remission duration (median, 46 weeks on arm A, 48 weeks on arm B, and 44 weeks on arm C), or overall survival (median, 52 weeks on arm A, 51 weeks on arm B, and 55 weeks on arm C). The degree of myelosuppression was significantly greater for the combination of ifosfamide and doxorubicin than for the other two regimens. Cardiotoxicity was also more frequent in this arm, but other toxicities were similar.
CONCLUSION: In advanced soft tissue sarcomas of adults, single-agent doxorubicin is still the standard chemotherapy against which more intensive or new drug treatments should be compared. Combination chemotherapy cannot be recommended outside a controlled clinical trial with the exclusion of some subsets of sarcoma patients for whom significant tumor volume reduction may be an important end point of a chemotherapy regimen.
A comparison of adriamycin versus vincristine and adriamycin, and cyclophosphamide versus vincristine, actinomycin-D, and cyclophosphamide for advanced sarcoma.
This randomized study, conducted by the Eastern cooperative Oncology Group, compared Adriamycin (doxorubicin) (70 mg/m2) versus vincristine (1.4 mg/m2) and Adriamycin (50 mg/m2); and cyclophosphamide (750 mg/m2) versus vincristine (1.4 mg/m2), actinomycin-D (0.4 mg/m2), and cyclophosphamide (750 mg/m2) for treatment of metastatic mesenchymal malignancies. The respective response rate seen in 200 evaluable patients to the treatments were, 27, 19, and 11%. The response rate to Adriamycin was significant better than the response to vincristine, actinomycin-D, and cyclophosphamide (P = 0.03, two-sided). The respective median survivals on the three treatments were 37, 34, and 41 weeks and were not significantly different. Moderate or severe vomiting occurred in 60% of patients receiving vincristine-cyclophosphamide-adriamycin, a greater frequency than in Adriamycin alone (P = .09 two-sided) Severe or life-threatening hematologic toxicity (leukocytes less than 2000, platelets less than 50,000) occurred in 30% of patients receiving the Adriamycin combination, a markedly increased frequency when compared to the other two regimens (P equals 0.07, P = 0.02, two-sided). This trial establishes that Adriamycin has a better response rate than the combination of vincristine-actinomycin-D-cyclophosphamide in advanced sarcomas. The combination of vincristine, Adriamycin, and cyclophosphamide increased toxicity and did not add to the therapeutic effect achieved with Adriamycin alone.
Options:
A: Combination chemotherapy significantly improved both response rates and overall survival, with no increase in adverse effects.
B: Combination chemotherapy showed a marginal increase in response rates but did not improve overall survival and was associated with increased adverse effects.
C: Combination chemotherapy did not improve response rates or overall survival and had fewer adverse effects compared to single-agent doxorubicin.
D: Combination chemotherapy significantly improved overall survival but did not affect response rates and had the same level of adverse effects as single-agent doxorubicin. | B |
283 | 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 transcranial magnetic stimulation (TMS) in the treatment of obsessive-compulsive disorder (OCD) based on the systematic review of randomised controlled trials? Please answer this question based on the information provided below:
Right prefrontal repetitive transcranial magnetic stimulation in obsessive-compulsive disorder: a double-blind, placebo-controlled study.
OBJECTIVE: The efficacy of repetitive transcranial magnetic stimulation (rTMS) of the right prefrontal cortex for patients with obsessive-compulsive disorder (OCD) was studied under double-blind, placebo-controlled conditions.
METHOD: Patients were randomly assigned to 18 sessions of real (N=10) or sham (N=8) rTMS. Treatments lasted 20 minutes, and the frequency was 1 Hz for both conditions, but the intensity was 110% of motor threshold for real rTMS and 20% for the sham condition.
RESULTS: No significant changes in OCD were detected in either group after treatment. Two patients who received real rTMS, with checking compulsions, and one receiving sham treatment, with sexual/religious obsessions, were considered responders.
CONCLUSIONS: Low-frequency rTMS of the right prefrontal cortex failed to produce significant improvement of OCD and was not significantly different from sham treatment. Further studies are indicated to assess the efficacy of rTMS in OCD and to clarify the optimal stimulation characteristics.
Effect of prefrontal repetitive transcranial magnetic stimulation in obsessive-compulsive disorder: a preliminary study.
OBJECTIVE: Prefrontal mechanisms are implicated in obsessive-compulsive disorder. The authors investigated whether prefrontal repetitive transcranial magnetic stimulation influenced obsessive-compulsive disorder symptoms.
METHOD: Twelve patients with obsessive-compulsive disorder were given repetitive transcranial magnetic stimulation (80% motor threshold, 20 Hz/2 seconds per minute for 20 minutes) to a right lateral prefrontal, a left lateral prefrontal, and a midoccipital (control) site on separate days, randomized. The patients' symptoms and mood were rated for 8 hours afterward.
RESULTS: Compulsive urges decreased significantly for 8 hours after right lateral prefrontal repetitive transcranial magnetic stimulation, but there were nonsignificant increases in compulsive urges after repetitive transcranial magnetic stimulation of the midoccipital site. A shorter-lasting (30 minutes), modest, and nonsignificant reduction in compulsive urges occurred after left lateral prefrontal repetitive transcranial magnetic stimulation. Mood improved during and 30 minutes after right lateral prefrontal stimulation.
CONCLUSIONS: These preliminary results suggest that right prefrontal repetitive transcranial magnetic stimulation might affect prefrontal mechanisms involved in obsessive-compulsive disorder.
Right versus left prefrontal transcranial magnetic stimulation for obsessive-compulsive disorder: a preliminary investigation.
BACKGROUND: There is preliminary evidence that repetitive transcranial magnetic stimulation (rTMS) may be useful for the treatment of obsessive-compulsive disorder (OCD), but no definitive study has been published, and the effect of laterality of stimulation is uncertain.
METHOD: Subjects (N = 12) with resistant OCD were allocated randomly to either right or left prefrontal rTMS daily for 2 weeks and were assessed by an independent rater at 1 and 2 weeks and 1 month later.
RESULTS: Subjects had an overall significant improvement in the obsessions (p < .01), compulsions (p < .01), and total (p < .01) scores on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) after 2 weeks and at 1-month follow-up. This improvement was significant for obsessions (p < .05) and tended to significance for total Y-BOCS scores (p = .06) after correction for changes in depression scores on the Montgomery-Asberg Depression Rating Scale. There was no significant difference between right- and left-sided rTMS on any of the parameters examined. Two subjects (33%) in each group showed a clinically significant improvement that persisted at I month but with relapse later in I subject.
CONCLUSION: A proportion (about one quarter) of patients with resistant OCD appear to respond to rTMS to either prefrontal lobe, although in the absence of a sham treatment group in this study, we cannot rule out the possibility of this being a placebo response. This treatment warrants further investigation to better establish its efficacy and examine the best parameters for response.
Options:
A: TMS showed a significant improvement in OCD symptoms compared to sham TMS.
B: TMS showed a significant improvement in mood but no change in OCD symptoms.
C: There was no significant difference between TMS and sham TMS in the treatment of OCD.
D: TMS was found to be harmful and increased OCD symptoms. | C |
284 | 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 anticholinergic drugs in the maintenance treatment of chronic asthma in children over the age of 2 years? Please answer this question based on the information provided below:
Combined treatment with ipratropium bromide and beta-2-adrenoceptor agonists in childhood asthma.
The effect of adding ipratropium bromide to treatment with beta-2-adrenoceptor agonists was studied in 13 asthmatic children in a double-blind cross-over trial. In the acute phase of the study inhalation of salbutamol 0.1 mg/kg followed by inhalation of 0.25 mg of ipratropium bromide was found to improve pulmonary function variables to a significantly greater extent than salbutamol followed by placebo. The combined therapy also provided significantly better protection than salbutamol plus placebo against exercise-induced asthma. Maintenance treatment with ipratropium bromide (two inhalations four times daily, 20 micrograms per inhalation) in combination with oral terbutaline and aerosolized salbutamol did not alleviate asthmatic symptoms or pulmonary function variables to a degree beyond that achieved with the beta-stimulants alone. There were no side effects associated with the ipratropium bromide treatment. These data suggest that higher doses of ipratropium bromide than are presently used should be tested for maintenance treatment of chronic asthma.
The effects of ipratropium bromide and fenoterol nebulizer solutions in children with asthma.
The effects of nebulized solutions of ipratropium bromide and fenoterol combined were compared with the response to either preparation alone in single dose and longer-term administration in children who had asthma. The combination produced a slightly greater response than either alone, especially in peak expiratory flow. Over a 1-month period, there were no significant differences in symptom scores or lung function parameters between the combination of ipratropium bromide and fenoterol and fenoterol alone in a group of children who had asthma. It is possible that the addition of ipratropium bromide to a sympathomimetic drug may be useful in a subgroup of asthmatics, particularly if there is a considerable large airway contribution to bronchial narrowing.
Long term atropine in chronic severe childhood asthma.
Ipratropium bromide in children with asthma.
Eighteen children between 6 and 14 years of age with perennial asthma were studied over two four-week treatment periods. Ipratropium bromide, given in addition to their current treatment, was compared with placebo using a double-blind crossover technique. The period of treatment with ipratropium was associated with a significant reduction in symptoms during both day and night and significantly higher morning peak expiratory flow rates.
Long-term effect of ipratropium bromide and fenoterol on the bronchial hyperresponsiveness to histamine in children with asthma.
We studied the effects of the anticholinergic ipratropium bromide (40 micrograms three times daily) and the beta-agonist, fenoterol (0.2 mg three times daily), both administered by powder inhaler, on bronchial hyperresponsiveness (BHR) to histamine in children, aged 7 to 15 years with mild stable asthma and limited bronchoconstriction who had a highly increased BHR. The double-blind, randomized, parallel study was conducted and performed in spring and early summer. BHR and FEV1 were measured on two occasions, before the start of treatment and monthly thereafter for 4 months. Symptoms, peak expiratory flow, and concomitant medication were registered daily. Nine of the 12 patients receiving ipratropium bromide and all eight patients receiving fenoterol completed the study. Patients completing treatment had few symptoms and were in a stable condition throughout the treatment period. Neither the administration of ipratropium bromide nor fenoterol resulted in a significant change of BHR. We concluded that long-term treatment with ipratropium bromide or fenoterol had no effect on BHR in children with mild stable asthma.
Failure of ipratropium bromide to modify the diurnal variation of asthma in asthmatic children.
Thirty one children with asthma were given 40 micrograms of ipratropium bromide and identical placebo by inhalation three times a day in a double blind, randomised crossover study to test the ability of an anticholinergic drug to modify the diurnal variation in airway calibre and bronchial reactivity. Subjects measured peak expiratory flow rate approximately eight hourly, before and after inhaled salbutamol, for four week periods. Paired t tests and cosinor analysis were used to assess the diurnal variation in airway calibre from the peak expiratory flow rate recorded before salbutamol and to assess the diurnal variation in bronchodilator responsiveness from the increase in peak expiratory flow rate after salbutamol. Maintenance treatment with ipratropium bromide 40 micrograms three times daily reduced the provocative dose of histamine which caused a 20% fall in FEV1 (geometric mean PD20 = 0.78 v 0.49 mg/ml, p less than 0.05), despite an eight to 12 hour gap between the last dose of ipratropium and histamine challenge. It did not, however, diminish the diurnal variation in airway calibre (mean amplitude = 12.7 v 10.1) or in bronchodilator responsiveness (mean amplitude = 62.4 v 63.5). There was no improvement in the clinical state of subjects while they were taking ipratropium bromide.
[Effectiveness of disodium cromoglycate, salbutamol, and ipratropium bromide in the inhibition of exercise-induced bronchospasm].
Forty-nine asymptomatic asthmatic children who showed exercise induced bronchospasm (EIB), received in a randomized double-blind fashion one of the four following drugs administered through nebulizer and facial mask: salbutamol 4 mg (13 patients), disodium chromoglycate 20 mg (12 patients), ipratroprium bromide 0.4 mg (12 patients), placebo (12 patients). They performed exercise fifteen minutes after receiving the drugs and spirometries were done 0, 5, 10, 15 and 20 minutes after the end of the exercise. Bronchodilation was noticed 15 minutes after the administration of salbutamol and ipratroprium bromide but not after cromoglycate or placebo. No patient receiving either salbutamol or cromoglycate had EIB whereas it occurred in 50% of those receiving ipratroprium bromide and 91.6% of those receiving placebo.
[Bronchial asthma in childhood. Therapy with fenoterol and ipratropium bromide powder].
In a double blind randomized study during a period of 2 weeks we compared the therapeutic effectiveness and side effects of IK-6-Inhaletten (0.1 mg Fenoterol + 0.04 mg Ipratropiumbromide) and SCH 1000-Inhaletten (0.2 mg Ipratropiumbromide) in 39 children (4-14 years) suffering from mild, moderate or severe asthma bronchiale. All measurements were performed with a whole body plethysmograph. In contrast to SCH 1000-inhalation after inhalation of IK-6-Inhaletten, we found a good improvement of the total airway resistance Rtot, the specific airway resistance SRaw and the forced exspiratory volume FEV1. Especially SRaw was significantly diminished compared to the less effective SCH 1000-inhalation. IK-6-inhalation allowed to decrease the amount of bronchospasmolytic therapy in our group of patients. We did not observe any severe side effects after inhalation of IK-6 or SCH 1000. In summary, we recommend the application of the IK-6-Inhaletten in children suffering from mild and moderate asthma bronchiale.
Options:
A: Anticholinergic drugs significantly improve symptom scores and reduce bronchial hyperresponsiveness compared to placebo.
B: Anticholinergic drugs show no statistically significant benefit over placebo in any of the outcome measures used.
C: Anticholinergic drugs combined with beta-2 agonists show significant long-term benefits compared to beta-2 agonists alone.
D: Anticholinergic drugs significantly improve diurnal variation in peak expiratory flow rate (PEFR) compared to placebo. | B |
285 | 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 occupational therapy interventions in improving functional ability, social participation, and health-related quality of life for multiple sclerosis patients? Please answer this question based on the information provided below:
Efficacy of an energy conservation course for persons with multiple sclerosis.
OBJECTIVE: To evaluate the efficacy of an energy conservation course on fatigue impact, self-efficacy, and quality of life (QOL) for persons with multiple sclerosis (MS).
DESIGN: Repeated measures with control and experimental interventions conducted during a 19-week study.
SETTING: Community-based treatment center.
PARTICIPANTS: A convenience sample of 54 individuals from 79 community-dwelling volunteers with fatigue secondary to MS.
INTERVENTION: A 6-session, 2-hr/wk energy conservation course taught by occupational therapists for groups of 8 to 10 participants.
MAIN OUTCOME MEASURES: Fatigue Impact Scale (self-report measure of fatigue impact on cognitive, physical, social functions), Self-Efficacy Gauge (self-report measure of confidence in ability to perform specific behaviors), and Medical Outcomes Study Short-Form Health Survey (QOL measure).
RESULTS: Participants reported, as predicted, significantly less fatigue impact, increased self-efficacy, and improved QOL (ie, 3 of 4 subscales expected to improve). There were no significant differences, as predicted, in any of the dependent variables after the control (ie, support group) and no intervention periods.
CONCLUSION: Results provide strong evidence for the efficacy of this energy conservation course for persons with MS.
Evaluation of the effectiveness of professionally guided self-care for people with multiple sclerosis living in the community: a randomized controlled trial.
OBJECTIVE: The aim of the study was to assess the efficacy of a patient-focused professionally guided self-care programme for the management of multiple sclerosis (MS) in the community.
DESIGN: This was a single-blind randomized controlled trial.
SETTING: The study was conducted with people with MS living in the community.
PARTICIPANTS: Two hundred and seventy-eight people with MS were invited to take part in the study. One hundred and eighty-nine people consented to take part (68%). Of these 183 began the study and 169 (92.3%) completed it. Seventy-three individuals were in the intervention group and 96 were in the control group.
INTERVENTION: The intervention comprised discussion of self-care based on client priorities, using an information booklet about self-care.
MAIN OUTCOME MEASURES: These included the Barthel Index, a measure of mobility, the SF-36, and the Standard Day Dependency Record (SDDR) which measures the need for assistance with daily activities. Assessments were conducted at baseline and again six months later.
RESULTS: Changes in health status were small. However, at follow-up the intervention group had better SF-36 health scores, in mental health (p = 0.04), and vitality (p = 0.05) and considered help with daily activities to be less essential, as measured by the SDDR (p = 0.04), than the control group. Participants in the intervention group had maintained levels of independence at follow-up (p = 0.62) while the control group showed a significant decrease in independence (p= 0.001).
CONCLUSION: This intervention could be a useful aid for health professionals who are supporting people with MS living in the community.
Effects of an energy conservation course on fatigue impact for persons with progressive multiple sclerosis.
OBJECTIVE: Fatigue is a common, troublesome symptom for persons with multiple sclerosis. This study evaluated the effects of an energy conservation course on fatigue impact for persons with multiple sclerosis whose symptoms cause moderate to severe disability.
METHODS: Thirty-seven persons with progressive multiple sclerosis participated in an 8-week experimental energy conservation course treatment and an 8-week control period of traditional treatment using a crossover design. The Fatigue Impact Scale (FIS) was used to assess fatigue impact before and after the experimental and control periods, and 8 weeks post-energy conservation course.
RESULTS: After participation in the energy conservation course, the average FIS total score and physical, cognitive, and psychosocial subscale scores decreased significantly, whereas the total and subscale scores did not change significantly during the control period. Additionally, decreased fatigue impact was maintained 8 weeks after course completion for evaluated participants.
CONCLUSION: This study provides evidence that this energy conservation course can be a beneficial intervention for persons with progressive multiple sclerosis.
Options:
A: Occupational therapy interventions significantly improve functional ability, social participation, and health-related quality of life for multiple sclerosis patients.
B: There is insufficient evidence to conclude that occupational therapy interventions improve functional ability, social participation, and health-related quality of life for multiple sclerosis patients.
C: Occupational therapy interventions have been proven to be ineffective in improving functional ability, social participation, and health-related quality of life for multiple sclerosis patients.
D: Occupational therapy interventions worsen the functional ability, social participation, and health-related quality of life for multiple sclerosis patients. | B |
286 | 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 overgowns worn by attendants and visitors in newborn nurseries for preventing neonatal morbidity and mortality? Please answer this question based on the information provided below:
Evaluation of modified gowning procedures in a neonatal intensive care unit.
The effect of modified gowning techniques in a neonatal intensive care unit was evaluated. During alternate two-month intervals, no gowns were worn over street clothes in patient care areas by staff or visitors. Mortality and infections rates during these "modified" gowning intervals were the same as during the gowning periods. However, the incidence of necrotizing enterocolitis was significantly greater in the modified gowning periods (7/353) than in the gowning periods (1/371). An expansion of this one-year study to include another year showed an even greater effect. The prevalence of bacteria at three anatomic sites (nares, umbilicus, and groin) on days 2, 4, 7, 10, 14, 21, and 28 of hospitalization was comparable between those studied during modified gowning and gowning intervals. Exceptions were the significantly increased prevalence of Staphylococcus epidermidis in the groin (days 21 and 28) during gowning and S aureus in the nares (day 28) during modified gowning periods.
Gowning on a postpartum ward fails to decrease colonization in the newborn infant.
We conducted a randomized study to evaluate the effect of gowning by visitors and hospital personnel on a postpartum ward on nose and umbilical colonization and disease in healthy newborn infants. Cultures were obtained in infants assigned to the gowning and nongowning groups within 6 hours of birth from the anterior part of the nares and the base of the umbilicus and at the time of discharge from the nursery. There were 102 infants in the gowning group and 100 infants in the nongowning group. No significant differences were noted between the two groups with respect to sex, length of stay, mode of delivery, weight, or status of nursery admission culture results. The use of gowns on a postpartum ward failed to decrease nose or umbilical colonization when compared with infants in the nongowning group. Seventy (68.6%) of 102 infants in the gowning group and 65 (65%) of 100 infants in the nongowning group had negative umbilical cord cultures on admission to the nursery that became positive at discharge. On follow-up, no differences were noted between the two groups with respect to their health. Only one infant in each group had an infection develop in the first 4 weeks of life. We conclude that the routine use of cover gowns on postpartum units in healthy full-term infants is ineffective and costly. It may discourage health care providers from examining patients and providing care.
Bacteriologic and clinical evaluation of gowning in a premature nursery.
Masking and gowning in nurseries for the newborn infant; effect on staphylococcal carriage and infection.
Gowning does not affect colonization or infection rates in a neonatal intensive care unit.
OBJECTIVE: To study the effect of gowning in a neonatal intensive care unit on colonization patterns, necrotizing enterocolitis, respiratory syncytial virus and other infections, mortality, and traffic and handwashing patterns.
METHODS: Alternate 2-month gowning and no-gowning cycles were established in a 24-bed level III neonatal intensive care unit for 8 months, with respiratory site, umbilical, and stool surveillance cultures done weekly on all patients. Traffic flow and handwashing compliance were evaluated by direct observation.
RESULTS: Demographic data did not differ between periods. There were no significant differences between the gowning and no-gowning periods in the rates of bacterial colonization, any type of infection, or mortality. There was no effect on traffic flow or handwashing compliance.
CONCLUSION: Gowning in the neonatal intensive care unit is an unnecessary custom without benefit in neonatal colonization, infection rates, mortality, traffic patterns, and handwashing behavior.
A randomized controlled trial of a nursery ritual: wearing cover gowns to care for healthy newborns.
The routine wearing of individual cover gowns by nurses and visitors for direct care of healthy newborns was usual practice on the maternity ward of a regional referral center. We conducted a randomized trial in which cover gowns were not provided for care of infants in the experimental group (n = 222), but were maintained for control infants (n = 230). The principal outcome measured was Staphylococcus aureus colonization of the newborn nares or umbilicus on day 3 or day of discharge. Twenty percent (n = 51) of the experimental group (no gown) had a positive culture compared with 21 percent (n = 47) of the controls. Of the infants with positive cultures, two in each group exhibited symptoms of overt S. aureus infection. Experimental infants were similar to controls with respect to feeding method, route of delivery, amount of time spent rooming-in, and average number of visitors per day. In the group of positively cultured infants, the mothers experienced longer labor, and more vaginal examinations in labor, and the number of males undergoing circumcision was higher. We concluded that routine use of cover gowns was unwarranted, and we have altered the ward policy accordingly. This also has had a positive economic effect.
Evaluation of precautions before entering a neonatal unit.
Does routine gowning reduce nosocomial infection and mortality rates in a neonatal nursery? A Singapore experience.
A 1 year prospective study on routine gowning before entering a neonatal unit was conducted in a maternity hospital in Singapore. This study was done based on previous work by Donowitz, Haque and Chagla and Agbayani et al., as there have been no known studies done in Singapore. The aim of the study was to test the hypothesis that routine gowning before entering a neonatal nursery does not reduce nosocomial infection and mortality rate. A total of 212 neonates from the neonatal intensive care unit (NICU) and 1694 neonates from the neonatal special care unit (NSCU) were studied. Neonates admitted during the 1 year study were assigned to the gowning (control) and no routine gowning (trial) group on every alternate 2 months. The hospital infection control nurse provided data on nosocomial infection. The overall nosocomial infection rate in the NICU was 24% (25 of 104 admissions) during gowning periods compared to 16.6% (18 of 108 admissions) when plastic aprons were not worn before entry. In the NSCU, the overall infection rate was 1.5% (12 of 800 admissions) during gowning periods compared to 2.1% (19 of 894 admissions) when no gown was worn before entry. Results of the study found no significant differences in the incidences of nosocomial infection and mortality in the neonates. The cost of gowns used during the no routine gowning periods was S$2012.8 compared to S$3708 used during the routine gowning procedure. The investigators recommend that routine gowning before entering a neonatal unit is not essential and cost effective for the purpose of reducing infection. Rather the focus should be on adequate handwashing by all hospital personnel and visitors before handling neonates.
Options:
A: Overgowns significantly reduced the incidence of systemic nosocomial infections in infants.
B: Overgowns significantly reduced the death rate in infants.
C: Overgowns had no significant effect on the incidence of infection, death, or bacterial colonisation in infants.
D: Overgowns significantly increased the frequency of handwashing among staff and visitors. | C |
287 | 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 cholinesterase inhibitors, specifically rivastigmine, in patients with dementia with Lewy bodies (DLB) in terms of neuropsychiatric symptoms, cognitive function, and adverse events? Please answer this question based on the information provided below:
Dementia with lewy bodies: findings from an international multicentre study.
OBJECTIVES: To describe the baseline demographic, neuropsychiatric and neurological data of a large selected clinical sample of patients with dementia with Lewy Bodies (DLB) from an international multicentre trial with rivastigmine. To examine the usefulness of the Consensus Criteria for the diagnosis of DLB in different countries.
METHODS: Seventeen centres from Spain, the UK and Italy recruited patients diagnosed clinically as probable DLB according to recent Consensus Criteria (McKeith et al., 1996). A standard clinical protocol including inclusion/exclusion criteria, collection of demographic and medical data, cognitive (Mini Mental State Examination: MMSE), motor (Unified Parkinson's Disease Rating Scale: UPDRS) and neuropsychiatric (Neuropsychiatric Inventory: NPI) examinations, was applied after obtaining informed consent. Data were summarised and compared across countries with uni- and multivariate analyses.
RESULTS: One hundred and twenty patients were recruited: 56.7% males, mean (SD) age 73.9 (6.4) years, range 57 - 87 years. Sixty percent fulfilled all three core diagnostic features of DLB, and 40% only two ('parkinsonism' 92.4%, 'cognitive fluctuations' 89.1%, 'visual hallucinations' 77.3%). 'Systematised delusions' (46%) and 'repeated falls' (42%) were the most frequent supportive diagnostic features. There were no differences across countries in demographic, diagnostic or clinical features. Patients showed a wide range of psychopathology which was weakly correlated with cognitive impairment. Some mild extrapyramidal signs (EPS) were observed in most patients.
CONCLUSIONS: The Consensus Criteria for DLB can be consistently applied across many different sites for multicentre studies. 'Parkinsonism' and 'cognitive fluctuations' as core features and 'systematised delusions' and 'repeated falls' as supportive features are the most frequent diagnostic clues. Neuropsychiatric disturbances, in particular apathy, delusions, hallucinations and anxiety, and mild symmetric EPS are frequent in DLB and are only related weakly to cognitive impairment.
Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study.
BACKGROUND: Dementia with Lewy bodies is a common form of dementia in the elderly, characterised clinically by fluctuating cognitive impairment, attention deficits, visual hallucinations, parkinsonism, and other neuropsychiatric features. Neuroleptic medication can provoke severe sensitivity reactions in patients with dementia of this type. Many deficits in cholinergic neurotransmission are seen in the brain of patients with Lewy-body dementia; therefore, drugs enhancing central cholinergic function represent a rationally-based therapeutic approach to this disorder. Rivastigmine, a cholinesterase inhibitor, was tested in a group of clinically characterised patients with Lewy-body dementia.
METHODS: A placebo-controlled, double-blind, multicentre study was done in 120 patients with Lewy-body dementia from the UK, Spain, and Italy. Individuals were given up to 12 mg rivastigmine daily or placebo for 20 weeks, followed by 3 weeks rest. Assessment by means of the neuropsychiatric inventory was made at baseline, and again at weeks 12, 20, and 23. A computerised cognitive assessment system and neuropsychological tests were also used, and patients underwent close medical and laboratory safety analysis.
FINDINGS: Patients taking rivastigmine were significantly less apathetic and anxious, and had fewer delusions and hallucinations while on treatment than controls. Almost twice as many patients on rivastigmine (37, 63%), than on placebo (18, 30%), showed at least a 30% improvement from baseline. In the computerised cognitive assessment system and the neuropsychological tests, patients were significantly faster and better than those on placebo, particularly on tasks with a substantial attentional component. Both predefined primary efficacy measures differed significantly between rivastigmine and placebo. After drug discontinuation differences between rivastigmine and placebo tended to disappear. Known adverse events of cholinesterase inhibitors (nausea, vomiting, anorexia) were seen more frequently with rivastigmine than with placebo, but safety and tolerability of the drug in these mostly multimorbid patients were judged acceptable.
INTERPRETATION: Rivastigmine 6-12 mg daily produces statistically and clinically significant behavioural effects in patients with Lewy-body dementia, and seems safe and well tolerated if titrated individually.
Effects of rivastigmine on cognitive function in dementia with lewy bodies: a randomised placebo-controlled international study using the cognitive drug research computerised assessment system.
This study was designed to assess the effects of rivastigmine (Exelon) on the cognitive functioning of patients suffering from dementia with Lewy bodies. This was a prospective, multi-centre, randomised, double-blind, placebo-controlled exploratory study conducted at sites in the UK, Spain and Italy. The treatment period was 20 weeks with a 3-week posttreatment follow-up. The primary outcome measures were the Cognitive Drug Research (CDR) computerised assessment system and the Neuropsychiatric Inventory. Testing was conducted prior to dosing and then again at weeks 12, 20 and 23. Analysis of the data from the 92 patients who completed the study identified a significant pattern of benefits of rivastigmine over placebo on the CDR system. These benefits were seen on tests of attention, working memory and episodic secondary memory. Taking attention for example, patients given placebo showed a significant deterioration from predosing scores at 12 and 20 weeks, whereas patients on rivastigmine performed significantly above their predosing levels. These effects were also large in magnitude, the decline under placebo at week 12 being 19%, while the improvement under rivastigmine was 23%. The clinical relevance of this 23% improvement was that it took the patients 33% towards being normal for their age on this assessment of attention. These benefits to cognitive function were accompanied by a significant improvement of the other primary outcome measure, the Neuropsychiatric Inventory. Three weeks after discontinuation of rivastigmine, most parameters of cognitive performance returned to predrug levels.
Options:
A: Rivastigmine significantly improved neuropsychiatric symptoms and cognitive function without increasing adverse events.
B: Rivastigmine showed significant improvement in neuropsychiatric symptoms only in observed cases, with no significant improvement in cognitive function, and was associated with more adverse events compared to placebo.
C: Rivastigmine showed no significant improvement in neuropsychiatric symptoms or cognitive function and had fewer adverse events compared to placebo.
D: Rivastigmine significantly improved both neuropsychiatric symptoms and cognitive function, but had a higher dropout rate due to adverse events. | B |
288 | 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 transcutaneous electrical nerve stimulation (TENS) in the treatment of dementia, based on the analysis of available trials? Please answer this question based on the information provided below:
Favorable effect of transcranial electrostimulation on behavior disorders in elderly patients with dementia: a double-blind study.
The efficacy of transcranial electrostimulation for sleep-wake and behavior disorders in elderly patients with dementia was tested in a double-blind study. The subjects were 27 inpatients with multi-infarct dementia (12 males and 15 females, aged 58-86). They were randomly divided into two groups: active treatment (n = 14) and placebo treatment (n = 13). For electrostimulation, a device (HESS-100) was used which delivered repetitive rectangular electric pulses of 6-8 V at increasing frequencies from 6 to 80 Hz, each pulse lasting 0.2 ms and with a root mean square value of 256-530 microA. Electrostimulation was performed for 20 minutes from 10:00 h every morning. The active or placebo treatment was performed for 2 weeks in each group. The electrostimulation was significantly effective in behavior disorders such as wandering or nocturnal delirium, and decreased motivation during the daytime. It was also effective in improving night sleep. Electroencephalograms confirmed increased vigilance levels in the daytime both during and after the treatment.
Effects of "isolated" transcutaneous electrical nerve stimulation on memory and affective behavior in patients with probable Alzheimer's disease.
BACKGROUND: In previous studies, transcutaneous electrical nerve stimulation (TENS), tactile stimulation, and a combination of the two resulted in cognitive and affective improvements in patients with Alzheimer's disease (AD). As in those studies the therapist was present during the treatment of the experimental and control group (sham stimulation), a positive effect of the combination of TENS with interpersonal communication could not be excluded. Therefore, the effects of "isolated" TENS, i.e., in the absence of the therapist, on memory and affective disturbances in AD patients were examined.
METHODS: Eighteen subjects (78-92 years old) met the NINCDS-ADRDA criteria for the clinical diagnosis of probable AD. To evaluate treatment effects, the experimental group (9) and the control group (9) underwent a number of neuropsychological tests and two observation scales.
RESULTS: Treatment effects were observed for nonverbal short-term (Visual Memory) and long-term (Face Recognition) memory, word fluency (Verbal Fluency), and need of help, whereas patients' affective behavior did not improve.
CONCLUSIONS: The results of the present study show that isolated TENS has a positive effect on patients' cognitive and independent functioning; however, isolated TENS appeared not to have a therapeutic effect on patients' affective behavior.
Effects of transcutaneous electrical nerve stimulation on memory and behavior in Alzheimer's disease may be stage-dependent.
BACKGROUND: In previous studies, transcutaneous electrical nerve stimulation (TENS) was shown to result in improvements in nonverbal short-term and long-term memory, verbal long-term memory, and verbal fluency in patients in an early stage of Alzheimer's disease (AD). In addition, the patients' physical, social, and affective functioning improved. As AD is a progressive disease, it was examined in the present study whether TENS would still be effective in the midstage of AD.
METHODS: Sixteen subjects (70-91 years old) met the NINCDS-ADRDA criteria for probable AD, as well as the criteria for stage 6 of the Global Deterioration Scale (midstage AD). To evaluate treatment effects, the subjects underwent a number of neuropsychological tests and two observation scales.
RESULTS: Compared to TENS in an early stage, TENS in the midstage of AD appears to yield less beneficial effects, i.e., as for cognition only nonverbal short-term memory improved. No treatment effects were observed for the patients' physical, social, and affective functioning.
CONCLUSIONS: In view of the small number of patients, the clinical relevance of TENS in patients in a midstage of AD remains to be confirmed in a larger group, after which more definite conclusions about the stage-dependency of TENS in AD can be drawn.
Transcutaneous electrical nerve stimulation (TENS) improves the rest-activity rhythm in midstage Alzheimer's disease.
Nightly restlessness in patients with Alzheimer's disease (AD) is probably due to a disorder of circadian rhythms. Transcutaneous electrical nerve stimulation (TENS) was previously reported to increase the strength of coupling of the circadian rest activity rhythm to Zeitgebers in early stage Alzheimer's disease (AD) patients. It was investigated in the present study whether TENS could also improve the rest activity rhythm of patients in a midstage. Sixteen patients who met the NINCDS ADRDA criteria for probable AD, and the stage 6 criteria of the Global Deterioration Scale were treated with TENS or placebo. Rest activity rhythm was assessed using actigraphy. Compared to the control group, stimulated patients showed an improvement in the rest activity rhythm of similar magnitude as observed previously in patients in an early stage. It is concluded that TENS increased the coupling between the rest activity rhythm and supposedly stable Zeitgebers in an advanced stage of AD.
Effects of transcutaneous electrical nerve stimulation (TENS) on cognition and behaviour in aging.
In previous studies, transcutaneous electrical nerve stimulation (TENS) improved cognition and behaviour in patients with Alzheimer's disease (AD). The rationale underlying these studies was that TENS could activate, e.g. the septo-hippocampal region and the hypothalamus through direct and indirect pathways. As these areas are also affected in normal aging, the present study examined the effects of TENS on cognition and behaviour in nondemented elderly persons. The results suggest an improvement in visual short-term and verbal long-term (recognition) memory, and semantic verbal fluency. Moreover, stimulated elderly persons felt less depressed. Limitations are discussed.
Cranial electrostimulation (CES) in patients with probable Alzheimer's disease.
In one study, behavioral disorders of patients with vascular dementia reacted positively to cranial electrostimulation (CES). In the present study, it was examined whether CES could improve cognition and (affective) behavior in patients with probable Alzheimer's disease (AD). Eighteen AD patients, divided into an experimental and a placebo group, were treated for 30 min per day, 5 days a week, for 6 weeks. No improvements in cognition and (affective) behavior were found after CES.
Effects of low-frequency cranial electrostimulation on the rest-activity rhythm and salivary cortisol in Alzheimer's disease.
OBJECTIVE: In previous studies, cranial electrostimulation (CES) had positive effects on sleep in depressed patients and in patients with vascular dementia. The present study examined the effects of low-frequency CES on the rest-activity rhythm and cortisol levels of patients with probable Alzheimer's disease (AD).
METHOD: It was hypothesised that a decreased level of cortisol would parallel a positive effect of low-frequency CES on nocturnal restlessness. Sixteen AD patients were randomly assigned to an experimental group (n = 8) or a control group (n = 8). The experimental group was treated with CES, whereas the control group received sham stimulation, for 30 minutes a day, during 6 weeks. The rest-activity rhythm was assessed by actigraphy. Cortisol was measured repeatedly in the saliva throughout the day by means of salivette tubes.
RESULTS: Low-frequency CES did not improve the rest-activity rhythm in AD patients. Moreover, both groups showed an increase instead of a decrease in the level of cortisol.
CONCLUSIONS: These preliminary results suggest that low-frequency CES has no positive effect on the rest-activity rhythm in AD patients. An alternative research design with high-frequency CES in AD is discussed.
Transcutaneous electrical nerve stimulation (TENS) improves circadian rhythm disturbances in Alzheimer disease.
In patients with Alzheimer disease (AD), an irregular day-night rhythm with behavioral restlessness during the night makes a strong demand on caregivers and is among the most important reasons for institutionalization. A dysfunctioning circadian timing system is supposed to underlie the disturbance or at least to contribute to it. The disturbance improves with increased environmental light, which, through the retinohypothalamic tract, activates the suprachiasmatic nucleus (SCN), the biological clock of the brain. Because recent studies have indicated both direct and indirect spinal projections to the SCN, we investigated whether excitation of spinal neurons by means of transcutaneous electrical nerve stimulation (TENS) could also improve circadian rhythm disturbances in AD patients. The actigraphically obtained rest-activity rhythm of 14 AD patients showed an improvement in its coupling to Zeitgeber after TENS treatment but not after placebo treatment.
Options:
A: TENS produced significant long-term improvements in all neuropsychological and behavioural measures evaluated.
B: TENS produced statistically significant short-term improvements in some neuropsychological measures, but no long-term effects were observed.
C: TENS had no significant impact on any neuropsychological or behavioural measures in both short-term and long-term evaluations.
D: TENS produced significant improvements in sleep disorders associated with dementia. | B |
289 | 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 tolerability of olanzapine in the treatment of acute mania? Please answer this question based on the information provided below:
Lamotrigine and the treatment of mania in bipolar disorder.
Anticonvulsants, including valproate and carbamazepine, have established efficacy in the treatment of mania. The anticonvulsant, lamotrigine. has been reported to have antimanic and antidepressant efficacy, and mood-stabilising effects in case reports and preliminary open trials. The efficacy and tolerability of lamotrigine has been compared with olanzapine and lithium in a randomised, prospective, controlled fashion over a period of 4 weeks treatment in a total of 45 hospitalised patients with DSM-IV-defined mania. Significant improvements of a similar magnitude were observed for all treatment groups and lamotrigine was well tolerated. Mechanisms of action proposed to explain the antimanic activity of lamotrigine include inhibition of voltage-sensitive and use-dependent sodium channels, inhibition of glutamate release and calcium channel blockade. Platelet studies have indicated supersensitivity of glutamate receptors and increased intracellular calcium concentrations in patients with mania. Further clinical and mechanistic studies of lamotrigine use in mania are warranted.
Olanzapine compared to lithium in mania: a double-blind randomized controlled trial.
Neuroleptics are of established efficacy in mania. Controlled data on the use of olanzapine in mania is however, absent. In this study, 30 patients meeting DSM-IV criteria for mania were randomly allocated to receive either olanzapine or lithium in a 4 week double-blind randomized controlled design. There were no significant outcome differences between the two groups on any of the primary outcome measures, the Brief Psychiatric Rating Scale (lithium 28.2; olanzapine 28.0; P = 0.44); Clinical Global Impression (CGI) improvement scale (lithium 2.75, olanzapine 2.36; P = 0.163) or the Mania Scale (lithium 13.2, olanzapine 10.2; P = 0.315). Olanzapine was however, significantly superior to lithium on the CGI-severity scale at week 4 (lithium 2.83, olanzapine 2.29; P = 0.025). Olanzapine did not differ from lithium in terms of treatment emergent extrapyramidal side-effects as measured by the Simpson-Angus Scale. Olanzapine appears to be at least as effective as lithium in the treatment of mania.
Lamotrigine compared with lithium in mania: a double-blind randomized controlled trial.
BACKGROUND: Preliminary data from case reports and small open trials suggest a role for lamotrigine in the treatment of bipolar disorder, although controlled data for the manic phase are lacking.
METHOD: Thirty inpatients with a DSM-IV diagnosis of bipolar I disorder, currently manic, were randomly allocated to receive either lamotrigine (25 mg once daily for 1 week, 50 mg once daily for the second week, and 100 mg once daily for the last 2 weeks) or lithium (400 mg twice daily) in a 4-week randomized, double-blind, clinical trial.
RESULTS: Both treatments improved symptoms of mania, as assessed by the Mania Rating Scale, Brief Psychiatric Rating Scale, Clinical Global Impression severity and improvement scales, and the Global Assessment of Functioning scale. There were no significant differences between groups at any time point, suggesting that the dose escalation required for lamotrigine did not adversely affect its onset of action. Secondary outcome measures, including the use of lorazepam as rescue medication, did not differ between the groups. No significant adverse events were noted in either group.
CONCLUSION: In this pilot study, lamotrigine was as effective as lithium in the treatment of patients with bipolar disorder hospitalised for acute mania.
Olanzapine versus placebo in the treatment of acute mania. Olanzapine HGEH Study Group.
OBJECTIVE: The primary intent of this study was to compare the efficacy and safety of olanzapine and placebo in the treatment of acute mania.
METHOD: The design involved a random-assignment, double-blind, placebo-controlled parallel group study of 3 weeks' duration. After a 2- to 4-day screening period, qualified patients were assigned to either olanzapine (N = 70) or placebo (N = 69). Patients began double-blind therapy with either olanzapine, 10 mg, or placebo given once per day. After the first day of treatment, the daily dose could be adjusted upward or downward, as clinically indicated, by one capsule (olanzapine, 5 mg/day) within the allowed range of one to four capsules. The primary efficacy measure in the protocol was defined as a change from baseline to endpoint in total score on the Young Mania Rating Scale. Clinical response was defined a priori as a decrease of 50% or more from baseline in Young Mania Rating Scale total score.
RESULTS: The olanzapine group experienced significantly greater mean improvement in Young Mania Rating Scale total score than the placebo group. On the basis of the clinical response criteria, significantly more olanzapine-treated patients (48.6%) responded than those assigned to placebo (24.2%). Somnolence, dizziness, dry mouth, and weight gain occurred significantly more often with olanzapine. There were no statistically significant differences between the olanzapine-treated and placebo-treated patients with respect to measures of parkinsonism, akathisia, and dyskinesias. No discontinuations of treatment due to adverse events occurred in the olanzapine treatment group.
CONCLUSIONS: The results from this study suggest that compared with placebo, olanzapine has superior efficacy for the symptoms of acute mania.
Efficacy of olanzapine in combination with valproate or lithium in the treatment of mania in patients partially nonresponsive to valproate or lithium monotherapy.
BACKGROUND: A 6-week double-blind, randomized, placebo-controlled trial was conducted to determine the efficacy of combined therapy with olanzapine and either valproate or lithium compared with valproate or lithium alone in treating acute manic or mixed bipolar episodes.
METHODS: The primary objective was to evaluate the efficacy of olanzapine (5-20 mg/d) vs placebo when added to ongoing mood-stabilizer therapy as measured by reductions in Young Mania Rating Scale (YMRS) scores. Patients with bipolar disorder (n = 344), manic or mixed episode, who were inadequately responsive to more than 2 weeks of lithium or valproate therapy, were randomized to receive cotherapy (olanzapine + mood-stabilizer) or monotherapy (placebo + mood-stabilizer).
RESULTS: Olanzapine cotherapy improved patients' YMRS total scores significantly more than monotherapy (-13.11 vs -9.10; P = .003). Clinical response rates (> or = 50% improvement on YMRS) were significantly higher with cotherapy (67.7% vs 44.7%; P< .001). Olanzapine cotherapy improved 21-item Hamilton Depression Rating Scale (HAMD-21) total scores significantly more than monotherapy (4.98 vs 0.89 points; P< .001). In patients with mixed-episodes with moderate to severe depressive symptoms (DSM-IV mixed episode; HAMD-21 score of > or = 20 at baseline), olanzapine cotherapy improved HAMD-21 scores by 10.31 points compared with 1.57 for monotherapy (P< .001). Extrapyramidal symptoms (Simpson-Angus Scale, Barnes Akathisia Scale, Abnormal Involuntary Movement Scale) were not significantly changed from baseline to end point in either treatment group. Treatment-emergent symptoms that were significantly higher for the olanzapine cotherapy group included somnolence, dry mouth, weight gain, increased appetite, tremor, and slurred speech.
CONCLUSION: Compared with the use of valproate or lithium alone, the addition of olanzapine provided superior efficacy in the treatment of manic and mixed bipolar episodes.
Efficacy of olanzapine in acute bipolar mania: a double-blind, placebo-controlled study. The Olanzipine HGGW Study Group.
BACKGROUND: We compared the efficacy and safety of olanzapine vs placebo for the treatment of acute bipolar mania.
METHODS: Four-week, randomized, double-blind, parallel study. A total of 115 patients with a DSM-IV diagnosis of bipolar disorder, manic or mixed, were randomized to olanzapine, 5 to 20 mg/d (n = 55), or placebo (n = 60). The primary efficacy measure was the Young-Mania Rating Scale (Y-MRS) total score. Response and euthymia were defined, a priori, as at least a 50% improvement from baseline to end point and as a score of no less than 12 at end point in the Y-MRS total score, respectively. Safety was assessed using adverse events, Extrapyramidal Symptom (EPS) rating scales, laboratory values, electrocardiograms, vital signs, and weight change.
RESULTS: Olanzapine-treated patients demonstrated a statistically significant greater mean (+/- SD) improvement in Y-MRS total score than placebo-treated patients (-14.8 +/- 12.5 and -8.1 +/- 12.7, respectively; P<.001), which was evident at the first postbaseline observation 1 week after randomization and was maintained throughout the study (last observation carried forward). Olanzapine-treated patients demonstrated a higher rate of response (65% vs 43%, respectively; P =.02) and euthymia (61% vs 36%, respectively; P =. 01) than placebo-treated patients. There were no statistically significant differences in EPSs between groups. However, olanzapine-treated patients had a statistically significant greater mean (+/- SD) weight gain than placebo-treated patients (2.1 +/- 2.8 vs 0.45 +/- 2.3 kg, respectively) and also experienced more treatment-emergent somnolence (21 patients [38.2%] vs 5 [8.3% ], respectively).
CONCLUSION: Olanzapine demonstrated greater efficacy than placebo in the treatment of acute bipolar mania and was generally well tolerated.
Olanzapine versus divalproex in the treatment of acute mania.
OBJECTIVE: The effects of olanzapine and divalproex for the treatment of mania were compared in a large randomized clinical trial.
METHOD: A 3-week, randomized, double-blind trial compared flexibly dosed olanzapine (5-20 mg/day) to divalproex (500-2500 mg/day in divided doses) for the treatment of patients hospitalized for acute bipolar manic or mixed episodes. The Young Mania Rating Scale and the Hamilton Depression Rating Scale were used to quantify manic and depressive symptoms, respectively. Safety was assessed with several measures.
RESULTS: The protocol defined baseline-to-endpoint improvement in the mean total score on the Young Mania Rating Scale as the primary outcome variable. The mean Young Mania Rating Scale score decreased by 13.4 for patients treated with olanzapine (N=125) and 10.4 for those treated with divalproex (N=123). A priori categorizations defined response and remission rates: 54.4% of olanzapine-treated patients responded (> or = 50% reduction in Young Mania Rating Scale score), compared to 42.3% of divalproex-treated patients; 47.2% of olanzapine-treated patients had remission of mania symptoms (endpoint Young Mania Rating Scale < or = 12), compared to 34.1% of divalproex-treated patients. The decrease in Hamilton depression scale score was similar in the two treatment groups. Completion rates for the 3-week study were similar in both groups. The most common treatment-emergent adverse events (incidence >10%) occurring more frequently during treatment with olanzapine were dry mouth, increased appetite, and somnolence. For divalproex, nausea was more frequently observed. The average weight gain with olanzapine treatment was 2.5 kg, compared to 0.9 kg with divalproex treatment.
CONCLUSIONS: The olanzapine treatment group had significantly greater mean improvement of mania ratings and a significantly greater proportion of patients achieving protocol-defined remission, compared with the divalproex treatment group. Significantly more weight gain and cases of dry mouth, increased appetite, and somnolence were reported with olanzapine, while more cases of nausea were reported with divalproex.
Options:
A: Olanzapine was less effective than placebo in reducing manic symptoms and had fewer adverse effects.
B: Olanzapine was more effective than placebo in reducing manic symptoms, but caused more weight gain and somnolence.
C: Olanzapine was equally effective as haloperidol in reducing manic symptoms and had a similar adverse effect profile.
D: Olanzapine was less effective than divalproex in reducing manic symptoms and caused fewer adverse effects. | B |
290 | 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 main conclusion regarding the choice of drug treatments for dysthymia based on the systematic review of randomised controlled trials? Please answer this question based on the information provided below:
Ritanserin, imipramine, and placebo in the treatment of dysthymic disorder.
Fifty outpatients with dysthymic disorder (DSM-III) were divided by double-blind randomized assignment into three groups given ritanserin, imipramine, and placebo, respectively. The trial was of 7 weeks' duration; by week 6, imipramine was clearly superior to placebo, whereas by week 7, both drugs caused significantly more improvement than the placebo. Although imipramine had slightly greater efficacy than ritanserin, it also had significantly more side effects. This was particularly evident in the higher dropout rate with imipramine. The efficacy and side effect profile of ritanserin makes it well tolerated and acceptable with dysthymic patients who, although they do not respond as quickly as patients with major depressive disorder, do show significant improvement, given sufficient time.
Psychopharmacological treatment response of patients with a DSM-III diagnosis of dysthymic disorder.
In spite of its significant morbidity, dysthymic disorder has been under-researched, therefore effective treatment options are limited. This article presents data suggesting that dysthymia can be treated effectively with psychopharmacologic agents. A double-blind, placebo-controlled 7-week drug trial comparing imipramine to ritanserin, a serontonin-2 antagonist, indicated that both drugs were significantly more effective than placebo in alleviating dysthymia symptoms. Imipramine was slightly more effective than ritanserin, as indicated by ratings on the Hamilton Depression Rating Scale and the Zerssen Self-Rating Scale; however, imipramine also produced more side effects. On the basis of this study, we continued an open protocol for treating dysthymic patients with a specific serotonin reuptake inhibitor, fluoxetine. This open-label study indicated that fluoxetine was successful in reducing the dysthymia symptoms, particularly in the subaffective sub-type. These studies confirm the need for further research into the treatment options for patients suffering from dysthymia.
Efficacy of tianeptine in anxious-depressed patients: results of a controlled multicenter trial versus amitriptyline.
265 adult outpatients with dysthymic disorder (DSM-III) associated with clinically manifest anxiety (according to FDA criteria) were included in a multicenter, randomized double-blind study. The trial consisted of three phases: placebo pretreatment phase and inclusion in the trial, treatment phase, placebo posttreatment phase. Patients were treated in monotherapy for 42 days with a mean dosage of 3 tablets per day corresponding to 37.5 mg/day of tianeptine or 75 mg/day of amitriptyline respectively. The following assessment instruments were used: the Montgomery and Asberg Depression Rating Scale (MADRS), the Hamilton Anxiety Rating Scale (HARS), and the Check-List for the Evaluation of Somatic Symptoms of J.D. Guelfi and C.B. Pull (CHESS 82). Analysis of MADRS total scores showed an important and rapid improvement in tianeptine and amitriptyline groups, reaching statistical significance as soon as D7. At the end of the 6-week treatment period the tianeptine group reached a decrease of 64% in the initial MADRS total score versus 69% in the amitriptyline group. 78% of patients treated with tianeptine and 83% of patients treated with amitriptyline were considered as treatment responders. There was no difference in drop-out rates between the two groups. HARS scores showed a decrease in psychic as well as somatic anxiety in both groups. The action of tianeptine on anxious-depressive symptomatology was confirmed by the concomitant improvement of global clinical rating and patients' self-rating (HSCL). Statistical comparison of all clinical rating-scale scores in patients having completed the trial failed to show any significant group differences.(ABSTRACT TRUNCATED AT 250 WORDS)
Long-term treatment of double depression: a preliminary study with serotonergic antidepressants.
1. There is increasing evidence that many patients with major depression also have coexisting dysthymia, and that antidepressant treatment may alleviate both conditions. 2. Open-label study of fluoxetine and trazodone for 18 patients meeting DSM-III-R criteria for concurrent dysthymia and major depression. 3. Fourteen patients completed three-month medication trials, and seven (50%) of completers) responded to treatment. At five months, eight (57.1%) were in remission. Fluoxetine was significantly better tolerated than trazodone, with respective dropout rates of 7.7% and 80%. 4. Findings are consistent with efficacy of serotonergic agents in this condition.
[Comparison of the effect of amisulpride and viloxazine in the treatment of dysthymia].
An evaluation of the therapeutic efficacy of Amisulpride as compared with Viloxazine in a group of patients diagnosed as dysthymic, according to the DSM-III-R criteria is presented. Study was a double-blind, randomized controlled trial: Subjects were assessed during an initial examination with informed consent, then entering a 4-week treatment trial. The Hamilton Depression Scale, the Widlocher Psychomotor Retardation Scale, and the Andreasen Negative Symptoms Scale were used for evaluating cases. Both the efficacy and safety of drugs were assessed. An analysis of results suggests a better therapeutic response among the Amisulpride group subjects.
A preliminary study of serotonergic antidepressants in treatment of dysthymia.
There is increasing evidence that antidepressants may alleviate symptoms of dysthymia, but few prior studies on selective serotonergic agents. Twenty patients meeting criteria for dysthymia, but not meeting criteria for major depression, received open label trials of a serotonergic antidepressant, either fluoxetine or trazodone. Seventeen (85%) completed three-month medication trials, and of these, twelve (70.6% of completers) responded to treatment. Seven (41.2% of completers) were still in remission on follow-up at five months. Both fluoxetine and trazodone were well tolerated in dysthymics, and showed similar short-term effectiveness in treating dysthymic symptoms.
Multicentric double-blind study comparing efficacy and safety of minaprine and imipramine in dysthymic disorders.
This multicentre study compares the therapeutic efficacy and safety of minaprine (200 mg) to that of imipramine (50, 75, 100 mg) in the treatment of patients over 40 years suffering from dysthymic disorders as diagnosed according to DSM III. After 4-7 days on placebo, 67 patients were randomly assigned to receive either drug for a period of 6 weeks in a double-blind manner. As rated by the Hamilton Depression Rating Scale and evaluated by exploratory statistics, minaprine showed similar efficacy to imipramine in these patients. Minaprine was better tolerated than imipramine according to the physicians' tolerance rating (p < 0.05) and produced significantly fewer symptoms of the autonomic nervous system as compared to imipramine (p < 0.01).
Amisulpride versus fluoxetine in patients with dysthymia or major depression in partial remission: a double-blind, comparative study.
In a multicentre, double blind, parallel group study 281 patients with DSM III-R diagnosis of dysthymia or a single episode of major depression in partial remission were randomised to 3 months of treatment with amisulpride 50 mg/day or fluoxetine 20 mg/day. The baseline Montgomery and Asberg Depression Rating Scale (MADRS) total score was reduced by at least 50% in 74.1% of patients (103/139) with amisulpride and 67.4% (87/129) with fluoxetine (P =0.230). No significant differences between treatment groups were found in the reductions in mean total score with the MADRS, Widlöcher psychomotor retardation scale, Sheehan disability scale, and CGI. Anxiety measured by HAM-A total mean score decreased significantly more with amisulpride (63%) than with fluoxetine (54%; P = 0.021). There were 13 dropouts due to adverse events with amisulpride and ten with fluoxetine. The number of patients reporting at least one adverse event was similar in the two groups (amisulpride 47.5%; fluoxetine 40.9%). As expected, in the amisulpride group endocrine-like adverse events in female patients were the most common, while nausea, dyspepsia, anorexia and insomnia occurred more frequently with fluoxetine.
Relevance of DMS-III depressive subtype and chronicity of antidepressant efficacy in atypical depression. Differential response to phenelzine, imipramine, and placebo.
One hundred ninety-four nonmelancholic depressed outpatients with features of atypical depression took part in a 6-week randomized trial of imipramine hydrochloride, phenelzine sulfate, and placebo. Their courses of illness were also rated for chronicity. Significantly more patients responded to phenelzine (71%) than to imipramine (48%), which benefited significantly more patients than placebo (26%). Both chronicity and DMS-III diagnosis predicted response on several outcome measures. For example, patients with dysthymic disorder responded better to treatment than did those with major depression, suggesting that dysthymic disorder can be treated with medication. Placebo response correlated inversely with chronicity, regardless of DMS-III diagnosis. Atypical depression and longitudinal course of illness may add to the usefulness of DMS-III depressive diagnosis as a predictor of antidepressant response.
A placebo-controlled, randomized clinical trial comparing sertraline and imipramine for the treatment of dysthymia.
BACKGROUND: Despite the high prevalence of dysthymia and its associated morbidity, few controlled trials have evaluated the efficacy of antidepressant medication for this disorder. A 12-week, double-blind, placebo-controlled, randomized, multicenter trial was performed to evaluate the safety and efficacy of sertraline hydrochloride and imipramine hydrochloride in treating dysthymia.
METHODS: A total of 416 outpatients (271 women and 145 men) aged 25 to 65 years with DSM-III-R-defined, early-onset, primary dysthymia without concurrent major depression were randomized to 12 weeks of treatment with sertraline, imipramine, or placebo.
RESULTS: Both active treatments resulted in significantly reduced scores on the 17-item Hamilton Rating Scale for Depression (P = .04 and P = .01 for sertraline and imipramine vs placebo, respectively), the Montgomery-Asberg Depression Rating Scale (P = .01 and P = .003 vs placebo, respectively), Hopkins Symptom Checklist (P < .05), and the self-rated version of the Inventory of Depressive Symptoms (P < .05). With the use of a Clinical Global impressions improvement score of 1 or 2 (very much or much improved) to define response, response rates were 59% for sertraline, 64% for imipramine, and 44% for placebo (P = .02 for sertraline vs placebo and P < .001 for imipramine vs placebo). A significantly greater proportion of patients receiving imipramine than those receiving sertraline or placebo discontinued treatment because of adverse events (P = .001 and P < .001, respectively).
CONCLUSIONS: Pharmacotherapy provides considerable relief from the symptoms of dysthymia in patients suffering from this chronic affective disorder, with both sertraline and imipramine being more effective than placebo. The greater tolerability of sertraline is an important consideration because of the chronicity of dysthymia, which may require prolonged treatment with antidepressant medication.
Double-blind study of imipramine versus phenelzine in Melancholias and Dysthymic Disorders.
In a 6-week double-blind trial, the efficacy of imipramine and high dose phenelzine were compared in the treatment of Major Depression with Melancholia, and Dysthymic Disorder (DSM-III). Both drugs were found to be equally efficacious in the treatment of 32 patients suffering from Major Depression. In 32 Dysthymic patients, phenelzine in high doses was found to be superior to imipramine. The clinical implications of these findings are discussed.
Moclobemide and imipramine in chronic depression (dysthymia): an international double-blind, placebo-controlled trial. International Collaborative Study Group.
An international, multicenter, placebo-controlled study was undertaken to determine the safety and antidepressant efficacy of moclobemide, a new reversible inhibitor of monoamine oxidase A, and imipramine in the treatment of dysthymia (DSM-III-R). A total of 315 patients were enrolled and randomly assigned to an 8-week treatment in one of three groups (moclobemide, imipramine and placebo). Patients were male or female outpatients aged between 18 and 65 years meeting DSM-III-R criteria for dysthymia, primary type, with late or early onset. Of the patients in each group 85% completed the 8-week treatment period. The percentage of patients who no longer fulfilled DSM-III-R symptom criteria at treatment endpoint was significantly higher in the moclobemide (60%) and imipramine (49%) treatment groups than in the placebo group (22%). Differences to placebo were also statistically significant both for moclobemide and for imipramine on the other efficacy variables (i.e. Hamilton Rating Scale for Depression, final overall efficacy assessment, Clinical Global Impression and symptom check list self-rating). A significant superiority of moclobemide and imipramine over placebo was found in pure dysthymia and in double-depression, as well as in early and late onset subgroups. In early onset cases, moclobemide was significantly more effective than was imipramine on the Hamilton Rating Scale for Depression. Anticholinergic symptoms and sleepiness were significantly more frequent side effects on imipramine than on moclobemide or on placebo, and the investigators' final overall assessment of tolerability significantly favoured moclobemide over imipramine. This study demonstrates the efficacy of high dose moclobemide (mean dose 675 mg/day) and high dose imipramine (220 mg/day) against placebo in the treatment of dysthymia. Moclobemide was better tolerated than was imipramine.
Options:
A: All studied drugs had significantly different clinical responses, making it difficult to determine the best treatment.
B: The choice of drug should be based on the consideration of drug-specific side effect properties, as all studied drugs promoted similar clinical responses.
C: There was no evidence to support the use of any specific drug treatment for dysthymia.
D: Only TCAs and SSRIs were found to be effective, while other drug treatments showed no clinical response. | B |
291 | 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 transcutaneous electrical nerve stimulation (TENS) in the treatment of rheumatoid arthritis (RA) of the hand? Please answer this question based on the information provided below:
Transcutaneous electrical nerve stimulation in rheumatoid arthritis.
The therapeutic effect of once weekly transcutaneous electrical nerve stimulation in patients with rheumatoid arthritis was compared with placebo in a randomised, double-blind, non-crossover study lasting three weeks. Thirty-two patients with classic or definite rheumatoid arthritis and wrist involvement were evaluated. Transcutaneous electrical nerve stimulation was better than the placebo in relieving pain at rest and while gripping. In addition, grip strength, measured as power and work done, immediately improved following transcutaneous electrical nerve stimulation but returned almost to initial values between assessments. No significant improvement was shown for the placebo group.
The analgesic effects of transcutaneous electrical nerve stimulation and placebo in chronic pain patients. A double-blind non-crossover comparison.
The analgesic effects of high frequency transcutaneous electrical nerve stimulation (TNS), "acupuncture-like" TNS and placebo TNS were evaluated in 33 patients with rheumatoid arthritis and chronic hand pain using a randomized, double-blind, non-crossover design. An oscilloscope was employed to monitor the stimulator output in the TNS treatment groups and to provide strong suggestion and a focus of attention in the placebo treatment group. The two forms of TNS were applied at the highest intensity that could be tolerated by patients. Assessments of resting pain, joint tenderness, grip strength and grip pain were made before and after treatment. The pain and joint tenderness measurements showed high frequency TNS, "acupuncture-like" TNS and placebo TNS to be equally effective in producing analgesia of similar degree and trend over time. The grip strength measurements showed no significant change. The results obtained with placebo are probably due to the suggestion and attention effects of the visual stimulus. The implications of these results in respect to pain control pathways are discussed. Although TNS given at high intensity was shown to be no better than placebo applied with strong suggestion, this does not preclude its use as a method of pain control in rheumatoid arthritis.
The effect of transcutaneous electrical nerve stimulation (TNS) on joint pain in patients with rheumatoid arthritis.
The effect of transcutaneous nerve stimulation (TNS) on joint pain was studied in patients with rheumatoid arthritis. Three different forms of TNS were used in an attempt to evaluate the influence of placebo effects. The results were evaluated by means of loading tests and from the patients' own assessments of pain relief. High intensity TNS near the painful joint gave pain relief of varying degree in 95% of the patients, while TNS of low intensity and TNS applied at a remote site gave an improvement in 75% and 5% respectively. It seems quite clear that TNS is effective in reducing joint pain. There are a number of factors which intimate that this improvement is not merely a placebo effect.
Options:
A: AL-TENS significantly reduced rest pain and improved muscle power scores compared to placebo, while C-TENS showed no clinical benefit on pain intensity but had a clinical benefit on patient assessment of change in disease.
B: Both AL-TENS and C-TENS significantly reduced rest pain and grip pain compared to placebo, with no differences between the two modes.
C: Neither AL-TENS nor C-TENS showed any significant benefits over placebo in reducing pain intensity or improving muscle power scores.
D: C-TENS significantly reduced rest pain and improved muscle power scores compared to placebo, while AL-TENS showed no clinical benefit on pain intensity but had a clinical benefit on patient assessment of change in disease. | A |
292 | 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 outcome of the systematic review assessing the effects of psychological interventions for treating depression in young adults and adults with congenital heart disease? Please answer this question based on the information provided below:
No effect of vitamin B-12 treatment on cognitive function and depression: a randomized placebo controlled study.
BACKGROUND: Associations between vitamin B-12 deficiency and impaired cognitive function and depression have been reported.
METHODS: A randomized placebo controlled study including 140 individuals with an increased plasma methylmalonic acid (0.40-2.00 micromol/l) not previously treated with vitamin B-12. Cognitive function was assessed by the Cambridge Cognitive Examination (CAMCOG), Mini-Mental State Examination (MMSE), and a 12-words learning test. Symptoms of depression were evaluated by the Major Depression Inventory. The main outcome measure was change in cognitive function and depression score from baseline to follow-up 3 months later.
RESULTS: At baseline 78 (56%) individuals had cognitive impairment judged from the CAMCOG score and 40 (29%) according to the MMSE; 18 (13%) individuals had symptoms of depression. No improvement was found in cognitive function comparing the treatment and placebo group (total CAMCOG score: P = 0.43), nor among individuals with only slightly impaired cognitive function (n = 44, total CAMCOG score: P = 0.42). The treatment group did not improve in depression score as compared to the placebo group (P = 0.18).
LIMITATIONS: The duration of impaired cognitive function was unknown.
CONCLUSIONS: A high proportion of individuals with an increased plasma methylmalonic acid had impaired cognitive function, and a rather high prevalence of depression was observed. However, vitamin B-12 treatment did not improve cognitive function or symptoms of depression within the 3-months study period.
A randomized, double-blind, placebo-controlled study of oral vitamin B12 supplementation in older patients with subnormal or borderline serum vitamin B12 concentrations.
OBJECTIVES: To determine the effect of small doses of oral cyanocobalamin supplements in older patients with low or borderline serum vitamin B12 concentrations but no other evidence of pernicious anemia (PA).
DESIGN: Randomized, double-blind, placebo-controlled study assessing the efficacy of oral cyanocobalamin 10 microg and 50 microg daily for 1 month.
SETTING: Two geriatric hospitals in the North Western Health Care Network, Melbourne, Australia.
PARTICIPANTS: Thirty-one inpatients with serum vitamin B12 levels between 100 and 150 pmol/L, without PA, other malabsorption disorders, or progressive neurological or terminal illness. The mean age was 81.4 years.
INTERVENTION: After informed consent, a medical and drug history was taken and the Mini-Mental State Examination (MMSE) completed. A dietitian made assessment of oral cobalamin intake. Blood was taken for serum vitamin B12, serum and red cell folate assay, full blood examination, fasting serum gastrin, parietal and intrinsic factor antibodies, fasting serum homocysteine, and creatinine. Patients were then randomized to receive 10 microg oral cyanocobalamin, 50 microg oral cyanocobalamin, or placebo treatment for 1 month, after which the investigations and clinical examinations were repeated.
MEASUREMENTS: Percentage change in the level of vitamin B12, homocysteine, folate, and red cell parameters and absolute changes in MMSE were calculated and compared between groups. The groups were compared on the number of responders who improved their level of B12 by 20%. Chi-square calculations on changes in serum vitamin B12 concentration were also performed.
RESULTS: Mean serum vitamin B12 +/- standard deviation improved by 51.7 +/- 47.1% in the 50-microg group, 40.2 +/- 34.4% in the 10-microg group, and 11.7 +/- 24.5% in the placebo group. The change in the 50-microg cyanocobalamin group was significantly greater than that in the placebo group (P=.044). The change in the 10-microg cyanocobalamin group was not significantly different from that in the placebo group (P=.186). Eight of 10 subjects in each treatment group were classified as responders, compared with two of 11 in the placebo group (P=.004). Homocysteine levels fell in patients receiving cyanocobalamin, but this fall failed to reach statistical significance. There were no significant changes in the other parameters measured.
CONCLUSION: Cyanocobalamin supplementation of 50 microg but not 10 microg daily produced a significant increase in serum vitamin B12. This result has implications for the management of patients with subnormal or borderline serum vitamin B12 concentrations and for food fortification with vitamin B12.
Options:
A: Several randomised controlled trials demonstrated the effectiveness of psychological interventions.
B: No randomised controlled trials were identified.
C: Psychological interventions were found to be ineffective.
D: Psychological interventions were found to be harmful. | B |
293 | 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 risks of using continuous inhaled beta-agonists compared to intermittent inhaled beta-agonists for the treatment of acute asthma in the emergency department? Please answer this question based on the information provided below:
Continuous versus intermittent nebulization of salbutamol in acute severe asthma: a randomized, controlled trial.
STUDY OBJECTIVE: This study was conducted to compare the clinical and spirometric effects of continuous and intermittent nebulization of salbutamol in acute severe asthma.
METHODS: Forty-two consecutive patients presenting to the emergency department for acute severe asthma (peak expiratory flow [PEF] mean+/-SD, 24%+/-12% predicted) were prospectively randomly assigned to receive 27.5 mg of salbutamol by either continuous or intermittent nebulization over a 6-hour period. The continuous nebulization group received 15 mg of salbutamol during the first hour and 12.5 mg over the next 5 hours. The intermittent nebulization group received 5 mg of salbutamol every 20 minutes during the first hour and 2.5 mg hourly over the next 5 hours. All participants received oxygen and intravenous hydrocortisone. Clinical and spirometric assessment was performed at baseline, 40 minutes, 60 minutes, and at 3 and 6 hours after the start of the nebulization. Secondary endpoints were the respective rates of hospitalization and treatment failure.
RESULTS: A significant clinical and spirometric improvement was observed in both groups over baseline as soon as the 40th minute and was sustained thereafter (absolute PEF increase at the sixth hour 30%+/-18% and 32%+/-22% in the continuous and intermittent nebulization groups, respectively; P <.01 over baseline). PEF and the clinical score evolved similarly in both groups. There was no difference between the groups regarding the failure rate of the initial bronchodilator treatment to terminate the asthma attack (3 [14%] in the continuous nebulization group and 2 [9.5%] in the intermittent nebulization group, absolute difference 4.5% [95% confidence interval -14% to 23%]). Eight (38%) patients and 9 (43%) patients from the continuous and intermittent nebulization groups, respectively, required hospitalization according to predefined criteria (absolute difference 4.8% [95% confidence interval -24% to 34%]).
CONCLUSION: We did not observe an appreciable difference between continuous and intermittent nebulization of salbutamol in acute severe asthma. The decision to use one of these nebulization methods should be based on logistical considerations.
Continuous nebulization of albuterol (salbutamol) in acute asthma.
We studied the safety and efficacy of albuterol (salbutamol) delivered by continuous nebulization (CN) in the initial emergency department treatment of asthma. In a randomized fashion 21 patients received 5 mg of albuterol by bolus nebulization (BN) at time 0 and again 60 minutes later. Twenty-one others received albuterol (0.2 mg/ml) by CN using a calibrated nebulizer with a known output of 25 ml/h. Thus, each patient had received 10 mg of albuterol over two hours. FEV1, blood pressure (BP), heart rate (HR), respiratory rate (RR), and hand tremor were recorded at 30-minute intervals. The FEV1 was 1.48 +/- 0.64 L prior to BN and increased to a maximum of 2.20 +/- 0.94 L (p less than 0.05) 90 minutes later. The FEV1 prior to CN was 1.13 +/- 0.51 L and improved to 2.20 +/- 1.02 L (p less than 0.05) at 120 minutes. The FEV1 did not differ significantly between regimens over the 2-hour period. Both modes of therapy were well tolerated. There was a slight but significant increase in HR at 30 and 90 minutes in the BN group when compared with CN. There was no significant difference in BP, RR, or tremor between the groups. Thus, albuterol by CN was found to be equally effective as the same medication by BN in the early treatment of asthma in patients seen in the emergency department.
Randomised pragmatic comparison of UK and US treatment of acute asthma presenting to hospital.
BACKGROUND: Systemic corticosteroids and inhaled beta(2) agonists are accepted first line treatments for acute severe asthma, but there is no consensus on their optimum dosage and frequency of administration. American regimens include higher initial dosages of beta(2) agonists and corticosteroids than UK regimens.
METHODS: In a prospective, pragmatic, randomised, parallel group study, 170 patients of mean (SD) age 37 (12) years with acute asthma (peak expiratory flow (PEF) 212 (80) l/min) presenting to hospital received treatment with either high dose prednisolone and continuous nebulised salbutamol as recommended in the US or lower dose prednisolone and bolus nebulised salbutamol as recommended in the UK by the BTS.
RESULTS: Outcome measures were: deltaPEF at 1 hour (BTS 89 l/min, US 106 l/min, p=0.2, CI -8 to 41) and at 2 hours (BTS 49 l/min, US 101 l/min, p<0.0001, CI 28 to 77); time to discharge if admitted (BTS 4 days, US 4 days); rates of achieving discharge PEF (>60%) at 2 hours (BTS 64%, US 78%, p=0.04); time to regain control of asthma as measured by PEF >/=80% best with </=20% variability (BTS 3 days, US 4 days, p=0.6); PEF at 24 hours in patients admitted (BTS 293 l/min, US 288 l/min, p=0.8); and control of asthma in the subsequent month (no significant differences).
CONCLUSIONS: Treatment with higher doses of continuous nebulised salbutamol leads to a greater immediate improvement in PEF but the degree of recovery at 24 hours and speed of recovery thereafter is achieved as effectively with lower corticosteroid doses as recommended in the British guidelines.
Continuous vs intermittent nebulized albuterol for emergency management of asthma.
OBJECTIVE: To compare the efficacy and safety of continuous nebulized (CN) albuterol therapy with those of intermittent nebulized (IN) albuterol therapy in the ED treatment of children with moderate to severe asthma exacerbations.
METHODS: A prospective, randomized, single-blind study was conducted at a children's hospital ED. Patients aged 2 to 18 years with a moderate to severe asthma exacerbation (asthma score > or = 8) were enrolled. Patients were randomized to receive either IN albuterol (0.15 mg/kg/dose every 30 min) or CN albuterol (0.3 mg/kg/hr) for a maximum of 2 hours. All patients received prednisone at entry. All released patients were evaluated by telephone, 48 hours after the ED visit. Estimates of respiratory therapist (RT) time commitments for the 2 delivery systems were calculated.
RESULTS: There were 35 patients assigned to IN therapy and 35 to CN therapy. Nine of the 35 patients (26%) in the IN group and 8 of the 35 patients (22%) in the CN group were hospitalized (p = NS). Although the durations of ED therapy were comparable in the 2 groups, the time spent by the RTs in delivering asthma therapy was significantly less for the CN group than it was for the IN group (30.3 min vs 51.9 min per patient; p < 0.001). There was no major adverse effect in either study group.
CONCLUSION: There was no difference in efficacy or safety between CN therapy and IN therapy in the ED management of moderate to severe asthma exacerbations in children. Moreover, CN therapy provided a significant time savings in the delivery of asthma therapy to patients in a busy ED.
Continuous versus intermittent albuterol nebulization in the treatment of acute asthma.
STUDY OBJECTIVES: To compare bronchodilation, chronotropic effects, and side effects of the same dose of nebulized albuterol when given by either intermittent or continuous administration.
DESIGN: A randomized assignment of patients to one of the two methods of albuterol nebulization.
SETTING: Adult emergency department in an urban public hospital.
TYPE OF PARTICIPANTS: Adult patients with acute exacerbations of asthma.
INTERVENTIONS: Administration of 30 mg albuterol given over 110 minutes by either continuous or intermittent aerosolization.
MEASUREMENTS: FEV1, forced vital capacity, heart rate, and systolic and diastolic blood pressures were measured immediately before treatment and then hourly for two hours. Side effects, symptoms, subsequent admission, and discharge also were noted.
MAIN RESULTS: An overall significant decrease in heart rate was observed, indicating the lack of significant chronotropic effects with this dose of albuterol. Both treatments resulted in significant spirometric improvement without a significant treatment difference for the entire group. A difference, however, was found in the relative rates of FEV1 improvement with the two treatments depending on whether patients had an initial FEV1 less than or more than 50% predicted (P = .05). A secondary analysis on patients with an initial FEV1 less than percent predicted demonstrated a higher rate of percent predicted FEV1 increase with the continuously nebulized albuterol group (P = .03).
CONCLUSION: This study demonstrates that albuterol can be given safely at this dose by either intermittent or continuous nebulization. Future studies should examine whether continuous nebulization has a reproducible advantage over intermittent nebulization in patients with more severe obstruction.
Continuous versus frequent intermittent nebulization of albuterol in acute asthma: a randomized, prospective study.
BACKGROUND: In acute severe asthma the optimal dose, frequency, duration and method of administration of beta-2 agonists is unknown. No study to date has evaluated the efficacy of high dose beta-2 agonists beyond the initial two hours.
OBJECTIVE: (1) To determine whether high-dose continuous nebulization of albuterol (7.5 mg/h) is as safe and as efficacious as high-dose intermittent nebulization of albuterol (2.5 mg every 20 minutes) for four hours. (2) To evaluate whether there is a continual improvement using high dose therapy beyond two hours.
METHODS: We devised a simple means of continuous nebulization calibrated to deliver 7.5 mg albuterol per hour. Twenty-two nonsmoking, patients with acute, severe asthma who presented to the emergency department with less than 60% predicted normal PEFR were randomized to either the continuous or intermittent group. All patients received intravenously 125 mg methyl prednisolone on initiation of the study. No theophylline was administered. Spirometry and vital signs were measured at baseline and every 30 minutes thereafter. Electrocardiograms were obtained on all patients and all patients had continuous cardiac monitoring.
RESULTS: Both groups doubled their baseline spirometric values over the four-hour period (P < .0001). The FEV1 did not differ significantly between regimens at any time interval. Improvement from 120 minutes to 240 minutes was statistically significant (P < .0001). There was no significant difference in vital signs at the end of the study compared with baseline in either group, nor between the two groups at any time interval.
CONCLUSION: High-dose continuous nebulization of albuterol is as safe and as efficacious as intermittent nebulization of albuterol in the early treatment of asthma in an emergency department. To our knowledge, this is the first study showing continued significant improvement beyond the initial two hours of therapy using high dose nebulized beta-2 agonists.
Comparison of intermittent and continuously nebulized albuterol for treatment of asthma in an urban emergency department.
STUDY OBJECTIVE: To compare continuously nebulized albuterol with intermittent bolus nebulization of albuterol.
DESIGN: Consecutive block enrollment in groups of ten to continuous or intermittent therapy.
SETTING: Urban emergency department.
TYPE OF PARTICIPANTS: Patients who presented to the ED with moderate to severe asthma and did not improve after one treatment with nebulized albuterol.
INTERVENTIONS: All patients received an initial nebulized treatment with 2.5 mg albuterol followed by 125 mg solumedrol. Patients in the intermittent group received 2.5 mg nebulized albuterol at 30, 60, 90, and 120 minutes after the initial treatment. Patients in the continuous group received 10 mg albuterol nebulized in 70 mL over two hours.
RESULTS: There was no difference between groups in age, sex, or initial peak expiratory flow rate (PEFR). Ninety-nine patients were included in the study (47 continuous and 52 intermittent). There was no statistically significant difference in PEFRs or admission rate between groups over the two-hour study period. One subgroup analysis was performed on patients with PEFRs on presentation to the ED of 200 L/min or less. Mean +/- SD baseline PEFR at presentation to the ED was 135 +/- 35 in the 35 patients in the continuous group and 137 +/- 45 in the 34 patients in the intermittent group). At 120 minutes, PEFR was 296 +/- 98 in the continuous group and 244 +/- 81 in the intermittent group (P = .01). Admission: discharge ratios for this subgroup analysis were 11:24 in the continuous group and 19:14 in the intermittent group (P = .03). Mean +/- SD heart rate in the subgroup analysis was 102 +/- 21 at baseline for the continuous group and 109 +/- 22 at baseline in the intermittent group. At 120 minutes, heart rate was 90 +/- 18 in the continuous group and 104 +/- 16 in the intermittent group (P = .002).
CONCLUSIONS: Continuous nebulization offers no benefit over intermittent therapy in patients with an initial PEFR of more than 200 L/min. In PEFRs of 200 or less, continuous nebulization may decrease admission rate and improve PEFRs when compared with standard therapy.
Comparison of intermittent and continuously nebulized albuterol for treatment of asthma in an urban emergency department.
STUDY OBJECTIVE: To compare continuously nebulized albuterol with intermittent bolus nebulization of albuterol.
DESIGN: Consecutive block enrollment in groups of ten to continuous or intermittent therapy.
SETTING: Urban emergency department.
TYPE OF PARTICIPANTS: Patients who presented to the ED with moderate to severe asthma and did not improve after one treatment with nebulized albuterol.
INTERVENTIONS: All patients received an initial nebulized treatment with 2.5 mg albuterol followed by 125 mg solumedrol. Patients in the intermittent group received 2.5 mg nebulized albuterol at 30, 60, 90, and 120 minutes after the initial treatment. Patients in the continuous group received 10 mg albuterol nebulized in 70 mL over two hours.
RESULTS: There was no difference between groups in age, sex, or initial peak expiratory flow rate (PEFR). Ninety-nine patients were included in the study (47 continuous and 52 intermittent). There was no statistically significant difference in PEFRs or admission rate between groups over the two-hour study period. One subgroup analysis was performed on patients with PEFRs on presentation to the ED of 200 L/min or less. Mean +/- SD baseline PEFR at presentation to the ED was 135 +/- 35 in the 35 patients in the continuous group and 137 +/- 45 in the 34 patients in the intermittent group). At 120 minutes, PEFR was 296 +/- 98 in the continuous group and 244 +/- 81 in the intermittent group (P = .01). Admission: discharge ratios for this subgroup analysis were 11:24 in the continuous group and 19:14 in the intermittent group (P = .03). Mean +/- SD heart rate in the subgroup analysis was 102 +/- 21 at baseline for the continuous group and 109 +/- 22 at baseline in the intermittent group. At 120 minutes, heart rate was 90 +/- 18 in the continuous group and 104 +/- 16 in the intermittent group (P = .002).
CONCLUSIONS: Continuous nebulization offers no benefit over intermittent therapy in patients with an initial PEFR of more than 200 L/min. In PEFRs of 200 or less, continuous nebulization may decrease admission rate and improve PEFRs when compared with standard therapy.
Continuous vs intermittent albuterol, at high and low doses, in the treatment of severe acute asthma in adults.
Adult patients suffering from acute asthma presenting to the Emergency Department with an FEV1 of less than 40% of predicted were randomized into four treatment groups. They were treated with nebulized albuterol at a high (7.5 mg) or standard (2.5 mg) dose given either continuously through 1 h, or intermittently every hour, for 2 h. When the FEV1 improvements for the different groups at 2 h were compared, the groups treated with continuous nebulization had the greatest improvement. The improvements (1.07 L for the high-dose group, and 1.02 L for the standard-dose group) were significantly greater than the improvement seen with standard-dose intermittent treatment (0.72 L; p < 0.05). The improvement in FEV1 of the high-dose, hourly treated group was intermediate in magnitude between these (0.09 L). There was no difference in the improvement seen between the two groups treated with continuous nebulization. The potassium fall, present in all groups, was more pronounced in the groups treated with high doses of albuterol. Only one person (high dose, continuous treatment group) developed hypokalemia of less than 3.0 mmol/L. The high-dose hourly treated group had the highest incidence of side effects, and the standard-dose continuously treated group had the lowest. The standard-dose continuous-treatment regimen had the greatest improvement in FEV1 with the least number of side effects.
Continuous vs intermittent albuterol, at high and low doses, in the treatment of severe acute asthma in adults.
Adult patients suffering from acute asthma presenting to the Emergency Department with an FEV1 of less than 40% of predicted were randomized into four treatment groups. They were treated with nebulized albuterol at a high (7.5 mg) or standard (2.5 mg) dose given either continuously through 1 h, or intermittently every hour, for 2 h. When the FEV1 improvements for the different groups at 2 h were compared, the groups treated with continuous nebulization had the greatest improvement. The improvements (1.07 L for the high-dose group, and 1.02 L for the standard-dose group) were significantly greater than the improvement seen with standard-dose intermittent treatment (0.72 L; p < 0.05). The improvement in FEV1 of the high-dose, hourly treated group was intermediate in magnitude between these (0.09 L). There was no difference in the improvement seen between the two groups treated with continuous nebulization. The potassium fall, present in all groups, was more pronounced in the groups treated with high doses of albuterol. Only one person (high dose, continuous treatment group) developed hypokalemia of less than 3.0 mmol/L. The high-dose hourly treated group had the highest incidence of side effects, and the standard-dose continuously treated group had the lowest. The standard-dose continuous-treatment regimen had the greatest improvement in FEV1 with the least number of side effects.
Options:
A: Continuous inhaled beta-agonists reduce hospital admissions and improve pulmonary function tests, with no significant differences in adverse events compared to intermittent inhaled beta-agonists.
B: Continuous inhaled beta-agonists increase hospital admissions and worsen pulmonary function tests, with more adverse events compared to intermittent inhaled beta-agonists.
C: Continuous inhaled beta-agonists have no effect on hospital admissions or pulmonary function tests, but result in more adverse events compared to intermittent inhaled beta-agonists.
D: Continuous inhaled beta-agonists reduce hospital admissions but have no effect on pulmonary function tests, with fewer adverse events compared to intermittent inhaled beta-agonists. | A |
294 | 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 cyproterone acetate, alone or in combination with ethinyl estradiol, in reducing hair growth in women with hirsutism secondary to ovarian hyperandrogenism? Please answer this question based on the information provided below:
Comparative effects of cyproterone acetate or a long-acting gonadotropin-releasing hormone agonist in polycystic ovarian disease.
A randomized cross-over study was done to compare the therapeutic efficacy of cyproterone acetate (CPA) and a depot preparation of the LHRH superagonist (DTrp6-LHRH) in 10 patients with polycystic ovarian disease (PCO). All patients were treated with both agents (50 mg/day CPA, orally and (3 mg DTrp6-LHRH, im, approximately once a month) for 3 months, the 2 treatment periods being separated by 6 months. Both treatments resulted in marked clinical improvement, with diminished acne and seborrhoea and normalization of ovarian size by ultrasonographic criteria. In response to CPA treatment, basal plasma gonadotropin levels decreased, but the response to a LHRH test was not completely suppressed. Plasma estradiol, estrone, testosterone, and androstenedione levels significantly decreased, but urinary 3 alpha-androstanediol and plasma dehydroepiandrosterone sulfate levels did not change significantly. In contrast to CPA treatment, both basal and stimulated gonadotropin levels were completely suppressed after 3 weeks of treatment with DTrp6-LHRH. After a slight initial evaluation on day 2, plasma estrogen and androgen levels, with the exception of dehydroepiandrosterone sulfate fell into the castrate range urinary 3 alpha-androstanediol excretion decreased significantly. Thus, in patients with PCO, LHRH-A induced more complete gonadotropin inhibition than did CPA. After cessation of either therapy, the disease rapidly recurred.
Comparison of spironolactone-oral contraceptive versus cyproterone acetate-estrogen regimens in the treatment of hirsutism.
OBJECTIVE: To compare the efficacy of two antiandrogens, cyproterone acetate (CPA) and spironolactone, in the treatment of hirsutism.
DESIGN: Prospective randomized single-blinded study.
SETTING: A tertiary hirsutism clinic.
PATIENTS: Forty-two premenopausal patients with hirsutism were selected.
INTERVENTIONS: Subjects were randomized to receive either 100 mg spironolactone and an oral contraceptive (OC) containing 150 microg desogestrel and 30 microg ethinyl E2 or 50 mg CPA daily on days 1 to 10 of the menstrual cycle, which was administered with 35 microg ethinyl E2 daily on days 1 to 21.
MAIN OUTCOME MEASURES: Hirsutism scores were measured according to Ferriman-Gallwey scoring system and side effects were monitored for 9 months of treatment. Blood samples were taken at each visit for assessment of endocrine, biochemical, and hematologic parameters.
RESULTS: Hirsutism scores were decreaded significantly in both groups at the end of 9 months. The percent of change in hirsutism scores in CPA and spironolactone group were as follows: 19.23% +/- 14.77% and 24.48% +/- 14.27% at 3 months; 39.01% +/- 19.77% and 37.46% +/- 16.90% at 6 months; and 51.89% +/- 20.87% and 46.39% +/- 16.10% at 9 months, respectively. There was a trend toward a better response with CPA treatment, which did not achieve significance. None of the patients stopped treatment because of side effects.
CONCLUSION: The present data suggest that both spironolactone and CPA were similarly effective in treatment of hirsutism.
Treatment of hirsutism: comparisons between different antiandrogens with central and peripheral effects.
OBJECTIVE: To compare the clinical and endocrinologic effects of cyproterone acetate (CPA), an antiandrogen with progestational activity; flutamide, a nonsteroidal antiandrogen, and finasteride, an inhibitor of 5alpha-reductase.
DESIGN: Randomized, open, controlled clinical study.
SETTING: Department of Obstetrics and Gynecology, University of Pisa, Pisa, Italy.
PATIENT(S): Forty-five hirsute women were enrolled in the study: 29 were hyperandrogenic and 16 had idiopathic hirsutism. Three women dropped out of the study.
INTERVENTION(S): Women were randomly treated with finasteride (5 mg/d; n = 14), CPA (25 mg plus ethinyl E2 (EE); n = 13), or flutamide (500 mg/d; n = 15) for 1 year.
MAIN OUTCOME MEASURE(S): Hirsutism was assessed using the Ferriman-Gallwey method. Levels of total and free T, androstenedione (A), DHEAS, sex hormone-binding globulin, dihydrotestosterone, and 3alpha-androstanediol glucuronide were evaluated at the beginning of the study and every 3 months.
RESULT(S): Treatment with finasteride, flutamide, and CPA significantly decreased the Ferriman-Gallwey score. The percent decreases in the hirsutism score induced by the different treatments were similar. Treatment with CPA plus EE significantly decreased levels of total and free T, A, dihydrotestosterone, and 3alpha-androstanediol glucuronide. These parameters were unchanged with flutamide therapy. Finasteride significantly increased total T levels but reduced dihydrotestosterone and 3alpha-androstanediol glucuronide concentrations.
CONCLUSION(S): Finasteride, CPA, and flutamide are equally effective in decreasing hirsutism, despite different mechanisms of action.
Comparison of four different treatment regimes in hirsutism related to polycystic ovary syndrome.
Polycystic ovary syndrome is the most common endocrinological problem associated with hirsutism. The objective of this study was to compare four different treatment modalities for hirsutism related to this syndrome. Pelvic ultrasonography was performed on all patients who were referred to our Reproductive Endocrinology Outpatient Clinic because of complaints of hirsutism. After exclusion of hyperandrogenism caused by endocrine abnormalities other than polycystic ovary syndrome, 141 patients were included in the study. Patients were divided into four groups in regard to the drug chosen for treatment. Group 1 (n = 48) received low-dose combined oral contraceptive. Group 2 (n = 65) was treated with cyproterone acetate 100 mg daily for the first 10 days of a 21-day cycle with an oral contraceptive containing 2 mg cyproterone acetate, Group 3 (n = 12) with spironolactone (100-200 mg daily) and Group 4 (n = 16) with ketoconazole (400 mg daily). All patients were followed frequently with respect to side-effects, hirsutism scoring, and lipid and hormonal levels. All four drug regimens were effective in the treatment of hirsutism related to polycystic ovary syndrome, but the most effective seemed to be ketoconazole. The decrement level in hirsutism scoring was the largest in the ketoconazole group, followed by the cyproterone, oral contraceptive and spironolactone groups (34.6 +/- 2.2%, 20.1 +/- 2.7%, 18.1 +/- 2.7% and 12.8 +/- 3.7%, respectively, p < 0.05). Although high-density lipoprotein-cholesterol levels increased in all groups, this increment was smaller in Group 4 than in Groups 1 and 2 (5.1 +/- 2.8%, 34.1 +/- 5.5% and 29.1 +/- 4.9%, respectively, p < 0.05), but not statistically different from that in Group 3 (22.3 +/- 5.9%). The free testosterone levels decreased after treatment in all groups, but the decrement ratios did not differ significantly among groups, although the decrease in free testosterone levels with treatment seemed to be higher in the ketoconazole group than in Groups 1, 2 and 3 (57.0 +/- 2.5%, 22.7 +/- 10.2%, 26.7 +/- 6.5% and 9.5 +/- 19.9%, respectively). In conclusion, ketoconazole seems to be an excellent alternative to more-recognized therapies, but its effect on lipoprotein profile requires further study, because the hyperandrogenism, and the other problems related to hyperandrogenism besides hirsutism, should also be treated.
Comparison of flutamide and cyproterone acetate in the treatment of hirsutism: a randomized controlled trial.
The objective of this study was to compare the efficacy of flutamide and cyproterone acetate in the treatment of hirsutism. Twenty-two women with idiopathic hirsutism were randomized to receive either flutamide or cyproterone acetate. Each patient underwent a complete gynecological examination as well as an endocrinological profile and hematological, hepatic and renal function analyses. Hirsutism scores were determined using a modified Ferriman-Gallwey scoring system. These tests were then repeated at 3 and 9 months of therapy. Eleven patients received 250 mg of flutamide twice daily and 11 patients received 100 mg of cyproterone acetate on days 5-14 of the menstrual cycle. Ferriman-Gallwey scores were decreased significantly in both groups at the end of 9 months. There was a trend towards a better response with flutamide, that did not achieve significance. Another significant difference was the increased sex hormone-binding globulin in both groups. A statistically significant decrease was also observed for the levels of testosterone on both drugs. No subject withdrew from the study due to a side-effect. The data suggest that both flutamide and cyproterone acetate were similarly effective in treatment of hirsutism, and that the pure antiandrogen flutamide is a safe, well-tolerated and effective alternative in treatment.
Comparison of sequential cyproterone acetate/estrogen versus spironolactone/oral contraceptive in the treatment of hirsutism.
The effects of the antiandrogen drugs cyproterone acetate (CPA) and spironolactone on hair growth and androgen levels were compared in a randomized study of 48 hirsute women. Twenty six subjects completed 6 months of therapy with 100 mg/day CPA and 19 subjects completed 6 months of 100 mg/day spironolactone. All except 10 subjects received concomitant estrogen therapy. Measured objectively, total hair diameter fell by 17.1% with spironolactone (P less than 0.001), and by 16.8% with CPA (P less than 0.001). The diameter of the hair medulla fell by 17.8% with spironolactone (P less than 0.01), and by 31.7% with CPA (P less than 0.001). There was no difference between the drugs in their effect on hair diameter. Plasma testosterone levels also fell significantly with both drugs. As a subjective assessment of treatment efficacy, the frequency with which subjects performed cosmetic measures was recorded. This fell by 38% with spironolactone and by 44.7% with CPA (P less than 0.001 both drugs), and again there was no difference between the drugs. Side effects caused cessation of treatment in one subject taking CPA and two subjects taking spironolactone, and milder side effects were noted in two further subjects from each treatment group. We conclude that spironolactone and CPA, in the dosages used in this study, are effective and well tolerated agents for the treatment of hirsutism, and that neither drug demonstrates a particular advantage over the other.
Prospective randomized study comparing the long-acting gonadotropin-releasing hormone agonist triptorelin, flutamide, and cyproterone acetate, used in combination with an oral contraceptive, in the treatment of hirsutism.
OBJECTIVE: To compare triptorelin, cyproterone acetate (CPA), and flutamide, in combination with an oral contraceptive, in the treatment of hirsutism.
DESIGN: Prospective randomized study.
SETTING(S): Tertiary care hospital.
PATIENT(S): Thirty-nine hirsute women with idiopathic or functional ovarian hyperandrogenism.
INTERVENTION(S): Patients were randomly assigned to receive triptorelin (3.75 mg IM every 28 days), CPA (100 mg/d orally on days 1-10 of the menstrual cycle), or flutamide (250 mg orally twice daily). All the patients also received a triphasic oral contraceptive.
MAIN OUTCOME MEASURE(S): Before and after 3 and 9 months of treatment, the Ferriman-Gallwey score, hepatic function, and gonadal and adrenal steroid profiles were evaluated.
RESULTS: Thirty-three patients completed the 9-month study period. The Ferriman-Gallwey score decreased in all the groups. In the patients treated with CPA or flutamide, a decrease in the hirsutism score was noted as soon as after 3 months of treatment. This decrease was more pronounced after 9 months of treatment, especially in the patients who received flutamide, who had lower hirsutism scores compared with the other treatment groups. None of the patients had abnormal liver function test results. There was a mild increase in serum lipid concentrations, mostly in the group treated with triptorelin.
CONCLUSION(S): Triptorelin, CPA, and flutamide are effective drugs for the treatment of hirsutism. Flutamide results in a greater reduction in the hirsutism score, but CPA also offers satisfactory results at a much lower cost. Triptorelin has no advantages over flutamide and CPA, and is the most expensive of the three drugs tested.
Options:
A: Cyproterone acetate alone was found to be significantly more effective than placebo in reducing hair growth.
B: Cyproterone acetate combined with ethinyl estradiol showed a subjective improvement in hirsutism compared to placebo.
C: Cyproterone acetate combined with ethinyl estradiol was less effective than other drug therapies in reducing hair growth.
D: There were no significant differences in clinical outcomes between cyproterone acetate and other drug therapies. | B |
295 | 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 use of intravenous immunoglobulins (IVIG) for the prevention of relapses in relapsing-remitting multiple sclerosis (MS)? Please answer this question based on the information provided below:
Intravenous immunoglobulin treatment in multiple sclerosis. Effect on relapses.
We conducted a double-blind, placebo-controlled study of 40 patients (aged 19 to 60 years) with clinical definite relapsing remitting (RR) MS and brain MRI confirmed. Patients were randomly assigned to receive a loading dose of immunoglobulin IgG (0.4 g/kg/body weight per day for 5 consecutive days), followed by single booster doses (0.4 g/kg/body weight) or placebo once every 2 months for 2 years. The primary outcome measures were change in the yearly exacerbation rate (YER), proportion of exacerbation-free patients, and time until first exacerbation. Neurologic disability, exacerbation severity, and changes in brain MRI lesion score were the secondary outcome measures, all determined at baseline, 1 year, and on completion. Treated patients showed a reduction in YER from 1.85 to 0.75 after 1 year and 0.42 after 2 years versus 1.55 to 1.8 after 1 year and to 1.4 after 2 years in the placebo group (p = 0.0006, overall), reflecting a 38.6% reduction in relapse rate. Six patients in the IVIg group were exacerbation free throughout the 2-year period of the study, whereas none were exacerbation free in the placebo group. The median time to first exacerbation was 233 days in the IVIg group versus 82 days in the placebo group (p = 0.003). Neurologic disability as measured by the Expanded Disability Status Scale (EDSS score) decreased by 0.3 in the IVIg group and increased by 0.15 in the placebo group. Total lesion score evaluated by brain MRI did not show a significant difference between groups. Side effects were minor and occurred in only 19 of 630 (3.0%) infusions administered in both groups. Our results suggest that IVIg may be safe and effective in reducing the frequency of exacerbations in RR-MS.
Randomised placebo-controlled trial of monthly intravenous immunoglobulin therapy in relapsing-remitting multiple sclerosis. Austrian Immunoglobulin in Multiple Sclerosis Study Group.
BACKGROUND: Multiple sclerosis is an autoimmune disorder characterised by the repeated occurrence of demyelinating lesions within the central nervous system. Uncontrolled studies and experimental evidence suggest beneficial effects of repeated administration of intravenous immunoglobulin (IVIg) by immunomodulating mechanisms and induction or remyelination. We aimed to investigate the efficacy of IVIg in a randomised double-blind multicentre study.
METHODS: Patients with relapsing-remitting multiple sclerosis were randomly assigned a monthly dose of IVIg (0.15-0.2 g/kg bodyweight) or placebo. Duration of treatment was 2 years. The primary outcome measures were the effect of treatment on clinical disability-measured by the absolute change in Kurtzke's expanded disability status scale (EDSS) score- and the proportion of patients with improved, stable, or worse clinical disability (> or = 1.0 grade on EDSS score).
FINDINGS: Of the 243 patients screened, 150 met our eligibility criteria and were randomly assigned to IVIg or placebo. Before the start of treatment two patients in the placebo group dropped out, so there were 75 patients in the IVIg group and 73 in the placebo group. Intention-to-treat analysis showed that IVIg treatment had a beneficial effect on the course of clinical disability. The EDSS score decreased in the IVIg-treated patients and increased in the placebo group (-0.23 [95% CI -0.43 to -0.03] vs 0.12 [-0.13 to 0.37], p = 0.008). In the IVIg group, the numbers of patients with improved, stable, or worse clinical disability were 23 (31%), 40 (53%), and 12 (16%) compared with ten (14%), 46 (63%), and 17 (23%) in the placebo group. Side-effects were reported in three (4%) IVIg-treated patients and in four (5%) placebo-group patients, but were not directly linked to study medication.
INTERPRETATION: Monthly IVIg is an effective and well-tolerated treatment for patients with relapsing-remitting multiple sclerosis.
Intravenous immunoglobulin in relapsing-remitting multiple sclerosis: a dose-finding trial.
OBJECTIVE: Several studies have reported a reduction of relapses after the long-term administration of IV immunoglobulin (IVIG) to patients with relapsing-remitting multiple sclerosis (RRMS), but they were mostly small and differed in terms of predefined outcome variables and treatment regimen. We therefore set out to test two different doses of a new formulation of immunoglobulin termed IGIV-C 10% for suppression of both clinical and MRI disease activity as well as safety.
METHODS: One hundred twenty-seven patients with RRMS participated in this multicenter, randomized, double-blind, placebo-controlled trial. Forty-four and 42 patients received treatment with 0.2 and 0.4 g/kg of IGIV-C 10%, and 41 patients received an equal volume of placebo (0.1% albumin) every 4 weeks for 48 weeks. The primary endpoint was the proportion of relapse-free patients. The main secondary endpoint was lesion activity assessed by 6-weekly MRI.
RESULTS: Baseline variables were similar in IVIG- and placebo-treated groups. After 1 year, the proportion of relapse-free patients did not differ statistically according to treatment (IVIG 0.2 g/kg: 57%; IVIG 0.4 g/kg: 60%; placebo: 68%), and there was no difference regarding the cumulative number of unique newly active MRI lesions (median numbers: IVIG 0.2 g/kg: 8.0; IVIG 0.4 g/kg: 5.0; placebo: 7.2) after 48 weeks. There were no significant between-group differences in the rates of adverse events.
CONCLUSION: Although IV immunoglobulin (IVIG) treatment was well tolerated, this study did not substantiate a beneficial effect of IVIG in doses ranging from 0.2 to 0.4 g/kg. This result seriously questions the utility of IVIG for the treatment of relapsing-remitting multiple sclerosis.
Intravenous immunoglobulin in secondary progressive multiple sclerosis: randomised placebo-controlled trial.
BACKGROUND: Several double-blind placebo-controlled trials of relapsing-remitting multiple sclerosis have shown beneficial effects of intravenous immunoglobulin (IVIG) on relapse rate and disability. The European Study on Intravenous Immunoglobulin in Multiple Sclerosis set out to test IVIG in the secondary progressive phase of the disease.
METHODS: 318 patients with clinically definite secondary progressive multiple sclerosis (mean age 44 years [SD 7]) were randomly assigned IVIG 1 g/kg per month (n=159) or an equivalent volume of placebo (albumin 0.1%; n=159) for 27 months. After baseline investigation, clinical assessments were made every 3 months and MRI was repeated after 12 months and 24 months. The primary outcome was confirmed worsening of disability as defined by the time to first confirmed progression on the expanded disability status scale (EDSS). Analyses were by intention to treat.
FINDINGS: 19 patients in the IVIG group and 39 in the placebo group terminated study treatment prematurely but were included in the analyses. IVIG treatment had no beneficial effect on time to confirmed EDSS progression (hazard ratio 1.11 [95% CI 0.80-1.53] for IVIG versus placebo). The annual relapse rate was 0.46 in both groups. No significant differences between the treatment groups were found in any of the other clinical outcome measures or in the change of T2-lesion load over time. The treatment was generally well tolerated, although deep venous thrombosis, pulmonary embolism, or both occurred in seven patients with risk factors for thromboembolism (IVIG six, placebo one).
INTERPRETATION: Treatment with IVIG in this study did not show any clinical benefit and therefore cannot be recommended for patients with secondary progressive multiple sclerosis.
No difference in efficacy of two different doses of intravenous immunoglobulins in MS: clinical and MRI assessment.
We performed a double-blind, placebo-controlled study to evaluate the efficacy of low and high dose of intravenous immunoglobulins (IVIG) in relapsing/remitting (RR) multiple sclerosis (MS). Patients (n = 49) with clinical definite RR MS were randomly allocated to three groups and treated with 0.2 g/kg (n = 17) or 0.4 g/kg (n = 15) once a month of IVIG and placebo (n = 17) for 12 months. Clinical data were assessed monthly and magnetic resonance imaging (MRI) was performed every 3 months during the study period. Annual relapse rate (ARR) and change of the mean Expanded Disability Status Scale (EDSS) and Neurological Rating Scale Score (NRSS) from baseline to study conclusion were used as the clinical end-points. For MRI activity total lesion volume on T2-weighted image (T2WI), new lesions and gadolinium (Gd)-enhanced lesions on T1WI were analysed. ARR in both IVIG groups (0.88 for 0.2 g/kg and 0.86 for 0.4 g/kg) was reduced compared with placebo (1.24) during treatment period. Neurological disability measured with EDSS decreased slightly in both the IVIG groups (0.029 and 0.066, respectively) and increased by 0.29 in placebo (P = 0.0117). The neurologic impairment measured by NRSS showed similar trend. The total lesion volume on T2WI increased by 13.56% in placebo whereas in the 0.4 g/kg IVIG group decreased by -3.95% and in the 0.2 g/kg IVIG group increased by 3.6%. The cumulative numbers of Gd-enhancing lesions and new T2WI lesions in the IVIG groups were reduced in comparison with the placebo group. Our findings suggest that the dose 0.2 g/kg of IVIG is equally effective as 0.4 g/kg in reducing MS activity.
Intravenous immunoglobulin in primary and secondary chronic progressive multiple sclerosis: a randomized placebo controlled multicentre study.
In patients with relapsing-remitting multiple sclerosis (MS), IVIG was shown to reduce the relapse rate and progression of disability. In patients with chronic progressive MS, a beneficial effect of IVIG was not documented in placebo controlled studies. This trial investigated the influence of IVIG in primary (PPMS) and secondary (SPMS) chronic progressive MS. Two-hundred and thirty-one patients stratified for PPMS (n=34) and SPMS (n=197) were randomly assigned to IVIG 0.4 g/kg per month or to placebo for 24 months. Primary endpoints were 1) the time to sustained progression of disease identified as worsening of the expanded disability status scale (EDSS) sustained for 3 months, and 2) the improvement of neurological functions defined by a patient's best EDSS score. Secondary endpoints were the proportion of patients with sustained progression, the relapse rate, the assessment of fine motor skills, visual evoked potentials, contrast sensitivity, depression and quality of life. Analysis of the intention-to-treat (ITT) population of combined PPMS and SPMS patients showed that the mean time to sustained progression was 74 weeks in the IVIG compared with 62 weeks in the placebo group (P=0.0406). When PPMS and SPMS patients were analysed separately, the time to sustained progression was also longer in the IVIG group, but the difference was not significant. There was no IVIG-mediated improvement in neurological functions. In the combined per protocol (PP) treated patients, IVIG treatment prolonged time to sustained progression by 13 weeks (P=0.0396). PPMS patients, but not SPMS patients showed a slight favourable IVIG effect on the best EDSS score. In the combined ITT population there were less patients with sustained progression in the IVIG than in the placebo group (P=0.028). The difference was significant in PPMS (P=0.016), but not in SPMS patients. In the combined PP population, there was a trend for a favorable IVIG effect on the rates of patients with sustained progression. In patients with PPMS, this IVIG effect reached significance (P=0.036). Other secondary endpoints did not show significant differences between treatment groups. Eighteen patients with PPMS and 102 patients with SPMS withdrew from the study for various reasons. Treatment was generally well tolerated. It was concluded that monthly IVIG infusion could delay progression of disease in patients with PPMS, and that there was a trend in favour of IVIG treatment in patients with SPMS.
Options:
A: IVIG is conclusively proven to prevent relapses and slow disease progression in relapsing-remitting MS.
B: IVIG shows some evidence of reducing relapse rates and increasing time to first relapse, but further studies are needed to confirm its effectiveness and impact on disease progression.
C: IVIG has no effect on relapse rates or disease progression in relapsing-remitting MS.
D: IVIG is associated with a high risk of adverse events and is not recommended for use in relapsing-remitting MS. | B |
296 | 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 harms of selenium supplementation in preterm or very low birthweight infants? Please answer this question based on the information provided below:
Randomised clinical trial of parenteral selenium supplementation in preterm infants.
AIM: To determine whether selenium supplementation of parenteral nutrition with 3 micrograms/kg/day of selenious acid is safe and effective in improving the selenium status of preterm infants.
METHODS: Thirty eight preterm infants with mean (SEM) birthweight of 1171 (38) g and gestational age 29 (0.3) weeks were randomly allocated to a non-supplemented (PN-selenium, n = 19) or supplemented (PN+selenium, n = 19) group. The study began at 2.8 (0.2) (range 1-5) days of age. Term breastfed (n = 23) and formula fed (n = 8) infants were used as a reference group.
RESULTS: Initially there was no difference between the preterm groups in plasma or erythrocyte selenium or glutathione peroxidase activity. Plasma selenium declined by a mean (SEM) of -13.3 (3.2) micrograms/l from 28 (4) to 16 (3) micrograms/l over the first three weeks in the PN-selenium group, but there was no fall in the supplemented infants and no net change in either group over six weeks. Over six weeks, there was a net decline in erythrocyte selenium of -106 (27) ng/g haemoglobin in the PN-selenium group, but no change in the PN+selenium group, such that at week 6 erythrocyte selenium was lower in the PN-selenium group (401 (17) ng/g haemoglobin) than the PN+selenium group (493 (25) ng/g haemoglobin). Urinary selenium was substantially higher in the PN+selenium group at each week. Initially term and preterm plasma selenium concentrations were similar, but they increased in term breastfed infants (+17 (2) micrograms/l), with both groups of preterm infants having lower plasma selenium concentrations at week 6 compared with term breastfed infants (PN-selenium 22 (3) micrograms/l; PN+selenium 23 (4) micrograms/l and term breastfed 49 (2) micrograms/l).
CONCLUSIONS: Selenium supplementation of PN at 3 g/kg/day prevented depletion in newborns, but was inadequate to achieve selenium concentrations equivalent to those of breastfed term infants. Whether higher doses are more effective remains to be determined, particularly in light of the high urinary selenium secretion in supplemented infants. Selenium supplementation of both parenteral nutrition and formulas is recommended, but the optimal form and dose remain unclear.
The effect of selenium supplementation on outcome in very low birth weight infants: a randomized controlled trial. The New Zealand Neonatal Study Group.
BACKGROUND: Low selenium (SE) status has been documented in preterm infants and has been suggested to be a risk factor for chronic lung disease.
METHODS: A total of 534 infants with birth weight <1500 g were enrolled in 8 New Zealand centers in a double-blind placebo-controlled randomized trial of SE supplementation from week 1 of life until 36 weeks' postmenstrual age or discharge home. Supplemented infants received 7 microg/kg/d of SE when fed parenterally and 5 microg/kg/d when fed orally. Plasma SE and glutathione peroxidase concentrations were measured in mothers after delivery and in infants before randomization and at 28 days and 36 weeks' postmenstrual age. Primary outcome measures were oxygen dependency at 28 days and total days oxygen dependency.
RESULTS: No significant differences were seen between the groups with respect to primary or secondary outcome measures, with the exception that fewer supplemented infants had an episode of sepsis after the first week of life (P <.038). Mean plasma SE concentrations were 0.33 micromol/L before randomization in both groups and at 28 days had risen in the supplemented group (0.56 micromol/L) but fallen in the control group (0.29 micromol/L) (P <.0001). There was no association between outcome measures and SE concentrations at 28 days or 36 weeks' postmenstrual age. However, lower maternal and infant prerandomization SE concentrations were associated with increased respiratory morbidity.
CONCLUSIONS: Postnatal SE supplementation in very low birth weight infants did not improve neonatal outcome. Further investigation of SE supplementation of mothers from the second half of pregnancy is warranted.
The effect of selenium supplementation on outcome in very low birth weight infants: a randomized controlled trial. The New Zealand Neonatal Study Group.
BACKGROUND: Low selenium (SE) status has been documented in preterm infants and has been suggested to be a risk factor for chronic lung disease.
METHODS: A total of 534 infants with birth weight <1500 g were enrolled in 8 New Zealand centers in a double-blind placebo-controlled randomized trial of SE supplementation from week 1 of life until 36 weeks' postmenstrual age or discharge home. Supplemented infants received 7 microg/kg/d of SE when fed parenterally and 5 microg/kg/d when fed orally. Plasma SE and glutathione peroxidase concentrations were measured in mothers after delivery and in infants before randomization and at 28 days and 36 weeks' postmenstrual age. Primary outcome measures were oxygen dependency at 28 days and total days oxygen dependency.
RESULTS: No significant differences were seen between the groups with respect to primary or secondary outcome measures, with the exception that fewer supplemented infants had an episode of sepsis after the first week of life (P <.038). Mean plasma SE concentrations were 0.33 micromol/L before randomization in both groups and at 28 days had risen in the supplemented group (0.56 micromol/L) but fallen in the control group (0.29 micromol/L) (P <.0001). There was no association between outcome measures and SE concentrations at 28 days or 36 weeks' postmenstrual age. However, lower maternal and infant prerandomization SE concentrations were associated with increased respiratory morbidity.
CONCLUSIONS: Postnatal SE supplementation in very low birth weight infants did not improve neonatal outcome. Further investigation of SE supplementation of mothers from the second half of pregnancy is warranted.
Selenium supplementation in low-birthweight premature infants: relationship to trace metals and antioxidant enzymes.
We attempted to study the effect of selenium supplementation upon trace metal metabolism in low-birthweight infants less than 1000 g birthweight. Serum levels of the trace metals copper, zinc, and selenium; and white blood cell glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were measured in conjunction with the trace metals when parenteral nutrition (TPN) was begun (sample A), at the initiation of enteral nutrition (sample B), and when TPN was discontinued (sample C). Two randomly selected groups of infants were evaluated: group S received selenium supplementation (1.34 micrograms/kg per d) in their parenteral nutrition solutions; group C was a control which did not receive selenium supplementation. Selenium levels declined to equally low levels in both groups by sample C, but were significantly higher in group S at sample B. GSH-Px activities demonstrated a significant increase at sample B in group S and then tended to decrease. In group C, GSH-Px tended to increase, then decreased significantly by sample C. Both groups received 20 micrograms/kg per d of copper in TPN, however, serum copper declined significantly at sample B in group S whereas there were no significant changes in group C. There were no significant changes in zinc and SOD levels. There were no significant differences between groups in clinical characteristics or outcome. This study suggests that a dose of supplemental selenium of 1.34 micrograms/kg per d in TPN is inadequate for low-birthweight premature infants. Selenium supplementation may also affect copper metabolism.
Options:
A: Selenium supplementation significantly reduces the incidence of sepsis but does not improve survival, reduce neonatal chronic lung disease, or retinopathy of prematurity.
B: Selenium supplementation significantly improves survival and reduces the incidence of neonatal chronic lung disease and retinopathy of prematurity.
C: Selenium supplementation has no significant impact on the incidence of sepsis, survival, neonatal chronic lung disease, or retinopathy of prematurity.
D: Selenium supplementation significantly reduces the incidence of sepsis and improves survival, but does not reduce neonatal chronic lung disease or retinopathy of prematurity. | A |
297 | 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 steroid therapy in reducing morbidity and mortality in newborn infants with meconium aspiration syndrome? Please answer this question based on the information provided below:
The role of pulmonary inflammation in the development of pulmonary hypertension in newborn with meconium aspiration syndrome (MAS).
1. There was no clear correlation between the tracheal aspirate cytokines and the elevation of pulmonary arterial pressure in newborn piglets with MAS. The use of dexamethasone significantly suppressed tracheal aspirate cytokines but did not significantly alter pulmonary arterial pressure. Dexamethasone significantly increased the cardiac stroke volume and blood pressure. 2. Early dexamethasone therapy (< 12 hrs) for one week in infants with MAS significantly improved pulmonary ventilation and facilitated weaning from mechanical ventilation. 3. The mechanisms for the improvement in cardiopulmonary status following early dexamethasone therapy in MAS remain unclear. An overall improvement in cardiac hemodynamics, along with a significant decrease in lung inflammation may be responsible for the improvement.
Hydrocortisone therapy in meconium aspiration syndrome: a controlled study.
To evaluate the efficacy of glucocorticoids in the treatment of infants with meconium aspiration syndrome, a double-blind study using hydrocortisone or a lactose placebo was undertaken. Thirty-five infants were included in the study. No significant differences in arterial Po2, Pco2, pH, A-aDo2 gradients, in requirement for assisted ventilation, or in survival were domonstrated between the groups. In control infants, a significant decrease (p less than 0.01) in respiratory distress score was found at 48 to 72 hours of age; in treated infants, it was seen only after 72 hours. The infants in the treated group took a significantly longer (p less than 0.01) period of time to wean to room air than those in the control group (68.9 +/- 9.6 hours vs 36.6 +/- 6.9 hours). On the basis of these observations, hydrocortisone is not recommended for treatment of MAS.
Options:
A: Steroid therapy significantly reduced mortality and morbidity.
B: Steroid therapy significantly reduced the duration of hospital stay.
C: Steroid therapy significantly increased the duration of oxygen therapy.
D: Steroid therapy significantly reduced the incidence of air leak. | C |
298 | 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 intranasal corticosteroids (INCS) on asthma outcomes in people with coexisting asthma and rhinitis? Please answer this question based on the information provided below:
Investigation of the tendency to wheeze in pollen sensitive patients.
We have undertaken a double blind placebo controlled study of the effect of nasal beclomethasone on the tendency to wheeze in 20 unselected hay fever sufferers, half with a history of previous seasonal wheezing. We found no difference between either bronchial hyperresponsiveness, as measured by methacholine challenge, home-monitored PEFR, nor recorded wheeze nor cough between treated and placebo groups although the numbers were small. All were allowed the antihistamine cetirizine hydrochloride 10 mg daily. Eighteen out of the 19 patients had either bronchial hyperresponsiveness (PD20 methacholine < 8 mumol or a > 2 doubling dose change in their PD20 during the pollen season). We have shown a significant positive correlation between a hay fever score (HFS) (created by taking the sum of the home scored; nasal discharge, nasal blockage, eye irritation, sneeze and antihistamine use) and peak seasonal specific IgE to mixed grass pollen (Spearman correlation coefficient 0.5 P < 0.02). There was also a positive correlation between the rise in specific IgE from pre to peak season and the HFS, correlation coefficient 0.6 P = 0.03).
Different effects of nasal and bronchial glucocorticosteroid administration on bronchial hyperresponsiveness in patients with allergic rhinitis.
Disorders of the upper respiratory tract, particularly allergic rhinitis, are commonly associated with bronchial hyperresponsiveness. The latter may be due to postnasal drip or to mediator or chemotactic factors into the lower airways that either directly alter airway reactivity or cause airway inflammation. The aim of this study was to compare the effect of an identical dose of nasal or bronchial corticosteroid administration on bronchial hyperresponsiveness in patients with allergic rhinitis. Eleven patients were studied. All of them were judged atopic on the basis of positive skin tests to common allergens. During control, spirometry, flow-volume curves, and specific airway conductance (SGaw) were measured. Bronchial challenges were then performed with increasing concentrations of carbachol, and dose-response curves were constructed. The concentration of carbachol that decreased SGaw by 35% from baseline (PD35) was determined by interpolating from the dose-response curve. Control measurements were repeated at 1-wk intervals to ensure that PD35 was stable in all the patients. Then the patients received for 2 wk, in a double-blind randomized crossover fashion, a topical administration of either an aerosol of 400 micrograms of beclamethasone dipropionate (B) into the nose (100 micrograms four times per day) or into the bronchi. During each trial period, identical sprays of placebo were used, the latter being administered into the nose when B was administered into the bronchi and vice versa. Measurements were then performed after 2 wk of intranasal administration and after 2 wk of intrabronchial administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Nasal beclomethasone prevents the seasonal increase in bronchial responsiveness in patients with allergic rhinitis and asthma.
Experimental studies have demonstrated that induction of a nasal allergic reaction can lead to an increase in bronchial responsiveness (BR). To assess the clinical relevance of these experimental changes to chronic asthma, we sought to determine the effect of nasal beclomethasone dipropionate (Bdp) on BR in patients with seasonal allergic rhinitis and asthma. Eighteen subjects with histories of seasonal allergic rhinitis and asthma during the fall pollen season with positive skin tests to short ragweed and bronchial hyperresponsiveness to inhaled methacholine were assigned to receive either nasal Bdp (336 micrograms/day) or placebo for the entire ragweed season. Patients recorded daily nasal and chest symptoms, nasal blockage index, oral peak expiratory flow rates, and supplemental medication use. BR to methacholine was measured during the baseline period and 6 weeks into the ragweed season. Although the Bdp group did have a significant improvement in nasal blockage index, there was no improvement in daily asthma symptom scores, oral peak expiratory flow, or asthma medication use. However, subjects treated with Bdp were protected from the increase in BR seen in the placebo group (geometric mean PC20 placebo group: baseline = 0.70, week 6 = 0.29; Bdp group: baseline = 0.80, week 6 = 0.93; intergroup difference, p = 0.022). We conclude that nasal corticosteroid therapy can prevent the increase in BR associated with seasonal pollen exposure in patients with allergic rhinitis and asthma.
Once daily intranasal fluticasone propionate (200 micrograms) reduces nasal symptoms and inflammation but also attenuates the increase in bronchial responsiveness during the pollen season in allergic rhinitis.
BACKGROUND: Fluticasone propionate aqueous nasal spray, a new topical corticosteroid, has been proved to be an effective treatment for seasonal allergic rhinitis.
OBJECTIVES: We studied the effect of fluticasone propionate on nasal symptoms, circulating eosinophils, and nasal inflammation in patients with seasonal allergic rhinitis after high-load pollen exposure. Moreover, we examined its efficacy in preventing the increase in bronchial responsiveness to methacholine (PD20) during the pollen season.
METHODS: We conducted a double-blind, placebo-controlled, parallel-group study in patients who had a history of allergic rhinitis in response to pollens of grass and Parietaria species and were living in northern Italy. After a run-in period of 2 weeks, 24 patients were treated with fluticasone propionate (200 micrograms, once daily), and 26 patients received matched placebo for 6 weeks, starting from the beginning of the pollen season. Assessment of efficacy was based on scores of daily nasal symptoms. Nasal lavage was performed at the end of the season, and differential cell count was expressed as percent of total cells. PD20 methacholine was measured at the beginning and end of the season and after the season had ended.
RESULTS: Fluticasone propionate significantly reduced nasal obstruction, itching, and rhinorrhea. Eosinophils in blood (p < 0.01) and nasal lavage (p < 0.001) were also reduced. Moreover, fluticasone significantly attenuated the decrease in mean PD20 methacholine (from 1.95 to 0.89 mg) compared with placebo (from 1.38 to 0.37 mg: p < 0.01). After the season, no difference in PD20 methacholine was found between treatment groups.
CONCLUSIONS: The results of this study indicate that fluticasone propionate is effective in decreasing nasal symptoms and eosinophil inflammation in patients with seasonal allergic rhinitis after high-load pollen exposure. Our results also demonstrate that treatment with fluticasone propionate partially prevents the increase in bronchial responsiveness provoked by the inhalation of seasonal pollens in allergic rhinitis.
Effect of an intranasally administered corticosteroid (budesonide) on nasal obstruction, mouth breathing, and asthma.
The effect of intranasally administered corticosteroid (budesonide) on nasal symptoms, mode of respiration (nasal versus mouth breathing), and asthma was investigated in 37 asthmatic children who were mouth breathers because of chronic nasal obstruction. After a 2-wk run-in period, the children were allocated randomly to 4 wk of intranasal therapy with either budesonide (400 micrograms/day) or placebo spray. A double-blind, parallel design was used. Diaries for peak expiratory flow, asthma, and rhinitis symptom scores and degree of mouth breathing were recorded at home. Nasal eosinophilia, nasal airway resistance at a flow of 0.2 L/s (NAR0.2), and lung function at rest and after exercise challenge were assessed at the clinic immediately before and at end of the 4-wk treatment. Budesonide, when compared with placebo, significantly decreased nasal obstruction (p less than 0.05), secretion (p less than 0.01), and eosinophilia (p less than 0.02), as well as NAR0.2 (p less than 0.05) and mouth breathing (p less than 0.01). The improvement in nasal obstruction correlated closely to the changes in mouth breathing (r = 0.80, n = 17, p less than 0.001). Furthermore, intranasally administered budesonide resulted in less exercise-induced asthma (EIA) (p less than 0.02) and decreased cough and asthma severity significantly. Pulmonary mechanics were only marginally improved. The present study showed that intranasally administered budesonide is effective in the treatment of perennial allergic rhinitis. An attenuation of EIA and a tendency to less asthma after budesonide therapy suggest a decrease in bronchial reactivity, but the results gave no clear evidence of an association between nasal airway function and asthma.
Simultaneous treatment of rhinitis and asthma by nasal inhalation of corticosteroid from a spacer.
Nasal inhalation of the glucocorticoid budesonide from a spacer for the treatment of patients with pollen rhinitis and asthma.
Glucocorticoid sprays are increasingly used for the treatment of allergic rhinitis and asthma. This therapy is highly effective, and side effects are few and mild. It was the aim of the present study to evaluate a physiological nasal inhalation technique, which results in airway deposition of the steroid molecule similar to that of inhaled allergen particles. Thirty adults with grass pollen-induced rhinitis and asthma inhaled the steroid molecule budesonide through the nose from a pressurized aerosol attached to a spacer device. Compared with inhalation of placebo, the treatment resulted in a significant reduction of nasal symptoms (P = 0.005), of bronchial symptoms (P = 0.005), but not of eye symptoms. In addition, nasal peak inspiratory flow (P = 0.0003) and oral peak expiratory flow (P = 0.02) increased. There was no difference between budesonide and placebo with regard to local side effects, such as nose bleeding, hoarseness, and irritation in mouth and throat. It is concluded that nasal inhalation of a steroid from a spacer offers effective therapy of pollen rhinitis and asthma without significant local side effects. This therapeutic modality may have advantages over the ordinarily used nasal and bronchial spray treatment in patients with both rhinitis and asthma, especially when conventional spray therapy is associated with local side effects.
Nasal inhalation of budesonide from a spacer in children with perennial rhinitis and asthma.
The standard treatment of allergic rhinitis and asthma consists of topical corticosteroids administered intranasally and inhaled through the mouth. Although this therapy is highly effective, and side-effects are few and mild, it may be possible further to improve the therapeutic index and patient compliance with the treatment. In the present study, we evaluated a nasal inhalation system used for the simultaneous treatment of rhinitis and asthma. In principle, it results in an airway deposition of the corticosteroid similar to that of inhaled allergens. Twenty-four children with perennial rhinitis and asthma inhaled budesonide through the nose from a pressurized aerosol, attached to a spacer device, in a double-blind, placebo-controlled, crossover study. Compared with placebo, budesonide treatment resulted in a significant reduction of nasal symptoms (P<0.01) and of asthma symptoms (P<0.05), and in an increase of nasal peak inspiratory flow (P < 0.001) and of oral peak expiratory flow (P=0.01). There were no differences between budesonide and placebo in local side-effects, such as dry nose, nosebleed, and hoarseness. We conclude that nasal inhalation of a corticosteroid from a spacer offers a simple and effective treatment for both rhinitis and asthma in children, but it is an open question whether the nasal inhalation system can improve the ratio of antirhinitis/antiasthma effects to side-effects.
Effect of intranasal azelastine and beclomethasone dipropionate on nasal symptoms, nasal cytology, and bronchial responsiveness to methacholine in allergic rhinitis in response to grass pollens.
BACKGROUND: We compared the effect of nasal azelastine (0.56 mg/day), nasal beclomethasone dipropionate (BDP, 200 micrograms/day) and matched placebo on seasonal symptoms, nasal cytology, and the increase in bronchial responsiveness occurring during pollen season in a group of subjects with history of allergic rhinitis to grass pollens only.
METHODS: The study was completed by nine subjects in the azelastine group, 13 subjects in the BDP group, and 13 subjects in the placebo group. Treatments were randomly administered for 6 weeks. Each subject recorded daily nasal, eye and chest symptoms and additional treatment requirement for the entire pollen season. Each subject performed nasal lavage 4 weeks into the pollen season. Bronchial responsiveness to methacholine was measured before and 4 weeks into the pollen season. Response was expressed as provocative dose causing a 20% fall in forced expiratory volume in 1 second in micromoles.
RESULTS: Azelastine-treated subjects had significantly fewer nasal symptoms during week 4 (p < 0.05), and BDP-treated subjects had fewer nasal symptoms during week 4 (p < 0.05) and week 5 (p < 0.05) compared with subjects given placebo. Both treatments significantly reduced the need for additional medications. BDP, but not azelastine, treatment significantly reduced the percent of eosinophils recovered in nasal lavage (p < 0.05). Neither azelastine nor BDP protected against the increase in bronchial responsiveness to methacholine occurring during the pollen season.
CONCLUSION: We demonstrated that both azelastine and BDP are effective treatments for nasal symptoms of seasonal allergic rhinitis after 4 weeks of therapy. However, we were not able to demonstrate an antiinflammatory activity of nasally administered azelastine. Nasal therapy with azelastine and BDP did not block the increase in bronchial responsiveness to methacholine caused by seasonal allergen exposure.
A double-blinded, comparative study of the effects of short preseason specific immunotherapy and topical steroids in patients with allergic rhinoconjunctivitis and asthma.
BACKGROUND: Both specific immunotherapy (SIT) and nasal steroid (NS) have been shown to effectively reduce symptoms of allergic rhinitis. Although a number of investigators have convincingly shown anti-inflammatory effects of both treatments in separate studies, few comparative studies have been performed.
OBJECTIVE: The purpose of this study was to compare the effects of preseason SIT with a standardized allergen extract and NS in seasonal allergic disease (rhinoconjunctivitis and asthma).
METHODS: We examined 41 patients allergic to birch pollen, 21 with rhinoconjunctivitis and 20 with both rhinoconjunctivitis and asthma; they were treated in a randomized, double-blinded comparative study with birch SIT and NS (budesonide 400 microg daily). Bronchial hyperresponsiveness was measured before and during the season. Changes in eosinophil number, eosinophil cationic protein, and eosinophil chemotactic activity (ECA) in peripheral blood were investigated.
RESULTS: Symptoms of rhinoconjunctivitis increased significantly less in the NS-treated patients than in the SIT-treated patients during the final 2 weeks of the season (P = .03 and P = .04, respectively). Seasonal peak expiratory flow values decreased significantly only in the NS-treated patients (P = .01). In the NS-treated patients, bronchial hyperresponsiveness increased significantly during the season (P = .0001); however, SIT treatment prevented seasonal PC(20) increase in the asthmatic patients. Measurement of blood eosinophils, eosinophil cationic protein, and eosinophil chemotactic activity demonstrated significant seasonal increase only in the NS-treated asthmatic patients.
CONCLUSION: Treatment with NS was more effective than short-course preseason SIT in reducing symptoms of rhinoconjunctivitis; however, the 2 therapies were equivalent in terms of the need for rescue medication. SIT prevented seasonal increase in bronchial hyperresponsiveness, eosinophil number, eosinophil cationic protein, and eosinophil chemotactic activity only in asthmatic patients. The mechanisms underlying bronchial hyperresponsiveness developing during allergen exposure in rhinitis might be different from those operating in asthma.
Effects of topical nasal treatment on asthma symptoms.
During the ragweed season of 1984 we studied 120 patients with hay fever; 58 had a history of asthma during the ragweed season the year before. They were divided into four treatment groups to receive nasal sprays of placebo, cromolyn sodium, flunisolide, or beclomethasone. In controlling hay fever symptoms all medications were superior to placebo; the glucocorticoids were more effective than was cromolyn sodium. Chest symptoms in the 58 patients with a history of asthma were also relieved by the topical nasal treatment. Various explanations for the beneficial effect of topical nasal treatment in asthma symptoms are conceivable. We consider the most likely to be improvement of nasal airway function. With restoration of the filtering action of the nose, less allergen would penetrate to the intrathoracic airways because of reduction in mouth breathing.
Efficacy of beclomethasone nasal solution, flunisolide, and cromolyn in relieving symptoms of ragweed allergy.
Although three effective topical treatments for allergic rhinitis are available, little information to assist the clinician in choosing among them has been reported. Therefore, we conducted a randomized clinical trial to compare beclomethasone nasal solution, flunisolide, and cromolyn with placebo in 120 patients with hay fever during the ragweed season of 1984. We found that all three agents were superior to placebo (P less than 0.001) and that the glucocorticoids were more effective than cromolyn (P less than 0.001). Surprisingly, we also found that these intranasal treatments considerably reduced the symptoms of seasonal asthma. Further study of this therapeutic advantage is needed.
Influence of intranasal steroids during the grass pollen season on bronchial responsiveness in children and young adults with asthma and hay fever.
BACKGROUND: It has been reported that intranasal corticosteroids can influence bronchial hyperresponsiveness (BHR) in asthmatic subjects with seasonal rhinitis. The purpose of the present study was to evaluate the effect of intranasal fluticasone propionate and beclomethasone dipropionate on BHR and bronchial calibre (forced expiratory volume in one second, FEV(1)) in children and young adults with seasonal rhinitis and mild asthma during two consecutive grass pollen seasons.
METHODS: In the first pollen season 25 patients aged 8-28 years were included in a double blind, placebo controlled study. The active treatment group used fluticasone aqueous spray 200 microgram once daily. In the second pollen season 72 patients aged 8-28 years participated in a double blind, placebo controlled study of a similar design to that of the previous year except that an additional treatment group of patients using beclomethasone 200 microg twice daily was included. FEV(1) was measured before and after three and six weeks of treatment; BHR to methacholine (PD(20)) was measured before and after six weeks of treatment.
RESULTS: In the first season the mean (SD) logPD(20) of the patients decreased significantly both in the fluticasone group (from 2.43 (0.8) microgram to 1.86 (0.85) microgram) and in the placebo group (from 2.41 (0.42) microgram to 1.87 (0.78) microgram) without any intergroup difference in the change in logPD(20). In the second pollen season the mean logPD(20) in the fluticasone, beclomethasone, and placebo groups did not change significantly.
CONCLUSIONS: Intranasal steroids did not influence BHR during two grass pollen seasons in children and young adults with seasonal rhinitis and mild asthma.
Influence of intranasal steroids during the grass pollen season on bronchial responsiveness in children and young adults with asthma and hay fever.
BACKGROUND: It has been reported that intranasal corticosteroids can influence bronchial hyperresponsiveness (BHR) in asthmatic subjects with seasonal rhinitis. The purpose of the present study was to evaluate the effect of intranasal fluticasone propionate and beclomethasone dipropionate on BHR and bronchial calibre (forced expiratory volume in one second, FEV(1)) in children and young adults with seasonal rhinitis and mild asthma during two consecutive grass pollen seasons.
METHODS: In the first pollen season 25 patients aged 8-28 years were included in a double blind, placebo controlled study. The active treatment group used fluticasone aqueous spray 200 microgram once daily. In the second pollen season 72 patients aged 8-28 years participated in a double blind, placebo controlled study of a similar design to that of the previous year except that an additional treatment group of patients using beclomethasone 200 microg twice daily was included. FEV(1) was measured before and after three and six weeks of treatment; BHR to methacholine (PD(20)) was measured before and after six weeks of treatment.
RESULTS: In the first season the mean (SD) logPD(20) of the patients decreased significantly both in the fluticasone group (from 2.43 (0.8) microgram to 1.86 (0.85) microgram) and in the placebo group (from 2.41 (0.42) microgram to 1.87 (0.78) microgram) without any intergroup difference in the change in logPD(20). In the second pollen season the mean logPD(20) in the fluticasone, beclomethasone, and placebo groups did not change significantly.
CONCLUSIONS: Intranasal steroids did not influence BHR during two grass pollen seasons in children and young adults with seasonal rhinitis and mild asthma.
Influence of intranasal steroids during the grass pollen season on bronchial responsiveness in children and young adults with asthma and hay fever.
BACKGROUND: It has been reported that intranasal corticosteroids can influence bronchial hyperresponsiveness (BHR) in asthmatic subjects with seasonal rhinitis. The purpose of the present study was to evaluate the effect of intranasal fluticasone propionate and beclomethasone dipropionate on BHR and bronchial calibre (forced expiratory volume in one second, FEV(1)) in children and young adults with seasonal rhinitis and mild asthma during two consecutive grass pollen seasons.
METHODS: In the first pollen season 25 patients aged 8-28 years were included in a double blind, placebo controlled study. The active treatment group used fluticasone aqueous spray 200 microgram once daily. In the second pollen season 72 patients aged 8-28 years participated in a double blind, placebo controlled study of a similar design to that of the previous year except that an additional treatment group of patients using beclomethasone 200 microg twice daily was included. FEV(1) was measured before and after three and six weeks of treatment; BHR to methacholine (PD(20)) was measured before and after six weeks of treatment.
RESULTS: In the first season the mean (SD) logPD(20) of the patients decreased significantly both in the fluticasone group (from 2.43 (0.8) microgram to 1.86 (0.85) microgram) and in the placebo group (from 2.41 (0.42) microgram to 1.87 (0.78) microgram) without any intergroup difference in the change in logPD(20). In the second pollen season the mean logPD(20) in the fluticasone, beclomethasone, and placebo groups did not change significantly.
CONCLUSIONS: Intranasal steroids did not influence BHR during two grass pollen seasons in children and young adults with seasonal rhinitis and mild asthma.
Treatment of allergic rhinitis with intranasal corticosteroids in patients with mild asthma: effect on lower airway responsiveness.
The effect of treatment of allergic rhinitis with intranasal corticosteroids on lower airway responsiveness was assessed in a randomized, double-blind, placebo-controlled, crossover study. Twenty-one young patients with perennial allergic rhinitis and asthma, with documented lower airway hyperresponsiveness (PC20 methacholine < 8 mg/ml), were treated with intranasal aqueous beclomethasone dipropionate and placebo, each given for 4 weeks. Patients recorded rhinitis and asthma symptom scores and monitored peak expiratory flow rates every morning and evening. Patients recorded global assessment of rhinitis and global asthma symptom scores at the beginning and end of each treatment. PC20 methacholine was performed at baseline and at the end of each treatment period. Intranasal beclomethasone dipropionate significantly reduced global rhinitis symptom scores (p = 0.05) after 4 weeks of treatment. Global asthma scores did not change significantly (p = 0.2). Geometric mean PC20 methacholine improved significantly after 4 weeks of intranasal beclomethasone, but not after placebo (p = 0.04). Daily morning and evening rhinitis symptom scores were lower in patients treated with intranasal corticosteroids over the first 4 weeks of treatment, but carryover effect of steroids precluded comparative analysis of the second 4-week block (morning p = 0.06, evening p = 0.03). Morning asthma scores tended to decrease (p = 0.07). Evening asthma scores were significantly decreased at weeks 2 and 3 (p = 0.001, p = 0.02, respectively). No change in peak expiratory flow rate was seen. This study confirms that treatment of inflammation in the upper airways indirectly improves asthma symptoms and decreases bronchial hyperreactivity. Ignoring inflammation in the upper airway may lead to suboptimal results in asthma treatment.
The effects of intranasal steroids on nasal and pulmonary responses to cat exposure.
To test the hypothesis that nasal antiinflammatory treatment can modify both upper and lower airway responses to allergen exposure, 12 cat-allergic subjects underwent 1 h cat exposure challenges at baseline, with nasal occlusion, and after 1 wk of treatment with either intranasal triamcinolone acetonide or placebo in a double-blind crossover trial. Challenges were performed in a room containing two cats with airborne Fel d I levels ranging from 35 to 37,525 ng/m3. Overall, nasal symptoms were moderately reduced by treatment (p = 0.06), with the greatest reduction occurring in the first 15 and 30 min of the challenge (p < 0.01 and p < 0.05, respectively). Mean lower respiratory symptoms were also diminished by treatment (p = 0.02), although those effects were most evident during the last 15 min of the challenge. Maximum changes in FEV1 were slightly reduced by the nasal therapy (p = 0.07), reaching statistical significance only at the 30-min intervals (p < 0.05). There were no significant differences in nasal histamine or TAME esterase levels. When challenges were repeated with nasal occlusion, no significant differences were detected in chest symptoms or FEV1 changes. We conclude that treatment with an intranasal corticosteroid led to significant reductions in both upper and lower airway responses to intense cat exposure.
Options:
A: INCS significantly improved asthma outcomes, including symptom scores and forced expiratory volume in one second.
B: INCS showed a trend towards improving asthma symptoms and forced expiratory volume in one second, but the results were not statistically significant.
C: INCS had no effect on asthma outcomes and were poorly tolerated by patients.
D: INCS significantly worsened asthma outcomes and should not be used in clinical practice. | B |
299 | 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 providing both written and verbal health information to patients and/or significant others being discharged from acute hospital settings to home, compared to providing verbal information only? Please answer this question based on the information provided below:
Standardized instructions: do they improve communication of discharge information from the emergency department?
To determine whether standardized instructions enhance communication of discharge information, we provided 197 parents of children in whom otitis media was diagnosed with one of three types of instruction at the time of discharge from a pediatric emergency department: (1) instruction by individual housestaff and medical students after consultation with an attending physician (control group); (2) standardized verbal instructions given by housestaff and students trained in their use (verbal group); or (3) the same instructions given to the verbal group, together with a type-written copy of the information to take home (verbal + written group). Prior to leaving the emergency department and, again, by phone, 1 and 3 days later, parents were questioned concerning the prescribed medication's name, dose, frequency, and duration of administration (medication data), three signs of improvement, and eight signs indicating the need for medical advice (worrisome signs). The mean percentage of correct responses per parent in each group was computed for each information category. Both at exit interview and at follow-up, parents receiving either form of standardized instructions showed significantly greater knowledge of information related to their child's illness than did controls. Information regarding medication data was more likely to be communicated to parents in all groups than were signs of improvement or worrisome signs. The addition of written instructions to standardized verbal instructions did not improve parental recall of discharge information.
A randomized single-blind evaluation of a discharge teaching book for pediatric patients with burns.
To evaluate the influence of a modular, multidisciplinary, pediatric burn discharge book on burn-care-related knowledge and satisfaction of caregivers, we studied children less than 17 years of age admitted with an acute thermal injury to the pediatric burn unit of a large, tertiary care hospital in Winnipeg, Canada over a 32 month period. Demographic characteristics of the population are similar to published profiles of other pediatric burn units with the exception that North American Indian (NAI) families were disproportionately admitted, with 59 out of the 123 (48%) admissions from a geographic area that has less than 15% NAIs. We randomly assigned the families to receive discharge instructions with the book (intervention group) or routine discharge teaching without the book (comparison group). Knowledge levels of burn care and satisfaction with discharge teaching of caregivers were evaluated with a questionnaire administered in single-blind fashion at the first outpatient follow-up visit. Sixty-two families received the book and 61 families received standard discharge teaching. Bivariate analysis showed greater knowledge in the intervention group, with an average score (range, 0.0 to 1.0) of 0.79 +/- 0.15 versus 0.73 +/- 0.15 in the comparison group (p < 0.05). We did not observe this positive effect of the book when we analyzed NAI families separately: 28 families instructed with the book scored 0.68 +/- 0.14 versus 0.63 +/- 0.13 in 31 families provided with routine teaching (p = 0.18). Stepwise multiple-regression analysis found that the influence of the book was limited to families with children who sustained scald burns (p < 0.05). Factors negatively related to the knowledge levels of caregivers (p < 0.05) were being of NAI origin and being NAI with no safety devices in the home. A positive correlation (p < 0.05) was found with having English as the first language, having a child with more extensive burns, having a younger age of the child with burns, and having fewer children in the home. In conclusion, we found that the discharge book improved the burn-care-related knowledge of caregivers. However, other factors, particularly ethnic and language background, were of greater influence.
Options:
A: It significantly increased knowledge and satisfaction scores.
B: It had no significant effect on knowledge and satisfaction scores.
C: It significantly decreased knowledge and satisfaction scores.
D: It significantly increased readmission rates and recovery time. | A |
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