Showing papers on "Randomized controlled trial published in 2000"

Randomized, controlled trials, observational studies, and the hierarchy of research designs.

Abstract: Background In the hierarchy of research designs, the results of randomized, controlled trials are considered to be evidence of the highest grade, whereas observational studies are viewed as having less validity because they reportedly overestimate treatment effects. We used published meta-analyses to identify randomized clinical trials and observational studies that examined the same clinical topics. We then compared the results of the original reports according to the type of research design. Methods A search of the Medline data base for articles published in five major medical journals from 1991 to 1995 identified meta-analyses of randomized, controlled trials and meta-analyses of either cohort or case–control studies that assessed the same intervention. For each of five topics, summary estimates and 95 percent confidence intervals were calculated on the basis of data from the individual randomized, controlled trials and the individual observational studies. Results For the five clinical topics and 99 r...

A comparison of observational studies and randomized, controlled trials.

Abstract: Background For many years it has been claimed that observational studies find stronger treatment effects than randomized, controlled trials We compared the results of observational studies with those of randomized, controlled trials Methods We searched the Abridged Index Medicus and Cochrane data bases to identify observational studies reported between 1985 and 1998 that compared two or more treatments or interventions for the same condition We then searched the Medline and Cochrane data bases to identify all the randomized, controlled trials and observational studies comparing the same treatments for these conditions For each treatment, the magnitudes of the effects in the various observational studies were combined by the Mantel-Haenszel or weighted analysis-of-variance procedure and then compared with the combined magnitude of the effects in the randomized, controlled trials that evaluated the same treatment Results There were 136 reports about 19 diverse treatments, such as calcium-channel-blocker therapy for coronary artery disease, appendectomy, and interventions for subfertility In most cases, the estimates of the treatment effects from observational studies and randomized, controlled trials were similar In only 2 of the 19 analyses of treatment effects did the combined magnitude of the effect in observational studies lie outside the 95 percent confidence interval for the combined magnitude in the randomized, controlled trials Conclusions We found little evidence that estimates of treatment effects in observational studies reported after 1984 are either consistently larger than or qualitatively different from those obtained in randomized, controlled trials

Design and Analysis of Cluster Randomization Trials in Health Research

Abstract: Acknowledgements. Preface. 1. Introduction. 1.1 Why randomize clusters? 1.2 What is the impact of cluster randomization on the design and analysis of a trial? 1.3 Quantifying the effect of clustering. 1.4 Randomized versus non-randomized comparisons. 1.5 The unit of inference. 1.6 Terminology: what's in a name? 2. The historical development of cluster randomized trials. 2.1 Randomized trials before 1950. 2.2 Cluster randomized trials between 1950 and 1978. 2.3 Cluster randomized trails since 1978. 3. Issues arising in the planning of cluster randomization trials. 3.1 Selecting interventions. 3.2 Setting eligibility criteria. 3.3 Measuring subject response. 3.4 The most commonly used experimental designs. 3.5 Factorial and crossover designs. 3.6 Selecting an experimental design. 3.7 The importance of cluster-level replication. 3.8 Strategies for conducting successful trials. 4. The role of informed consent and other ethical issues. 4.1 The risk of harm. 4.2 Informed consent. 4.3 Subject blindness and informed consent. 4.4 Randomized consent designs. 4.5 Ethical issues and trial monitoring. 5. Sample size estimation for cluster randomization designs. 5.1 General issues of sample size estimation. 5.2 The completely randomized design. 5.3 The matched-pair design. 5.4 The stratified design. 5.5 Issues involving losses to follow-up. 5.6 Strategies for achieving desired power. 6. Analysis of binary outcomes. 6.1 Selecting the unit of analysis. 6.2 The completely randomized design. 6.3 The matched-pair design. 6.4 The stratified design. 7. Analysis of quantitative outcomes. 7.1 The completely randomized design. 7.2 The matched-pair design. 7.3 The stratified design. 8. Analysis of count, time to event and categorical outcomes. 8.1 Count and time to event data. 8.2 Categorical data. 9. Reporting of cluster randomization trials. 9.1 Reporting of study design. 9.2 Reporting of study results. References. Index.

Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis

Abstract: Background Treatment with interferon beta has been shown to help patients with established multiple sclerosis, but it is not known whether initiating treatment at the time of a first clinical demyelinating event is of value. Methods We conducted a randomized, double-blind trial of 383 patients who had a first acute clinical demyelinating event (optic neuritis, incomplete transverse myelitis, or a brain-stem or cerebellar syndrome) and evidence of prior subclinical demyelination on magnetic resonance imaging (MRI) of the brain. After initial treatment with corticosteroids, 193 patients were randomly assigned to receive weekly intramuscular injections of 30 μg of interferon beta-1a and 190 were assigned to receive weekly injections of placebo. The study end points were the development of clinically definite multiple sclerosis and changes in findings on MRI of the brain. The trial was stopped after a preplanned interim efficacy analysis. Results During three years of follow-up, the cumulative probability of ...

A randomized, wait-list controlled clinical trial: the effect of a mindfulness meditation-based stress reduction program on mood and symptoms of stress in cancer outpatients.

Abstract: Objective: The objective of this study was to assess the effects of participation in a mindfulness meditation‐ based stress reduction program on mood disturbance and symptoms of stress in cancer outpatients. Methods: A randomized, wait-list controlled design was used. A convenience sample of eligible cancer patients enrolled after giving informed consent and were randomly assigned to either an immediate treatment condition or a wait-list control condition. Patients completed the Profile of Mood States and the Symptoms of Stress Inventory both before and after the intervention. The intervention consisted of a weekly meditation group lasting 1.5 hours for 7 weeks plus home meditation practice. Results: Ninety patients (mean age, 51 years) completed the study. The group was heterogeneous in type and stage of cancer. Patients’ mean preintervention scores on dependent measures were equivalent between groups. After the intervention, patients in the treatment group had significantly lower scores on Total Mood Disturbance and subscales of Depression, Anxiety, Anger, and Confusion and more Vigor than control subjects. The treatment group also had fewer overall Symptoms of Stress; fewer Cardiopulmonary and Gastrointestinal symptoms; less Emotional Irritability, Depression, and Cognitive Disorganization; and fewer Habitual Patterns of stress. Overall reduction in Total Mood Disturbance was 65%, with a 31% reduction in Symptoms of Stress. Conclusions: This program was effective in decreasing mood disturbance and stress symptoms in both male and female patients with a wide variety of cancer diagnoses, stages of illness, and ages. Key words: meditation, cancer, stress, mood, intervention, mindfulness. ANOVA 5 analysis of variance; MANOVA 5 multiple analysis of variance; POMS 5 Profile of Mood States; SOSI 5 Symptoms of Stress Inventory.

Randomized Intergroup Trial of Cisplatin–Paclitaxel Versus Cisplatin–Cyclophosphamide in Women With Advanced Epithelial Ovarian Cancer: Three-Year Results

Abstract: BACKGROUND: A randomized trial conducted by the Gynecologic Oncology Group (GOG, study #111) in the United States showed a better outcome for patients with advanced ovarian cancer on the paclitaxel-cisplatin regimen than for those on a standard cyclophosphamide-cisplatin regimen. Before considering the paclitaxel-cisplatin regimen as the new "standard," a group of European and Canadian investigators planned a confirmatory phase III trial. METHODS: This intergroup trial recruited 680 patients with broader selection criteria than the GOG #111 study and administered paclitaxel as a 3-hour instead of a 24-hour infusion; progression-free survival was the primary end point. Patient survival was analyzed by use of the Kaplan-Meier technique. Treatment effects on patient survival were estimated by Cox proportional hazards regression models. All statistical tests were two-sided. RESULTS: The overall clinical response rate was 59% in the paclitaxel group and 45% in the cyclophosphamide group; the complete clinical remission rates were 41% and 27%, respectively; both differences were statistically significant (P =.01 for both). At a median follow-up of 38.5 months and despite a high rate of crossover (48%) from the cyclophosphamide arm to the paclitaxel arm at first detection of progression of disease, a longer progression-free survival (log-rank P =.0005; median of 15.5 months versus 11.5 months) and a longer overall survival (log-rank P =. 0016; median of 35.6 months versus 25.8 months) were seen in the paclitaxel regimen compared with the cyclophosphamide regimen. CONCLUSIONS: There is strong and confirmatory evidence from two large randomized phase III trials to support paclitaxel-cisplatin as the new standard regimen for treatment of patients with advanced ovarian cancer.

Estrogen Replacement Therapy for Treatment of Mild to Moderate Alzheimer Disease: A Randomized Controlled Trial

Abstract: ContextSeveral reports from small clinical trials have suggested that estrogen replacement therapy may be useful for the treatment of Alzheimer disease (AD) in women.ObjectiveTo determine whether estrogen replacement therapy affects global, cognitive, or functional decline in women with mild to moderate AD.DesignThe Alzheimer's Disease Cooperative Study, a randomized, double-blind, placebo-controlled clinical trial conducted between October 1995 and January 1999.SettingThirty-two study sites in the United States.ParticipantsA total of 120 women with mild to moderate AD and a Mini-Mental State Examination score between 12 and 28 who had had a hysterectomy.InterventionsParticipants were randomized to estrogen, 0.625 mg/d (n = 42), or 1.25 mg/d (n = 39), or to identically appearing placebo (n = 39). One subject withdrew after randomization but before receiving medication; 97 subjects completed the trial.Main Outcome MeasuresThe primary outcome measure was change on the Clinical Global Impression of Change (CGIC) 7-point scale, analyzed by intent to treat; secondary outcome measures included other global measures as well as measures of mood, specific cognitive domains (memory, attention, and language), motor function, and activities of daily living; compared by the combined estrogen groups vs the placebo group at 2, 6, 12, and 15 months of follow-up.ResultsThe CGIC score for estrogen vs placebo was 5.1 vs 5.0 (P = .43); 80% of participants taking estrogen vs 74% of participants taking placebo worsened (P = .48). Secondary outcome measures also showed no significant differences, with the exception of the Clinical Dementia Rating Scale, which suggested worsening among patients taking estrogen (mean posttreatment change in score for estrogen, 0.5 vs 0.2 for placebo; P = .01).ConclusionsEstrogen replacement therapy for 1 year did not slow disease progression nor did it improve global, cognitive, or functional outcomes in women with mild to moderate AD. The study does not support the role of estrogen for the treatment of this disease. The potential role of estrogen in the prevention of AD, however, requires further research.

A 5-month, randomized, placebo-controlled trial of galantamine in AD

Abstract: Objective: To investigate the efficacy and tolerability of galantamine, using a slow dose escalation schedule of up to 8 weeks, in 978 patients with mild to moderate AD. Methods: A 5-month multicenter, placebo-controlled, double-blind trial. Following a 4-week placebo run-in, patients were randomized to one of four treatment arms: placebo or galantamine escalated to final maintenance doses of 8, 16, or 24 mg/day. Outcome measures included the cognitive subscale of the AD Assessment Scale (ADAS-cog), the Clinician’s Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus), the AD Cooperative Study Activities of Daily Living inventory, and the Neuropsychiatric Inventory. Standard safety evaluations and adverse event monitoring were carried out. Results: After 5 months, the galantamine–placebo differences on ADAS-cog were 3.3 points for the 16 mg/day group and 3.6 points for the 24 mg/day group ( p Conclusions: Galantamine 16 and 24 mg/day significantly benefits the cognitive, functional, and behavioral symptoms of AD as compared with placebo. Slow dose escalation appears to enhance the tolerability of galantamine, minimizing the incidence and severity of adverse events.

Pramipexole vs Levodopa as initial treatment for Parkinson disease: A randomized controlled trial

Abstract: CONTEXT Pramipexole and levodopa both ameliorate the motor symptoms of early Parkinson disease (PD), but no controlled studies have compared long-term outcomes after initiating dopaminergic therapy with pramipexole vs levodopa. OBJECTIVE To compare the development of dopaminergic motor complications after initial treatment of early PD with pramipexole vs levodopa. DESIGN Multicenter, parallel-group, double-blind, randomized controlled trial. SETTING Academic movement disorders clinics at 22 sites in the United States and Canada. PATIENTS Three hundred one patients with early PD who required dopaminergic therapy to treat emerging disability, enrolled between October 1996 and August 1997. INTERVENTIONS Subjects were randomly assigned to receive pramipexole, 0.5 mg 3 times per day, with levodopa placebo (n = 151); or carbidopa/levodopa, 25/100 mg 3 times per day, with pramipexole placebo (n = 150). For patients with residual disability, the dosage was escalated during the first 10 weeks. From week 11 to month 23.5, investigators were permitted to add open-label levodopa to treat continuing or emerging disability. MAIN OUTCOME MEASURES Time to the first occurrence of any of 3 dopaminergic complications: wearing off, dyskinesias, or on-off motor fluctuations; changes in scores on the Unified Parkinson's Disease Rating Scale (UPDRS), assessed at baseline and follow-up evaluations; and, in a subgroup of 82 subjects evaluated at baseline and 23.5 months, ratio of specific to nondisplaceable striatal iodine 123 2-beta-carboxymethoxy-3-beta-(4-iodophenyl)tropane (beta-CIT) uptake on single photon emission computed tomography imaging of the dopamine transporter. RESULTS Initial pramipexole treatment resulted in significantly less development of wearing off, dyskinesias, or on-off motor fluctuations (28%) compared with levodopa (51%) (hazard ratio, 0.45; 95% confidence interval [CI], 0. 30-0.66; P<.001). The mean improvement in total UPDRS score from baseline to 23.5 months was greater in the levodopa group than in the pramipexole group (9.2 vs 4.5 points; P<.001). Somnolence was more common in pramipexole-treated patients than in levodopa-treated patients (32.4% vs 17.3%; P =.003), and the difference was seen during the escalation phase of treatment. In the subgroup study, patients treated initially with pramipexole (n = 39) showed a mean (SD) decline of 20.0% (14.2%) in striatal beta-CIT uptake compared with a 24.8% (14.4%) decline in subjects treated initially with levodopa (n = 39; P =.15). CONCLUSIONS Fewer patients receiving initial treatment for PD with pramipexole developed dopaminergic motor complications than with levodopa therapy. Despite supplementation with open-label levodopa in both groups, the levodopa-treated group had a greater improvement in total UPDRS compared with the pramipexole group. JAMA. 2000;284:1931-1938.

A Controlled Trial of a Critical Pathway for Treatment of Community-Acquired Pneumonia

Abstract: ContextLarge variations exist among hospitals in the use of treatment resources for community-acquired pneumonia (CAP). Lack of a common approach to the diagnosis and treatment of CAP has been cited as an explanation for these variations.ObjectiveTo determine if use of a critical pathway improves the efficiency of treatment for CAP without compromising the well-being of patients.DesignMulticenter controlled clinical trial with cluster randomization and up to 6 weeks of follow-up.SettingNineteen teaching and community hospitals in Canada.PatientsA total of 1743 patients with CAP presenting to the emergency department at 1 of the participating institutions between January 1 and July 31, 1998.InterventionHospitals were assigned to continue conventional management (n = 10) or implement the critical pathway (n = 9), which consisted of a clinical prediction rule to guide the admission decision, levofloxacin therapy, and practice guidelines.Main Outcome MeasuresEffectiveness of the critical pathway, as measured by health-related quality of life on the Short-Form 36 Physical Component Summary (SF-36 PCS) scale at 6 weeks; and resource utilization, as measured by the number of bed days per patient managed (BDPM).ResultsQuality of life and the occurrence of complications, readmission, and mortality were not different for the 2 strategies; the 1-sided 95% confidence limit of the between-group difference in the SF-36 PCS change score was 2.4 points, which was within a predefined 3-point boundary for equivalence. Pathway use was associated with a 1.7-day reduction in BDPM (4.4 vs 6.1 days; P = .04) and an 18% decrease in the admission of low-risk patients (31% vs 49%; P = .01). Although inpatients at critical pathway hospitals had more severe disease, they required 1.7 fewer days of intravenous therapy (4.6 vs 6.3 days; P = .01) and were more likely to receive treatment with a single class of antibiotic (64% vs 27%; P<.001).ConclusionIn this study, implementation of a critical pathway reduced the use of institutional resources without causing adverse effects on the well-being of patients.

A randomized controlled trial of cognitive-behavioral therapy for persistent symptoms in schizophrenia resistant to medication.

Abstract: Background Research evidence supports the efficacy of cognitive-behavioral therapy in the treatment of drug-refractory positive symptoms of schizophrenia. Although the cumulative evidence is strong, early controlled trials showed methodological limitations. Methods A randomized controlled design was used to compare the efficacy of manualized cognitive-behavioral therapy developed particularly for schizophrenia with that of a nonspecific befriending control intervention. Both interventions were delivered by 2 experienced nurses who received regular supervision. Patients were assessed by blind raters at baseline, after treatment (lasting up to 9 months), and at a 9-month follow-up evaluation. Patients continued to receive routine care throughout the study. An assessor blind to the patients' treatment groups rated the technical quality of audiotaped sessions chosen at random. Analysis was by intention to treat. Results Ninety patients received a mean of 19 individual treatment sessions over 9 months, with no significant between-group differences in treatment duration. Both interventions resulted in significant reductions in positive and negative symptoms and depression. At the 9-month follow-up evaluation, patients who had received cognitive therapy continued to improve, while those in the befriending group did not. These results were not attributable to changes in prescribed medication. Conclusion Cognitive-behavioral therapy is effective in treating negative as well as positive symptoms in schizophrenia resistant to standard antipsychotic drugs, with its efficacy sustained over 9 months of follow-up.

Lumbar spinal stenosis: conservative or surgical management?: A prospective 10-year study.

Abstract: Study design A cohort of 100 patients with symptomatic lumbar spinal stenosis, characterized in a previous article, were given surgical or conservative treatment and followed for 10 years. Objectives To identify the short- and long-term results after surgical and conservative treatment, and to determine whether clinical or radiologic predictors for the treatment result can be defined. Summary of background data Surgical decompression has been considered the rational treatment. However, clinical experience indicates that many patients do well with conservative treatment. Methods In this study, 19 patients with severe symptoms were selected for surgical treatment and 50 patients with moderate symptoms for conservative treatment, whereas 31 patients were randomized between the conservative (n = 18) and surgical (n = 13) treatment groups. Pain was decisive for the choice of treatment group. All patients were observed for 10 years by clinical evaluation and questionnaires. The results, evaluated by patient and physician, were rated as excellent, fair, unchanged, or worse. Results After a period of 3 months, relief of pain had occurred in most patients. Some had relief earlier, whereas for others it took 1 year. After a period of 4 years, excellent or fair results were found in half of the patients selected for conservative treatment, and in four fifths of the patients selected for surgery. Patients with an unsatisfactory result from conservative treatment were offered delayed surgery after 3 to 27 months (median, 3.5 months). The treatment result of delayed surgery was essentially similar to that of the initial group. The treatment result for the patients randomized for surgical treatment was considerably better than for the patients randomized for conservative treatment. Clinically significant deterioration of symptoms during the final 6 years of the follow-up period was not observed. Patients with multilevel afflictions, surgically treated or not, did not have a poorer outcome than those with single-level afflictions. Clinical or radiologic predictors for the final outcome were not found. There were no dropouts, except for 14 deaths. Conclusions The outcome was most favorable for surgical treatment. However, an initial conservative approach seems advisable for many patients because those with an unsatisfactory result can be treated surgically later with a good outcome.

Effectiveness of Manual Physical Therapy and Exercise in Osteoarthritis of the Knee: A Randomized, Controlled Trial

Abstract: Background: Few investigations include both subjective and objective measurements of the effectiveness of treatments for osteoarthritis of the knee. Beneficial interventions may decrease the disability associated with osteoarthritis and the need for more invasive treatments. Objective: To evaluate the effectiveness of physical therapy for osteoarthritis of the knee, applied by experienced physical therapists with formal training in manual therapy. Design: Randomized, controlled clinical trial. Setting: Outpatient physical therapy department of a large military medical center. Patients: 83 patients with osteoarthritis of the knee who were randomly assigned to receive treatment (n = 42; 15 men and 27 women [mean age, 60 ± 11 years]) or placebo (n = 41; 19 men and 22 women [mean age, 62 ± 10 years]). Intervention: The treatment group received manual therapy, applied to the knee as well as to the lumbar spine, hip, and ankle as required, and performed a standardized knee exercise program in the clinic and at home. The placebo group had subtherapeutic ultrasound to the knee at an intensity of 0.1 W/cm 2 with a 10% pulsed mode. Both groups were treated at the clinic twice weekly for 4 weeks. Measurements: Distance walked in 6 minutes and sum of the function, pain, and stiffness subscores of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). A tester who was blinded to group assignment made group comparisons at the initial visit (before initiation of treatment), 4 weeks, 8 weeks, and 1 year. Results: Clinically and statistically significant improvements in 6-minute walk distance and WOMAC score at 4 weeks and 8 weeks were seen in the treatment group but not the placebo group. By 8 weeks, average 6-minute walk distances had improved by 13.1 % and WOMAC scores had improved by 55.8% over baseline values in the treatment group (P < 0.05). After controlling for potential confounding variables, the average distance walked in 6 minutes at 8 weeks among patients in the treatment group was 170 m (95% Cl, 71 to 270 m) more than that in the placebo group and the average WOMAC scores were 599 mm higher (95% Cl, 197 to 1002 mm). At 1 year, patients in the treatment group had clinically and statistically significant gains over baseline WOMAC scores and walking distance; 20% of patients in the placebo group and 5% of patients in the treatment group had undergone knee arthroplasty. Conclusions: A combination of manual physical therapy and supervised exercise yields functional benefits for patients with osteoarthritis of the knee and may delay or prevent the need for surgical intervention.

Efficacy and safety of galantamine in patients with mild to moderate Alzheimer's disease: multicentre randomised controlled trial

Abstract: Objective: To evaluate the efficacy and safety of galantamine in the treatment of Alzheimer9s disease. Design: Randomised, double blind, parallel group, placebo controlled trial. Setting: 86 outpatient clinics in Europe and Canada. Participants: 653 patients with mild to moderate Alzheimer9s disease. Intervention: Patients randomly assigned to galantamine had their daily dose escalated over three to four weeks to maintenance doses of 24 or 32 mg. Main outcome measures: Scores on the 11 item cognitive subscale of the Alzheimer9s disease assessment scale, the clinician9s interview based impression of change plus caregiver input, and the disability assessment for dementia scale. The effect of apolipoprotein E4 genotype on reponse to treatment was also assessed. Results: At six months, patients who received galantamine had a significantly better outcome on the 11 item cognitive subscale of the Alzheimer9s disease assessment scale than patients in the placebo group (mean treatment effect 2.9 points for lower dose and 3.1 for higher dose, intention to treat analysis, P Conclusion: Galantamine is effective and well tolerated in Alzheimer9s disease. As galantamine slowed the decline of functional ability as well as cognition, its effects are likely to be clinically relevant.

Why Do Patients With Atrial Fibrillation Not Receive Warfarin

Abstract: Atrial fibrillation (AF) is a growing public health problem associated with significant morbidity and mortality. Numerous randomized controlled trials of warfarin have conclusively demonstrated that long-term anticoagulation therapy can reduce the risk for stroke by approximately 68% per year in patients with nonvalvular AF, and even more in patients with valvular AF. However, available data show that of those patients with AF and no contraindication to warfarin therapy, only 15% to 44% are prescribed warfarin. Our literature review has identified patient-, physician-, and health care system‐related barriers to warfarin prescription. However, the relative importance of these specific barriers remains unknown. Further work is needed to understand the discrepancy between the randomized controlled trial evidence and clinical practice patterns. Arch Intern Med. 2000;160:41-46

Exercise therapy for low back pain: A systematic review within the framework of the cochrane collaboration back review group

Abstract: Study design A systematic review of randomized controlled trials was performed. Summary of background data Exercise therapy is a widely used treatment for low back pain. Objectives To evaluate the effectiveness of exercise therapy for low back pain with regard to pain intensity, functional status, overall improvement, and return to work. Methods The Cochrane Controlled Trials Register, Medline, Embase, PsycLIT, and reference lists of articles were searched. Randomized trials testing all types of exercise therapy for subjects with nonspecific low back pain with or without radiation into the legs were included. Two reviewers independently extracted data and assessed trial quality. Because trials were considered heterogeneous with regard to study populations, interventions, and outcomes, it was decided not to perform a meta-analysis, but to summarize the results using a rating system of four levels of evidence: strong, moderate, limited, or none. Results In this review, 39 trials were identified. There is strong evidence that exercise therapy is not more effective for acute low back pain than inactive or other active treatments with which it has been compared. There is conflicting evidence on the effectiveness of exercise therapy compared with inactive treatments for chronic low back pain. Exercise therapy was more effective than usual care by the general practitioner and just as effective as conventional physiotherapy for chronic low back pain. Conclusions The evidence summarized in this systematic review does not indicate that specific exercises are effective for the treatment of acute low back pain. Exercises may be helpful for patients with chronic low back pain to increase return to normal daily activities and work.

Indications for early aspirin use in acute ischemic stroke : A combined analysis of 40 000 randomized patients from the chinese acute stroke trial and the international stroke trial. On behalf of the CAST and IST collaborative groups.

Abstract: Background and Purpose—Long-term daily aspirin is of benefit in the years after ischemic stroke, and 2 large randomized trials (the Chinese Acute Stroke Trial [CAST] and the International Stroke Trial [IST]), with 20 000 patients in each, have shown that starting daily aspirin promptly in patients with suspected acute ischemic stroke also reduces the immediate risk of further stroke or death in hospital and the overall risk of death or dependency. However, some uncertainty remains about the effects of early aspirin in particular categories of patient with acute stroke. Methods—To assess the balance of benefits and risks of aspirin in particular categories of patient with acute stroke (eg, the elderly, those without a CT scan, or those with atrial fibrillation), a prospectively planned meta-analysis is presented of the data from 40 000 individual patients from both trials on events that occurred in the hospital during the scheduled treatment period (4 weeks in CAST, 2 weeks in IST), with 10 characteristics...

Meta-analysis of benzodiazepine use in the treatment of insomnia

Abstract: OBJECTIVE: To systematically review the benefits and risks associated with the use of benzodiazepines to treat insomnia in adults. DATA SOURCES: MEDLINE and the Cochrane Controlled Trials Registry were searched for English-language articles published from 1966 to December 1998 that described randomized controlled trials of benzodiazepines for the treatment of insomnia. Key words included "benzodiazepines" (exploded), "randomized controlled trial" and "insomnia." Bibliographies of relevant articles were reviewed for additional studies and manufacturers of benzodiazepines were asked to submit additional randomized controlled trial reports not in the literature. STUDY SELECTION: Articles were considered for the meta-analysis if they were randomized controlled trials involving patients with insomnia and compared a benzodiazepine with placebo or another active agent. Of the 89 trials originally identified, 45 met our criteria, representing a total of 2672 patients. DATA EXTRACTION: Data were extracted regarding the participants, the setting, details of the intervention, the outcomes (including adverse effects) and the methodologic quality of the studies. DATA SYNTHESIS: The meta-analyses of sleep records indicated that, when compared with placebo, benzodiazepines decreased sleep latency by 4.2 minutes (non-significant; 95% confidence interval (CI -0.7 to 9.2) and significantly increased total sleep duration by 61.8 minutes (95% CI 37.4 to 86.2). Patient-reported outcomes were more optimistic for sleep latency; those randomized to benzodiazepine treatment estimated a sleep latency decrease of 14.3 minutes (95% CI 10.6 to 18.0). Although more patients receiving benzodiazepine treatment reported adverse effects, especially daytime drowsiness and dizziness or light-headedness (common odds ratio 1.8, 95% CI 1.4 to 2.4), dropout rates for the benzodiazepine and placebo groups were similar. Cognitive function decline including memory impairment was reported in several of the studies. Zopiclone was not found to be superior to benzodiazepines on any of the outcome measures examined. INTERPRETATION: The use of benzodiazepines in the treatment of insomnia is associated with an increase in sleep duration, but this is countered by a number of adverse effects. Additional studies evaluating the efficacy of nonpharmacological interventions would be valuable.

Effect of a community intervention on patient delay and emergency medical service use in acute coronary heart disease: The Rapid Early Action for Coronary Treatment (REACT) Trial.

Abstract: ContextDelayed access to medical care in patients with acute myocardial infarction (AMI) is common and increases myocardial damage and mortality.ObjectiveTo evaluate a community intervention to reduce patient delay from symptom onset to hospital presentation and increase emergency medical service (EMS) use.Design and SettingThe Rapid Early Action for Coronary Treatment Trial, a randomized trial conducted from 1995 to 1997 in 20 US cities (10 matched pairs; population range, 55,777-238,912) in 10 states.ParticipantsA total of 59,944 adults aged 30 years or older presenting to hospital emergency departments (EDs) with chest pain, of whom 20,364 met the primary population criteria of suspected acute coronary heart disease on admission and were discharged with a coronary heart disease–related diagnosis.InterventionOne city in each pair was randomly assigned to an 18-month intervention that targeted mass media, community organizations, and professional, public, and patient education to increase appropriate patient actions for AMI symptoms (primary population, n=10,563). The other city in each pair was randomly assigned to reference status (primary population, n=9801).Main Outcome MeasuresTime from symptom onset to ED arrival and EMS use, compared between intervention and reference city pairs.ResultsGeneral population surveys provided evidence of increased public awareness and knowledge of program messages. Patient delay from symptom onset to hospital arrival at baseline (median, 140 minutes) was identical in the intervention and reference communities. Delay time decreased in intervention communities by −4.7% per year (95% confidence interval [CI], −8.6% to −0.6%), but the change did not differ significantly from that observed in reference communities (−6.8% per year; 95% CI, −14.5% to 1.6%; P=.54). EMS use by the primary study population increased significantly in intervention communities compared with reference communities, with a net effect of 20% (95% CI, 7%-34%; P<.005). Total numbers of ED presentations for chest pain and patients with chest pain discharged from the ED, as well as EMS use among patients with chest pain released from the ED, did not change significantly.ConclusionsIn this study, despite an 18-month intervention, time from symptom onset to hospital arrival for patients with chest pain did not change differentially between groups, although increased appropriate EMS use occurred in intervention communities. New strategies are needed if delay time from symptom onset to hospital presentation is to be decreased further in patients with suspected AMI.

Statistics notes: blinding in clinical trials and other studies.

Abstract: Human behaviour is influenced by what we know or believe. In research there is a particular risk of expectation influencing findings, most obviously when there is some subjectivity in assessment, leading to biased results. Blinding (sometimes called masking) is used to try to eliminate such bias. It is a tenet of randomised controlled trials that the treatment allocation for each patient is not revealed until the patient has irrevocably been entered into the trial, to avoid selection bias. This sort of blinding, better referred to as allocation concealment, will be discussed in a future statistics note. In controlled trials the term blinding, and in particular “double blind,” usually refers to keeping study participants, those involved with their management, and those collecting and analysing clinical data unaware of the assigned treatment, so that they should not be influenced by that knowledge. The relevance of blinding will vary according to circumstances. Blinding patients to the treatment they have received in a controlled trial is particularly important when the …

Randomized trials or observational tribulations

Abstract: The role of observational studies in the evaluation of treatments is a long-standing and contentious topic.1 In this issue of the Journal, Concato et al.2 and Benson and Hartz3 report that observational studies give results similar to those of randomized, controlled trials. If these claims lead to more observational studies of therapeutic interventions and fewer randomized, controlled trials, we see considerable dangers to clinical research and even to the well-being of patients. Any systematic review of evidence on a therapeutic topic needs to take into account the quality of the evidence. Any study, whether randomized or observational, may have flaws . . .