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Biomedical subjects

D Moher

Publications and source records attributed to D Moher.

At least 55 records · Page 3Linked to original sources

The effectiveness of glucocorticoids in treating croup: meta-analysis.

OBJECTIVE: To determine the effectiveness of glucocorticoid treatment in children with croup. DESIGN: Meta-analysis of randomised controlled trials that examine the effectiveness of glucocorticoid treatment in children with croup. MAIN OUTCOME MEASURES: Score on scale measuring severity of croup, use of cointerventions (adrenaline (epinephrine), antibiotics, or supplemental glucocorticoids), length of stay in accident and emergency or in hospital, and rate of hospitalisation. RESULTS: Twenty four studies met the inclusion criteria. Glucocorticoid treatment was associated with an improvement in the croup severity score at 6 hours with an effect size of -1.0 (95% confidence interval -1.5 to -0.6) and at 12 hours -1.0 (-1.6 to -0.4); at 24 hours this improvement was no longer significant (-1.0, -2.0 to 0.1). There was a decrease in the number of adrenaline treatments needed in children treated with glucocorticoids: a decrease of 9% (95% confidence interval 2% to 16%) among those treated with budesonide and of 12% (4% to 20%) among those treated with dexamethasone. There was also a decrease in the length of time spent in accident and emergency (-11 hours, 95% confidence interval -18 to 4 hours), and for inpatients hospital stay was reduced by 16 hours (-31 to 1 hour). Publication bias seems to play a part in these results. CONCLUSIONS: Dexamethasone and budesonide are effective in relieving the symptoms of croup as early as 6 hours after treatment. Fewer cointerventions are used and the length of time spent in hospital is decreased in patients treated with glucocorticoids.

Anti-Bacterial Agents↗

Surveying physicians to determine the minimal important difference: implications for sample-size calculation.

The minimal important difference (MID) is the smallest benefit of treatment that would result in clinicians recommending it to their patients. The MID is necessary to calculate sample size for randomized clinical trials, but its chosen value is often arbitrary. This study set out to determine the practicability of surveying physicians to elicit the MID for clinical trial sample-size calculation. Using a mail survey, we elicited the MID of different physician specialties (family medicine, internal medicine, vascular surgery) for using propranolol to slow abdominal aortic aneurysm (AAA) growth assuming that propranolol was efficacious in this condition. We used different outcome measures (growth rate or proportion of patients requiring surgery) and different methods of data presentation for the proportion of patients requiring surgery (absolute risk reduction or number needed to treat). The MID varied significantly by physician specialty, experience with AAA and propranolol, and the method used to elicit the MID. Consequently, sample-size calculations using these various MIDs varied from 116 to 3015. Future attempts to elicit the MID need to consider carefully who is surveyed, how data are presented, and how opinions are elicited.

Adrenergic beta-Antagonists↗

Meta-analysis: an adolescent in need of evidence and a watchful eye.

Meta-analysis is a relatively new development in medicine. It is conceptually appealing, summarizing the medical literature in a rigorous manner and providing clinicians with a global picture regarding the merits of interventions. This process can help clinicians choose appropriate, evidence-based management options for their patients. The early enthusiasm for this approach has more recently been called into question. The reliability, and therefore the usefulness, of meta-analysis will improve as more evidence concerning the rigorous ways to conduct and report such studies is developed.

Cost-Benefit Analysis↗

Carotid endarterectomy for asymptomatic carotid stenosis: a meta-analysis.

OBJECTIVE: To assess the value of carotid endarterectomy for prevention of stroke in patients with asymptomatic carotid stenosis. DESIGN: Systematic review and meta-analysis of randomised controlled trials in patients with asymptomatic carotid stenosis in which subjects were allocated to carotid endarterectomy or to medical treatment alone. SUBJECTS: Five trials enrolled 2440 patients with stenosis >/ 50%. MAIN OUTCOME MEASURES: Stroke ipsilateral to the stenosis, all strokes, and perioperative complications (stroke or death). RESULTS: In patients who underwent carotid endarterectomy (n=1215) there was a significant reduction in the odds of ipsilateral stroke plus perioperative stroke or death (odds ratio 0.62; 95% confidence interval 0.44 to 0.86), corresponding to a 2% absolute risk reduction over about 3.1 years. The prevalence of stroke in any location was also reduced (0.68; 0.51 to 0.9) in patients undergoing carotid endarterectomy. During the immediate postoperative period there was an increased prevalence of stroke or death among such patients (4.51; 2.36 to 8.64). CONCLUSION: Carotid endarterectomy in patients with asymptomatic carotid stenosis unequivocally reduces the incidence of ipsilateral stroke, though the absolute benefit is relatively small. Given the modest benefit of surgery for unselected patients with asymptomatic carotid artery stenosis carotid endarterectomy cannot be routinely recommended for these patients pending reliable identification of high risk subgroups, and medical management is a sensible alternative for most patients.

Aged↗

Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses?

BACKGROUND: Few meta-analyses of randomised trials assess the quality of the studies included. Yet there is increasing evidence that trial quality can affect estimates of intervention efficacy. We investigated whether different methods of quality assessment provide different estimates of intervention efficacy evaluated in randomised controlled trials (RCTs). METHODS: We randomly selected 11 meta-analyses that involved 127 RCTs on the efficacy of interventions used for circulatory and digestive diseases, mental health, and pregnancy and childbirth. We replicated all the meta-analyses using published data from the primary studies. The quality of reporting of all 127 clinical trials was assessed by means of component and scale approaches. To explore the effects of quality on the quantitative results, we examined the effects of different methods of incorporating quality scores (sensitivity analysis and quality weights) on the results of the meta-analyses. FINDINGS: The quality of trials was low. Masked assessments provided significantly higher scores than unmasked assessments (mean 2.74 [SD 1.10] vs 2.55 [1.20]). Low-quality trials (score < or = 2), compared with high-quality trials (score > 2), were associated with an increased estimate of benefit of 34% (ratio of odds ratios [ROR] 0.66 [95% CI 0.52-0.83]). Trials that used inadequate allocation concealment, compared with those that used adequate methods, were also associated with an increased estimate of benefit (37%; ROR=0.63 [0.45-0.88]). The average treatment benefit was 39% (odds ratio [OR] 0.61 [0.57-0.65]) for all trials, 52% (OR 0.48 [0.43-0.54]) for low-quality trials, and 29% (OR 0.71 [0.65-0.77]) for high-quality trials. Use of all the trial scores as quality weights reduced the effects to 35% (OR 0.65 [0.59-0.71]) and resulted in the least statistical heterogeneity. INTERPRETATION: Studies of low methodological quality in which the estimate of quality is incorporated into the meta-analyses can alter the interpretation of the benefit of intervention, whether a scale or component approach is used in the assessment of trial quality.

Bias↗

Methodology and reports of systematic reviews and meta-analyses: a comparison of Cochrane reviews with articles published in paper-based journals.

CONTEXT: Review articles are important sources of information to help guide decisions by clinicians, patients, and other decision makers. Ideally, reviews should include strategies to minimize bias and to maximize precision and be reported so explicitly that any interested reader would be able to replicate them. OBJECTIVE: To compare the methodological and reporting aspects of systematic reviews and meta-analyses published by the Cochrane Collaboration with those published in paper-based journals indexed in MEDLINE. DATA SOURCES: The Cochrane Library, issue 2 of 1995, and a search of MEDLINE restricted to 1995. STUDY SELECTION: All 36 completed reviews published in the Cochrane Database of Systematic Reviews and a randomly selected sample of 39 meta-analyses or systematic reviews published in journals indexed by MEDLINE in 1995. DATA EXTRACTION: Number of authors, trials, and patients; trial sources; inclusion and exclusion criteria; language restrictions; primary outcome; trial quality assessment; heterogeneity testing; and effect estimates. Updating by 1997 was evaluated. RESULTS: Reviews found in MEDLINE included more authors (median, 3 vs 2; P<.001), more trials (median, 13.5 vs 5; P<.001), and more patients (median, 1280 vs 528; P<.001) than Cochrane reviews. More Cochrane reviews, however, included a description of the inclusion and exclusion criteria (35/36 vs 18/39; P<.001) and assessed trial quality (36/36 vs 12/39; P<.001). No Cochrane reviews had language restrictions (0/36 vs 7/39; P<.01). There were no differences in sources of trials, heterogeneity testing, or description of effect estimates. By June 1997, 18 of 36 Cochrane reviews had been updated vs 1 of 39 reviews listed in MEDLINE. CONCLUSIONS: Cochrane reviews appear to have greater methodological rigor and are more frequently updated than systematic reviews or meta-analyses published in paper-based journals.

Meta-Analysis as Topic↗

Nebulized budesonide and oral dexamethasone for treatment of croup: a randomized controlled trial.

CONTEXT: The effectiveness of glucocorticoids for patients with croup is well established but it remains uncertain which glucocorticoid regimen is most effective. OBJECTIVE: To determine the effectiveness of 3 glucocorticoid regimens in patients with croup. DESIGN: Randomized controlled trial with parallel design. SETTING: Emergency departments of 2 Canadian pediatric tertiary care hospitals. PARTICIPANTS: Children with a clinical syndrome consistent with croup, aged 3 months to 5 years, with a croup score of 2 or greater following at least 15 minutes of mist therapy. INTERVENTIONS: Oral dexamethasone, 0.6 mg/kg, and nebulized placebo; oral placebo and nebulized budesonide, 2 mg; or oral dexamethasone, 0.6 mg/kg, and nebulized budesonide, 2 mg. MAIN OUTCOME MEASURES: Westley croup score (primary outcome), hospital admission rates, time spent in the emergency department, return visits to the emergency department, or ongoing symptoms at 1 week. RESULTS: The mean change in the croup score from baseline to the final study assessment was -2.3 (95% confidence interval [CI], -2.6 to -2.0) in the budesonide group (n = 65), -2.4 (95% CI, -2.6 to -2.2) in the dexamethasone group (n = 69), and -2.4 (95% CI, -2.7 to -2.1) in the budesonide and dexamethasone group (n = 64, P = .70). CONCLUSIONS: Based on the similar outcomes in the 3 groups, oral dexamethasone is the preferred intervention because of its ease of administration, lower cost, and more widespread availability.

Administration, Intranasal↗

The efficacy of folic acid and folinic acid in reducing methotrexate gastrointestinal toxicity in rheumatoid arthritis. A metaanalysis of randomized controlled trials.

OBJECTIVE: To assess the efficacy of folic acid and folinic acid in reducing the mucosal and gastrointestinal (GI) side effects of low dose methotrexate (MTX) in patients with rheumatoid arthritis (RA). METHODS: A systematic review was carried out using the methods recommended by the Cochrane Collaboration. We used MEDLINE and performed hand searches that included bibliographic references, Current Contents, abstracts of rheumatology meetings, and 4 rheumatology journals to select double blind randomized controlled trials (RCT) in which adult patients with RA were treated with low doses of MTX (< 20 mg/week), concurrently with folic or folinic acid. The quality of the RCT was assessed. The overall treatment effect across trials (reduction in toxicity) was estimated using a fixed effects model. Disease activity was evaluated using standardized mean differences to ensure comparability across outcome measures. Sensitivity analyses were conducted evaluating different doses and the quality of the trials. Costs per month in different countries were compared. RESULTS: Of 11 trials retrieved, 7 met inclusion criteria. The total sample included 307 patients, of which 147 were treated with folate supplementation, 67 patients with folic, and 80 with folinic acid. A 79% reduction in mucosal and GI side effects was observed for folic acid [OR = 0.21 (95% CI 0.10 to 0.44)]. For folinic acid, a clinically but nonstatistically significant reduction of 42% was found [OR = 0.58 (95% CI 0.29 to 1.16)]. No major differences were observed between low and high doses of folic or folinic acid. Hematologic side effects could not be analyzed, since details by patients of each event were not provided. No consistent differences in disease activity variables were observed when comparing placebo and folic acid or folinic acid at low doses; patients receiving high dose folinic acid had increased tender and swollen joint counts. Substantial differences in costs across countries were found; folinic acid was more expensive. CONCLUSION: Our results support the protective effect of folate supplementation in reducing MTX side effects related to the oral and GI systems.

Adult↗

Management of intermittent claudication with pentoxifylline: meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the efficacy of pentoxifylline therapy in improving the walking capacity of patients with moderate intermittent claudication. DATA SOURCES: A search of MEDLINE for trials published between 1976 and 1994 inclusive, and a bibliographic review of all articles retrieved. STUDY SELECTION: Randomized, placebo-controlled, double-blind clinical trials were selected that evaluated the pain-free walking distance (the distanced walked on a treadmill before the onset of calf pain) and the absolute claudication distance (the maximum distance walked on a treadmill) among patients with moderate intermittent claudication. Twelve study groups in 11 trials were included in the analysis. DATA EXTRACTION: In addition to information regarding the trial design, patient characteristics, dosages and treatment periods, the means and standard deviations were collected for both the pain-free walking and absolute claudication distances. Trial quality was also assessed. DATA SYNTHESIS: Overall, there was a statistically significant improvement in the pain-free walking distance after pentoxifylline therapy (weighted mean difference 29.4 m [95% confidence interval (CI) 13.0 to 45.9 m]); this finding was based on a total sample of 612 patients (308 in the treatment groups and 304 in the control groups). A significant improvement was also noted in the absolute claudication distance (weighted mean difference 48.4 m [95% CI 18.3 to 78.6 m]); this was based on a total sample of 511 patients (258 in the treatment group and 253 in the control group). In a sensitivity analysis of the pain-free walking distance, significant treatment effects and no statistically significant heterogeneity were found when only trials were included that were "medically eligible" (involved patients with stage II disease and a pain-free walking distance of 50 to 200 m). In a similar sensitivity analysis of the absolute claudication distance, the two conditions resulting in a significant treatment effect and no significant heterogeneity were the inclusion of "medically eligible" trials and those with a shorter treatment duration (13 weeks or less). CONCLUSION: Pentoxifylline therapy may be efficacious in improving the walking capacity of patients with moderate intermittent claudication. However, properly conducted clinical trials are required to provide a true estimate of the benefit.

Chi-Square Distribution↗