Search

In most cases, the results of a large clinical trial will agree with the meta-analysis of the smaller trials on that same topic. This was demonstrated by researchers who identified 79 meta-analyses that included one large study of 1,000 or more patients and 61 meta-analyses that included one large study based on statistical power. In 82% to 90% of the cases, the large trial confirmed the results of the meta-analysis. In the 15 cases where the large trial did not confirm the meta-analysis, most of the difference could be accounted for., Objective.--To evaluate the results of large clinical trials vs the pooled results of smaller trials. Data Identification.--Meta-analyses with at least I "large" study were identified from the Cochrane Pregnancy and Childbirth Database and from MEDLINE (1966-1995). Study Selection.--We used a sample size approach to select 79 meta-analyses with at least 1 large study of 1000 or more patients. We used a statistical power approach to select 61 meta-analyses with at least 1 large study based on statistical power considerations. Data Extraction.--The outcome of interest for each meta-analysis was the primary one stated in the original publication or, when not clearly specified, was decided on clinically. Data Synthesis.--By random effects calculations, we found agreement between large and smaller trials in 90% of the meta-analyses selected by the sample size approach and in 82% of the meta-analyses selected by the statistical power approach. Twice as many disagreements appeared when the variability among large studies and among smaller studies was not considered (ie, fixed effects calculations). Of the 15 disagreements between results of large and smaller trials using the random effects model, plausible explanations were identified in 10 meta-analyses: 5 with differences in the control rate of events between large and smaller trials, 4 with specific protocol or study differences, and 1 with potential publication bias. Two other disagreements were not clinically important, and tentative reasons could be identified for 2 of the remaining 3 disagreements. Conclusions.--Results of smaller studies are usually compatible with the results of large studies, but discrepancies do occur even when the diversity among both large studies and smaller studies is considered. Clinically important differences without a potential explanation are extremely uncommon. Future research should further examine sources of heterogeneity between the results of large and smaller trials. JAMA. 1996;276:1332-1338

Research articles that appear in supplements to medical journals appear to be of lower quality than articles that appear in the journals themselves. Three independent reviewers, who were unaware of whether they were reviewing articles from supplements or parent journals, studied 242 articles from three different medical journals. A score was assigned to each article based on the quality of the research. Almost 28% of the articles were found to have originally appeared in supplements. Those that appeared in parent journals had an average score of 38.5% out of 100%, while those that appeared in supplements had an average score of 33.6%., Objectives.--To determine the relationship between the quality of articles and whether they were published in a supplement or in the parent journal. Data Sources and Study Selection.--All randomized control trials of drug therapies in adults published in the American Journal of Cardiology, the American Journal of Medicine, and the American Heart Journal from January 1990 and obtained in November 1992 by means of a MEDLINE search. A total of 318 abstracts appeared to meet our inclusion criteria, and these articles were obtained and reviewed in further detail. An additional 76 were excluded. Data Extraction.--Three reviewers who were "blinded" and thus unaware of supplement status independently assessed the quality of each of the remaining 242 articles according to a standard quality scoring system. Data Synthesis.--Overall, 67 (27.7%) of the articles were published in journal supplements. Article quality scores ranged from 4.2% to 87.5%, with a mean ([+ or -]SD) score of 37.2%[+ or -]13.1%. Quality scores were lower in articles published in journal supplements than in those published in the parent journal (t[240]=2.61, P--.01). The mean quality score for articles published in journal supplements was 33.6%[+ or -]12.8% compared with a score of 38.5%[+ or -]13.1% for articles published in the parent journal. Supplement articles included in their final analysis a smaller proportion of the patients initially randomized (t[75]=2.8, P=.007). Conclusion.--Our findings suggest that randomized control trials published in journal supplements are generally of inferior quality compared with articles published in the parent journal. The review process surrounding the publication of journal supplements should be consistent with that of the parent journal. (JAMA. 1994;272:108-113)

Surgical closure of patent ductus arteriosus may be more effective and less expensive than implanting an occluder device with a catheter. Patent ductus arteriosus is a birth defect characterized by an opening between the aorta and the pulmonary artery. Among 631 children treated for patent ductus arteriosus from 1982 to 1987, 185 had an occluder implanted and 446 had conventional surgical closure. The surgical closure was successful in all cases. The implant procedure was successful in only 86.5% of cases, even after some patients had further surgery. There were fewer significant complications in the surgical closure group. Average costs per patient for the procedures, including hospital care and follow-up, were $8,838 for surgical closure and $11,466 for occluder implantation. The occluder implantation involves more sophisticated and costly technology and has a lower success rate than the standard surgical closure method.

Antibiotics may be an effective short-term treatment for otitis media (OME) in children. Their effectiveness may be limited for long-term prevention and treatment of OME. OME is inflammation of the middle ear that usually resolves spontaneously with time. Researchers reviewed studies published in the medical literature that examined the use of antibiotics to prevent or treat OME in children. Nine studies found that treatment with antibiotics prevented recurrent OME in children. Twelve studies found that antibiotics were an effective treatment for OME. These studies evaluated the effectiveness of antibiotics using short-term patient outcome. Eight studies that examined long-term patient outcome found no significant difference between treatment with an antibiotic and treatment with a placebo, or inactive substance., Objective.--To determine the efficacy of antibiotics for prophylaxis of recurrent otitis media and treatment of otitis media with effusion (OME) in children. Data Sources.--MEDLINE from 1966 through April 1993, textbooks, Current Contents, and bibliographies of selected articles. Study Selection.--Thirty-three studies initially identified were reviewed by three blinded reviewers assessing study quality and suitability for inclusion. Twenty-seven met inclusion criteria for the meta-analyses. Data Extraction.--We abstracted quantitative data and calculated rate differences (RDs) using tympanometry as the preferred outcome measure. Data Synthesis.--Nine studies of antibiotic prophylaxis of recurrent otitis media with 958 subjects had an RD of 0.11 (95% confidence interval [CI], 0.03 to 0.19) favoring antibiotic treatment. Twelve studies of short-term patient outcomes of OME with 1697 subjects had an RD favoring antibiotics of 0.16 (95% CI, 0.03 to 0.29), while eight studies using the ear as the outcome measure with 2052 ears studied had an RD of 0.25 (95% CI, 0.10 to 0.40). No significant difference was shown between placebo and antibiotics (RD, 0.06; 95% CI, -0.03 to 0.14) in the eight studies of longer-term outcome of OME. Subgroup analyses by antibiotic grouping, duration of treatment, and duration of disease did not show significant differences. Conclusions.--Antibiotics appear to have beneficial but limited effect on recurrent otitis media and short-term resolution of OME. Longer-term benefit for OME has not been shown. The finding are limited by the failure of most studies to consider potential confounders and by inability to identify groups of patients most likely to benefit. (JAMA. 1993;270:1344-1351)

Supplementation of diet with vitamin A may decrease the number of deaths among children with measles, whether hospitalized or still in the community. Vitamin A deficiency is common among children in many developing countries. A survey of the medical literature found that supplementation with vitamin A decreased the number of deaths among children hospitalized with measles. Supplementation with vitamin A had a protective effect against death from a respiratory infections among these children. The protective effect of vitamin A was greater in children under two years old than in older children, and in higher-risk areas. Supplementation with vitamin A also decreased the number of deaths among children in the community. The protective effect of Vitamin A was slightly higher in younger children than in older children in the community. Vitamin A should be given to all children suffering from measles regardless of whether they have a vitamin A deficiency.

Changes in coronary arteriograms over time may be used to evaluate a patient's risk of death from atherosclerotic coronary heart disease (ACHD). A coronary arteriogram is an X-ray of the arteries of the heart that is taken after injection of a contrast dye. Among 838 patients with ACHD, 421 underwent surgery to treat ACHD and 417 did not undergo surgery. Among 695 patients who had an arteriogram taken at the time of diagnosis with ACHD and three years later, changes between the initial and three-year arteriogram were associated with death from ACHD. Changes in sequential arteriograms were associated with a higher risk of a heart attack or death from ACHD both among patients who underwent surgery and those who did not. Fewer patients who underwent surgery died or had a heart attack, compared with those who did not undergo surgery. An arteriogram provides a radiographic image of atherosclerotic lesions.

Cumulative meta-analysis may be an effective method for comparing the findings of clinical trials evaluating the use of drugs or medical procedures. Cumulative meta-analysis was used to analyze 33 clinical trials between 1959 and 1988 that evaluated the use of intravenous streptokinase to break up blood clots in heart attack patients. After eight clinical trials using 2,432 patients, there was a significant decrease in the number of deaths from a heart attack among patients treated streptokinase. No significant increase in effectiveness was seen in the next 25 clinical trials that examined the use of streptokinase in 34,542 patients. Cumulative meta-analysis was also used to compare clinical trials that evaluated the use of fourteen other drugs used to treat heart attack patients.

Cumulative meta-analysis is a statistical technique which helps to identify the year when the combined results of medical research in multiple randomized control trials (RCT) reach a level of statistical significance. When results reach this level, the technique shows whether one treatment is better than another and allows researchers to assess the impact of new RCTs on current treatment recommendations. Because of the lag between the publication of research results and these results reaching practicing physicians and opinion leaders, there are many differences between treatment recommendations from new RCTs and treatment recommended by physicians and medical experts. Overcoming this lag is one of the goals of the Agency for Health Care Policy and Research, part of the Heart, Cancer and Stroke program established by Congress in 1965.

Objectives. Individual epidemiological investigations into the association between chlorination by-products in drinking water and cancer have been suggestive but inconclusive. Enough studies exist to provide the basis for a meaningful meta-analysis. Methods. An extensive literature search was performed to identify pertinent case-control studies and cohort studies. Consumption of chlorinated water, surface water, or water with high levels of chloroform was used as a surrogate for exposure to chlorination by-products. Relative risk estimates were abstracted from the individual studies and pooled. Results. A simple meta-analysis of all cancer sites yielded a relative risk estimate for exposure to chlorination by-products of 1.15 (95% CI: 1.09, 1.20). Pooled relative risk estimates for organ-specific neoplasms were 1.21 (95% CI: 1.09, 1.34) for bladder cancer and 1.38 (95% CI: 1.01, 1.87) for rectal cancer. When studies that adjusted for potential confounders were pooled separately, estimates of relative risks did not change substantially. Conclusions. The results of this meta-analysis suggest a positive association between consumption of chlorination by-products in drinking water and bladder and rectal cancer in humans. (Am J Public Health. 1992;82:955-963)

Patients with actively bleeding ulcers of the stomach (gastric) or intestine (duodenal) may require surgery. A bleeding ulcer is examined with a flexible instrument called an endoscope. Hemostasis, the cessation of bleeding, and repair of blood vessels may be accomplished using lasers or sclerotherapy, injection of a solution that causes scarring or fibrosis of the ulcerous area. Reported cases of patients with bleeding ulcers treated with endoscopic hemostatic procedures were evaluated. Three variables were examined for each patient: the need for emergency surgery, in-hospital mortality (risk for death), and recurrence of bleeding. Endoscopic hemostasis produced significant reductions in the three end points when compared with non-invasive medical management. The need for emergency surgery and death rates can be reduced by treating actively bleeding patients. It was not clearly determined which method of endoscopic hemostasis is best; however, injection sclerotherapy may be the standard against which other treatments should be measured. (Consumer Summary produced by Reliance Medical Information, Inc.)