Criticism of Hartung's analysis.
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Anesthetics, Inhalation↗
Biomedical subjects
B Kupelnick
Publications and source records attributed to B Kupelnick.
Searching for signals: mortality and cardiovascular events in published randomized control trials of nifedipine in ischemic heart disease and hypertension.
UNLABELLED: META-ANALYSIS: A meta-analysis of published randomized control trials of nifedipine in hypertension and stable angina pectoris was performed. RESULTS: The results suggest a formulation-dependent increased risk of mortality and adverse cardiovascular outcomes for monotherapy use in patients with stable angina pectoris. No increased risk was seen in the hypertension studies.
Humans↗
Efficacy and safety of different aspirin dosages on vascular diseases in high-risk patients. A metaregression analysis.
PURPOSE: To compare the efficacy and safety of different aspirin dosages in trials with patients at increased risk of vascular disease. DATA SOURCES: Pertinent studies were selected using MEDLINE (1966 through 1992), weekly reviews of Current Contents (1970 through 1992), and references from review articles and editorials. STUDY SELECTION: Thirty-six randomized control trials of aspirin compared with another dosage of aspirin or with placebo. METHODS: The Mantel-Haenszel method of pooling odds ratios and metaregression involving log odds ratio (and the risk difference) on aspirin dosage, adjusting for the control rate and the mean length of follow up of the studies. RESULTS: For all patients and for subgroups of patients with previous vascular conditions, there was no relationship between dose and vascular events. For all patients, a dose-response relation was not found with gastrointestinal hemorrhages and hemorrhagic stroke, but was found with gastrointestinal symptoms and withdrawals from side effects. For every 25 mg/day increase in aspirin dosage, the odds ratio of gastrointestinal symptoms and withdrawals increased, respectively, by 0.87% (99% Cl, 0.18 to 1.57%) and 0.94% (99% Cl, 0.06 to 1.82%). The corresponding absolute risk increases were 0.58 and 0.78 per 1,000 patients. CONCLUSIONS: Direct and indirect comparisons of high-risk patients suggest no statistical differences in efficacy, gastrointestinal bleeds, and hemorrhagic strokes across aspirin dosages. These comparisons, however, suggest decreased risk of gastrointestinal symptoms and of withdrawals with lower doses of aspirin. More direct comparison studies are warranted that should contrast the benefits and risks to determine the net benefit.
Aspirin↗
Use of prophylactic tinidazole to avoid the serious infections associated with total abdominal hysterectomy.
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Antitrichomonal Agents↗
Cognitive behavioral techniques for hypertension: are they effective?
PURPOSE: To assess by analysis of published controlled trials the efficacy of cognitive behavioral therapies (such as biofeedback, relaxation, meditation) for essential hypertension. DATA IDENTIFICATION: Randomized controlled trials published in the English language between 1970 and 1991 identified from the MEDLINE database and bibliographic references from these articles. STUDY SELECTION: Limited to studies involving randomized assignment to a treatment group consisting of one or more cognitive behavioral interventions or a concurrent control group consisting of no therapy, a waiting list, regular monitoring, or placebo intervention. RESULTS OF DATA SYNTHESIS: Although we identified more than 800 published works, only 26 met entry criteria. We identified a number of methodologic short-comings, including small sample size, inconsistencies regarding baseline blood pressure determinations and types of control groups, and the possibility of confounding by multiple noncognitive cointerventions (diet, exercise) and expectancy (the placebo effect). In meta-analyses involving 1264 patients, differences in mean blood pressure reduction varied according to the duration of baseline blood pressure measurements and type of control groups studied. In 16 comparisons involving baseline periods of more than 1 day, with patients (n = 368) assigned to either a cognitive therapy or a placebo intervention (sham biofeedback, "pseudo-meditation"), systolic and diastolic blood pressures decreased by 2.8 mm Hg (95% CI, -0.8 to 6.4) and 1.3 mm Hg (CI, -1.3 to 3.8), respectively. These changes were neither statistically nor clinically significant. CONCLUSION: Cognitive interventions for essential hypertension are superior to no therapy but not superior to credible sham techniques or to self-monitoring alone. The literature on this subject is limited by a variety of methodologic inadequacies. No single cognitive behavioral technique appears to be more effective than any other.
Behavior Therapy↗
Early angiography and angioplasty following thrombolytic therapy of acute myocardial infarction. Metaanalysis of the randomized control trials.
STUDY OBJECTIVE: There have been at least 10 randomized control trials (RCTs) of early intervention in patients with acute myocardial infarction published, and all are inconclusive with regard to impact on mortality. Metaanalysis offers an opportunity to assess the efficacy of an early intervention following thrombolytic therapy in the treatment of acute myocardial infarction. DESIGN: Data on the number of patients who died in the hospital, and the total number of patients randomized to aggressive versus conservative therapies, were drawn from 9 publications and combined using both a fixed and a random-effects metaanalysis model. Quality of the trials was assessed under blinded conditions. SETTING: The 10 RCTs to be combined were each carried out in individual institutions. PATIENTS: A total of 5882 patients have been randomized, with 305 deaths (5.2%), indicating that this group of patients had a relatively low mortality rate compared to patients in general with acute myocardial infarction. COMPARISON OF TREATMENTS: No matter how the 10 trials were combined for analysis, there was no evidence that aggressive intervention was trending towards saving lives. Data on other endpoints such as need for repeat percutaneous transluminal coronary angioplasty (PTCA), coronary artery bypass grafting (CABG), or recurrent myocardial infarction were sparse, but the same adverse trend was apparent. CONCLUSION: In spite of the fact that early angiography and PTCA when indicated have been advocated for more than a decade, there is still no evidence that they reduce overall mortality after fibrinolysis in a specific subgroup. Further studies of early intervention should be done in an effort to answer subgroup questions which include the search for appropriate timing and patient selection for PTCA after fibrinolysis. As more RCTs with mortality data are published they will be added to these metaanalyses in The Online Journal of Current Clinical Trials.
Angioplasty, Balloon, Coronary↗
Avoiding serious infections associated with abdominal hysterectomy: a meta-analysis of antibiotic prophylaxis.
OBJECTIVE: Our objective was to determine whether the use of preoperative antibiotics prevents serious infections associated with total abdominal hysterectomy. STUDY DESIGN: We identified 25 randomized controlled trials of antibiotic prophylaxis that used rigorous protocols. We performed meta-analysis and cumulative meta-analyses for all of the trials, and then we performed separate meta-analysis for cefazolin, metronidazole, and tinidazole. RESULTS: Overall, 21.1% (373 of 1768) of the patients who did not receive antibiotic prophylaxis had serious infections after abdominal hysterectomy. Among patients who received any antibiotics, we found that 9.0% (166/1836) had serious postoperative infections; among those who received cefazolin, metronidazole, or tinidazole, 11.4% (70 of 615), 6.3% (17 of 269), and 5.0% (5 of 101), respectively, had serious postoperative morbidity. The differences in the prevalence of infection between women who received prophylaxis and women who did not receive prophylaxis were statistically significant (any antibiotics, p = 0.00001; cefazolin, p = 0.00021; metronidazole, p = 0.015; and tinidazole, p = 0.034). CONCLUSION: Because preoperative antibiotics are highly effective in the prevention of serious infections associated with total abdominal hysterectomy, we believe they should be used routinely. In addition, we believe that the use of controls who receive no treatment is no longer justified in trials of antibiotic prophylaxis for total abdominal hysterectomy.
Abdomen↗
Cumulative meta-analysis of therapeutic trials for myocardial infarction.
BACKGROUND: The large volume of published randomized, controlled trials has led to a need for meta-analyses to track therapeutic advances. Performing a new meta-analysis whenever the results of a new trial of a particular therapy are published permits the study of trends in efficacy and makes it possible to determine when a new treatment appears to be significantly effective or deleterious. We describe the use of such a procedure, cumulative meta-analysis, to assess therapeutic trials among patients with myocardial infarction. METHODS: We performed cumulative meta-analyses of clinical trials that evaluated 15 treatments and preventive measures for acute myocardial infarction. RESULTS: An example of this method is its application to the use of intravenous streptokinase as thrombolytic therapy for acute infarction. Thirty-three trials evaluating this therapy were performed between 1959 and 1988. We found that a consistent, statistically significant reduction in total mortality (odds ratios, 0.74; 95 percent confidence interval, 0.59 to 0.92) was achieved in 1973, after only eight trials involving 2432 patients had been completed. The results of the 25 subsequent trials, which enrolled an additional 34,542 patients through 1988, had little or no effect on the odds ratio establishing efficacy, but simply narrowed the 95 percent confidence interval. In particular, two very large trials, the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico trial in 1986 (11,712 patients) and the Second International Study of Infarct Survival trial in 1988 (17,187 patients) did not modify the already established evidence of efficacy. We used a similar approach to study the accumulating evidence of efficacy (or lack of efficacy) of 14 other therapies and preventive measures for myocardial infarction. CONCLUSIONS: Cumulative meta-analysis of therapeutic trials facilitates the determination of clinical efficacy and harm and may be helpful in tracking trials, planning future trials, and making clinical recommendations for therapy.
Confidence Intervals↗
A comparison of results of meta-analyses of randomized control trials and recommendations of clinical experts. Treatments for myocardial infarction.
OBJECTIVE: To examine the temporal relationship between accumulating data from randomized control trials of treatments for myocardial infarction and the recommendations of clinical experts writing review articles and textbook chapters. DATA SOURCES: (1) MEDLINE search from 1966 to present; search terms used were myocardial infarction, clinical trials, multicenter studies, double-blind method, meta-analysis, and the text word "random:"; (2) references from pertinent articles and books; and (3) all editions of English-language general medical texts and manuals and review articles on treatment of myocardial infarction. STUDY SELECTION: Randomized control trials of therapies for reducing the risk of total mortality in myocardial infarction (acute and secondary prevention). Review articles and textbook chapters dealing with the general clinical management of patients with myocardial infarction. DATA EXTRACTION: Two authors read the material and recorded the results; disagreements were resolved by conference. DATA SYNTHESIS: We used the technique of cumulative meta-analysis (performing a new meta-analysis when the results of a new clinical trial are published) and compared the results with the recommendations of the experts for various treatments for myocardial infarction. Discrepancies were detected between the meta-analytic patterns of effectiveness in the randomized trials and the recommendations of reviewers. Review articles often failed to mention important advances or exhibited delays in recommending effective preventive measures. In some cases, treatments that have no effect on mortality or are potentially harmful continued to be recommended by several clinical experts. CONCLUSIONS: Finding and analyzing all therapeutic trials in a given field has become such a difficult and specialized task that the clinical experts called on to summarize the evidence in a timely fashion need access to better databases and new statistical techniques to assist them in this important task.
Humans↗
Meta-analysis to assess the efficacy of interferon-alpha in patients with follicular non-Hodgkin's lymphoma.
The authors wanted to determine whether adding interferon-alpha (IFN-alpha) to chemotherapy regimens, in either induction or maintenance settings, provides additional survival benefits in follicular non-Hodgkin's lymphoma (NHL). A meta-analysis was performed based on published data from randomized controlled clinical trials involving nine separate study populations. Patients receiving IFN-alpha (in either induction or maintenance therapy) had significantly increased 5-year and progression-free survival rates at 3 and 5 years compared with concurrent controls. The advantages of IFN-alpha therapy were most marked in studies using anthracycline-containing induction chemotherapy; in these studies, patients who received IFN-alpha had approximately 20% increased progression-free survival rates compared with controls and a lesser survival advantage. The available literature did not allow a determination of the relative benefit of IFN-alpha in induction or maintenance treatments for NHL or a determination of the optimum duration of IFN-alpha treatment. Although questions remain about its optimal use. IFN-alpha appears to prolong survival time in patients with follicular NHL.
Aged↗
Impact of intravesical chemotherapy on recurrence rate of recurrent superficial transitional cell carcinoma of the bladder: results of a meta-analysis.
BACKGROUND: The impact of in tranvesical chemotherapy on preventing recurrence of superficial transitional cell carcinoma of the bladder is controversial. The objective of this report is to present a meta-analysis of the available clinical trial data to quantify the effect of intravesical chemotherapy on tumor recurrence following trans-urethral resection (TURB) in patients with recurrent superficial bladder cancer. METHODS: A prospective study protocol outlining a meta-analysis was developed followed by a thorough search of the existing published literature using strict eligibility criteria. Eight randomized trials were found which met protocol specifications. These studies contained data on 1,609 patients which were statistically combined using a fixed effects model (Peto). The outcome of interest was the proportion of patients with tumor recurrence at one, two and three years post-TURB. RESULTS: Combining all 8 studies using 1 year recurrence as the outcome measure yielded a Peto odds ratio (ORp) of 0.62, demonstrating a 38% reduction in one year recurrence among patients treated with intravesical chemotherapy versus TURB alone. Using 2 and 3 year recurrence as the outcome measure yielded ORp's of 0.46 and 0.35 respectively, favoring TURB + intravesical chemotherapy versus TURB alone. A statistical test for heterogeneity (Q) showed the 2 and 3 year outcome data to be heterogeneous (i.e. the studies are not measuring an effect of the same magnitude). Sensitivity analyses showed that drug type appeared to account for the observed heterogeneity with a stratified analysis demonstrating that adriamycin is less effective in reducing subsequent tumor recurrences than all other drugs studied. CONCLUSION: Intravesical chemotherapy appears to have a major impact on decreasing the chance of recurrence of recurrent superficial bladder cancer. Three year recurrence is decreased by as much as 70% when compared with TURB alone. These data are in contrast to prior analyses suggesting only modest efficacy of such treatment in this clinical setting.
Administration, Intravesical↗
Dietary beta-carotene intake and the risk of epithelial ovarian cancer: a meta-analysis of 3,782 subjects from five observational studies.
OBJECTIVE: The etiology of epithelial ovarian cancer is unknown. Prior work suggests that high dietary beta-carotene intake is associated with a decreased risk of this tumor although this association remains speculative. A meta-analysis was performed to evaluate this suspected relationship. METHODS: Using previously described methods, a protocol was developed for a meta-analysis examining the association between high dietary beta-carotene intake versus low intake and the risk of epithelial ovarian cancer. Literature search techniques, study inclusion criteria and statistical procedures were prospectively defined. Data from observational studies were pooled using a general variance based meta-analytic method employing confidence intervals previously described by Greenland. The outcome of interest was a summary relative risk (RRs) reflecting the risk of ovarian cancer associated with high beta-carotene intake versus low dietary intake. Sensitivity analyses were performed when necessary to evaluate any observed statistical heterogeneity. RESULTS: Five observational studies enrolling 3,782 subjects were initially pooled in a meta-analysis subsequent to an analysis showing a lack of statistical heterogeneity. The meta-analysis showed a summary relative risk of 0.84 with a 95% confidence interval of 0.75-0.94, a statistically significant result. These data suggest that high (versus low) dietary intake of beta-carotene is associated with a sixteen percent decrease in ovarian cancer risk. Sensitivity analyses showed no impact of study design or differences in quantitative measure of beta-carotene intake across studies on the summary relative risk. CONCLUSIONS: High dietary intake of beta-carotene appears to represent a protective factor for the development of ovarian cancer although its magnitude is modest. Further work is needed to clarify factors that may modify the effects of beta-carotene in vivo.
Adult↗
Paternal smoking during pregnancy and the risk of childhood brain tumors: results of a meta-analysis.
OBJECTIVE: Prior epidemiological studies suggest a possible association between paternal smoking during pregnancy and risk of childhood brain tumors (CBT). A meta-analysis was performed statistically pooling all available observational studies on this topic in order to evaluate this suspected association. METHODS: Using previously described methods, a protocol was developed for a meta-analysis examining the association between paternal smoking during pregnancy and subsequent development of primary brain tumors in their offspring. Literature search techniques study inclusion criteria and statistical procedures were prospectively defined. Data from epidemiological studies were pooled using a general variance based meta-analytic method employing confidence intervals previously described by Greenland. The outcome of interest was a summary relative risk (RRs) reflecting the risk of childhood brain tumor development associated with father's smoking during the index pregnancy. Sensitivity analyses were performed when necessary to explain any observed statistical heterogeneity and/or to evaluate the impact of demographic or study characteristics on the summary estimate of effect. RESULTS: Seven observational studies meeting protocol specified inclusion criteria were obtained via a comprehensive literature search. These studies enrolled a total of 3,600 patients. Analysis for homogeneity demonstrated that the data were homogeneous (P = 0.52) and could be statistically combined. Pooling all seven reports yielded a RRs of 1.29 (1.07-1.53), a statistically significant result suggesting a 29% increased risk of brain tumor development associated with paternal smoking during pregnancy. An analysis of father's smoking impact on CBT risk based on "ever" versus "never" smoking history gave a RRs of 1.14 (0.98-1.34), a marginally non-statistically significant result. CONCLUSION: The available epidemiological data suggest an association between paternal smoking during pregnancy and pediatric brain tumor development. Although this association is biologically plausible, limitations in study designs limit definitive conclusions based on available data.
Adolescent↗
Meta-analysis: an update.
A fairly new type of research, termed meta-analysis, attempts to analyze and combine the results of previous reports. In 1992 we updated our 1987 survey of 86 meta-analyses of randomized control trial reports in the english language literature with an additional 78. We evaluated the quality of these meta-analyses using a scoring method that lists 23 items in six major areas: study design, combinability, control of bias, statistical analysis, sensitivity analysis, and application of results. Of the 23 individual items, the mean number satisfactorily addressed was 7.63 +/- 2.84 (mean +/- S.D.) for 40 papers published from 1955 through 1982, 6.80 +/- 3.86 for 66 papers published from 1983 through 1986, and 11.91 +/- 4.79 for 58 papers published from 1987 through 1990 (F = 31.3, p < .001). We noted that methodology has definitely improved since our first survey of meta-analyses, but an urgent need still exists for a better search of the literature, quality evaluation of trials, and a synthesis of the results. Recently, meta-analysis has expanded to cover non-randomized studies, including evaluation of diagnostic tests and pooling of epidemiologic studies. There is growing concern for standards, and several methodologic issues remain unresolved.
Bias↗
A systematic review and meta-analysis of the incidence of cancer in randomized, controlled trials of verapamil.
We conducted a systematic review of all published randomized, controlled trials to assess the risk of cancer or death in patients receiving verapamil for hypertension, angina pectoris, or cardiac arrhythmias. Meta-analysis comparing the risk of new cancers, cancer deaths, and all deaths was performed. Thirty-nine trials comprising 11,201 patients were eligible. Study durations ranged from 8 days-6 years (mean 29.5 wks). Nine trials (6507 patients) were 24 weeks in duration or longer. For cancer and cancer death, OR was 1.20 (95% CI = 0.60-2.42) for verapamil versus active controls and 0.73 (95% CI = 0.39-1.39) for verapamil versus placebo. For all deaths, OR was 1.13 (95% CI = 0.70-1.82) for verapamil versus active controls and 0.85 (95% CI = 0.71-1.00) for verapamil versus placebo. Sensitivity analysis for the 9 trials 24 weeks' duration or longer gave similar results. There is no statistically significant increased risk of cancer or deaths with verapamil compared with active controls or placebo.
Calcium Channel Blockers↗