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The use of meta-analysis in technology assessment: a meta-analysis of the enzyme immunosorbent assay human immunodeficiency virus antibody test.

The purpose of this study is to demonstrate the usefulness of meta-analysis and regression analysis in evaluating technologies by applying these techniques to an evaluation of the enzyme immunosorbent assay (EIA) human immunodeficiency virus (HIV) antibody test. This meta-analysis synthesizes 26 studies which report on sensitivity and specificity of the EIA HIV antibody test. Sensitivity and specificity values vary widely, ranging between 89-100% sensitivity and 67-100% specificity. To examine this variation, a regression model is tested that explains specificity as a function of the year the study was published, the population being sampled, and a quality rating. The model explains 29% of the total variation. The most significant determinant of specificity is the type of population sampled; studies with low prevalence samples have higher specificity. This study demonstrated that meta-analysis can be used to synthesize literature on technologies, and that regression analysis can be used to examine the sources of variation that meta-analysis uncovers. It also demonstrates the need for studies of test performance to use standardized research procedures and to fully report their methods and results.

AIDS Serodiagnosis

Cyclophosphamide plus cisplatin versus cyclophosphamide, doxorubicin, and cisplatin chemotherapy of ovarian carcinoma: a meta-analysis. The Ovarian Cancer Meta-Analysis Project.

Four randomized clinical trials comparing cyclophosphamide plus cisplatin (CP) versus cyclophosphamide, doxorubicin, and cisplatin (CAP) individually failed to show a significant survival difference in the treatment of ovarian carcinoma. However, by pooling 1,194 patients from these trials in a meta-analysis, there is a statistically significant survival benefit for CAP (P = .02); in addition, there is a significant advantage for CAP in frequency of negative second-look laparotomy (CAP, 30%; CP, 23%; P = .01). Because the dose intensity of CAP was greater than CP in three of the trials, it remains unresolved to what extent the benefit of CAP is from greater dose intensity and to what extent it is from the doxorubicin itself. Either interpretation suggests directions for improving the chemotherapy of ovarian carcinoma.

Antineoplastic Combined Chemotherapy Protocols

Suction-assisted ureteroscopy compared with traditional ureteroscopy for renal stones ≤ 2 cm: a systematic review, Bayesian network meta-analysis and meta-regression.

INTRODUCTION AND OBJECTIVE: Suction-enhanced flexible ureteroscopy (URS) aims to improve stone clearance and reduce complications. We performed a Bayesian network meta-analysis to compare the efficacy and safety of flexible aspiration navigable sheaths (FANS) and direct in-scope suction (DISS) for renal calculi ≤ 2 cm. METHODS: A systematic search of PubMed, MEDLINE, Scopus, Web of Science, and Google Scholar was conducted through June 2026. Comparative studies of FANS, DISS, or conventional access sheaths for renal stones ≤ 2 cm were included. The primary outcome was 30-day stone-free rate (SFR). Secondary outcomes included operative time, fever, sepsis, and complications. A Bayesian random-effects network meta-analysis synthesized direct and indirect evidence. RESULTS: Seventeen studies including 3,657 patients (1,677 FANS, 56 DISS, 1,924 control) were included. FANS showed higher SFR (OR 2.5, 95% CrI 2.0-3.1), while grouped DISS had a similar but less precise effect (OR 3.1, 95% CrI 1.0-8.8). Calyxo V2 had the highest SFR (OR 5.4, 95% CrI 1.0-29.0), whereas PUSEN showed no significant difference (OR 1.6, 95% CrI 0.41-6.3). FANS reduced postoperative fever and complications. FANS also showed lower odds of postoperative sepsis (OR 0.40, 95% CrI 0.12-0.97). CONCLUSIONS: Suction-assisted ureteroscopy improves SFR for renal calculi ≤ 2 cm. FANS was associated with shorter operative time, fever, and complications. DISS systems show promising but limited results, with performance differing by technology configuration. Larger prospective trials are needed.

Humans

Synthesis of research findings through meta-analysis.

Meta-analysis is an alternative, quantitative approach to the analysis and synthesis of multiple investigations of the same clinical question. The statistical approaches that have been developed since Glass coined the term meta-analysis in 1976 are discussed. Clinicians will find meta-analysis helpful when there are conflicting research findings about perplexing clinical problems.

Bias

Prevention of succinylcholine myalgias: a meta-analysis.

Meta-analysis is a term used to describe statistical methods for evaluating a series of research reports; this analysis transcends the limitations that may be inherent in each of the individual studies summarized. Forty-five research reports of clinical trials for the prevention of myalgias after succinylcholine were assembled. Four classes of preventive drugs (nondepolarizing muscle relaxants, benzodiazepines, succinylcholine in "self-taming" doses, and local anesthetics) were reported in detail sufficient to allow for inclusion in a meta-analysis of clinical efficacy. Each study was summarized by determining the difference in the incidence of myalgias on the first postoperative day between treatment and control groups. A random-effects variance components approach was used. Seven meta-analyses were performed (atracurium, d-tubocurarine, gallamine, pancuronium, diazepam, succinylcholine in self-taming doses, and lidocaine). For each meta-analysis there was statistically significant heterogeneity among studies. Atracurium, d-tubocurarine, gallamine, pancuronium, diazepam, and lidocaine all significantly decreased the frequency of myalgias by about 30%. Succinylcholine in self-taming doses alone was not efficacious.

Humans

The Effects of Intermittent Hypoxic Training Strategies on Maximal Oxygen Uptake in Healthy Humans: A Meta-analysis with Meta-regression.

BACKGROUND: Intermittent hypoxic training aims to enhance exercise performance and health, commonly assessed through maximal oxygen uptake (VO2max). Currently applied methods are live-high train-low (LHTL), live-low train-high (LLTH) and passive hypoxic conditioning (PHC). However, within these methods, numerous modes of application exist, and effectiveness is debated. OBJECTIVE: To determine the effect of LHTL, LLTH and PHC on VO2max in healthy participants, and identify factors associated with the amplitude of change in VO2max. METHODS: We conducted a systematic review with random-effects meta-analysis and meta-regression. Studies were identified through PubMed, EMBASE and Web of Science. We included controlled studies, calculating between-group standardised mean differences. Athlete and non-athlete populations were analysed separately. RoB2 was used to assess study quality and publication bias was investigated with funnel plots and the Egger's test. RESULTS: Of the 5244 identified studies, 62 were included for analysis, resulting in a sample size of 1332 participants (610 athletes, 722 non-athletes). LHTL increased VO2max significantly more than control in athletes (mean difference [MD] = 2.17; 95% CI = 0.77, 3.56) but not in non-athletes (MD = 3.1; 95% CI =  - 0.23, 6.43). LLTH did not increase VO2max significantly more than control in athletes (MD = 0.89; 95% CI =  - 0.27, 2.05) but it did in non-athletes (MD = 1.70; 95% CI = 0.85, 2.54). PHC did not increase VO2max significantly more than control in athletes (MD =  - 1.07; 95% CI =  - 3.51, 1.37) but it did in non-athletes (MD = 2.26; 95% CI = 1.00, 3.52). Multivariate meta-regressions identified the severity, duration, and frequency of hypoxic exposure to be significantly associated with the change in VO2max. CONCLUSIONS: LHTL showed a significant effect on VO2max in athletic populations while LLTH and PHC showed a significant effect on VO2max in non-athletic populations only. Future studies should target investigating which characteristics (e.g. severity, duration) of the hypoxic exposure are most beneficial.

Journal Article

Methods for trend estimation from summarized dose-response data, with applications to meta-analysis.

Meta-analysis often requires pooling of correlated estimates to compute regression slopes (trends) across different exposure or treatment levels. The authors propose two methods that account for the correlations but require only the summary estimates and marginal data from the studies. These methods provide more efficient estimates of regression slope, more accurate variance estimates, and more valid heterogeneity tests than those previously available. One method also allows estimation of nonlinear trend components, such as quadratic effects. The authors illustrate these methods in a meta-analysis of alcohol use and breast cancer.

Alcohol Drinking

Incorporating variations in the quality of individual randomized trials into meta-analysis.

Meta-analysis is a method of synthesizing evidence from multiple sources. It has been increasingly applied to combine results from randomized trials of therapeutic strategies. Unfortunately there is often variation in the quality of the trials that are included in meta-analyses, limiting the value of combining the results in an overview. This variation in quality can lead to both bias and reduction in precision of the estimate of the therapy's effectiveness. There are a number of methods for quantifying the quality of trials including the detailed Chalmers system and simple scales. The nature of the relationship between these quality scores and the true estimate of effectiveness is unknown at this time. We discuss four methods of incorporating quality into meta-analysis: threshold score as inclusion/exclusion criterion, use of quality score as a weight in statistical pooling, visual plot of effect size against quality score and sequential combination of trial results based on quality score. The last method permits an examination of the relation between quality and both bias and precision on the pooled estimates. We conclude that while it is possible to incorporate the effect of variation of quality of individual trials into overviews, this issue requires more study.

Bias

Classroom behavior of children and adolescents with learning disabilities: a meta-analysis.

Meta-analysis was used to review the results of 25 studies that compared the classroom behavior of children and adolescents with learning disabilities (LD) to children without learning disabilities. The data were analyzed from several different methodological perspectives. Results showed that both methodologically strong and weak studies demonstrated significant behavioral deficits of children with learning disabilities compared to their nondisabled peers in each of five overall areas: on-task behavior, off-task behavior, conduct disorders, distractibility, and shy/withdrawn behavior. Both observational and teacher rating data demonstrated these differences. Effect sizes for both groups of studies seemed to cluster around 1 standard deviation, suggesting noticeable and educationally significant impairment in the behavior of children with disabilities. Analysis of grade-level effect sizes suggests some explanation for the large number of referrals often witnessed during the elementary school years. Educational implications of these behavioral differences in terms of implications for mainstreaming are discussed.

Child

Lithium treatment and prophylaxis in unipolar depression: a meta-analysis.

Meta-analysis was used to establish the efficacy of lithium in acute treatment and prophylaxis of depressive illness from existing published clinical trials. Effect sizes were measured by the odds ratio using the Mantel-Haenszel method and the Pearson product-moment correlation coefficient. Some benefit from lithium, compared with other treatments, emerged from trials of acute treatment. Lithium was clearly superior to placebo in the acute treatment of bipolar depressed patients. In controlled studies of lithium prophylaxis over five months to three years, an impressive effect was found for lithium when compared with placebo. For uncontrolled studies there was a similar-sized effect, corresponding to an improvement in the rate of favourable outcome from 35% for placebo to 70% with lithium treatment. The comparison of lithium with other antidepressants in prophylaxis showed no conclusive advantage for lithium in unipolar illness. There is no reason to doubt the efficacy of lithium in the prophylaxis of unipolar depressive illness.

Antidepressive Agents

A review of mortality from choroidal melanoma. II. A meta-analysis of 5-year mortality rates following enucleation, 1966 through 1988.

With the use of data published during the period from 1966 through 1988, a pooled analysis (meta-analysis) of 5-year mortality rates among patients who had an eye enucleated for choroidal melanoma was performed to provide a more robust estimate of this rate than could be obtained from any single study. The literature concerning mortality following a diagnosis of choroidal melanoma has been reviewed systematically and described in a separate article. Of 76 reports published from 1966 through 1988, 29 were excluded from the meta-analysis because there were no cases treated by enucleation alone, mortality was not reported by time from enucleation, fewer than 10 cases were reported, or 5-year mortality rates were not reported or derivable from the data presented. Ten additional reports were excluded because they were based on data for the same set of patients as another article in the series. Of the remaining 37 reports, 29 contained data for patients with tumors of varying sizes that could not be separated into subgroups based on the size of the tumor at the time of treatment. The remaining eight articles reported 5-year mortality rates by tumor size, specifically for small, medium, or large tumors. The combined weighted estimates of 5-year mortality rates following enucleation were 16% for small tumors (95% confidence interval [CI]: [14%, 18%]), 32% for medium tumors (95% CI: [29%, 34%]), and 53% for large tumors (95% CI: [50%, 56%]). Different methods of pooling the data yielded consistent estimates for all three tumor size categories.(ABSTRACT TRUNCATED AT 250 WORDS)

Choroid Neoplasms

[Corticoid therapy in the treatment of acute alcoholic hepatitis. Results of a meta-analysis].

A meta-analysis of 10 randomized trials comparing steroid therapy with placebo or abstention was performed. Trials were pooled for severity of acute alcoholic hepatitis and time of analysis. Papers with survival analyses at one and three months were included. The robustness of this meta-analysis was analysed after exclusion of trials analysing survival at three months only, trials including mild forms, or atypical trials. Comparisons were made use the Der Simonian-Laird and Mantel-Haenszel-Peto methods. All results were statistically significant. However, if only one medium size trial were to be added, the results would no longer be significant. Taking into account the complications of steroid therapy, we conclude that further clinical trials are necessary to confirm the effectiveness of steroid therapy, especially for the group of patients with severe alcoholic hepatitis.

Acute Disease

Maternal spermicide use and adverse reproductive outcome: a meta-analysis.

A meta-analysis was performed to determine whether the literature provides evidence that periconceptual or postconceptual maternal use of spermicides is detrimental to the developing fetus. Nine studies that investigated teratogenicity met the inclusion criteria. The Mantel-Haenszel summary odds ratio was 1.02 (95% confidence interval = 0.78 to 1.32). The chi 2 analyses was 0.10 for significance from unity (p = 0.748) and 8.73 for homogeneity of effects (p = 0.365). Studies comparing specific abnormalities with other abnormalities also indicated no association (odds ratio = 0.96; 95% confidence interval = 0.72 to 1.28). Studies investigating other adverse events (spontaneous abortion, stillbirth, reduced fetal weight, prematurity, or increased incidence of female births) showed similar negative results. Cohen's d, the overall effect size as determined by Tukey's jackknife method, was -0.001 (95% confidence interval = -0.018 to 0.017). These results indicate that maternal use of spermicides is not associated with adverse fetal outcomes. Meta-analysis adds quantitative support for conclusions from traditional reviews of the subject.

Female

An overview of statistical issues and methods of meta-analysis.

A meta-analysis is a statistical analysis of the data from some collection of studies in order to synthesize the results. In this paper we discuss issues that frequently arise in meta-analysis and give an overview of the methods used, with particular attention to the use of fixed- and random-effects approaches. The methods are then applied to two sample datasets.

Biopharmaceutics

[Beta-blockers in the prevention of the rupture of esophageal varices. A meta-analysis].

The meta-analysis of 5 trials for primary prevention and of 18 trials of secondary prevention emphasizes the effect of beta-blockers in the decrease of variceal bleedings in cirrhosis. Beta-blockers are reducing the bleeding events with 32% in the primary prevention and with 28% in the secondary prevention. The mortality is reduced by 15%, respectively by 23%. This is the first meta-analysis reported in the Romanian gastroenterological literature.

Adrenergic beta-Antagonists

The effect of naftidrofuryl on intermittent claudication: a meta-analysis.

A meta-analysis was performed on four clinical trials, conducted during 1980-1989 in France (two trials) and in the Federal Republic of Germany (two trials). Altogether, 596 patients with peripheral arterial occlusive disease (Fontaine's classification stage II) entered these four multicenter studies. Four hundred fifty-two patients completed the trials, 241 were treated with 600 mg naftidrofuryl orally per day and 211 were given a placebo. The studies were of a double-blind parallel design and lasted for 3 or 6 months. Inclusion and exclusion criteria were comparable, as were the experimental methods used. Occasionally, differences in study design and methods were observed. Risk factors were recorded in three of the four studies. The outcome criterion of pain-free walking distance was studied for the four trials together and showed a significant improvement in the active drug tested group, following both 3- and 6-month duration of treatment. The type of treatment, the severity of the disease, the existence of blood lipid disorders, and smoking were found to be the predictive factors associated with the evolution of pain-free walking distance during 3 months. The meta-analysis confirms the beneficial effect of naftidrofuryl in treating peripheral arterial occlusive disease.

Adult

Menopausal hormone replacement therapy and breast cancer: a meta-analysis.

A meta-analysis was performed to determine whether the scientific literature provides enough evidence that hormone replacement therapy after menopause increases the risk of breast cancer. Studies were located by MEDLINE, supplemented by a hand search of all the references in the articles located. The papers were graded as to quality. Those considered unbiased were combined using Woolf's method. Thirty-seven original studies were found: 23 case-control, 13 cohort, and one clinical trial. Overall, a small but statistically significant relative risk (RR) figure of 1.06 was calculated. Women who experienced natural menopause seemed to be at increased risk (RR = 1.13). A significant weighted RR was observed in current hormone replacement therapy users, especially in those who had natural menopause (RR = 1.63). A nonsignificant increasing trend was found between duration of hormone replacement therapy and breast cancer risk, although the opposite was seen when the association was analyzed by time since last use. These results imply that hormone replacement therapy could promote breast cancer.

Breast Neoplasms

Sex differences in self-disclosure: a meta-analysis.

A meta-analysis of 205 studies involving 23,702 Ss was conducted to determine whether there are sex differences in self-disclosure. Across these studies, women disclosed slightly more than men (d = .18). This effect size was not homogeneous across studies. Several moderator variables were found. Sex of target and the interaction effect of relationship to target and measure of self-disclosure moderated the effect of sex on self-disclosure. Sex differences in self-disclosure were significantly greater to female and same-sex partners than to opposite-sex or male partners. When the target had a relationship with the discloser (i.e., friend, parent, or spouse), women disclosed more than men regardless of whether self-disclosure was measured by self-report or observation. When the target was a stranger, men reported that they disclosed similarly to women; however, studies using observational measures of self-disclosure found that women disclosed more than men.

Female