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PubMed1997

Strengths and limitations of meta-analysis: larger studies may be more reliable.

Meta-analysis of randomized controlled trials combines information from independent studies that address a similar question to provide more reliable estimates of treatment effects. At the present time, the methodology and usefulness of meta-analysis is under scrutiny. In the first part of this paper, we summarize the limitations of meta-analysis and make suggestions for improvements. In the second part, we illustrate strengths and limitations using examples of meta-analyses and subsequent large trials that address the same question. We develop the hypothesis that the size of the meta-analysis may be a useful measure of reliability. Small meta-analyses (i.e., those with less than 200 outcome events) may only be useful for summarizing the available information and generating hypotheses for future research. The results of small meta-analyses should be regarded with caution, even if the p value shows extreme statistical significance. Larger meta-analyses (i.e., those with several hundred events) are likely to be more reliable and may be clinically useful. Well-conducted meta-analyses of large trials using individual patient data may provide the best estimates of treatment effects in the cohort overall and in clinically important subgroups.

Bias↗

PubMed1997

Systematic reviews of medical evidence: the use of meta-analysis in obstetrics and gynecology.

OBJECTIVE: To review the technique of meta-analysis and its uses and limitations in obstetrics and gynecology. DATA SOURCES: We reviewed four major journals in obstetrics and gynecology (American Journal of Obstetrics and Gynecology, Fertility and Sterility, Journal of Reproductive Medicine, and Obstetrics & Gynecology). METHODS OF STUDY SELECTION: Journals were reviewed to determine frequency of meta-analysis as a method of systematic review in obstetrics and gynecology. We also summarized objectives and scientific guidelines for performing a meta-analysis. TABULATION, INTEGRATION, AND RESULTS: Meta-analysis is used with increased frequency in obstetrics and gynecology as a way of systematically reviewing medical evidence. This technique is an attempt to improve on traditional methods of narrative review by an expert and as a framework for evidence-based medicine and developing practice guidelines. By combining data from replicate studies, a meta-analysis can increase statistical power, more precisely estimate the typical effect size of treatment or risk factor, and attempt to resolve controversies in the medical literature. Meta-analysis is a retrospective look at data already collected and is therefore subject to the biases of all retrospective studies. CONCLUSIONS: The technique of meta-analysis requires all the scientific rigor of a randomized clinical trial with careful attention to study design, including a formal protocol for literature search strategies, quality assessment of candidate studies, specific inclusion and exclusion criteria, issues of sampling and publication bias, statistical tests of homogeneity, and sensitivity analysis.

Evidence-Based Medicine↗

PubMed2002

Quantifying heterogeneity in a meta-analysis.

The extent of heterogeneity in a meta-analysis partly determines the difficulty in drawing overall conclusions. This extent may be measured by estimating a between-study variance, but interpretation is then specific to a particular treatment effect metric. A test for the existence of heterogeneity exists, but depends on the number of studies in the meta-analysis. We develop measures of the impact of heterogeneity on a meta-analysis, from mathematical criteria, that are independent of the number of studies and the treatment effect metric. We derive and propose three suitable statistics: H is the square root of the chi2 heterogeneity statistic divided by its degrees of freedom; R is the ratio of the standard error of the underlying mean from a random effects meta-analysis to the standard error of a fixed effect meta-analytic estimate, and I2 is a transformation of (H) that describes the proportion of total variation in study estimates that is due to heterogeneity. We discuss interpretation, interval estimates and other properties of these measures and examine them in five example data sets showing different amounts of heterogeneity. We conclude that H and I2, which can usually be calculated for published meta-analyses, are particularly useful summaries of the impact of heterogeneity. One or both should be presented in published meta-analyses in preference to the test for heterogeneity.

Albumins↗

PubMed2004

Haplotype analysis of VDR gene polymorphisms: a meta-analysis.

INTRODUCTION: Although many studies have addressed the relationship between multiple individual polymorphisms in the vitamin D receptor (VDR) gene and bone health, few have analyzed this data in terms of haplotypes. We performed a meta-analysis of studies with data on the BsmI, ApaI, and TaqI polymorphisms in order to (a) estimate haplotype frequencies, (b) determine linkage disequilibrium (LD), and (c) estimate the magnitude of the association between haplotypes and osteoporosis/bone mineral density (BMD). METHODS: Haplotypes were inferred using the expectation-maximization algorithm (EM); log-linear models were used to determine association with osteoporosis; and regression analysis with variance components was used to determine association with BMD. RESULTS: Our results indicate that the most common haplotype for the VDR gene, regardless of ethnicity, is baT, followed by BAt and bAT in Caucasians, and bAT and BaT in Asians. This indicates strong LD between the BsmI and TaqI polymorphisms. We demonstrate a gain in power when considering the haplotypes rather than the individual polymorphisms separately, i.e., although BsmI, ApaI, and TaqI were not significantly associated with osteoporosis on their own, the haplotypes Bat and BAt were significantly associated, with an OR of approximately 4. CONCLUSION: We have applied haplotype analysis to the VDR polymorphisms and bone measures. We also highlight a number of methodologic issues, including linkage disequilibrium, the robustness of the EM algorithm in this context, and the potential for exploring effect modification.

Bone Density↗

PubMed2025

The Impact of Nutritional Status on Oral Health Outcomes and Management in Older Adults: A Systematic Review and Meta-Analysis.

OBJECTIVE: This systematic review and meta-analysis evaluated the relationship between nutritional status and the oral health of older adults (aged 75 years or older). The PECO focus question was, 'What is the occurrence, association and impact of nutritional state on the oral health outcomes and its management in older adults?' METHODS: A comprehensive literature search was performed across MEDLINE (PubMed), Embase and the Cochrane Library. Publications up to April 2025 were considered, yielding 3324 records for initial screening. Quality assessment of the included studies predominantly revealed a low to moderate risk of bias. RESULTS: Eighty-three studies were included for data analysis. Meta-analyses demonstrated that older adults at risk of malnutrition had fewer teeth (SMD = -0.29; 95% CI: -0.46, -0.11; p = 0.002). Those with < 20 teeth and who were not rehabilitated with dentures were more likely to be malnourished (OR = 4.00; 95% CI: 1.21, 13.18; p = 0.02). Malnutrition was associated with self-reported chewing problems (OR = 2.38; 95% CI: 1.74, 3.26; p < 0.0001), swallowing problems (OR = 3.18; 95% CI: 2.20, 4.61; p < 0.0001) or dry mouth (OR = 2.35; 95% CI: 1.91, 2.88; p < 0.0001). Conversely, those with oral pain showed lower odds of malnutrition risk (OR = 0.68; 95% CI: 0.52, 0.89; p = 0.005). CONCLUSIONS: Fewer teeth, existing chewing or swallowing problems, dry mouth and the absence of removable dentures where needed, were associated with malnutrition in care-dependent older adults. The current lack of longitudinal studies and proof of causality for malnutrition affecting oral health outcomes underscores the need for further research to better clarify the complex relationship between oral health and nutrition in older populations. TRIAL REGISTRATION: PROSPERO Registration: CRD420251003549.

Humans↗

PubMed1992

Meta-analysis for descriptive research.

Although nurses have begun to use meta-analysis, a review of the nursing literature demonstrates that its use has not been maximized. Meta-analysis can be employed to synthesize descriptive as well as experimental research, yet attention in nursing has focused almost exclusively on meta-analysis techniques for, and meta-analytic studies of, experimental research. Furthermore, nursing literature has emphasized use of the effect size index (d) rather than the correlation index (r); the latter may, in some cases, be the more suitable metric, particularly with meta-analysis of correlational studies. An argument is made for the value of meta-analysis as a technique for integrating descriptive research, and an overview of different meta-analytic approaches to data analysis using the correlational index with descriptive research is provided.

Humans↗

PubMed1999

Meta-analysis: formulating, evaluating, combining, and reporting.

Meta-analysis involves combining summary information from related but independent studies. The objectives of a meta-analysis include increasing power to detect an overall treatment effect, estimation of the degree of benefit associated with a particular study treatment, assessment of the amount of variability between studies, or identification of study characteristics associated with particularly effective treatments. This article presents a tutorial on meta-analysis intended for anyone with a mathematical statistics background. Search strategies and review methods of the literature are discussed. Emphasis is focused on analytic methods for estimation of the parameters of interest. Three modes of inference are discussed: maximum likelihood; restricted maximum likelihood, and Bayesian. Finally, software for performing inference using restricted maximum likelihood and fully Bayesian methods are demonstrated. Methods are illustrated using two examples: an evaluation of mortality from prophylactic use of lidocaine after a heart attack, and a comparison of length of hospital stay for stroke patients under two different management protocols.

Anti-Arrhythmia Agents↗

PubMed1990

Meta-analysis for dermatologists.

Meta-analysis is a relatively new statistical technique that is attracting a great deal of attention in the medical and social science literature. This technique is discussed in terms of its tenants, advantages, rudiments, and controversies.

Dermatology↗

PubMed1996

Prophylaxis with fluoroquinolones for bacterial infections in neutropenic patients: a meta-analysis.

We conducted a two-part meta-analysis to assess the effectiveness of fluoroquinolones for preventing bacterial infections in granulocytopenic patients who are receiving chemotherapy for malignancies. Overall, 19 randomized studies met selection criteria and were included in this meta-analysis of 2,112 patients. Thirteen studies that compared the fluoroquinolones alone with control regimens (co-trimoxazole, oral nonabsorbable antibiotics, or placebo) and six studies that compared the fluoroquinolones plus prophylaxis for bacteremia due to gram-positive bacteria with control regimens (fluoroquinolones or oral nonabsorbable antibiotics) were included in the two meta-analyses. The results of the first meta-analysis indicate that fluoroquinolones alone are effective in preventing gram-negative bacteremia (overall odds ratio [OR], 0.09; 95% confidence interval [CI], 0.05-0.16; P < .001), but not gram-positive bacteremia (OR, 1.05; 95% CI, 0.76-1.45; P = .7), fever-related morbidity (OR, 0.76; 95% CI, 0.56-1.04; P = .09), and infection-related mortality (OR, 0.79; 95% CI, 0.47-1.34; P = .4). The results of the second meta-analysis indicate that a combination of fluoroquinolones plus prophylaxis for gram-positive bacteremia (penicillin, vancomycin, or macrolides) significantly reduces the occurrence of gram-positive bacteremia (OR, 0.46; CI, 0.33-0.63; P < .001) without affecting the incidence of fever-related morbidity (OR, 0.83; 95% CI, 0.62-1.13; P = .2) and infection-related mortality (OR, 0.74; 95% CI, 0.40-1.38; P = .3)

Anti-Bacterial Agents↗

PubMed1994

Drug treatment of hypertension in the elderly: a meta-analysis.

PURPOSE: A meta-analysis of the effect of antihypertensive drug treatment on mortality and morbidity in elderly patients. DATA SOURCES: A literature search of published articles from January 1980 to February 1992. STUDY SELECTION: Randomized controlled trials of drug treatment of hypertension with end points for elderly patients reported separately. DATA EXTRACTION: Mortality or morbidity end points or both in patients older than 59 years were pooled by determination of typical odds ratio. A meta-regression was used to study heterogeneity. RESULTS: Nine major trials with 15,559 patients older than 59 years were identified. Death rates in the control group varied between 2.7% and 77.2%; stroke and coronary mortality increased with the severity-of-illness rank (P < 0.001). Overall, treated patients had an approximately 12% reduction in all-cause mortality (odds ratio, 0.88; 95% CI, 0.80 to 0.97; 953 events compared with 1069 events, P = 0.009). There was a 36% reduction in stroke mortality (odds ratio, 0.64; CI, 0.49 to 0.82; 94 events compared with 149 events, P < 0.001) and a 25% reduction in coronary heart disease mortality (odds ratio, 0.75; CI, 0.64 to 0.88; 263 events compared with 350 events, P < 0.001). Coronary morbidity was reduced 15% (odds ratio, 0.85; CI, 0.73 to 0.99; 325 events compared with 379 events, P = 0.036), and stroke morbidity was reduced 35% (odds ratio, 0.65; CI, 0.55 to 0.76; 247 events compared with 382 events, P < 0.001). CONCLUSION: Overall, treatment of hypertension in elderly patients produces a significant benefit in total mortality and cardiovascular morbidity and mortality. However, this benefit may be reduced in the oldest age groups.

Aged↗

PubMed1994

Do nonsteroidal anti-inflammatory drugs affect blood pressure? A meta-analysis.

PURPOSE: A meta-analysis of randomized trials studying the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on blood pressure. DATA SOURCES AND STUDY SELECTION: Eight databases were searched, yielding 38 randomized, placebo-controlled trials and 12 randomized but not placebo-controlled trials (comparing two or more NSAIDs). DATA EXTRACTION: Pooled mean treatment effects were computed in each trial for blood pressure, weight, creatinine clearance, plasma renin activity, and daily urinary excretion of sodium and prostaglandins. Meta-analyses of these variables were done for all randomized, controlled trials; for all randomized, uncontrolled trials; and for several subgroups. DATA SYNTHESIS: When pooled, NSAIDs elevated supine mean blood pressure by 5.0 mm Hg (95% CI, 1.2 to 8.7 mm Hg) but had no effect on variables other than blood pressure. Nonsteroidal anti-inflammatory drugs antagonized the antihypertensive effect of beta-blockers (blood pressure elevation, 6.2 mm Hg; CI, 1.1 to 11.4 mm Hg) more than did vasodilators and diuretics. Among NSAIDs, piroxicam produced the most marked elevation in blood pressure (6.2 mm Hg; CI, 0.8 to 11.5 mm Hg), whereas sulindac and aspirin had the least hypertensive effect. CONCLUSIONS: Nonsteroidal anti-inflammatory drugs may elevate blood pressure and antagonize the blood pressure-lowering effect of antihypertensive medication to an extent that may potentially increase hypertension-related morbidity. Although certain NSAIDs and antihypertensive agents could be more likely to produce these effects, the underlying mechanisms require further study.

Adult↗

PubMed2026

PYRAMA: an open-source tool for advanced meta-analysis of genome wide association studies.

MOTIVATION: Genome-wide association study (GWAS) meta-analysis tools are essential for integrating summary statistics across multiple cohorts, thereby increasing statistical power and validating genetic associations. Widely cited tools, such as METAL, PLINK, and GWAMA, have facilitated numerous significant discoveries in the field of GWAS. Nevertheless, these tools offer a limited set of meta-analysis methods and typically require users to have prior experience with command-line tools to be executed. RESULTS: We present here PYRAMA, an open-source tool which is designed for meta-analysis of genome wide association studies. This work introduces an easy-to-use software package that includes several meta-analysis methods that are absent in similar software packages. PYRAMA is faster compared to other tools, supports robust methods for analysis and meta-analysis, fixed-effects, random-effects and Bayesian meta-analysis and it is currently the only tool that supports meta-analysis with imputation of summary statistics. It is available both as a standalone tool and as a freely available web server. AVAILABILITY AND IMPLEMENTATION: https://github.com/pbagos/PYRAMA, https://doi.org/10.5281/zenodo.17830449.

Genome-Wide Association Study↗

PubMed2002

Age differences and the identity negative priming effect: an updated meta-analysis.

A recent meta-analysis (P. Verhaeghen & L. De Meersman, 1998a) revealed that older adults show a reliable but significantly reduced negative priming effect compared with young adults. The present study provides an updated quantitative review on the effect of aging on the magnitude of the negative priming effect in identity tasks. This analysis demonstrated that the negative priming effect was not significantly different between young and old adults. This result differs from P. Verhaeghen and L. De Meersman's study. The implications of this finding for inhibitory-based theories of cognitive aging are discussed.

Adult↗

PubMed1998

SPECT brain imaging in epilepsy: a meta-analysis.

UNLABELLED: A meta-analysis of SPECT brain imaging in epilepsy was performed to derive the sensitivity and specificity of interictal, postictal or ictal rCBF patterns to identify a seizure focus in medically refractory patients. METHODS: Papers were obtained by pooling all published articles identified by two independent literature searches: (a) Dialnet (EMBASE) or Radline by CD-ROM and (b) Current Contents searched manually. Literature inclusion criteria were: (a) patients had a localization-related epileptic syndrome; (b) more than six patients were reported; and (c) patients had at least an interictal EEG-documented epileptiform abnormality. Of 46 papers meeting these criteria, 30 contained extractable data. SPECT results were compared to localization by standard diagnostic evaluation and surgical outcome. Meta-analytic sensitivities for SPECT localization in patients with temporal lobe seizures relative to diagnostic evaluation were 0.44 (interictal), 0.75 (postictal) and 0.97 (ictal). Similar results were obtained relative to surgical outcome. False-positive rates were low relative to diagnostic evaluation (7.4% for interictal and 1.5% for postictal studies) and surgical outcome (4.4% for interictal and 0.0% for postictal studies). RESULTS: The results were not dependent on tracer used (or dose), the presence of CT-identified structural abnormalities, blinding of image interpretation or camera quality (although data were more variable with low-resolution cameras). There were insufficient data for conclusions regarding extratemporal-seizure or pediatric epilepsy populations. CONCLUSION: Insights gained from reviewing this literature yielded recommendations for minimal information that should be provided in future reports. Additional recommendations regarding the nature and focus of future studies also are provided. The most important of these is that institutions using SPECT imaging in epilepsy should perform ictal, preferably, or postictal scanning in combination with interictal scanning.

Brain↗

PubMed1994

Meta-analysis. A useful tool for the spine researcher.

Meta-analysis is a systematic and objective methodology for synthesizing research literature. The authors present the history and definition of meta-analysis, discuss the generic framework for design and implementation of a meta-analysis, and review the problems and pitfalls that can accompany meta-analyses. Their discussion draws on practical experience with several meta-analyses of the low back pain literature. Meta-analysis can be used to help answer the questions about various options for diagnosis and treatment of low back problems and also to point out gaps in our knowledge base that may have a high priority for research. Meta-analytic methods are an informative means of addressing health care controversies with major patient management and cost implications.

Humans↗

PubMed2000

Child sexual abuse prevention programs: a meta-analysis.

Conducted a meta-analytic evaluation of the effectiveness of school-based child abuse prevention programs. Literature searches identified 27 studies meeting inclusion criteria for use in this meta-analysis. The average effect size for all programs studied was 1.07, indicating that children who participated in prevention programs performed 1.07 SD higher than control group children on the outcome measures used in the studies. Analysis of moderator variables revealed significant effects for age, number of sessions, participant involvement, type of outcome measure, and use of behavioral skills training. Most important, programs presented over 4 or more sessions that allowed children to become physically involved produced the highest effect sizes. Although most often used only with younger children, findings suggest that active, long-term programs may be more effective for children of all ages.

Age Factors↗

PubMed1998

Aging and the Stroop effect: a meta-analysis.

In this meta-analysis, data from 20 studies comparing younger and older adults on the Stroop interference effect, contained in 15 articles, were analyzed. No significant difference was found in the Stroop interference effect, expressed as mean standardized difference, between the 2 age groups (for younger adults: d = 2.04; for older adults: d = 2.17). Moderator variables were present, but these did not produce age differences. Brinley analysis showed that a single regression line with a slowing factor of 1.9 described the data well (R2 = .83) and confirmed that no Age x Condition interaction was present in the data. Likewise, no Age x Condition interaction was found when the data were fitted to the information loss model; the age ratio of decay rates was estimated to be 1.4. Consequently, the apparent age-sensitivity of the Stroop interference effect appears to be merely an artifact of general slowing.

Adult↗

PubMed2002

When worlds collide. Social science, politics, and the Rind et al. (1998). Child sexual abuse meta-analysis.

A 1998 meta-analysis by B. Rind, P. Tromovitch, and R. Bauserman in Psychological Bulletin indicated that the relations between child sexual abuse and later psychopathology were weak in magnitude. Shortly thereafter, this article was condemned by media personality Dr. Laura Schlessinger and numerous conservative organizations and was denounced by the United States Congress. In addition, the American Psychological Association (APA) distanced itself from the authors' conclusions. This incident raises questions regarding (a) authors' responsibilities concerning the reporting of politically controversial findings, (b) academic and scientific freedom, (c) the role of the APA in disabusing the public and media of logical errors and fallacies, and (d) the substantial gap between popular and academic psychology and the responsibility of the APA to narrow that gap.

Child↗