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PubMed1991

A prototype for integrative review and meta-analysis of nursing research.

Meta-analysis has gained international recognition as a statistical approach to research synthesis. What is missing in research reviews, however, is the systematic compilation of results from non-experimentally designed studies. An approach is described which extends the rigours of integrative research review and meta-analysis to descriptive studies. A model for conceptualizing a systematically derived research synthesis is presented with selected accompanying generic elements. The model serves as a prototype for application to a variety of topical areas of interest. Generic elements contained in the prototype may be tailored to specific topics with relative ease. Resources and time required for topic development from conceptualization through to dissemination can be considerably reduced by adaptation of the generic elements.

Clinical Nursing Research↗
PubMed1992

How effective are current drugs for Crohn's disease? A meta-analysis.

We have conducted a meta-analysis of 12 placebo controlled trials to determine the efficacy of single drug therapy in Crohn's disease for both induction (seven trials) and maintenance (five trials) of remission. A total of 767 and 796 patients were studied, respectively. Various clinical criteria of success were analyzed. The Dersimonian-Laird method for meta-analysis was used to calculate the risk difference (RD). Therapeutic advantage, defined as the difference between drug and placebo response, was also determined. Using various criteria of success, we found that single drug therapy conferred an 11-29% therapeutic advantage (RD = 0.13-0.33) over placebo for the induction of remission. In trials for maintenance, no therapeutic advantage was found for single drug therapy over placebo. All forms of maintenance therapy followed nearly identical linear rates of relapse over time, showing an approximately 90% maintenance of remission rate at 3 months, which decreased to 25% at 36 months. In conclusion, meta-analysis has established a standard of reference against which future drug trials can be compared. This standard of reference for drug and placebo rates, as well as the corresponding risk differences and therapeutic advantages can help determine the relative value of newer agents in the therapy of Crohn's disease.

Crohn Disease↗
PubMed1990

Cigarette smoking-associated changes in blood lipid and lipoprotein levels in the 8- to 19-year-old age group: a meta-analysis.

In this meta-analysis it was demonstrated that, when compared with nonsmokers of similar age, smokers in the 8- to 19-year-old age group have significantly higher serum levels of triglyceride (+11.8%), very-low-density lipoprotein (VLDL)-cholesterol (+12.4%) and low-density lipoprotein (LDL)-cholesterol (+4.1%) and significantly lower serum levels of high-density lipoprotein (HDL)-cholesterol (-8.5%) and total cholesterol (-3.7%). All of these smoking-associated changes are in the same direction as those found in adults, with the exception of total cholesterol levels, which are significantly increased in adult smokers. The extent to which mean triglyceride, LDL-cholesterol, and HDL-cholesterol levels are shifted is significantly greater in the 8- to 19-year-old smokers than in adult smokers. The changes in mean total cholesterol levels among smokers in both age groups represent only the net shifts in the lipoprotein fractions and are therefore likely to be a less sensitive indicator of the possible lipid-related excess coronary artery disease risk in smokers.

Adolescent↗
PubMed2026

Socioeconomic differences in the effectiveness of oral health programs for dental caries prevention in Europe: A systematic review and meta-analysis.

AIM: The meta-analysis systematically summarized evidence on how socioeconomic status (SES), access to dental care, and oral health programs (OHP) affect caries prevalence and severity among children and adults in Europe. METHODS: Four electronic databases (PubMed, Scopus, Cochrane Library and Embase) were systematically screened from 1947-2026, supplemented by cross-referencing and manual searches, without language restrictions. Study selection, data extraction and quality assessment were done in duplicate. Methodological quality was assessed using the NHLBI Study Quality Assessment Tools according to study design. Certainty of evidence was graded using GRADE Profiler 3.6. Mean differences (MD) were calculated for changes in DMFT, and odds ratios (OR) for the presence of dental caries in individuals using fixed-or random-effects models. RESULTS: Electronic searching identified 1800 articles; 23 studies were included in the review (>169,000 participants) and 14 in the meta-analyses (>88,000). Nine studies evaluated the effectiveness of OHP stratified by SES, and ten examined OHP in low-SES populations. Among low-SES individuals, participation in OHP was associated with a significantly lower increase in DMFT (MD[95% CI]=-0.63[-0.94;-0.31];very low certainty) and significantly lower odds of having dental caries (OR[95% CI]=0.61[0.52;0.73];very low) compared with non-participation. Among program participants, individuals with low SES showed a significantly greater increase in DMFT than those with high SES (MD[95% CI]=0.79[0.30;1.21];very low) and had significantly higher odds of having dental caries (OR[95% CI]= 2.88[1.97;4.22];very low). CONCLUSION: Participation in OHP may be associated with reducing dental caries in European populations, but benefits are unequally distributed and increase with higher SES. However, this conclusion is based on a limited number of well-conducted trials.

Humans↗
PubMed1998

Cancer among farmers: a meta-analysis.

PURPOSE: We conducted a meta-analysis of 37 studies to assess whether farmers had elevated rates for several cancers, as was concluded in a previous meta-analysis of 21 studies. METHODS: We identified studies from the reference list of the previous meta-analysis and from a MEDLINE search through December 31, 1994. The primary purpose of our analysis was to identify and, if possible, understand the sources of heterogeneity in the literature. Stratified analyses of studies and linear modeling with inverse variance weights were used to assess the impact of study characteristics on results. We calculated summary relative risks as a weighted average of the log relative risks across studies using inverse variance weights. Fixed and random effects models were used as appropriate. RESULTS: The results for most cancers were markedly heterogeneous by study design and, for fewer cancers, by geographic location, and whether the studies focused on crop and livestock farmers. There was some indication of publication bias due to underreporting of near null or sub null findings. Lip cancer was the only cancer that was clearly elevated among farmers. CONCLUSIONS: The results do not suggest that farmers have elevated rates of several cancers. However, the known heterogeneity of exposures by type of farming, geographic area, time period, and other factors limits the informativeness of meta-analyses of these studies for assessing potential carcinogenic exposures in agriculture.

Agricultural Workers' Diseases↗
PubMed1998

Out of step with the Lancet homeopathy meta-analysis: more objections than objectivity?

The meta-analysis of homeopathy trials that appeared in the Lancet in 1997 seemed to endorse the experience of practitioners and patients that homeopathic medicines have specific clinically relevant effects. However, results from later unsuccessful trials, and negative inferences from a review of trials for a condition excluded from the meta-analysis--delayed onset muscle soreness (DOMS)--have since been presented to suggest that the meta-analysis may well have overestimated the positive effects of homeopathy, and that the "placebo question is still not resolved." This article reviews the evidence underlying this challenge to the meta-analysis and homeopathy, and demonstrates that it would be valid if it were based on: a comprehensive literature search; appropriate classification of primary studies; clear discrimination between clinical effectiveness and placebo questions; sound and transparent review methods; and a reliable and unconfounded clinical treatment model for testing the ultramolecular hypothesis. It is suggested that different models are needed to answer different questions.

Bias↗
PubMed1996

G-CSF for the prophylaxis of neutropenic fever in patients with small cell lung cancer receiving myelosuppressive antineoplastic chemotherapy: meta-analysis and pharmacoeconomic evaluation.

Standard meta-analytical and pharmacoeconomic techniques were used to study the clinical effectiveness and the cost-effectiveness ratio of the prophylactic (or pre-emptive) administration of G-CSF to patients with small cell lung cancer treated with conventional myelosuppressive cytotoxic chemotherapy. In the first part of our study, we conducted a meta-analysis of the randomized clinical trials evaluating G-CSF for this clinical indication. Three trials were identified by our literature search and were included in the meta-analysis (overall number of patients = 606). The end-points for evaluating G-CSF included mortality from infection and the cumulative incidence of neutropenic fever over six cycles of chemotherapy. The results of our meta-analysis demonstrate that prophylactic G-CSF did not affect mortality but significantly reduced the incidence of neutropenic fever from 68.3% to 38.7% (pooled odds ratio = 0.29, 95% CI: 0.21-0.40; P < 0.001). In the second part of our study, we carried out a pharmacoeconomic analysis to estimate the cost-effectiveness ratio of pre-emptive G-CSF (i.e. the 'average' cost associated with the prevention of an episode of neutropenic fever). This cost-effectiveness ratio was US$ 14,372 using the Italian price of the drug converted into dollars, or US$ 41 088 using the US price. Finally, we estimated the revenue-neutral price of G-CSF based on American data of the cost-of-illness. The price ranged from US$ 395 to US$ 569 per cycle, a figure higher than the value (US$ 150) previously reported in the literature.

Antineoplastic Agents↗
PubMed1994

Use of immune globulin to prevent symptomatic cytomegalovirus disease in transplant recipients--a meta-analysis.

The objective of this meta-analysis was to review the evidence for the use of immune globulin in the prevention of symptomatic cytomegalovirus (CMV) disease in transplant recipients. A computerized search of Medline from 1980 to October 1991 was conducted using the textword "cytomegalo:" and the subheading "prevention and control" for studies in all languages. Reference lists, a manual search of relevant literature and communication with internationally recognized experts were used to locate additional studies. Of the studies identified, 18 met the inclusion criteria (population: transplant recipients; intervention: immune globulin; outcome: symptomatic cytomegalovirus disease; study design: randomized controlled trial). The meta-analysis of the 18 studies showed a reduction in the incidence of symptomatic CMV disease in the group receiving immune globulin as compared to the untreated group. The common odds ratio was 0.58 (95% C.I. 0.42 to 0.77). Analyses of combining trials by subgroups of polyvalent immune globulin, hyperimmune globulin, bone marrow recipients and solid organ recipients resulted in common odds ratios comparable to the overall common odds ratio. Common odds ratios for the trials reporting cytomegalovirus interstitial pneumonia, cytomegalovirus death, overall death and graft loss ranged from 0.47 to 0.69. Common odds ratios for the effect of immune globulin prophylaxis analyzed by pre-transplant patient/donor cytomegalovirus antibody status ranged from 0.32 to 0.50. In conclusion, the use of immune globulin as passive immunization for the prevention of symptomatic cytomegalovirus disease in the transplant population is supported by this meta-analysis. The response is similar in both bone marrow and solid organ transplant recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytomegalovirus Infections↗
PubMed1989

Meta-analysis: whither narrative review?

Meta-analysis refers to methodologies that are used to integrate related empirical research to arrive at conclusions not possible by reviewing individual studies, or to improve generalizations of individual studies. It is distinguished from the traditional narrative review in that statistical methodologies are applied to derive more objective conclusions than those that typify narrative reviews. Meta-analysis has been slow to appear in the literature of clinical medicine, however, particularly when viewed in the context of the exponential expansion of literature and the availability of computer technology to facilitate its conduct.

Clinical Medicine↗
PubMed1995

The effects of endurance training on functional capacity in the elderly: a meta-analysis.

In this investigation, meta-analysis was used to delineate exercise induced changes in the VO2max of older individuals and test a null hypothesis of no significant training effects. Parameters included in the analysis were age of the subjects, length of the training regimen, frequency and duration of exercise bouts, pretraining VO2max, posttraining VO2max, and the difference between pretraining and posttraining VO2max (delta VO2max). Effect size for training-induced improvements in VO2max was calculated, corrected for bias, weighted, and analyzed according to contemporary meta-analysis procedures. The mean effect size was found to be 0.65 standard deviation units, representing an improvement in oxygen consumption of 22.8%. The mean effect size was also significantly different from 0 (P < 0.0001), and the null hypothesis was rejected. Stepwise regression analysis indicated that length of training, pretraining VO2max, and duration of training bouts accounted for 59% of the total variation in delta VO2max. In addition, age was found to be inversely correlated with pretraining VO2max (r = -0.56, P = 0.002), and delta VO2max (r = -0.56, P = 0.003). It was concluded that endurance training significantly increases functional capacity in the elderly, and that the increase is related to subject age, duration of exercise bouts, length of the training regimen, and pretraining VO2max.

Aged↗
PubMed1995

Guidelines for application of meta-analysis in environmental epidemiology. ISLI Risk Science Institute.

The use of meta-analysis in environmental epidemiology can enhance the value of epidemiologic data in debates about environmental health risks. Meta-analysis may be particularly useful to formally examine sources of heterogeneity, to clarify the relationship between environmental exposures and health effects, and to generate information beyond that provided by individual studies or a narrative review. However, meta-analysis may not be useful when the relationship between exposure and disease is obvious, when there are only a few studies of the key health outcomes, or when there is substantial confounding or other biases which cannot be adjusted for in the analysis. Recent increases in the use of meta-analysis in environmental epidemiology have highlighted the need for guidelines for the application of the technique. Guidelines, in the form of desirable and undesirable attributes, are presented in this paper for various components of a meta-analysis including study identification and selection; data extraction and analysis; and interpretation, presentation, and communication of results. Also discussed are the appropriateness of the use of meta-analysis in environmental health studies and when meta-analysis should or should not be used.

Environmental Exposure↗
PubMed1992

[Ginkgo biloba extract in peripheral arterial diseases. Meta-analysis of controlled clinical studies].

In the first part the statistical methods of meta-analysis are discussed. Meta-analysis is considered as a statistical tool for quantitatively summarizing the results of clinical trials with comparable aims (treatments) and designs. Meta-analysis can be based on the significance probabilities or effect values. The last procedure is preferable as it gives an estimate (and confidence interval) for the global effect of the treatment of interest, if homogeneity of the effects between the trials can be assumed. Such a homogeneity can be often achieved by a suitable standardization of the effect variables within the trials. In the second part the methods of meta-analysis are applied to controlled clinical trials with Ginkgo biloba extract EGb 761 in patients with peripheral arterial disease. Included were 5 placebo-controlled clinical trials with similar design and inclusion criteria. In all studies treatment effect was quantified by the increase of walking distance (measured in standardized treadmill exercise). The effect value of EGb 761 treatment was expressed by the standardized mean difference in walking distance increase between EGb 761 and placebo, standardized by the standard deviation. It could be shown that this effect value is homogeneous in all trials. The global effect size was estimated as 0.75. This means that the mean increase in walking distance achieved by EGb 761 is 0.75 times of the standard deviation higher than that achieved by placebo. This value is highly significant different from zero. So the meta-analysis revealed a highly significant therapeutic effect of EGb 761 for the treatment of peripheral arterial disease.

Arteries↗
PubMed1995

Qualitative assessment of studies included in a meta-analysis: DES and the risk of pregnancy loss.

Meta-analysis, the qualitative and quantitative integration of available research information, is increasingly used in clinical research. This report examines the qualitative elements of meta-analysis through critical review of two published examples that assessed the effect of diethylstilboestrol (DES) on miscarriage and neonatal mortality, respectively. Our subjective review showed the internal validity of three of five trials aggregated in the former meta-analysis to be severely compromised. The remaining two trials (data from which were aggregated in the latter meta-analysis), while internally valid, studied different clinical populations. Therefore, pooling of their results may have been clinically inappropriate. In conclusion, meta-analysis involves substantial elements of subjective judgment. Qualitative assessment of studies is of pivotal importance, because the validity of any summary estimate of effect hinges on both the methodologic quality and the combinability of the aggregated studies.

Abortion, Spontaneous↗
PubMed1997

The design and analysis of paired cluster randomized trials: an application of meta-analysis techniques.

The statistical issues in clinical trials where clusters, communities or groups rather than individuals are randomized are often not fully appreciated. In this paper we discuss the design and analysis of trials in which pairs of clusters are randomized in the context of one recent trial, the British Family Heart Study. Both sample size calculations and the analysis strategy need to take account of the between-cluster component of variance. The analysis can be considered as a random effects meta-analysis across cluster pairs, and can usefully be presented as such. Techniques developed in the context of meta-analysis can then be used in the analysis, for example using a profile likelihood method to derive a confidence interval for the overall treatment effect which takes into account the variability in the estimate of the between-cluster variance. The methods presented here are contrasted with previously published methods for cluster randomized trials.

Adult↗
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↗
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&#x2009;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&#x2009;=&#x2009;-0.29; 95% CI: -0.46, -0.11; p&#x2009;=&#x2009;0.002). Those with <&#x2009;20 teeth and who were not rehabilitated with dentures were more likely to be malnourished (OR&#x2009;=&#x2009;4.00; 95% CI: 1.21, 13.18; p&#x2009;=&#x2009;0.02). Malnutrition was associated with self-reported chewing problems (OR&#x2009;=&#x2009;2.38; 95% CI: 1.74, 3.26; p&#x2009;<&#x2009;0.0001), swallowing problems (OR&#x2009;=&#x2009;3.18; 95% CI: 2.20, 4.61; p&#x2009;<&#x2009;0.0001) or dry mouth (OR&#x2009;=&#x2009;2.35; 95% CI: 1.91, 2.88; p&#x2009;<&#x2009;0.0001). Conversely, those with oral pain showed lower odds of malnutrition risk (OR&#x2009;=&#x2009;0.68; 95% CI: 0.52, 0.89; p&#x2009;=&#x2009;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↗