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PubMed2004

Oral Pentasa in the treatment of active Crohn's disease: A meta-analysis of double-blind, placebo-controlled trials.

BACKGROUND & AIMS: The aim of this study was to perform a meta-analysis of the efficacy results from 3 placebo-controlled multicenter clinical trials of slow-release mesalamine (Pentasa) for the acute treatment of mild to moderate Crohn's disease. METHODS: Three trials fulfilled the selection criteria (double-blind, placebo-controlled, randomized studies in adult patients treated with Pentasa 4 g/day for active Crohn's disease). The efficacy and safety was evaluated in these trials by using the Crohn's Disease Activity Index (CDAI) as the primary efficacy variable. The study duration was 16 weeks in all 3 trials. The total numbers of patients were 304 in the Pentasa 4-g/day treatment groups and 311 in the placebo groups. A meta-analysis was performed based on the study reports. RESULTS: For the intent-to-treat patients in the Pentasa groups, the overall mean reduction of the CDAI from baseline to the final visit was -63 points. The corresponding CDAI change in the placebo groups was -45 points; the net difference was -18 points. Compared with placebo, the 4-g/day dose of Pentasa was associated with a statistically significant overall improvement in the CDAI from baseline to the final visit (P = 0.04). When the meta-analysis was restricted to protocol correct patients, the effect of Pentasa became more pronounced (overall mean reduction of -83 CDAI points; P = 0.02, compared with placebo). Contrary to the consistent effects with Pentasa, the trial-specific reductions of the CDAI with placebo differed significantly between the trials. CONCLUSIONS: The meta-analysis of 3 large, double-blind, randomized studies in the treatment of active Crohn's disease confirms that Pentasa 4 g/day is superior to placebo in reducing the CDAI but the clinical significance of the magnitude of this difference is not clear.

Adult↗

PubMed2004

Esomeprazole-based therapy in Helicobacter pylori eradication: a meta-analysis.

AIM: To perform a systematic review on the efficacy of esomeprazole-based therapies in Helicobacter pylori eradication, and to conduct a meta-analysis comparing the efficacy of esomeprazole and other proton pump inhibitors when co-prescribed with antibiotics. METHODS: Studies evaluating esomeprazole plus antibiotics were considered. Only randomised trials comparing esomeprazole and other proton pump inhibitors with antibiotics, and differing only in the proton pump inhibitor, were included in the meta-analysis. Electronic and manual bibliographical searches were conducted. The percentage (weighted mean) of eradication success was calculated. Meta-analysis was performed combining the odd ratios of the individual studies. RESULTS: Mean cure rates with dual regimens (esomeprazole plus clarithromycin) were 51 and 54%, respectively, by intention-to-treat and by per-protocol. Corresponding figures with triple regimens (esomeprazole plus clarithromycin and either amoxicillin or metronidazole) were 82% (intention-to-treat) and 86% (per-protocol). Four studies were included in the meta-analysis: mean H. pylori eradication rates (intention-to-treat) with esomeprazole plus antibiotics was 85 and 82% when omeprazole was used (odds ratio = 1.19; 95% confidence interval = 0.81-1.74), results being statistically homogeneous. When subanalysis included only high quality studies, the odds ratio for this comparison was closer to one (1.08; 95% confidence interval = 0.4-1.47) and results were more homogeneous. CONCLUSIONS: Esomeprazole-based triple therapy is highly effective for the eradication of H. pylori infection and offers comparable efficacy to omeprazole-based therapy.

Anti-Bacterial Agents↗

PubMed1991

Meta-analysis in epidemiology, with special reference to studies of the association between exposure to environmental tobacco smoke and lung cancer: a critique.

Meta-analysis, a set of statistical tools for combining and integrating the results of independent studies of a given scientific issue, can be useful when the stringent conditions under which such integration is valid are met. In this report we point out the difficulties in obtaining sound meta-analyses of either controlled clinical trials or epidemiological studies. We demonstrate that hastily or improperly designed meta-analyses can lead to results that may not be scientifically valid. We note that much care is typically taken when meta-analysis is applied to the results of clinical trials. The Food and Drug Administration, for example, requires strict adherence to the principles we discuss in this paper before it allows a drug's sponsor to use a meta-analysis of separate clinical studies in support of a New Drug Application. Such care does not always carry over to epidemiological studies, as demonstrated by the 1986 report of the National Research Council concerning the purported association between exposure to environmental tobacco smoke and the risk of lung cancer. On the basis of a meta-analysis of 13 studies, 10 of which were retrospective and the remaining 3 prospective in nature, the Council concluded that non-smokers who are exposed to environmental tobacco smoke are at greater risk of acquiring lung cancer than non-smokers not so exposed. In our opinion, this conclusion in unwarranted given the poor quality of the studies on which it is based.

Bias↗

PubMed1993

Predicting survival from in-hospital CPR: meta-analysis and validation of a prediction model.

OBJECTIVE: To better clarify patient factors that predict survival from in-hospital cardiopulmonary resuscitation (CPR), using two methods: 1) meta-analysis and 2) validation of a prediction model, the pre-arrest morbidity (PAM) index. DESIGN: Meta-analysis of previously published studies by standard techniques. Retrospective chart review of validation sample. SETTING: University-affiliated teaching hospital. PATIENTS/PARTICIPANTS: Meta-analytic sample of 21 previous studies from 1965-1989. The validation sample consisted of all patients surviving resuscitation from the authors' hospital during the period September 1986 to January 1991. A matched sample of patients who did not survive from the same time period was used as the comparison group. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The strongest negative predictors of survival, by meta-analysis, were renal failure (r = 0.088, p < 0.0002), cancer (r = 0.08, p < 0.0002), and age more than 60 years (r = 0.063, p < 0.006). Sepsis (r = 0.046, p < 0.02), recent cerebrovascular accident (CVA) (r = 0.038, p < 0.04), and congestive heart failure (CHF) class III/IV (r = 0.036, p < 0.05) were weaker negative predictors. Presence of acute myocardial infarction (AMI) was a significant positive predictor of survival (r = 0.15, p < 0.0001). The PAM score was highly predictive of survival in a logistic regression model (p < 0.0003, R2 = 9.6%). No patient who survived to discharge had a PAM score higher than 8. CONCLUSION: Meta-analysis reveals that the most significant negative predictors of survival from CPR are renal failure, cancer, and age more than 60 years, while AMI is a significant positive predictor. The PAM index is a useful method of stratifying probability of survival from CPR, especially for those patients with high PAM scores, who have essentially no chance of survival.

Age Factors↗

PubMed2000

Efficacy of oral long-term N-acetylcysteine in chronic bronchopulmonary disease: a meta-analysis of published double-blind, placebo-controlled clinical trials.

OBJECTIVE: This meta-analysis was performed to assess the possible prophylactic benefit of prolonged treatment with oral N-acetylcysteine (NAC) in chronic bronchitis (CB) based on qualifying clinical trials. Treatment of acute exacerbations with NAC was not investigated. BACKGROUND: Prolonged treatment with oral NAC has been investigated in a number of studies of patients with CB. NAC prevented acute exacerbations and symptoms of CB in some but not all trials. METHODS: The trials included in this analysis were selected from a MEDLINE search of the period from January 1, 1980, through June 30, 1995; references in the articles retrieved in the initial search; and consultation with 2 experts. Selection was based on the following criteria: published, double-blind, placebo-controlled, chronic bronchopulmonary disease, duration of therapy > or =2 months, and data sufficient to calculate an outcome variable permitting direct comparison of studies (effect size) for both NAC and placebo groups. The primary end point was the incidence of acute exacerbations in 7 of 8 trials and clinical assessment in the other. In 7 studies, inclusion criteria were based on Medical Research Council criteria for CB, with an additional criterion in some trials. For the meta-analysis, the end points of individual trials were transformed into an effect size as a common outcome. RESULTS: Of 21 trials initially identified, 8 qualified for inclusion. References from the 8 papers and consultation with the experts produced 8 additional publications, 1 of which qualified for inclusion. NAC was administered orally at a daily dose of 400 mg (1 study), 600 mg (5 studies), or 1200 mg (1 study). One other trial used a dose of 600 mg 3 times per week. The duration of treatment was 3 months (1 study), > or =5 months (2 studies), or 6 months (7 studies). The results of this meta-analysis showed a statistically significant effect size for NAC compared with placebo. The overall value of effect size was -1.37 (95% CI, -1.5 to -1.25). Sensitivity analyses did not significantly alter these results. In a subset analysis of trials with the number of acute exacerbations as a clinical end point, a mean difference of -0.32 clinical event (95% CI, -0.50 to -0.18) was found (ie, a 23% decrease in the number of acute exacerbations compared with placebo). CONCLUSION: These findings suggest that a prolonged course of oral NAC prevents acute exacerbations of CB, thus possibly decreasing morbidity and health care costs.

Acetylcysteine↗

PubMed2005

Meta-analysis of functional imaging data using replicator dynamics.

Despite the rapidly growing number of meta-analyses in functional neuroimaging, the field lacks formal mathematical tools for the quantitative and qualitative evaluation of meta-analytic data. We propose to use replicator dynamics in the meta-analysis of functional imaging data to address an important aspect of neuroimaging research, the search for functional networks of cortical areas that underlie a specific cognitive task. The replicator process requires as input only a list of activation locations, and it results in a network of locations that jointly show significant activation in most studies included in the meta-analysis. These locations are likely to play a critical role in solving the investigated cognitive task. Our method was applied to a meta-analysis of the Stroop interference task using data provided by the publicly accessible database BrainMap DBJ.

Brain↗

PubMed2005

Acellular dermal matrix for mucogingival surgery: a meta-analysis.

BACKGROUND: Many clinical studies revealed the effectiveness of acellular dermal matrix (ADM) in the treatment of mucogingival defects. The purpose of this meta-analysis was to compare the efficacy of ADM-based root coverage (RC) and ADM-based increase in keratinized tissues to other commonly used mucogingival surgeries. METHODS: Meta-analysis was limited to randomized clinical trials (RCT). Articles from January 1, 1990 to October 2004 related to ADM were searched utilizing the MEDLINE database from the National Library of Medicine, the Cochrane Oral Health Group Specialized Trials Registry, and through hand searches of reviews and recent journals. Relevant studies were identified, ranked independently, and mean data from each were weighted accordingly. Selected outcomes were analyzed using a meta-analysis software program. The significant estimates of the treatment effects from different trials were assessed by means of Cochrane's test of heterogeneity. RESULTS: 1) Few RCT studies were found to compile the data. In summary, selection identified eight RCT that met the inclusion criteria. There were four studies comparing ADM versus a connective tissue graft for root coverage procedures, two studies comparing ADM versus coronally advanced flap (CAF) for root coverage procedures, and two studies comparing ADM to free gingival graft in augmentation of keratinized tissue. 2) There were no statistically significant differences between groups for any of the outcomes measured (recession coverage, keratinized tissue formation, probing depths, and clinical attachment levels). 3) The majority of the analyses demonstrated moderate to high levels of heterogeneity. 4) Considering the heterogeneity values found among the studies, certain trends could be found: a) three out of four studies favored the ADM-RC group for recession coverage; b) a connective tissue graft tended to increase keratinized tissue compared to ADM (0.52-mm difference; P = 0.11); c) there were trends of increased clinical attachment gains comparing ADM to CAF procedures (0.56-mm difference; P = 0.16). CONCLUSIONS: Differences in study design and lack of data precluded an adequate and complete pooling of data for a more comprehensive analysis. Therefore, considering the trends presented in this study, there is a need for further randomized clinical studies of ADM procedures in comparison to common mucogingival surgical procedures to confirm our findings. It is difficult to draw anything other than tentative conclusions from this meta-analysis of ADM for mucogingival surgery, primarily because of the weakness in the design and reporting of existing trials.

Biocompatible Materials↗

PubMed2002

Commentary: meta-analysis of individual participants' data in genetic epidemiology.

The authors summarize their experience in the conduct of meta-analysis of individual participants' data (MIPD) with time-to-event analyses in the field of genetic epidemiology. The MIPD offers many advantages compared with a meta-analysis of the published literature. These include standardization of case definitions, outcomes, and covariates; inclusion of updated information; the ability to fully test the assumptions of time-to-event models; better control of confounding; standardization of analyses of genetic loci that are in linkage disequilibrium; evaluation of alternative genetic models and multiple genes; consistent treatment of subpopulations; assessment of sampling bias; and the establishment of an international collaboration with the capability to prospectively update the meta-analyses and synthesize new information on multiple genetic loci and outcomes. The disadvantages of a MIPD compared with a meta-analysis of the published literature are that a much greater commitment of time and resources is required to collect primary data and to coordinate a large collaborative project. An MIPD may collect additional, unpublished data, but it is possible that not all published data may be contributed at the individual level. For questions that justify the required intensive effort, the MIPD method is a useful tool to help clarify the role of candidate genes in complex human diseases.

Bias↗

PubMed2002

Age, gender, race, socioeconomic status, and birth cohort differences on the children's depression inventory: a meta-analysis.

A within-scale meta-analysis was performed on 310 samples of children (ages 8-16; N = 61,424) responding to the Children's Depression Inventory (CDI). Girls' depression scores stayed steady from ages 8 to 11 and then increased between ages 12 and 16. Boys' CDI scores were stable from ages 8 to 16 except for a high CDI score at age 12. Girls' scores were slightly lower than boys' during childhood, but girls scored higher beginning at age 13. There were no socioeconomic status effects and no differences between White and Black samples. However, Hispanic samples scored significantly higher on the CDI. Analyses for birth cohort showed a slight decrease in boys' CDI scores over time and no change for girls. Longitudinal studies demonstrated a marked testing effect.

Adolescent↗

PubMed2026

Systematic Review and Transcriptomic Meta-analysis of Environmental Enrichment Reveal Core Molecular Programs of Brain Plasticity.

Environmental enrichment (EE) paradigms in rodents have long demonstrated that enhanced sensory, cognitive, social, and motor stimulation positively impacts brain function, improving learning, memory, and neuroplasticity. These effects have significant implications for understanding cognitive development and mitigating cognitive decline and brain aging. While numerous transcriptomic studies have explored EE-induced molecular changes, a unified view of the genes and pathways consistently modulated remains lacking. To address this gap, we performed a systematic review and meta-analysis. We conducted a comprehensive PubMed search for all studies published up to February 2025 that matched all the following inclusion criteria: (1) employed EE paradigms; (2) were conducted on rodents; (3) utilized genome-wide transcriptomic methods; (4) examined brain regions or neuronal populations. The 323 retrieved articles were manually screened for relevance to the study aims and data availability. Datasets from 20 eligible RNA-seq reports were reprocessed using a unified analysis pipeline and subjected to a meta-analysis with three complementary statistical methods. Despite considerable heterogeneity across studies, our integrative analysis identified consistent gene expression signatures linked to synaptic function, plasticity and their transcriptional regulation. In particular, our findings highlight the upregulation of the activity-dependent transcriptional program, including Fos and Jun family members. These molecular insights advance our understanding of how EE impacts on neuronal and behavioral outcomes, and may inform therapeutic strategies aimed at replicating or enhancing EE benefits. To promote open science and foster further research, we developed an accessible web application, mEEtaBrain, that enables the neuroscience community to navigate and interrogate our meta-analysis results. Substantial methodological heterogeneity across source studies increased variability in the meta-analysis outcomes. The use of stressors or disease models, particularly in rat studies, introduced a major confounding factor and limited reliable interspecies comparison. Overall, the studies exhibited a low to moderate risk of bias.

Neuronal Plasticity↗

PubMed1999

Mood stabilizers in the prevention of recurrent affective disorders: a meta-analysis.

OBJECTIVE: To determine by meta-analysis the efficacy of mood stabilizers in preventing recurrence of bipolar or unipolar mood disorders and to consider the evidence for a lithium withdrawal-induced relapse syndrome. METHOD: Controlled studies of lithium, valproate and carbamazepine in preventing future episodes of affective disorders were classified according to methodological rigour, and meta-analyses were performed overall and on each type. RESULTS: A total of 19 blinded, randomized, controlled trials of prophylaxis in 865 patients found lithium highly effective (74% recurrence on placebo vs. 29% on lithium). In the mirror-image studies, whose substantial lithium vs. prior treatment difference cannot be explained by withdrawal relapse, lithium reduced relapse by 50% (bipolar) and 58%(unipolar). CONCLUSION: Maintenance lithium produces a highly significant reduction in relapses. The mirror-image studies had not been systematically analysed previously, and they support the effectiveness of lithium. We also failed to find sufficient evidence to prove that the lithium-withdrawal relapse phenomenon exists.

Antimanic Agents↗

PubMedDate not supplied

On combining dose-response data from epidemiological studies by meta-analysis.

Using data from a meta-analysis of the effects of oestrogen replacement therapy on the development of breast cancer, we compared alternative methods for combining dose-response slopes from epidemiological studies. We evaluated issues related both to summarizing data from single studies and to combining results from multiple studies. Findings related to the analysis of individual dose-response studies include: (1) a method of weighing studies that gives greater influence to dose-response slopes that conform to the linear relation of relative risk to duration can lead to large differences in calculated weights as a function of non-linearity; (2) a regression model using a variable-intercept resulted in a mean dose-response slope that increased as much as threefold when compared with the values obtained with a zero-intercept model. When combining results from multiple studies, we found: (1) calculating standard errors of mean dose-response slopes by methods that allow for both among-study and within-study variability (a random-effects type model) gave values different from a method that assumes homogeneity and equal within-study precision (a fixed-effects model); (2) the random-effects model gives mean and standard error results most similar to a bootstrap resampling method as increasing heterogeneity is observed (however, this model could give biased mean estimates compared with the bootstrap method); (3) a components-of-variance model compares favourably with the bootstrap and is easier to apply than the random-effects model. Based on these findings, we recommend the use of methods which incorporate heterogeneity to guard against underestimating the standard error. However, caution is urged because bias in point estimates can occur if extreme heterogeneity is present. Two other observations affect the interpretation of data combined from multiple studies. First, inclusion into a model of quality scores assigned by blinded reviewers had little effect on the mean dose-response slope and its standard error. Second, the number of studies required to achieve desired statistical power, varies with effect size.

Analysis of Variance↗

PubMed1999

Cost-utility of the cochlear implant in adults: a meta-analysis.

OBJECTIVE: To conduct a meta-analysis of the cost-utility of the cochlear implant in adults. DATA SOURCES: MEDLINE literature search, review of article bibliographies, and consultation with experts. STUDY SELECTION: Studies that reported (1) data on adults (age > or = 18 years) with bilateral, postlingual, profound deafness; (2) a health-utility gain from cochlear implantation on a scale from 0.00 (death) to 1.00 (perfect health); (3) a cost-utility ratio in terms of dollars per quality-adjusted life-year (QALY); and (4) at least 1 conventional statistical parameter (ie, SD, 95% confidence interval [CI], or P value). DATA EXTRACTION: From each study, we extracted the number of subjects, study design, health-utility instrument used, health-utility associated with profound deafness, health-utility gain from cochlear implantation, cost-utility of cochlear implantation, and reported statistical parameters. DATA SYNTHESIS: Weighted averages were calculated using a statistical weight of 1 per variance. Pooling 9 reports (n = 619), the health-utility of profoundly deaf adults without cochlear implants was 0.54 (95% CI, 0.52-0.56). Pooling 7 studies (n = 511), the health-utility of profoundly deaf adults after cochlear implantation was 0.80 (95% CI, 0.78-0.82). This improvement of 0.26 in health-utility resulted in a cost-utility ratio of $12,787 per QALY. CONCLUSIONS: Profound deafness in adults results in a substantial health-utility loss. Over half of that loss is restored after cochlear implantation, yielding a cost-utility ratio of $12,787 per QALY. This figure compares favorably with medical and surgical interventions that are commonly covered by third-party payers in the United States today.

Adult↗

PubMed1991

Is interhemispheric transfer of visuomotor information asymmetric? Evidence from a meta-analysis.

Using a meta-analytic procedure we have analysed 16 studies employing a simple unimanual reaction time (RT) paradigm and lateralized visual stimuli to provide an estimate of interhemispheric transfer time in normal right-handed subjects. We found a significant overall RT advantage of the left visual field over the right and of the right hand over the left. These asymmetries can be explained by a superiority of the right hemisphere for the detection of simple visual stimuli and by a corresponding superiority of the left hemisphere for the execution of the manual response, respectively. Alternatively, they may be interpreted as related to an asymmetry of interhemispheric transmission of visuomotor information, with transfer from the right hemisphere (side of stimulus entry) to the left (side of response generation) faster than in the reverse direction. Although a direct test of these hypotheses is still lacking, we think that the evidence available is more in keeping with the latter possibility.

Arousal↗

PubMed1991

Prevention of supraventricular arrhythmias after coronary artery bypass surgery. A meta-analysis of randomized control trials.

This meta-analysis was performed to determine the efficacy of digoxin, verapamil, and beta-adrenoceptor blockers as prophylaxis against supraventricular arrhythmias (SVAs) after coronary artery bypass graft surgery (CABG). Randomized control trials were included if the electrocardiographic monitoring technique was clearly defined and extended through at least the first 3 postoperative days. Twenty-four of 69 identified studies were included in the final analysis. A summary odds ratio (OR) of the likelihood of developing SVAs after CABG in the treatment versus control groups was calculated. The pooled mean ventricular rate during SVA in patients who developed such an arrhythmia was also calculated. Neither digoxin nor verapamil reduced the likelihood of SVAs after CABG (digoxin: OR = 0.97, 95% confidence interval [CI] = 0.62-1.49; verapamil: OR = 0.91, CI = 0.57-1.46). The likelihood of developing an SVA in patients treated with beta-blockers was markedly decreased compared with controls (OR = 0.28, CI = 0.21-0.36). The pooled ventricular rate when SVAs did occur was significantly lower in each of the treatment groups. Prophylactic beta-adrenoceptor blockers had a protective effect against the development of SVAs in a select population of patients undergoing CABG. No such beneficial effect was demonstrated for digoxin or verapamil. All three classes of agents reduced the ventricular rate in patients who developed the arrhythmia, although the ventricular rate reduction was not clinically optimal.

Adrenergic beta-Antagonists↗

PubMed2001

The role of method in treatment effectiveness research: evidence from meta-analysis.

A synthesis of 319 meta-analyses of psychological, behavioral, and educational treatment research was conducted to assess the influence of study method on observed effect sizes relative to that of substantive features of the interventions. An index was used to estimate the proportion of effect size variance associated with various study features. Study methods accounted for nearly as much variability in study outcomes as characteristics of the interventions. Type of research design and operationalization of the dependent variable were the method features associated with the largest proportion of variance. The variance as a result of sampling error was about as large as that associated with the features of the interventions studied. These results underscore the difficulty of detecting treatment outcomes, the importance of cautiously interpreting findings from a single study, and the importance of meta-analysis in summarizing results across studies.

Behavior Therapy↗

PubMed2003

Reconstructive neurosurgery for Parkinson's disease: a systematic review and preliminary meta-analysis.

This systematic review and meta-analysis aimed to identify the determinants for best practice and establish current benchmarks for recovery following reconstructive neurosurgery for people with Parkinson's disease. Eleven studies reporting results for 95 grafted patients were selected on the grounds of using optimal surgical techniques and the Core Assessment Program for Intracerebral Transplantation (CAPIT) protocol for data collection. Consistent trends demonstrating high levels of recovery were identified on most outcome measures. Determinants for best practice were identified as selecting younger patients; using low dose immunosuppression; bilateral grafting; and employing strategies to ensure the quantity and viability of the grafted cells. Secondary analysis of data demonstrated a correlation of rho=0.666 (P<0.05) between increases in striatal dopaminergic activity and UPDRS Motor (off) scores. Overall effect size 'd' was found to be 1.129 UPDRS Motor (off) condition and 0.719 for UPDRS Total (off) condition. The design of the studies and the variable standards for reporting the data precluded the use of more powerful and accurate meta-analyses. It was recommended that the creation of a collaborative database would improve the extraction of data and allow for more powerful statistical analyses for evaluating the overall harm and benefits associated with reconstructive neurosurgery.

Brain Tissue Transplantation↗

PubMed1994

Why sources of heterogeneity in meta-analysis should be investigated.

Although meta-analysis is now well established as a method of reviewing evidence, an uncritical use of the technique can be very misleading. One common problem is the failure to investigate appropriately the sources of heterogeneity, in particular the clinical differences between the studies included. This paper distinguishes between the concepts of clinical and statistical heterogeneity and exemplifies the importance of investigating heterogeneity by using published meta-analyses of epidemiological studies of serum cholesterol concentration and clinical trials of its reduction. Although not without some dangers of speculative conclusions, prompted by overzealous inspection of the data to hand, a sensible investigation of sources of heterogeneity should increase both the scientific and the clinical relevance of the results of meta-analyses.

Adult↗