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PubMed2005

CTLA-4 gene polymorphisms and susceptibility to type 1 diabetes mellitus: a HuGE Review and meta-analysis.

The authors performed a meta-analysis of 33 studies examining the association of type 1 diabetes mellitus with polymorphisms in the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) gene, including the A49G (29 comparisons), C(-318)T (three comparisons), and (AT)n microsatellite (six comparisons) polymorphisms. The studies included 5,637 cases of type 1 diabetes and 6,759 controls (4,775 and 5,829, respectively, for analysis of the A49G polymorphism). The random-effects odds ratio for the *G (Ala) allele versus the *A (Thr) allele was 1.45 (95% confidence interval (CI): 1.28, 1.65), with significant between-study heterogeneity (p < 0.001). The effect size tended to be higher in type 1 diabetes cases with age of onset <20 years (odds ratio (OR) = 1.61), and there was a significant association between the presence of glutamic acid decarboxylase-65 autoantibodies and the *G allele among type 1 diabetes cases (OR = 1.49). Larger studies showed more conservative results (p = 0.011). After exclusion of studies with fewer than 150 subjects and studies with significant deviation from Hardy-Weinberg equilibrium in the controls, the summary odds ratio was 1.40 (95% CI: 1.28, 1.54). Available data showed no strong association for the 106-base-pair allele of the microsatellite polymorphism (OR = 0.99, 95% CI: 0.64, 1.55) or the *T allele of the C(-318)T polymorphism (OR = 0.92, 95% CI: 0.45, 1.89). This meta-analysis demonstrates that the CTLA-4*G genotype is associated with type 1 diabetes.

Antigens, CD↗

PubMed2000

Sevoflurane versus propofol for anesthetic induction: a meta-analysis.

UNLABELLED: We performed this meta-analysis to compare the characteristics of sevoflurane and propofol for the induction of routine anesthesia and for laryngeal mask airway (LMA) insertion. The variables assessed were 1) time to loss of consciousness, 2) incidence of apnea during induction, 3) induction complications, 4) time for successful LMA insertion, 5) success with LMA insertion on first attempt, 6) patient dissatisfaction, and 7) postoperative nausea and vomiting. MEDLINE, Embase, and the Cochrane library databases between January 1992 and October 1999 were reviewed for randomized, controlled trials comparing anesthetic induction between sevoflurane/nitrous oxide and propofol. Data from the 12 randomized, controlled studies were used for the meta-analysis. Sevoflurane induction was associated with a trend toward higher patient dissatisfaction and higher first-time success with LMA. Apnea was less common in the sevoflurane group. The incidence of postoperative nausea and vomiting was significantly more frequent in the sevoflurane group (P < 0.05). This effect was still present when all other variables, except the induction methods, were controlled. The other pooled variables did not show a significant difference between sevoflurane and propofol. Sevoflurane and propofol had similar efficacy for anesthetic induction. However, for routine outpatient surgery, propofol may still be the preferred induction anesthetic because of its favorable induction of anesthesia characteristics, high patient satisfaction, and less frequent incidence of postoperative nausea and vomiting. IMPLICATIONS: Sevoflurane and propofol had similar efficacy for anesthetic induction. However, for routine outpatient surgery, propofol may still be the preferred induction anesthetic because of its favorable induction of anesthesia characteristics, high patient satisfaction, and less frequent incidence of postoperative nausea and vomiting.

Anesthesia↗

PubMed2000

Smoking as a risk factor for accident death: a meta-analysis of cohort studies.

This meta-analysis discusses the consistency, strength, dose-response, independence, and generalizability of published cohort data on accident death relative risks in smokers. To locate data, three authors independently searched MEDLINE, and bibliographies of the pertinent studies found, for data which allowed estimation of an appropriate cigarette smoker accident death relative risk (and 95% confidence interval). Relative risks and dose-response were summarized by fixed effects and Poisson modeling, respectively. Four pertinent cohort studies including eight populations were located. Cigarette smoking predicted summary accident death relative risks of 1.51 (95% confidence interval 1.27-1.78) versus never smokers and 1.35 (1.17-1.57) versus ex-smokers. Summary dose-response trends were significant (P = 0.0000) versus never or least smoking referents. In individual studies, the smoking/accident death association persisted after adjustment or, in effect stratification, for age, race, sex, and occupation; occupation and time period; or numerous cardiac risk factors. This meta-analysis found significant, consistent, dose-response, often strong and independent (of age, race, and sex), prospective associations of smoking with accident death, internationally. Further studies and warnings of the smoking/accident death associations seem merited.

Accidents↗

PubMed2006

Prosthesis infection: diagnosis after total joint arthroplasty with antigranulocyte scintigraphy with 99mTc-labeled monoclonal antibodies--a meta-analysis.

PURPOSE: To perform a meta-analysis of diagnostic studies regarding the accuracy of antigranulocyte scintigraphy (AGS) with monoclonal antibodies in the identification of prosthesis infection after total hip or knee arthroplasty. MATERIALS AND METHODS: PubMed and EMBASE searches were conducted for the identification of relevant studies. Data on the diagnostic performance of AGS with monoclonal antibodies were combined quantitatively across eligible studies, and the overall sensitivity and specificity, along with summary receiver operating characteristic (ROC) curves and likelihood ratios (LRs), were estimated. The above parameters were evaluated for all patients and for various subgroups among the eligible studies. The reference standard used in the individual studies was accepted. RESULTS: Thirteen eligible studies on nonoverlapping patient groups were included in the meta-analysis; there was a total sample size of 522 implants. The independent random effects summary estimates of sensitivity and specificity were 83% and 80%, respectively. The summary ROC curve estimate for weighted analysis was a sensitivity of 90% for a specificity of 80%. LR syntheses gave a weighted positive LR of 3.99 (95% confidence interval [CI]: 3.13, 5.09) and a weighted negative LR of 0.22 (95% CI: 0.15, 0.34); there was no statistically significant between-study heterogeneity for either metric. Various subgroup analyses did not reveal any statistically significant differences. CONCLUSION: AGS with monoclonal antibodies had a reasonably high discriminating ability to identify prosthesis infection in patients who underwent total joint arthroplasty.

Antibodies, Monoclonal↗

PubMed1996

Placental abruption and its association with hypertension and prolonged rupture of membranes: a methodologic review and meta-analysis.

OBJECTIVE: To conduct a meta-analysis of published studies on placental abruption to examine its incidence, recurrence, and association with hypertensive disorders (chronic hypertension and preeclampsia) and prolonged rupture of membranes (PROM) in pregnancy. DATA SOURCES: We reviewed studies on placental abruption published since 1950, based on a comprehensive literature search using MEDLINE, and by identifying studies cited in the references of published reports. METHODS OF STUDY SELECTION: We identified 54 studies, excluding case reports on placental abruption and studies relating to placenta previa and vaginal bleeding of unknown origin. We also restricted the search to articles published in English. TABULATION, INTEGRATION, AND RESULTS: Studies chosen for the meta-analysis were categorized based on their study design (case-control or cohort), where they were conducted (United States or other countries), source of the data (vital records versus other sources), and magnitude of risk (risk of abruption greater or less than 1.0%). We used both fixed- and random-effects analysis to identify sources of heterogeneity in results among studies. There were striking differences in the incidence of placental abruption between cohort (0.69%) and case-control (0.35%) studies. United States-based studies found a somewhat higher incidence both for cohort (0.81%) and case-control (0.37%) studies compared with studies conducted outside the U.S. (0.60% and 0.26%, respectively). Abruption was more than ten times more common in pregnancies preceded by a pregnancy with abruption. Chronically hypertensive patients were more than three times as likely to develop placental abruption (odds ratio [OR] 3.13, 95% confidence interval [CI] 2.04-4.80) as normotensive patients. The OR for placental abruption was 1.73 (95% CI 1.47-2.04) for patients with preeclampsia. Similarly, women with pregnancies complicated by PROM were more than three times as likely to develop placental abruption (OR 3.05, 95% CI 2.16-4.32). United States-based studies, case-control studies, and studies with an incidence of abruption greater than 1% demonstrated stronger associations between abruption and hypertension and PROM. CONCLUSION: Risk of abruption is strongly associated with chronic hypertension, PROM, and especially abruption in a prior pregnancy, and somewhat more modestly with preeclampsia. The criteria for the diagnosis of placental abruption, hypertensive disorders, and PROM may have introduced variability among the results of these studies. More standardized definitions of these pregnancy complications would improve the comparability of the study results.

Abruptio Placentae↗

PubMed1999

Protected specimen brush or bronchoalveolar lavage to diagnose bacterial nosocomial pneumonia in ventilated adults: a meta-analysis.

OBJECTIVE: We conducted a meta-analysis by using summary receiver operating characteristic curves to compare the diagnostic value for bacterial nosocomial pneumonia of the following: a) quantitative culture (colony-forming units per milliliter or CFU/mL) of respiratory secretions collected with a bronchoscopic protected specimen brush (PSB); b) quantitative culture of a bronchoscopic bronchoalveolar lavage (BAL); and c) the percentage of infected cells (IC) in BAL. DATA SOURCES: All studies published in the English or the French language, through January 1, 1995, on the evaluation of PSB or BAL for the diagnosis of pneumonia were considered for analysis. The relevant literature was identified through computer and reference searching and by experts in the field. STUDY SELECTION: A study was included if at least two of three independent readers regarded its purpose as the evaluation of CFU-PSB, CFU-BAL, or IC-BAL for the diagnosis in human beings of bacterial nosocomial pneumonia in ventilated adults and if the study was prospective and published in a peer-reviewed journal. DATA EXTRACTION: Three readers reviewed all published articles and decided whether to include each study; consensus was defined as agreement by at least two readers. The authors of each original article included in the meta-analysis were asked to complete a questionnaire in which they were asked to check and to correct the data extracted by one of the independent readers. DATA SYNTHESIS: Summary receiver operating characteristic curves were used to compare the efficacy of three diagnostic tests. Eighteen studies on CFU-PSB (795 patients) were included, as well as 11 studies on CFU-BAL (435 patients) and 11 on IC-BAL (766 patients). The accuracy of these tests was not different. However, it seems that administration of previous antibiotics markedly decreased accuracy of CFU-PSB (p = .0002) but not the accuracy of CFU-BAL and that of IC-BAL. CONCLUSION: Both PSB and BAL are reliable to diagnose bacterial nosocomial pneumonia. Because CFU-BAL and IC-BAL seemed more resistant to the effects of antibiotics, we recommend BAL rather than PSB if the patient is already receiving antibiotics.

Adult↗

PubMed1997

Effects of antihistamines in adult asthma: a meta-analysis of clinical trials.

A meta-analysis of clinical trials of antihistamines was performed to assess the risk-benefit ratio of this therapeutic class in asthma. Double-blind randomized placebo-controlled trials assessing lung function changes under repeated use of antihistamine in adult asthma were selected, and the quality of studies was scored. Morning peak expiratory flow rate (PEFR) was the primary outcome: an effect size was computed for each study, with a 95% confidence interval (95% CI), and a mean effect size was computed, combining all studies. Effect sizes were also determined for secondary outcomes: evening PEFR, forced expiratory volume in one second (FEV1) and daily use of inhaled beta-agonists. Nineteen studies were included in the meta-analysis. Mean quality score of studies was 59.4%; asthma was generally uncontrolled at study inclusion. Altogether, 582 antihistamine-treated and 557 placebo-treated asthma patients were evaluable. Antihistamines had little effect on airway calibre (mean increase in morning PEFR: 13 L x min(-1); 95 CI: 8-18 L x min(-1)) and on use of inhaled beta-agonists (mean reduction in daily use: 0.4 doses; 95% CI: 0-0.8 doses). Sedation occurred more often with antihistamines than with placebo (p<0.001); additional side-effects were mentioned, including weight gain, altered taste, headache and dry mouth. Respiratory and systemic effects observed after repeated use of antihistamines do not support the use of these medications in the treatment of asthma; better designed studies could affect this appraisal.

Adolescent↗

PubMed2006

Environmental tobacco smoke and coronary heart disease mortality in the United States--a meta-analysis and critique.

Several major meta-analyses have concluded that exposure to environmental tobacco smoke (ETS) increases the risk of coronary heart disease (CHD) by about 25% among never smokers. However, these reviews have excluded a large portion of the epidemiologic evidence on questionable grounds and have been inconsistent in the selection of the results that are included. We conducted an updated meta-analysis and critique of the evidence on ETS exposure and its relationship to death from CHD among never smokers. Our focus is on the U.S. cohort studies, which provide the vast majority of the available evidence. ETS exposure is assessed in terms of spousal smoking, self-reported estimates, and personal monitoring. The epidemiologic results are summarized by means of overall relative risks and dose-response relationships. The methodological issues of publication bias, exposure misclassification, and confounding are discussed. Several large studies indicate that spousal smoking history is a valid measure of relative exposure to ETS, particularly for females. Personal monitoring of nonsmokers indicates that their average ETS exposure from a smoking spouse is equivalent in terms of nicotine exposure to smoking less than 0.1 cigarettes per day. When all relevant studies are included in the meta-analysis and results are appropriately combined, current or ever exposure to ETS, as approximated by spousal smoking, is associated with roughly a 5% increased risk of death from CHD in never smokers. Furthermore, there is no dose-response relationship and no elevated risk associated with the highest level of ETS exposure in males or females. An objective assessment of the available epidemiologic evidence indicates that the association of ETS with CHD death in U.S. never smokers is very weak. Previous assessments appear to have overestimated the strength of the association.

Case-Control Studies↗

PubMed2004

Dietary alpha-linolenic acid is associated with reduced risk of fatal coronary heart disease, but increased prostate cancer risk: a meta-analysis.

The objective of this meta-analysis was to estimate quantitatively the associations between intake of alpha-linolenic acid [ALA, the (n-3) fatty acid in vegetable oils], mortality from heart disease, and the occurrence of prostate cancer in observational studies. We identified 5 prospective cohort studies that reported intake of ALA and mortality from heart disease. We also reviewed data from 3 clinical trials on ALA intake and heart disease. In addition, we identified 9 cohort and case-control studies that reported on the association between ALA intake or blood levels and incidence or prevalence of prostate cancer. We combined risk estimates across studies using a random-effects model. High ALA intake was associated with reduced risk of fatal heart disease in prospective cohort studies (combined relative risk 0.79, 95% CI 0.60-1.04). Three open-label trials also indicated that ALA may protect against heart disease. However, epidemiologic studies also showed an increased risk of prostate cancer in men with a high intake or blood level of ALA (combined relative risk 1.70; 95% CI 1.12-2.58). This meta-analysis shows that consumption of ALA might reduce heart disease mortality. However, the association between high intake of ALA and prostate cancer is of concern and warrants further study.

Adult↗

PubMed2026

Atopic dermatitis and the risk of osteoporosis and fractures: a meta-analysis of cohort studies.

BACKGROUND: This meta-analysis aims to evaluate the risk of osteoporosis and fractures in patients with atopic dermatitis (AD) by synthesizing data from cohort studies. We also provide a comprehensive analysis of fracture risks across different severities of AD and anatomical sites. METHODS: Following the PRISMA 2020 guidelines, a systematic search was conducted in PubMed, Embase, and the Cochrane Library up to May 30, 2025. Studies that investigated the relationship between AD and osteoporosis or fractures were included in the analysis. Data extraction and screening were performed independently by two reviewers. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). A random-effects meta-analysis was applied, alongside sensitivity and subgroup analyses. Publication bias was evaluated using funnel plots and Egger's test. RESULTS: Ten cohort studies, involving 368 to over 2 million AD patients, were included. NOS scores ranged from 7 to 8, indicating generally high study quality. The pooled analysis revealed a 56% increased risk of osteoporosis (OR = 1.56, 95% CI: 1.14-2.13; I2 = 99.9%, p < 0.0001) and an 8% increased risk of all-cause fractures (OR = 1.08, 95% CI: 1.05-1.10; I2 = 82.1%, p < 0.0001) in AD patients. Subgroup analyses demonstrated a progressive increase in fracture risk with the severity of AD. Specific risks were significantly higher for vertebral fractures (OR = 1.14, 95% CI: 1.08-1.20; I2 = 67.3%, p = 0.009) and lower limb fractures (OR = 1.11, 95% CI: 1.08-1.13; I2 = 65.0%, p = 0.014). Sensitivity analyses confirmed the robustness of these findings, and no significant publication bias was detected (p = 0.316). CONCLUSION: AD is associated with an increased risk of osteoporosis and fractures, particularly among patients with severe AD and those experiencing vertebral or lower limb fractures. These findings highlight the importance of targeted bone health monitoring in the clinical management of AD patients.Registration: (PROSPERO: CRD420251066550).

Humans↗

PubMed1995

Intrapartum electronic fetal heart rate monitoring versus intermittent auscultation: a meta-analysis.

OBJECTIVE: To use a meta-analysis of all published randomized trials to determine whether the use of continuous electronic fetal heart rate monitoring (EFM) as the main method of intrapartum fetal surveillance is associated with improved pregnancy outcome compared to intermittent auscultation. DATA SOURCES: We used the MEDLINE data base and reference lists of articles to identify all published randomized trials of EFM versus intermittent auscultation. METHODS OF STUDY SELECTION: A total of nine randomized trials published in peer-review journals were identified. The selection criterion was the use of EFM or intermittent auscultation as the main intrapartum fetal surveillance technique. DATA EXTRACTION AND SYNTHESIS: A total of 18,561 patients were included in the nine published randomized trials, 9398 in the EFM group and 9163 in the auscultation group. Measures of pregnancy outcome included cesarean delivery, cesarean for suspected fetal distress, overall use of forceps or vacuum, use of forceps or vacuum for suspected fetal distress, overall perinatal mortality, and perinatal mortality due to fetal hypoxia (intrapartum or early neonatal death) attributable to the method of intrapartum monitoring. The meta-analysis showed that the patients monitored electronically had a significantly higher overall cesarean rate (odds ratio [OR] 1.53, 95% confidence interval [CI] 1.17-2.01), higher cesarean rate for fetal distress (OR 2.55, 95% CI 1.81-3.53), overall increased use of forceps or vacuum (OR 1.23, 95% CI 1.02-1.49), increased use of forceps or vacuum for suspected fetal distress (OR 2.50, 95% CI 1.97-3.18), and decreased perinatal mortality due to fetal hypoxia (OR 0.41, 95% CI 0.17-0.98). CONCLUSION: Electronic fetal monitoring is associated with increased rates of surgical intervention and decreased perinatal mortality due to fetal hypoxia.

Cardiotocography↗

PubMed1998

Treatment of acute otitis media with a shortened course of antibiotics: a meta-analysis.

OBJECTIVE: To conduct a meta-analysis of randomized controlled trials of antibiotic treatment of acute otitis media in children to determine whether outcomes were comparable in children treated with antibiotics for less than 7 days or at least 7 days or more. DATA SOURCES: MEDLINE (1966-1997), EMBASE (1974-1997), Current Contents, and Science Citation Index searches were conducted to identify randomized controlled trials of the treatment of acute otitis media in children with antibiotics of different durations. STUDY SELECTION: Studies were included if they met the following criteria: subjects aged 4 weeks to 18 years, clinical diagnosis of acute otitis media, no antimicrobial therapy at time of diagnosis, and randomization to less than 7 days of antibiotic treatment vs 7 days or more of antibiotic treatment. DATA EXTRACTION: Trial methodological quality was assessed independently by 7 reviewers; outcomes were extracted as the number of treatment failures, relapses, or reinfections. DATA SYNTHESIS: Included trials were grouped by antibiotic used in the short course: (1) 15 short-acting oral antibiotic trials (penicillin V potassium, amoxicillin [-clavulanate], cefaclor, cefixime, cefuroxime, cefpodoxime proxetil, cefprozil), (2) 4 intramuscularceftriaxone sodium trials, and (3) 11 oral azithromycin trials. The summary odds ratio for treatment outcomes at 8 to 19 days in children treated with short-acting antibiotics for 5 days vs 8 to 10 days was 1.52 (95% confidence interval [CI], 1.17-1.98) but by 20 to 30 days outcomes between treatment groups were comparable (odds ratio, 1.22; 95% CI, 0.98 to 1.54). The risk difference (2.3%; 95% CI,-0.2% to 4.9%) at 20 to 30 days suggests that 44 children would need to be treated with the long course of short-acting antibiotics to avoid 1 treatment failure. This similarity in later outcomes was observed for up to 3 months following therapy (odds ratio, 1.16; 95% CI, 0.90-1.50). Comparable outcomes were shown between treatment with ceftriaxone or azithromycin, and at least 7 days of other antibiotics. CONCLUSION: This meta-analysis suggests that 5 days of short-acting antibiotic use is effective treatment for uncomplicated acute otitis media in children.

Acute Disease↗

PubMed1994

Meta-analysis and its problems.

Including all relevant material--good, bad, and indifferent--in meta-analysis admits the subjective judgments that meta-analysis was designed to avoid. Several problems arise in meta-analysis: regressions are often non-linear; effects are often multivariate rather than univariate; coverage can be restricted; bad studies may be included; the data summarised may not be homogeneous; grouping different causal factors may lead to meaningless estimates of effects; and the theory-directed approach may obscure discrepancies. Meta-analysis may not be the one best method for studying the diversity of fields for which it has been used.

Data Collection↗

PubMed2005

Identifying genetic variation affecting a complex trait in simulated data: a comparison of meta-analysis with pooled data analysis.

We explored the power and consistency to detect linkage and association with meta-analysis and pooled data analysis using Genetic Analysis Workshop 14 simulated data. The first 10 replicates from Aipotu population were used. Significant linkage and association was found at all 4 regions containing the major loci for Kofendrerd Personality Disorder (KPD) using both combined analyses although no significant linkage and association was found at all these regions in a single replicate. The linkage results from both analyses are consistent in terms of the significance level of linkage test and the estimate of locus location. After correction for multiple-testing, significant associations were detected for the same 8 single-nucleotide polymorphisms (SNP) in both analyses. There were another 2 SNPs for which significant associations with KPD were found only by pooled data analysis. Our study showed that, under homogeneous condition, the results from meta-analysis and pooled data analysis are similar in both linkage and association studies and the loss of power is limited using meta-analysis. Thus, meta-analysis can provide an overall evaluation of linkage and association when the original raw data is not available for combining.

Computer Simulation↗

PubMed2000

Interpreting epidemiological evidence: how meta-analysis and causal inference methods are related.

Interpreting observational epidemiological evidence can involve both the quantitative method of meta-analysis and the qualitative criteria-based method of causal inference. The relationships between these two methods are examined in terms of the capacity of meta-analysis to contribute to causal claims, with special emphasis on the most commonly used causal criteria: consistency, strength of association, dose-response, and plausibility. Although meta-analysis alone is not sufficient for making causal claims, it can provide a reproducible weighted average of the estimate of effect that seems better than the rules-of-thumb (e.g. majority rules and all-or-none) often used to assess consistency. A finding of statistical heterogeneity, however, need not preclude a conclusion of consistency (e.g. consistently greater than 1.0). For the criteria of strength of association and dose-response, meta-analysis provides more precise estimates, but the causal relevance of these estimates remains a matter of judgement. Finally, meta-analysis may be used to summarize evidence from biological, clinical, and social levels of knowledge, but combining evidence across levels is beyond its current capacity. Meta-analysis has a real but limited role in causal inference, adding to an understanding of some causal criteria. Meta-analysis may also point to sources of confounding or bias in its assessment of heterogeneity.

Causality↗

PubMedDate not supplied

Pharmacological and psychological treatments for depressed older patients: a meta-analysis and overview of recent findings.

A meta-analysis was carried out to evaluate data published between January 1974 and February 1998 comparing rates of treatment response and tolerability of pharmacological and psychological treatments for depression in persons over age 55. Drugs (tricyclic antidepressants, selective serotonin-reuptake inhibitors, and a mixed group of other drugs) were significantly better than placebo, with an average reduction in symptom severity of 48.0% versus 31.3% (analysis weighted by sample size; 50.6% vs. 21.4% unweighted). No single drug or group of drugs was superior in terms of efficacy, and no statistically significant differences in tolerability emerged between tricyclic antidepressants and selective serotonin-reuptake inhibitors, whether measured by total dropouts or by dropouts due to side effects. Compared to the data on pharmacological treatments, those for outcomes of psychological treatments are very limited. Existing data indicate that cognitive-behavioral, behavioral, and psychodynamic therapies are significantly better than placebo. In the current meta-analysis, response rates to these nondrug therapies did not differ significantly from those observed with tricyclic antidepressants or selective serotonin-reuptake inhibitors, but direct comparison data are insufficient for firm conclusions to be drawn about comparative efficacy. It is possible, even likely, that not only different subtypes of depression but also different patients vary in their treatment responses. However, lack of adequate data prevented the current meta-analysis from addressing these issues. Rigorously designed prospective studies on treatment outcome, taking into account the above differences, are urgently needed to provide robust data on which to base clinical recommendations for the treatment of depression in older patients.

Aged↗

PubMed1997

Meta-analysis of randomized trials: looking back and looking ahead.

Meta-analyses as currently practiced are usually retrospective. They can be made more rigorous by developing a protocol that incorporates prospectively the elements that are usually necessary in a well-designed trial. Meta-analysis and large trials are complementary. Meta-analysis of small trials is useful in generating the hypotheses and assisting in the design of the large trials that are needed. Once the large trials have been completed, they could be brought together within the framework of a meta-analysis to estimate the overall treatment effect with greater confidence and to explore the effects in various subgroups. This article explores the value and limitations of meta-analyses and suggests ways of improving their conduct and interpretation.

Humans↗

PubMed1992

Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: evidence in terms of response rate. Advanced Colorectal Cancer Meta-Analysis Project.

PURPOSE: A meta-analysis was performed on nine randomized clinical trials that compared fluorouracil (5-FU) with 5-FU plus intravenous (IV) leucovorin (LV) for the treatment of advanced colorectal cancer. DESIGN: The analysis was based on the most recently updated individual patient data from all trials. The end points of interest were tumor response and overall survival. RESULTS: Therapy with 5-FU plus LV administered either as weekly or monthly regimens showed a highly significant benefit over single-agent 5-FU in terms of tumor response rate (23% v 11%; response odds ratio (OR), 0.45; P less than 10(-7)). This increase in response did not result in a discernable improvement of overall survival (survival OR, 0.97; P = .57). The large number of patients who did not respond to treatment in both groups, and cross-overs from 5-FU alone to 5-FU plus LV are discussed as plausible explanations for the lack of a survival difference. CONCLUSION: These results confirm the advantage of 5-FU plus leucovorin over 5-FU alone in terms of objective tumor response. They also suggest that in planning future trials, tumor response should not be considered a valid surrogate end point for survival in patients with advanced colorectal cancer.

Colorectal Neoplasms↗