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[Meta-analysis: a structured bibliographic protocol].

Meta-analysis is a way of reviewing literature in a structured and systematic format. A formalized protocol for selection of the reviewed papers and a qualitative as well as quantitative evaluation are essential. Mathematical pooling of the results of the individual studies can be part of the process. A number of pitfalls are possible. However, when performed in a correct way and evaluated critically by the reader, a meta-analysis can add consistently to the medical knowledge concerning a specific subject.

Information Services↗

Effect of early and late GB virus C viraemia on survival of HIV-infected individuals: a meta-analysis.

OBJECTIVES: To conduct a meta-analysis to synthesize the evidence regarding the effect of co-infection with GB virus C (GBV-C) on survival of HIV-infected individuals, and to estimate the effect. METHODS: A Bayesian meta-analysis was conducted to synthesize evidence from eligible studies. Prospective survival studies of HIV-1-infected individuals, with outcome defined as time from baseline to all-cause death, were included and classified by whether GBV-C status was determined in early or late HIV disease. The primary measure was the hazard ratio (HR) of death for HIV-infected individuals with GBV-C infection versus those without GBV-C infection. RESULTS: Eleven studies from eight publications met the inclusion criteria. For studies with GBV-C status measured 2 years or less after HIV seroconversion (912 subjects), the combined HR was 0.88 [95% credible interval (CI) 0.30, 1.50]. For studies with GBV-C status measured more than 2 years after HIV seroconversion (1294 subjects), the combined HR was 0.41 (95% CI 0.23, 0.69). CONCLUSIONS: No conclusive evidence was found of an association between survival and GBV-C infection early in HIV disease. However, when GBV-C infection was present later in HIV disease, a significant reduction in the hazard for mortality was observed for those with co-infection. Potential explanations for this difference include a non-proportional benefit of GBV-C over time, possibly related to clearance of GBV-C infection early in HIV disease. The timing of GBV-C infection appears to account for the contradictory results of studies on the effect of GBV-C coinfection on survival of HIV-infected people.

Adult↗

Systematic reviews with individual patient data meta-analysis to evaluate diagnostic tests.

Systematic literature reviews with meta-analysis of reported data in diagnostic research studies about the accuracy of tests assist clinicians in decision-making. However, there are limitations to this approach as the analysis of such data often does not allow reviewers to explore the diagnostic information gained from combinations of tests. In recent years meta-analysis of individual patient data (IPD) has been introduced as gold standard analytic approach in systematic reviews of randomised controlled trials. Application of IPD meta-analysis in systematic reviews of diagnostic tests can allow advanced analysis to decipher the real value of testing. In particular, the additional information provided by testing can be examined in light of the information already known from history and examination. To our knowledge there are no IPD meta-analyses in diagnostic research so far. This commentary aims to highlight the benefits of IPD meta-analysis in the diagnostic domain and demonstrates how strategies for diagnostic work-up of women with postmenopausal bleeding could be improved using this approach in systematic reviews of diagnostic research on accuracy of ultrasound and hysteroscopy.

Diagnostic Tests, Routine↗

Behavior genetic research on gambling and problem gambling: a preliminary meta-analysis of available data.

A meta-analysis of family and twin studies on gambling and problem gambling was initiated in an effort to determine the probable role of genetic factors in high risk wagering. Two twin studies and 17 investigations employing the family history or family study method were included in this meta-analysis. A summation of the 19 studies produced a small but significant overall effect size (weighted phi = .10, unweighted phi = .13), with both family (weighted phi = .12, unweighted phi = .14) and twin (weighted phi = .06, unweighted phi = .05) studies achieving significant individual mean effects. Given the paucity of twin data, further analysis was confined to family studies and revealed a stronger familial effect for the sons of problem gambling fathers than for the daughters of problem gambling mothers and for more severe forms of problem gambling than for less severe forms of problem wagering, and was strongest for high severity problem gambling in males. The implications of these results are discussed.

Adult↗

A reappraisal of poststroke depression, intra- and inter-hemispheric lesion location using meta-analysis.

A recent publication based on a meta-analysis concluded that there was no association between poststroke depression (PSD) and lesion location. This study, therefore, was undertaken to reappraise the hypothesis using meta-analysis of the correlation between severity of depression following stroke and proximity of the lesion to the frontal pole, an issue that was not examined in the prior meta-analysis. Results showed there was a significant inverse correlation between severity of depression and distance of the lesion from the frontal pole among 163 patients with left hemisphere stroke but not among 106 patients with right hemisphere stroke. This study supports the hypothesis that risk of poststroke depression is related to the location of brain injury.

Brain Injuries↗

The effects of early prevention programs for families with young children at risk for physical child abuse and neglect: a meta-analysis.

In this article, a meta-analysis is presented on 40 evaluation studies of early prevention programs for families with young children at risk for physical child abuse and neglect with mostly nonrandomized designs. The main aim of all programs was to prevent physical child abuse and neglect by providing early family support. For the meta-analysis, a multilevel approach was used. A significant overall positive effect was found, pointing to the potential usefulness of these programs. The study demonstrated a significant decrease in the manifestation of abusive and neglectful acts and a significant risk reduction in factors such as child functioning, parent-child interaction, parent functioning, family functioning, and context characteristics.

Age Factors↗

Postoperative hemorrhage with nonsteroidal anti-inflammatory drug use after tonsillectomy: a meta-analysis.

OBJECTIVE: To use standard meta-analysis techniques to determine the risk of postoperative hemorrhage associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) after tonsillectomy. DATA SOURCES: The MEDLINE database (1966-2001) restricted to the English language was searched using the keywords tonsillectomy, hemorrhage, analgesics, and NSAID in various combinations. Additionally, published articles were cross-referenced. To ensure completeness, the search was rerun using the Science Citation Index database. STUDY SELECTION: Of the 110 articles identified, 7 were selected. Selected studies were prospective trials comparing the effects of an NSAID and a control drug on posttonsillectomy pain and hemorrhage in pediatric and/or adult patients. In all cases, the NSAID or control was administered through an enteric route in the postoperative period. Patients were monitored for early and delayed hemorrhage. DATA EXTRACTION: Data were extracted independently by 2 investigators. DATA SYNTHESIS: A random effects model was used to compute a pooled odds ratio. For the 1368 patients included in analysis, the pooled odds ratio of posttonsillectomy hemorrhage with NSAIDs compared with controls was 1.29 and was not statistically significant (95% confidence interval, 0.85-1.73; P>/=.05). A subgroup analysis revealed an odds ratio of 0.93 (95% confidence interval, 0.44 -1.95; P>/=.05) for the nonaspirin NSAID group, while the aspirin group had a statistically significant odds ratio of 1.94 (95% confidence interval, 1.09-3.42; P =.02). CONCLUSIONS: There is an increased risk of posttonsillectomy hemorrhage with the use of aspirin after tonsillectomy; however, there appears to be no significant increased risk of bleeding for nonaspirin NSAIDs in this meta-analysis.

Adolescent↗

[Meta-analysis in neurobehavioral toxicological studies].

Meta-analysis was used to deal with the data collected in neurobehavioral toxicological studies to synthesize their findings quantitatively. Results revealed neurotoxic chemicals could cause changes in cognitive abilities, psychomotor function and emotion of persons exposed. However, each toxicant had its distinct effects on neurobehavior, for example, lead mainly impairs touch sense, memory, emotion and cognitive abilities, mercury does intelligence, concentration and motor stability, and carbon disulfide does eye-hand coordination. It suggested meta-analysis could be directive to selecting the best combination of neurobehavioral tests.

Carbon Disulfide↗

The efficacy of 5-HT3 receptor antagonists for the prevention of postoperative nausea and vomiting after craniotomy: a meta-analysis.

The purpose of this meta-analysis was to assess the efficacy of prophylactic administration of 5-HT3 receptor antagonists for postoperative nausea and vomiting in neurosurgical patients at 24 and 48+ hours. After a systematic search, 7 published randomized placebo controlled trials involving 448 craniotomy patients (222 treatment, 226 control) were included in the meta-analysis. Study drugs included ondansetron, granisetron, and tropisetron. The cumulative incidence of emesis was significantly reduced in the treatment group at 24 hours [relative risk (RR)=0.50, 95% confidence interval (CI): 0.38-0.66] and 48+ hours (RR=0.52, 95% CI: 0.36-0.75). There were no differences between the treatment and control groups in the cumulative incidence of nausea at 24 hours (RR=0.76, 95% CI: 0.54-1.06) and 48+ hours (RR=0.81, 95% CI: 0.62-1.06). The cumulative incidence of both nausea and vomiting continued to increase after 24 hours in both groups. Despite the ability of 5-HT3 receptor antagonists to reduce emetic episodes, future investigations should seek to address the control of postoperative nausea and to reduce further postoperative emesis in this population.

Antiemetics↗

Effects of general and locoregional anesthesia on reproductive outcome for in vitro fertilization: a meta-analysis.

The objective of this meta-analysis was to evaluate prospective trials of general or locoregional anesthesia on reproductive outcomes (cleavage and pregnancy rate) for in vitro fertilization (IVF). Of 115 published studies retrieved from a search of articles indexed on MEDLINE from 1966 to February 1999, four studies with distinct general and locoregional anesthesia were deemed eligible for meta- analysis. The pooled relative risk and odds ratios were calculated. A test for homogeneity was also performed. The pooled log odds ratio was 1.03 (95% CI 0.90-1.18) in cleavage rate and 0.71 (95% CI 0.47-1.08) in pregnancy rate. Heterogeneity was negative. Cleavage and pregnancy rates were not significantly different in both the general anesthesia and locoregional anesthesia groups. Both anesthetic techniques were favorable to IVF procedure by available published evidence when anesthesia was needed.

Anesthesia, Conduction↗

Adult age differences in repetition priming: a meta-analysis.

This article reports a meta-analysis comparing the size of repetition priming effects in young and older adults. The main analysis included 39 effect sizes. Of these, 23 effect sizes could be classified as involving item priming and 16 as involving associative priming. The weighted mean effect size for the age difference was .304, with a confidence interval from .217 to .392. Because the confidence interval did not include 0, the hypothesis of no age difference in repetition priming was rejected. Subsidiary analyses, however, revealed that the weighted mean effect size for repetition priming was smaller than those for recognition or recall measures from the set of experiments included in the effect-size meta-analysis. Difficulties in drawing conclusions about process dissociations in old age in the face of only a partial dissociation in experimental measures are considered.

Aged↗

Fluoride varnishes (Duraphat): a meta-analysis.

In the present article we analyze a series of studies designed to detect the caries preventive effect of Duraphat by means of meta-analysis. Meta-analysis is a collection of statistical methods designed to investigate and to summarize a series of investigations. It may be a valuable tool to complement traditional narrative reviews. During the last years meta-analysis has attracted increasing interest in sociology, psychology and medicine. In order to find previous studies concerned with the clinical effects of Duraphat we applied a systematic literature search. Papers were included independent of results when they fulfilled a checklist of well defined methodological selection criteria. In order to aggregate the results of the Duraphat-studies we used different complementary statistical approaches: Firstly, the so-called file drawer problem is considered. This may help to get a better insight into the problem of underreporting non-significant results or publication bias. It was found to be very unlikely that underreporting of non-significant results could reverse the conclusion into an overall null-result. After that, the inhomogeneity between studies is investigated. The overall variation of caries reduction R is separated into two components: A between study component of variance and a variance pertaining to the individual studies (random effects model). It was found that the overall variation is dominated by the between studies variation and not by the sampling variation. Due to the pronounced variation between studies the confidence interval of the overall effect size (R = 0.38) is quite large (95%-Cl: 0.19-0.57).(ABSTRACT TRUNCATED AT 250 WORDS)

Bias↗

Insulin pump therapy: a meta-analysis.

OBJECTIVE: To conduct a meta-analysis of the metabolic and psychosocial impact of continuous subcutaneous insulin infusion (CSII) therapy on adults, adolescents, and children. RESEARCH DESIGN AND METHODS: Studies were identified and data regarding study design, year of publication, sample size, patient's age, diabetes duration, and duration of CSII therapy were collected. Means and SDs for glycohemoglobin, blood glucose, insulin dosages, and body weight for CSII and comparison conditions were subjected to meta-analytic procedures. Data regarding pump complications and psychosocial functioning were reviewed descriptively. RESULTS: A total of 52 studies, consisting of 1,547 patients, were included in the meta-analysis. Results indicate that CSII therapy is associated with significant improvements in glycemic control (decreased glycohemoglobin and mean blood glucose). A descriptive review of potential complications of CSII use (e.g., hypoglycemia, diabetic ketoacidosis [DKA], pump malfunction, and site infections) suggests a decreased frequency of hypoglycemic episodes but an increased frequency of DKA in studies published before 1993. CONCLUSIONS: CSII therapy is associated with improved glycemic control compared with traditional insulin therapies (conventional therapy and multiple daily injections) and does not appear to be associated with significant adverse outcomes. Additional studies are needed to further examine the relative risks of CSII therapy, including the potential psychosocial impact of this technologically advanced therapy.

Age Factors↗

Effect of modest salt reduction on blood pressure: a meta-analysis of randomized trials. Implications for public health.

Two recent meta-analyses of randomised salt reduction trials have concluded that there is little purpose in reducing salt intake in the general population. However, the authors, as with other previous meta-analyses, included trials of very short duration (eg 1 week or less) and trials of acute salt loading followed by abrupt reductions to very low salt intake (eg from 20 to less than 1 g of salt/day). These acute salt loading and salt depletion experiments are known to increase sympathetic tone, and with salt depletion cause a rise in renin release and, thereby, plasma angiotensin II. These trials are not appropriate, therefore, for helping to inform public health policy, which is for a more modest reduction in salt intake, ie, from a usual intake of approximately 10 to approximately 5 g of salt per day over a more prolonged period of time. We carried out a meta-analysis to assess the effect of a modest salt reduction on blood pressure. Our data sources were MEDLINE, EMBASE, Cochrane library, CINAHL, and the reference lists of original and review articles. We included randomised trials with a modest reduction in salt intake and a duration of 4 or more weeks. Meta-analysis, meta-regression, and funnel plots were performed. A total of 17 trials in hypertensives (n=734) and 11 trials in normotensives (n=2220) were included in our study. The median reduction in 24-h urinary sodium excretion was 78 mmol (equivalent to 4.6 g of salt/day) in hypertensives and 74 mmol in normotensives. The pooled estimates of blood pressure fall were 4.96/2.73+/-0.40/0.24 mmHg in hypertensives (P<0.001 for both systolic and diastolic) and 2.03/0.97+/-0.27/0.21 mmHg in normotensives (P<0.001 for both systolic and diastolic). Weighted linear regression analyses showed a dose response between the change in urinary sodium and blood pressure. A reduction of 100 mmol/day (6 g of salt) in salt intake predicted a fall in blood pressure of 7.11/3.88 mmHg (P<0.001 for both systolic and diastolic) in hypertensives and 3.57/1.66 mmHg in normotensive individuals (systolic: P<0.001; diastolic: P<0.05). Our results demonstrate that a modest reduction in salt intake for a duration of 4 or more weeks does have a significant and, from a population viewpoint, important effect on blood pressure in both hypertensive and normotensive individuals. This meta-analysis strongly supports other evidence for a modest and long-term reduction in population salt intake, and would be predicted to reduce stroke deaths immediately by approximately 14% and coronary deaths by approximately 9% in hypertensives, and reduce stroke and coronary deaths by approximately 6 and approximately 4%, in normotensives, respectively.

Blood Pressure↗

The five-factor model of personality and smoking: a meta-analysis.

This article describes a meta-analysis of the relationship between the Five-Factor Model of personality and smoking. The results, based on nine studies and a total of 4730 participants, show that smoking was associated with the following five-factor traits: low conscientiousness, low agreeableness, and high neuroticism. Smokers outside Canada and the United States had significantly higher extraversion than nonsmokers, while extraversion was not significantly related to smoking in Canada and the United States. The results, which for the first time quantified precisely through meta-analysis the association between the five-factor model of personality and smoking, provide support for the relevance of the Five-Factor Model to an important behavior and for the trait element of Gilbert's (1995) Situation-Trait-Adaptation-Response model of smoking. The results also suggest possible avenues for smoking prevention and treatment and for further smoking research.

Extraversion, Psychological↗

Age-related changes in initiation and maintenance of sleep: a meta-analysis.

The purpose of this meta-analysis was to determine the magnitude of change over the adult life span in four key sleep characteristics and to explore research design features that may account for variability in reported age-related sleep change. Forty-one published studies (combined N = 3293) provided 99 correlational effect sizes. Waking frequency and duration increased with age as previously concluded by narrative reviewers. Although narrative reviewers were less certain whether nighttime sleep amount or the ability to initiate sleep decreased with age, the meta-analysis suggested that both decreased. When sleep variables were measured by polysomnography rather than self-report, larger age-related changes were found. Few researchers who studied normal sleep controlled for important health moderators or studied women.

Adult↗

The value of the CAGE in screening for alcohol abuse and alcohol dependence in general clinical populations: a diagnostic meta-analysis.

OBJECTIVE: To perform a meta-analysis to assess diagnostic characteristics of the CAGE in screening for alcohol abuse or dependence in a general clinical population and to test a new method for pooling of ROC curves. METHODS: Medline search performed over the period 1/1/1974 to 31/12/2001. MEASUREMENT: Calculation of diagnostic values. RESULTS: We identified 35 articles using the DSM criteria as the gold standard to test the diagnostic value of the CAGE. Only 10 studies could be included for the meta-analysis. With a cutoff point > or =2, the pooled sensitivity is far better in inpatients (0.87) than in primary care patients (0.71) or ambulatory patients (0.60). The pooled specificity also differs for each group. The likelihood ratios seem to be relatively constant over the populations (overall LR+:3.44;LR-:0.18). We calculated a pooled AUC of 0.87 (95% CI 0.85-0.89). At low specificity values, the sensitivity was homogeneous over the studies, and at a low sensitivity, the specificity was heterogeneous. CONCLUSION: The diagnostic value of the CAGE is of limited value using this test for screening purposes at his recommended cutpoint of > or =2.

Alcoholism↗

The dopamine D4 receptor gene 48-base-pair-repeat polymorphism and mood disorders: a meta-analysis.

BACKGROUND: We conducted a meta-analysis to re-evaluate the role of the dopamine D4 receptor gene 48-base-pair- repeat (DRD4) polymorphism in mood disorders. METHODS: DRD4 allele frequencies were compared between 917 patients with unipolar (UP) or bipolar affective disorder (BP) and 1164 control subjects from 12 samples, using the Cochrane Review Manager. RESULTS: An association was found between all mood disorder groups and DRD4.2. After correcting for multiple testing, the association between DRD4.2 and BP dropped to insignificance; however, the evidence of an association between the DRD4.2 allele and UP (p < .001) and the combined group (p < .001) remained. There was no evidence for heterogeneity or publication bias. CONCLUSIONS: These findings suggest that the DRD4.2 allele is a risk allele for depression symptomatology. Meta-analysis may be a valuable objective tool for a quantitative summary of evidence for association studies in psychiatric genetics.

Alleles↗