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PubMed1989

Meta-analysis in medicine. Where we are and where we want to go.

An epidemiologically impeccable study does not bring answers to all the important questions. A structured and systematic integration of information from different studies of a given problem with a view to answering the original question or bringing additional information is the essence and objective of the meta-analytic approach to health problem solving. Original studies in medicine, being very heterogeneous in nature and structure require not only a quantitative approach (as in classical meta-analysis) but also an additional "qualitative meta-analysis" as well. The latter represents not only a systematic accumulation of both information and the characteristics of different studies, but also an assessment of quality, uncertainty, missing data, random error and bias across studies of interest. The greatest challenge of meta-analysis in medicine lies in the integration of the qualitative and quantitative assessment of given information (scoring of quality, weighing of the effect size by quality score, etc.). Meta-analysis in medicine must go beyond a simple pooling of data. It should become the "epidemiology of results of independent studies of a common topic of interest". Further development of meta-analysis in such an expanded way may have an important impact on decision-making in clinical medicine, and in health policies.

Clinical Trials as Topic↗

PubMed1997

Efficacy of beta2-agonists in bronchiolitis: a reappraisal and meta-analysis.

OBJECTIVE: To evaluate the efficacy of beta2-agonists in bronchiolitis. DESIGN: Critical review and meta-analysis of randomized controlled trials of inhaled beta2-agonists. RESULTS: Three inpatient and five outpatient studies were identified. Inpatient studies (82 patients) were characterized by wide variability in therapeutic regimens and measurement of outcomes. Several problems were identified in the selection and specification of patients, such as failure to assess the prestudy duration of illness or to exclude patients already taking bronchodilators. Meta-analysis was not possible for inpatient trials due to the great variability in study outcomes, timing of outcome assessment, and drug regimens. Results of inpatient trials were contradictory: one found significant reductions in the clinical score and a shorter hospital stay with treatment, whereas two others found only significant oxygen desaturations. Outpatient studies (251 patients) examined immediate changes in physiologic measures and clinical scores after two treatments, but have not examined the effects of the longer-term regimen customarily used by clinicians. Meta-analysis revealed that short-term beta2-agonist therapy had no impact on the hospitalization rate or respiratory rate, and had a statistically significant but clinically insignificant impact on oxygen saturation and heart rate. The diversity of scoring systems precluded pooling of clinical score data. CONCLUSIONS: Despite eight clinical trials, conclusive evidence for the efficacy of beta2-agonist therapy for bronchiolitis remains unavailable. Well-designed inpatient trials are needed. Meta-analysis of outpatient studies does not support the use of beta2-agonist therapy for bronchiolitis, but investigators have not studied the outcomes and the long-term outpatient regimen customarily used by clinicians.

Adrenergic beta-Agonists↗

PubMed2005

Intraocular pressure-lowering effects of all commonly used glaucoma drugs: a meta-analysis of randomized clinical trials.

OBJECTIVE: To estimate the intraocular pressure (IOP) reduction achieved by the most frequently prescribed glaucoma drugs and a placebo in a meta-analysis of randomized clinical trials. DESIGN: Meta-analysis of randomized clinical trials. PARTICIPANTS: Twenty-seven articles reporting on 28 randomized clinical trials. These articles reported 6953 participants for the trough and 6841 for the peak. METHODS: Articles published up to December 2003 were identified in the following data sources: Medline, Embase, and the Cochrane Controlled Trials Register, and references from relevant articles. Over 85% of the patients had to be diagnosed with primary open-angle glaucoma (POAG) or ocular hypertension (OH), and articles had to be written in English, German, French, or Dutch. Quality of trials was assessed by a Delphi list with additions. The pooled 1-month IOP-lowering effect from baseline at peak and trough was calculated by performing meta-analysis using the random effects model. MAIN OUTCOME MEASURES: Absolute and relative change in IOP from baseline, for peak and trough moments. RESULTS: Relative IOP reductions from baseline [mean (95% confidence interval)] were -23% (-25% to -22%) for a peak and -20% (-23% to -17%) for a trough for 0.5% betaxolol; peak, -27% (-29% to -25%), and trough, -26% (-28% to -25%), for 0.5% timolol; peak, -22% (-24% to -20%), and trough, -17% (-19% to -15%), for 2.0% dorzolamide; peak, -17% (-19% to -15%), and trough, -17% (-19% to -15%) for 1.0% brinzolamide; peak, -25% (-28% to -22%), and trough, -18% (-21% to -14%) for 0.2% brimonidine; peak, -31% (-33% to -29%), and trough, -28% (-30% to -26%) for 0.005% latanoprost; peak, -31% (-32% to -29%), and trough, -29% (-32% to -25%) for 0.004% travoprost; peak, -33% (-35% to -31%), and trough, -28% (-29% to -27%) for 0.03% bimatoprost; and peak, -5% (-9% to -1%), and trough, -5% (-10% to -0%) for the placebo. The difference in absolute IOP reduction from baseline between timolol and prostaglandin analogs or prostamide varied from -0.4 to 0.1 mmHg at trough and from 1.0 to 1.5 mmHg at peak. Quality scores of included studies were generally high, a mean of 14.2 on a scale from 0 to 20 (interquartile range, 13-16). CONCLUSION: This meta-analysis suggests that bimatoprost, travoprost, latanoprost, and timolol are the most effective intraocular pressure-reducing agents in POAG and OH patients.

Adrenergic alpha-Agonists↗

PubMed1997

Maximum androgen blockade in advanced prostate cancer: a meta-analysis of published randomized controlled trials using nonsteroidal antiandrogens.

OBJECTIVES: To assess the survival benefit of maximum androgen blockade (MAB) using nonsteroidal antiandrogens (NSAAs) through meta-analysis of published randomized controlled trials (RCTs). METHODS: All RCTs comparing treatment with NSAA plus either luteinizing hormone-releasing hormone (LHRH) or orchiectomy versus treatment with LHRH or orchiectomy alone were included if the necessary statistical summaries were present in the publication. Estimates and standard errors of log hazard ratio for overall survival and progression-free survival were derived from published studies using two methods: (1) reconstructing an annual life table from graphical presentations of survival distributions and fitting discrete proportional hazard models, and (2) reconstructing the log hazard ratio from reported P values and numbers of deaths. An alternative set of log hazard ratios was derived from figures presented in a summary report by the Prostate Cancer Trialists' Collaborative Group (PCTCG). Comparative meta-analyses were performed using the random effects approach of DerSimonian and Laird. Additionally, published studies were used in a random-effects-based meta-analysis of objective tumor response. RESULTS: Nine studies provided enough information to perform a meta-analysis for survival using one of the two methods. Estimates of relative risks (RR) comparing treatment with NSAA plus either LHRH or orchiectomy versus treatment with LHRH or orchiectomy alone with respect to overall survival were 0.78 (95% confidence intervals [CIs] 0.67 to 0.90) using method 1, and 0.84 (95% CI 0.76 to 0.93) using method 2. Sensitivity analyses based on PCTCG data showed that a favorable survival result for MAB was associated with NSAAs but not with steroidal antiandrogens and depended on randomization blinding and overall trial quality. Additionally, random-effects-based meta-analysis of published studies showed a significant increase in time-to-progression (RR = 0.74; 95% CI 0.63 to 0.86) and an increase in objective tumor responses for MAB using NSAAs compared with castration alone (odds ratio = 0.65; 95% CI 0.51 to 0.81; P = 0.00022). CONCLUSIONS: Inconsistent results have been published about the benefit of MAB in advanced prostate cancer. This meta-analysis supports a beneficial effect for MAB using NSAAs compared with castration alone, and sensitivity analyses suggest that the design of future trials should carefully address issues of patient characterization, randomization blinding, and other study quality issues.

Androgen Antagonists↗

PubMed1996

Uncertainty of the time of first significance in random effects cumulative meta-analysis.

We propose a process for evaluating quantities of clinical and statistical interest in cumulative meta-analysis. We use Monte Carlo simulation studies to assess the error variance of the time to significance in cumulative meta-analysis. For the specific cumulative meta-analyses that we simulated, the 95% confidence interval of the treatment effect, estimated by the random effects method at the time of earliest significance, appears to be approximately appropriate except when the hypothesized treatment effect is near the null. The Monte Carlo approach that we used can also estimate the power of a cumulative meta-analysis when two treatments differ in efficacy. We illustrate these issues in the context of five cumulative meta-analyses, each comparing two treatments for preventing mortality from myocardial infarction. These simulated meta-analyses demonstrate our main point, which is that the time of first significance, however parameterized, is itself a random variable with error variance.

Bias↗

PubMed2005

Can telepsychiatry replace in-person psychiatric assessments? A review and meta-analysis of comparison studies.

OBJECTIVE: The authors conducted a review and meta-analysis of the literature comparing telepsychiatry with "in-person" psychiatric assessments. METHOD: Approximately 380 studies on telepsychiatry published between 1956 and 2002 were identified using MEDLINE, PsycINFO, and cross-referenced bibliographies. Of these, 14 studies with an N > 10 compared telepsychiatry with in-person psychiatry (I-P) using objective assessment instruments or satisfaction instruments. Three of these studies compared high bandwidth (HB) with low bandwidth (LB) telepsychiatry. RESULTS: Fourteen studies of 500 patients met inclusion criteria and were included in the meta-analysis. Telepsychiatry was found to be similar to I-P for the studies using objective assessments. Effect sizes were on average quite small, suggesting no difference between telepsychiatry and I-P. Bandwidth was found to be a significant moderator. Three moderators were tested, effect sizes remained largely heterogeneous, and further analyses are needed to determine the direction of effect. There was no difference between I-P and telepsychiatry between the HB and LB groups, although there are anecdotal data suggesting that HB was slightly superior for assessments requiring detailed observation of subjects. CONCLUSION: Out of a large telepsychiatry literature published over the past 40+ years, only a handful of studies have attempted to compare telepsychiatry with I-P directly using standardized assessment instruments that permit meaningful comparisons. However, in those studies, the current meta-analysis concludes there is no difference in accuracy or satisfaction between the two modalities. Over the next few years, we expect telepsychiatry to replace I-P in certain research and clinical situations.

Humans↗

PubMed2004

Intravesical bacillus Calmette-Guérin is superior to mitomycin C in reducing tumour recurrence in high-risk superficial bladder cancer: a meta-analysis of randomized trials.

OBJECTIVE: To assess, in a systematic review and meta-analysis, the relative effectiveness of intravesical mitomycin C and bacillus Calmette-Guérin (BCG) for tumour recurrence, disease progression and overall survival in patients with medium- to high-risk Ta and T1 bladder cancer. METHODS: The major medical databases were searched comprehensively up to June 2003, and relevant journals hand-searched for randomized controlled trials, in any language, that compared intravesical mitomycin C with BCG in medium- to high-risk patients with Ta or T1 bladder cancer. RESULTS: Twenty-five articles were identified but only seven were considered eligible for the analysis. This represented 1901 evaluable patients in all, 820 randomized to mitomycin C and 1081 to BCG. Six trials had sufficient data for meta-analysis and included 1527 patients, 693 in the mitomycin and 834 in the BCG arm. There was no significant difference between mitomycin C and BCG for tumour recurrence in the six trials, with a weighted mean log hazard ratio, LHR, (variance) of -0.022 (0.005). However, there was significant heterogeneity between trials (P = 0.001). A subgroup analysis of three trials that included only high-risk Ta and T1 patients indicated no heterogeneity (P = 0.25) and a LHR for recurrence of -0.371 (0.012). With mitomycin C used as the control in the meta-analysis, a negative ratio is in favour of BCG and, in this case, was highly significant (P < 0.001). The seventh trial (in abstract form only) used BCG in low doses for two arms of the trial (27 mg and 13.5 mg) compared with a standard dose of mitomycin C (30 mg), and reported a significantly lower recurrence rate with BCG (27 mg) than for mitomycin C (P = 0.001). Only two trials included sufficient data to analyse disease progression and survival, representing 681 patients (338 randomized to BCG and 343 to mitomycin C). There was no significant difference between mitomycin C and BCG for disease progression, with a LHR of 0.044 (0.04) (P = 0.16), or survival, at -0.112 (0.03) (P = 0.50). Adverse events were slightly more frequent with BCG. Local toxicity (dysuria, cystitis, frequency and haematuria) were associated with both mitomycin C (30%) and BCG (44%). Systemic toxicity, e.g. chills, fever and malaise, occurred with both agents (12% and 19%, respectively) although skin rash was more common with mitomycin C. CONCLUSION: Tumour recurrence was significantly lower with intravesical BCG than with mitomycin C only in those patients at high risk of tumour recurrence. However, there was no difference in disease progression or survival, and the decision to use either agent might be based on adverse events and cost.

Adjuvants, Immunologic↗

PubMed1995

Immune response factors in rheumatic heart disease: meta-analysis of HLA-DR associations and evaluation of additional class II alleles.

OBJECTIVES: This study used a meta-analysis to examine HLA-DR frequencies in rheumatic heart disease and prospectively examined other class II allelic disease associations. BACKGROUND: Studies of rheumatic heart disease have reported HLA class II allelic associations, but these are inconsistent. METHODS: A meta-analysis combined all known (n = 10) studies to determine disease risk associated with HLA-DR antigen expression. Meta-analysis of studies grouped by ethnic derivation of subjects was also performed. The present study also examined DQA, DQB and DPB allele frequencies by DNA-based strategies. RESULTS: Meta-analysis showed a significant negative disease association with DR5 (odds ratio [OR] 0.67, p < 0.00003) for all combined studies. Among black patients, DR1 was increased (OR 2.80, p < 0.004); DR6 was increased (OR, 2.03, p < 0.003); and DR 8 was decreased (OR 0.32, p < 0.02). Among Eastern Indian patients, DR3 was increased (OR 2.44, p < 0.00003), with decreased expression for DR2 (OR 0.31, p < 0.00001) and DR5 (OR 0.52, p < 0.05). DR4 was increased among American whites (OR 1.74, p < 0.03), although there was significant heterogeneity among studies of whites. DQA, DQB and DPB allele frequencies were similar for control subjects and patients. CONCLUSIONS: Our findings support an association between major histocompatibility complex class II alleles and risk for rheumatic heart disease. However, heterogeneity in associations was observed among different ethnic and racial groups; regional and temporal differences in streptococcal outbreaks may compound this heterogeneity. Further studies are necessary to elucidate the respective contributions of these variables.

Alleles↗

PubMed2002

An epidemiological re-appraisal of the association between blood pressure and blood lead: a meta-analysis.

Studies on the possible association between blood pressure and blood lead have reached divergent conclusions. In a previous meta-analysis, a doubling of the blood lead concentration was associated with a 1.0/0.6 mm Hg increase in systolic and diastolic blood pressure (BP). This meta-analysis updates the analysis originally performed in 1994. Articles on the association between BP and blood lead were identified from computer searches from January 1980 to February 2001 using the Medical Literature Analysis and Retrieval System. Of the studies reviewed, 31 provided sufficient details to be considered. The meta-analysis included 58518 subjects recruited from the general population in 19 surveys and from occupationally exposed groups in 12 studies. In all but four studies, the results were adjusted for age, and most studies took into account additional confounding factors such as body mass index and the use of alcohol and medication. Weighted joint P-values were calculated using Stouffer's procedure. The association between BP and blood lead was similar in both men and women. In the combined studies, a two-fold increase in blood lead concentration was associated with a 1.0 mm Hg rise in the systolic pressure (95% CI +0.5 to +1.4 mm Hg; P < 0.001) and with a 0.6 mm Hg increase in the diastolic pressure (95% CI +0.4 to +0.8 mm Hg; P < 0.001). On balance, this meta-analysis suggests that there can only be a weak association between BP and blood lead.

Adolescent↗

PubMed2025

Evaluation of Prevalence of Obstetric Violence and its Associated Factors: A Systematic Review and Meta-Analysis.

Obstetric violence (OV) begins with a woman's initial contact with a health institution and can persist throughout pregnancy, labor, and the postpartum period. Despite this, previous research has largely focused on the labor process. This systematic review and meta-analysis aimed to determine the prevalence and associated factors of OV experienced by women during pregnancy, labor, or the postpartum period. We conducted systematic searches in five electronic databases (Web of Science, Scopus, CINAHL Ultimate, MEDLINE Ultimate, and OVID) between April 27 and August 7, 2024. Studies were included if they involved women aged 18 and above who experienced mistreatment, abuse, disrespect, or OV during pregnancy, childbirth, or the postpartum period; employed quantitative cohort, descriptive, or cross-sectional designs; were written in English; reported the prevalence of OV and/or associated factors; and were published between January 1, 2007 and December 31, 2023. Data synthesis involved meta-analysis, meta-regression, and narrative synthesis methods. A total of 41 studies, including 43,977 participants from 17 countries, were included. The meta-analysis revealed that the pooled prevalence of OV was 61.7% (95% CI [0.549, 0.680]; I²: 99.258%). The meta-regression analysis showed that variables such as the country of study, income level of countries, study setting, study design, and risk of bias had statistically significant effects on OV. In addition, 40 risk factors and 14 protective factors were identified through narrative synthesis. This highlights the high prevalence of OV and the need to address the associated factors.

Humans↗

PubMed1988

Meta-analysis of clinical trials: summary of an international conference.

An international conference of clinicians, clinical investigators and biostatisticians discussed meta-analysis in relation to clinical trials, i.e. the combination of data from separate studies for the purpose of obtaining information that cannot be derived from the individual studies. Meta-analysis can be a helpful tool for generating hypotheses for future trials, for studying the consistency of trials of the same or similar goals, and for generating more precise estimates of effect. There are still a number of unresolved questions about the methodology and interpretation of meta-analysis. Better and more uniform reporting of primary studies would increase the usefulness of meta-analysis.

Clinical Trials as Topic↗

PubMed2006

[Comparison of different vehicles for nebulized salbutamol in treatment of bronchial asthma exacerbations: a Meta-analysis].

OBJECTIVE: To assess the efficacy of two vehicles for nebulized salbutamol in treatment of asthma exacerbations with Meta-analysis. METHODS: All relevant randomized controlled clinical trials (RCT) with isotonic magnesium sulphate and saline as vehicles for inhaled salbutamol in treatment of asthma exacerbations were searched. A Meta-analysis was performed to evaluate the results of the two therapies. RESULT: Five relevant RCTs from literature were collected and total 219 cases were included for analysis. The meta-analysis indicated that the significant improvements were obtained from isotonic magnesium sulphate as a vehicle for nebulized salbutamol, in comparison with saline [pooled standardized mean difference (SMD)=0.55(95% CI 0.28 - 0.83), P <0.001]. By further subgroup analysis, this change was properly significant in the subgroup of severe patients with their baseline FEV1% <30% [FEV1 weighted mean difference (WMD)=0.72 L(95% CI 0.30 L - 1.14 L), P <0.01]. The pooled results of vital signs between two vehicles did not demonstrate statistical significance. Overall, the risk of admission to hospital was not statistically reduced in patients using magnesium sulphate, who presented to the emergency department with an asthma exacerbation [pooled RR=0.64(95% CI 0.38 - 1.08), P >0.05]. CONCLUSION: Compared with saline,the use of isotonic magnesium sulfate as an adjuvant to nebulize salbutamol is a beneficial therapy with improving spirometric airway function in the severe asthma exacerbation.

Adrenergic beta-Agonists↗

PubMed2002

Meta-analysis of method comparison studies.

Methods for the meta-analysis of results from randomized controlled trials are well established. However, there are currently no methods for the meta-analysis of method comparison studies. Here the combination of results from studies comparing two methods of measurement on the same unit of observation is required. We compare standard methods for the pooling of k samples from the same Normal population to those for pooling parameter estimates, in order to estimate the pooled mean difference and 95 per cent limits of agreement. Methods for investigating heterogeneity across studies and for calculating random effects estimates are proposed. We postulate that for published studies either the estimated mean or variance of the difference between measurements will tend to be smaller than for unpublished studies and investigate the evidence for the existence of such publication bias. The methods are illustrated with an example evaluating the accuracy of temperature measured at the axilla compared to the rectum in children.

Axilla↗

PubMed2004

The effects of an edgeline on speed and lateral position: a meta-analysis.

This paper presents a meta-analysis of studies that have evaluated the effects of an edgeline on speed and lateral position of motorised road users. Together with many other study characteristics, 41 estimates of the effects of an edgeline on speed and 65 on lateral position were extracted from the studies. The results of the evaluation studies show a great variety in effects. Both negative and positive effects on speed and lateral position were found; amongst others, increases in speed up to 10.6 km/h, as well as decreases in speed up to 5.0 km/h, and shifts of the lateral position towards the centre of the road up to 30 cm, as well as shifts towards the edge of the road up to 35 cm. Further analyses resulted in the determination of study characteristics that influence the effects of an edgeline on speed and lateral position. It is concluded that the effects of an edgeline on speed are related to the presence of a centreline. Applying an edgeline to a road without a centreline increases the speed of road users, and replacing a centreline by an edgeline decreases the speed. Results with respect to adding an edgeline to a road with a centreline were unclear. Another conclusion is that shoulder width and road environment contribute to the effects of an edgeline on lateral position. In combination with wide shoulders or buildings and/or trees next to the road, edgelines lead to shifts of the lateral position towards the edge of the road, and in combination with narrow shoulders or open fields, edgelines lead to shifts towards the centre of the road.

Accidents, Traffic↗

PubMed2006

Isoflavone therapy for menopausal flushes: a systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis of all randomized, controlled trials of isoflavone supplementation to determine the efficacy of isoflavone therapy in reducing the number of daily menopausal flushes. METHODS: A comprehensive search of published studies of isoflavone treatment and menopausal flushing was undertaken. Studies were selected if they were randomized, were placebo controlled, provided the number of baseline flushes, the variance in flushes and the reduction in flushes. Effects for isoflavone treatment compared to control were calculated and a meta-analysis was performed. Regression analysis, weighted for the size of the study was performed to investigate the relationship between the dose of isoflavone, or number of baseline flushes and the reduction in flushes achieved compared to control. RESULTS: Isoflavone supplementation was found to be associated with a significant reduction in flushes (effect size -0.28, 95% confidence intervals -0.39 to -0.18, P < 0.0001). Marked heterogeneity was found between the studies, but the effect remained significant when analyzed using a random effects model (delta = -0.49, 95% confidence intervals -0.81 to -0.17, P = 0.001). The percentage reduction in flushes was significantly related to the number of baseline flushes per day and the dose of isoflavone studied (beta = -0.49 and -0.26, respectively, both P < 0.0001). CONCLUSIONS: These results suggest that isoflavone supplementation may produce a slight to modest reduction the number of daily flushes in menopausal women and that the benefit may be more apparent in women experiencing a high number of flushes per day.

Clinical Trials as Topic↗

PubMed1998

Meta-analysis of multiple outcomes by regression with random effects.

Earlier work showed how to perform fixed-effects meta-analysis of studies or trials when each provides results on more than one outcome per patient and these multiple outcomes are correlated. That fixed-effects generalized-least-squares approach analyzes the multiple outcomes jointly within a single model, and it can include covariates, such as duration of therapy or quality of trial, that may explain observed heterogeneity of results among the trials. Sometimes the covariates explain all the heterogeneity, and the fixed-effects regression model is appropriate. However, unexplained heterogeneity may often remain, even after taking into account known or suspected covariates. Because fixed-effects models do not make allowance for this remaining unexplained heterogeneity, the potential exists for bias in estimated coefficients, standard errors and p-values. We propose two random-effects approaches for the regression meta-analysis of multiple correlated outcomes. We compare their use with fixed-effects models and with separate-outcomes models in a meta-analysis of periodontal clinical trials. A simulation study shows the advantages of the random-effects approach. These methods also facilitate meta-analysis of trials that compare more than two treatments.

Clinical Trials as Topic↗

PubMed2007

Bivariate random-effects meta-analysis and the estimation of between-study correlation.

BACKGROUND: When multiple endpoints are of interest in evidence synthesis, a multivariate meta-analysis can jointly synthesise those endpoints and utilise their correlation. A multivariate random-effects meta-analysis must incorporate and estimate the between-study correlation (rhoB). METHODS: In this paper we assess maximum likelihood estimation of a general normal model and a generalised model for bivariate random-effects meta-analysis (BRMA). We consider two applied examples, one involving a diagnostic marker and the other a surrogate outcome. These motivate a simulation study where estimation properties from BRMA are compared with those from two separate univariate random-effects meta-analyses (URMAs), the traditional approach. RESULTS: The normal BRMA model estimates rhoB as -1 in both applied examples. Analytically we show this is due to the maximum likelihood estimator sensibly truncating the between-study covariance matrix on the boundary of its parameter space. Our simulations reveal this commonly occurs when the number of studies is small or the within-study variation is relatively large; it also causes upwardly biased between-study variance estimates, which are inflated to compensate for the restriction on rhoB. Importantly, this does not induce any systematic bias in the pooled estimates and produces conservative standard errors and mean-square errors. Furthermore, the normal BRMA is preferable to two normal URMAs; the mean-square error and standard error of pooled estimates is generally smaller in the BRMA, especially given data missing at random. For meta-analysis of proportions we then show that a generalised BRMA model is better still. This correctly uses a binomial rather than normal distribution, and produces better estimates than the normal BRMA and also two generalised URMAs; however the model may sometimes not converge due to difficulties estimating rhoB. CONCLUSION: A BRMA model offers numerous advantages over separate univariate synthesises; this paper highlights some of these benefits in both a normal and generalised modelling framework, and examines the estimation of between-study correlation to aid practitioners.

CD4 Lymphocyte Count↗

PubMed1996

Effectiveness and safety of once-daily aminoglycosides: a meta-analysis.

The effectiveness and safety of once-daily versus several-times-daily aminoglycosides were studied in a meta-analysis. MEDLINE for 1988 to 1995 was searched, and additional studies were identified from review articles and references in retrieved articles. Studies selected for meta-analysis were randomized controlled clinical trials in nonneutropenic adult patients comparing the clinical effectiveness or nephrotoxicity or ototoxicity of once-daily with several-times-daily aminoglycosides. Differences between groups were expressed as odds ratios. The results were combined by the procedure of Mantel and Haenszel, and 95% confidence intervals and exact confidence intervals were computed. An odds ratio smaller than 1 would indicate a lesser likelihood of a given endpoint in the once-daily group, and an odds ratio greater than 1 would indicate a greater likelihood. Eighteen studies involving 2317 patients were included in the meta-analysis. Summary odds ratios were 1.47 for effectiveness (95% CI = 1.13-1.94), 0.56 for ototoxicity (95% CI = 0.26-1.16), and 0.60 for nephrotoxicity (95% CI = 0.40-0.86). A meta-analysis showed that treatment with single daily doses of aminoglycosides seems to be more effective, less nephrotoxic, and as ototoxic as multiple doses daily.

Adult↗