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PubMed1997

Is metronidazole teratogenic? A meta-analysis.

AIM: In order to assess whether the use of metronidazole during pregnancy is associated with a higher risk of congenital malformations, a meta-analysis was conducted. METHODS: All epidemiological studies (cohort and case-control) which estimate risk of congenital malformations after exposure to metronidazole during early pregnancy were included in the meta-analysis. To obtain a summary odds ratio, the Mantel-Haenszel method was used. A test to verify absence of heterogeneity was also performed. RESULTS: One unpublished case-control and four published cohort studies fulfilled the inclusion criteria and were not statistically heterogeneous. A summary odds ratio was calculated for metronidazole exposure during the first trimester: OR = 1.08, 95% CI: 0.90-1.29, heterogeneity test chi2 = 4.72, P = 0.32. CONCLUSIONS: This meta-analysis did not find any relationship between metronidazole exposure during the first trimester of pregnancy and birth defects.

Case-Control Studies↗

PubMed1998

Estimating the accuracy of screening mammography: a meta-analysis.

OBJECTIVE: To estimate the accuracy of mammographic screening. DESIGN: A meta-analysis of published literature. DATA SOURCES: Published English-language randomized controlled trials, case-control studies, and demonstration projects involving screening mammography were identified using recent review articles. We found additional references using MEDLINE searches combining the MeSH terms "mammography," "screening," and/or study authors and locations. STUDY SELECTION: We included all studies that provided information to calculate the true-positive rate (TPR) and the false-positive rate (FPR) for breast cancer screening. DATA EXTRACTION: Reported data were reviewed independently by the authors; calculations were compared and discrepancies resolved. We calculated the sensitivity as the number of breast cancers detected during the first round of screening (true positives) divided by the sum of the true positives and the false negatives (defined as cancer discovered within 1 year of screening). False-positives were determined by biopsy. DATA SYNTHESIS: TPR and FPR values from each study were plotted in receiver operating characteristic (ROC) space. Tests of homogeneity were performed to assess the validity of using summary ROC curves or a single point to summarize the data. The reported TPR and FPR of mammography ranged from 83% to 95% and 0.9% to 6.5%, respectively. The sensitivity of mammography is higher in women over the age of 50 years. CONCLUSIONS: The accuracy of mammography should be recognized and included in discussions about policies for screening for breast cancer. This meta-analysis, by quantifying the expected TPR/FPR, should assist program planners, physicians, and women to understand better the cost and clinical implications of such screening programs.

Adult↗

PubMed1992

Zuclopenthixol, melperone and haloperidol/levomepromazine in the elderly. Meta-analysis of two double-blind trials at 15 nursing homes in Norway.

A meta-analysis was carried out of the data from two double-blind, multi-centre studies with identical methodology which compared the effectiveness of treatment of elderly patients with zuclopenthixol and with other antipsychotic drugs. In one study, patients were treated for 4 weeks with either zuclopenthixol or melperone; in the other, with either zuclopenthixol or a combination of haloperidol and levomepromazine. The meta-analysis evaluated the results of 96 patients, 49 in the zuclopenthixol group and 47 in the comparison group. Doses, which were adjusted to individual patient's needs, were low as shown by the percentages of defined daily doses for each of the study drugs. The results indicated that all three treatment alternatives were effective in the treatment of elderly patients with symptoms of agitation and hostility/aggressiveness. There was a trend, however, for zuclopenthixol to have a more rapid onset of effect. Zuclopenthixol also has the advantage for both patients and nursing staff that dosage is once daily. Only few and mild side-effects were reported with the three drug regimens.

Aged↗

PubMed1997

Meta-analysis for the evaluation of potential surrogate markers.

We describe a meta-analysis approach for the evaluation of a potential surrogate marker. Surrogate markers are useful in helping to identify therapeutic mechanisms of action and disease pathogenesis, and for selecting therapies to take forward from phase II to phase III clinical trials. They have also become increasingly important for regulatory purposes by providing a basis for preliminary approval of drugs pending clinical outcome studies. Methodology for evaluating surrogate markers has focused on determining the difference in the effects of two treatments on clinical outcome in an individual clinical trial, and then estimating the proportion of this difference explained by the treatment's effects on the potential marker. Studies are, however, frequently underpowered or cease before they accumulate sufficient evidence to draw strong conclusions about the value of a potential surrogate marker using this approach, and there are also some technical difficulties with the approach. Consideration of the association between the difference in treatment effects on the clinical outcome and the difference in treatment effects on the potential marker over a range of trials provides an alternative means to evaluate a potential marker. We describe a meta-analysis approach using Bayesian methods to model this association. Importantly, this approach enables one to obtain prediction intervals for the true difference in clinical outcome for a given estimated treatment difference in the effect on the potential marker. We illustrate the methodology by applying it to results from studies of the AIDS Clinical Trials Group to assess the value of CD4 T-lymphocyte cell count as a potential surrogate marker for the treatment effects on the development of AIDS or death.

Anti-HIV Agents↗

PubMed2005

Directional atherectomy before stenting versus stenting alone in percutaneous coronary interventions: a meta-analysis.

Plaque debulking before stenting is still controversial. We performed a meta-analysis of 12 randomized and non-randomized trials comparing directional coronary atherectomy (DCA) before stenting versus stenting alone. Angiographic end points were acute gain, late loss and angiographic restenosis rate. Clinical end points were early major adverse cardiac events [MACEs: death, Q-wave myocardial infarction (MI), non-Q-wave MI], late MACEs (death, Q-wave MI) and target lesion revascularization (TLR). Data are expressed as odds ratio (OR) with 95% confidence intervals (CI) or weighted mean difference (WMD) with 95% CI, as appropriate. A total of 1216 patients undergoing DCA before stent and 1484 patients undergoing stent alone have been included. DCA before stent was associated to a better acute gain compared to stenting alone (WMD 0.23, [0.18-0.28]; p<0.0001), to a striking reduction of angiographic restenosis rate (OR of 0.67, [0.54-0.84], p=0.0003) and to a significantly lower rate of late TLR (OR 0.73 [0.59-0.91], p=0.006). Late loss did not differ between the two groups (WMD 0.00 [-0.08 and 0.08], p=0.98). We found a higher rate of early MACEs for the combined approach (OR 1.87 [1.16-3.02], p=0.01), with similar prevalence of late MACEs (OR 0.83 [0.65-1.06], p=0.13). In conclusion, this meta-analysis demonstrates that DCA before stenting is superior to stenting alone with regard to acute angiographic results and TLR with a similar prevalence of late MACEs. The higher prevalence of early MACEs with DCA before stenting, however, is disturbing and probably related to distal embolization.

Aged↗

PubMed2005

Imaging for predicting the risk factors--the circumferential resection margin and nodal disease--of local recurrence in rectal cancer: a meta-analysis.

The aim of the present study was to conduct a meta-analysis of English literature on the accuracy of preoperative imaging in predicting the two most important risk factors for local recurrence in rectal cancer, the circumferential resection margin (CRM) and the nodal status (N-status). Articles published between 1985 and August 2004 that report on the diagnostic accuracy of endoluminal ultrasound (EUS), computed tomography (CT), or magnetic resonance imaging (MRI) in the evaluation of lymph node involvement were included. A similar search was done for the assessment of the circumferential resection margin in rectal cancer in the period from January 1985 till January 2005. The inclusion criteria were as follows: (1) more than 20 patients with histologically proven rectal cancer were included, (2) histology was used as the gold standard, and (3) results were given in a 2 x 2 contingency table or this table could otherwise be extracted from the article by two independent readers. Based on the results summary receiver operating characteristic (ROC) curves were constructed. Only 7 articles matching inclusion criteria were found concerning the CRM. The meta-analysis shows that MRI is rather accurate in diagnosing a close or involved CRM. For nodal status 84 articles could be included. The diagnostic odds ratio of EUS is estimated at 8.83. For MRI and CT, the diagnostic odds ratio are 6.53 and 5.86, respectively. The results show that EUS is slightly, but not significantly, better than MRI or CT for identification of nodal disease. There is no significant difference between the different modalities with respect to staging nodal status. At present, MRI is the only modality that predicts the circumferential resection margin with good accuracy, making it a good tool to identify high and low risk patients. Predicting the N-status remains a problem for the radiologist for every modality, although considering the new developments in MR imaging, this may change in the near future.

Diagnostic Imaging↗

PubMed1995

Meta-analysis: weighing the evidence.

Use of meta-analytical (quantitative overview) techniques is now commonplace in a wide range of medical research contexts, with a rapid rise in its frequency of use being particularly apparent in the last decade. The history of meta-analyses in other fields, particularly psychology and educational research, is longer. Many methods have been proposed and used, from crude 'vote counting' of studies showing significant or non-significant results, through methods for combination of effect size estimates based on fixed or random effects models, to general linear mixed models and Bayesian methods. The history of meta-analysis and the advantages and disadvantages of various approaches to it are briefly reviewed in this paper, with reference to pharmaceutical product licence applications, other reviews of clinical trials and epidemiological studies, and health services research.

Bayes Theorem↗

PubMed1995

Meta-analysis of best-evidence synthesis?

This article examines the usefulness of meta-analysis, and articulates many of the criticisms that have been made of its workings. An attempt is made to outline the precautions that have to be taken before a scientifically useful and meaningful meta-analysis can be carried out. The problems encountered include heterogeneity of samples, conditions, interventions and end-points; narrow focus; curvilinearity of regression; lack of independence of determinants; synergistic interactions; contradictory experimental results. It is suggested that best-evidence synthesis, or theory-directed analysis, might be a safer option.

Bias↗

PubMedDate not supplied

Meta-analysis: apples and oranges, or fruitless.

Meta-analysis is an impressive tool for systematic synthesis of health care management and policy research findings. Used wisely, it can impose an appealing order on the chaos of a large body of evidence. Occasionally, it can even contribute to resolution of a clinical controversy. However, the technique is currently in a state of evolution. Until it is further refined and standardized, its consumers must be mindful of its limitations and use meta-analytic reviews with care.

Health Services Research↗

PubMed2002

[Meta-analysis in medicine].

Systematic reviews are widely used in medicine as a method of decision making based on evidences. The systematic review is a method of locating and evaluation of a synthesising evidence. Meta-analysis refers to quantitative synthesis of the results of clinical trials or other primary studies. Simple introductory account about meta-analysis is given. We describe two examples of meta-analysis application and strengths and weaknesses of this research method.

Evidence-Based Medicine↗

PubMed2001

ACE gene polymorphism and IgA nephropathy: an ethnically homogeneous study and a meta-analysis.

BACKGROUND: Conflicting results have implicated the angiotensin-converting enzyme (ACE) D allele in the progression of renal damage in patients with IgA nephropathy (IgAN). Most of these findings have been obtained by heterogeneous studies. METHODS: We investigated the ACE insertion/deletion (I/D) gene polymorphism by polymerase chain reaction (PCR) amplification of genomic DNA in an ethnically homogeneous sample size of IgAN patients from Southern Italy. The association between ACE I/D gene polymorphism and the development of the disease was examined in 247 biopsy-proven IgAN patients and 205 healthy subjects. The association with the progression of renal damage was evaluated in 136 patients with a follow-up of > or =3 years according to the slope of the creatinine clearance against time, and in 221 patients with a follow-up of > or =1 year assessing by univariate and multivariate analyses of renal survival. These associations were further estimated in a meta-analysis of seven studies retrieved in the Medline database. The meta-analysis was performed according to the Mantel-Haenszel-Peto method when homogeneity of the studies was established using the chi(2) test by Breslow-Day. RESULTS: No difference in the ACE I/D gene distribution between patients and controls and between patients with stable and those with deteriorating renal function was found in our study. A meta-analysis performed separately for Caucasian and Asian studies showed that the ACE I/D gene polymorphism did not contribute to the genetic susceptibility of the development of IgAN (total OR 0.93, 95% CI, 0.71 to 1.23; and 0.95, 95% CI, 0.64 to 1.42, respectively) or the progression of the renal damage (total OR 1.12, 95% CI, 0.67 to 1.88; and 2.26, 95% CI, 0.75 to 6.79, respectively) in both groups. CONCLUSIONS: Our study and meta-analysis suggest caution in the interpretation of results from association studies enrolling heterogeneous populations. Further studies using new tests, which are free of the bias due to population stratification and ethnicity, are warranted.

Adolescent↗

PubMed2026

Does Inquiry-Based Learning Improve Students' Critical Thinking? A Meta-Analysis Accounting for Control Group Variations.

BACKGROUND: Inquiry learning is widely recognized, through empirical studies, as an appropriate instruction in enhancing students' critical thinking, yet the results were varied across context. The previous meta-analysis did not include the control group variations as a potential moderator and the studies subject domain was limited only to science subjects. Consequently, it is difficult to generalize the effectiveness of IBL in enhancing critical thinking. This meta-analysis aims to investigate whether inquiry learning is effective in improving the students' critical thinking skills and examine the moderating roles of each study characteristic. Methods The literature search applying the PRISMA protocol 2020 was conducted by utilizing SCOPUS, ERIC, and DOAJ databases. A total of 57 studies from 51 articles, published from 2015 to 2025, were synthesized using a random-effects model with standardized mean difference (SMD). RESULTS: The analysis revealed that IBL has a large and significant effect on enhancing students' critical thinking (g = 1.336; 95% CI [1.061, 1.611]). However, substantial heterogeneity was observed (I 2 = 92.09%), suggesting variability across contexts. Moderator analyses revealed that the main moderator, control group variations, was statistically significant in moderating the effectiveness of IBL (Qm = 5.21; p = .022). in contrast, subject domain (Qm = 1.43; p = .698), education level (Qm = 1.11; p = .774), and country ( Q m  = 3.33; p = .650), were insignificantly moderating the effectiveness of inquiry learning. CONCLUSIONS: The present meta-analysis highlighted that IBL is effective in improving students' critical thinking. However, the effectiveness of IBL was relative to the type of control group variations. Its effect on critical thinking was greater when compared with teacher-centered learning but smaller when compared with other student-centered learning.

Thinking↗

PubMed2002

[Moyamoya and Down syndrome: study conducted by meta-analysis].

We present a clinic-epidemiological study of two patients and meta-analysis (period 1977-2000 ) of the co-morbidity of the Down syndrome (DS) and moyamoya syndrome (MMS). Among the 42 patients listed in this survey, meta-analysis permitted to find the highest number of publications by researchers from Japan and United States, followed by Brazil and Italy; prevalence of cerebrovascular disease in suckling and pre school children; first symptomatology was hemiparesis (78.6%), speech disorders (26.2%); ischemic infarction (76.2%); recurring ischemic episodes (62%); bilateral impairment (83.3%). This analysis led to the conclusion that in the clinic-neurological investigation of DS patients with acute hemiparesis episodes, MMS should be included as the most probable diagnosis.

Adolescent↗

PubMed2007

Alcohol intake and colorectal cancer risk: a dose-response meta-analysis of published cohort studies.

The epidemiologic evidence support that alcohol intake might be associated with increased colorectal cancer risk. However, the results by anatomic site in the large bowel are inconsistent. We conducted a meta-analysis of prospective cohort studies published between 1990 and June 2005 on the relationship between alcohol intake and colon and rectal cancer. We quantified associations with colon and rectal cancer using meta-analysis of relative risk (RR) associated to the highest versus the lowest category of alcohol intake and meta-analysis of study-specific dose-response slopes using fixed or random effect models depending on the heterogeneity of effects among studies. Sixteen prospective cohort studies including more than 6,300 patients with colorectal cancer were eligible for inclusion. High alcohol intake was significantly associated with increased risk of colon (RR = 1.50; 95% CI = 1.25, 1.79) and rectal cancer (RR = 1.63; 95% CI = 1.35, 1.97) when comparing the highest with the lowest category of alcohol intake, equivalent to a 15% increase of risk of colon or rectal cancer for an increase of 100 g of alcohol intake per week. The relationship did not differ significantly by anatomical site (colon, rectum). Using meta-regression analysis, we identified geographical area where the study was conducted as a possible source of between-study heterogeneity of effects among studies. Lifestyle recommendations for prevention of colorectal cancer should consider limiting alcohol intake.

Alcohol Drinking↗

PubMed2005

Effects of behavioral marital therapy: a meta-analysis of randomized controlled trials.

This meta-analysis summarizes results from 30 randomized experiments that compare behavioral marital therapy with no-treatment control with distressed couples. Results showed that behavioral marital therapy is significantly more effective than no treatment (d=.585). Although behavioral marital therapy research studies tend to be conducted under conditions that are less clinically representative than other samples of studies, representativeness was not significantly related to outcome. However, evidence also suggested that publication bias may exist in this literature whereby small sample studies with small effects are systematically missing compared with other studies. This bias may inflate the effects of behavioral marital therapies reported in previous meta-analyses, though we also explore a number of alternative explanations for this small sample bias.

Behavior Therapy↗

PubMed2006

Does neuraxial anesthesia reduce intraoperative blood loss? A meta-analysis.

STUDY OBJECTIVE: To perform a meta-analysis of available randomized controlled trials to determine if neuraxial anesthesia would decrease blood loss, compared with general anesthesia. DESIGN: Retrospective analysis. SETTING: University medical center. MEASUREMENTS: The National Library of Medicine's PubMed database was searched from the period of 1966 to December 10, 2003 for all abstracts containing words related to neuraxial anesthesia and general anesthesia. The search was limited to randomized controlled trials and the English language and yielded 667 articles. MAIN RESULTS: A total of 66 articles met inclusion criteria and were used for the analysis. Overall, the use of spinal anesthesia resulted in significantly less estimated blood loss (EBL) (P < 0.0001), compared with epidural anesthesia (EA), which, in turn, resulted in significantly less EBL compared with general anesthesia (GA) or combined GA-EA (P < 0.0001). No significant difference between GA and GA-EA was noted when analysis was limited to studies directly comparing GA-EA and GA. CONCLUSIONS: Use of spinal anesthesia or EA is associated with a significant decrease in EBL when compared with that for GA or combined GA-EA.

Anesthesia, Epidural↗

PubMed2000

Clinical outcomes after ablation and pacing therapy for atrial fibrillation : a meta-analysis.

BACKGROUND: Radiofrequency ablation of the atrioventricular node and permanent pacing are used for symptomatic relief in patients with medically refractory atrial fibrillation. In this study, meta-analysis was used to clarify clinical outcomes and survival after ablation and pacing therapy using data from the published literature. METHODS AND RESULTS: We used 21 studies with a total of 1181 patients in the meta-analysis. All patients had medically refractory atrial tachyarrhythmias, primarily atrial fibrillation (97%). Nineteen measures of clinical outcome, encompassing quality of life, ventricular function, exercise duration, and healthcare use, were derived from the studies. The meta-analysis demonstrated significant improvement after ablation and pacing therapy in all outcome measures except fractional shortening, which demonstrated a trend toward improvement (P=0.08). Ejection fraction did show significant improvement (P<0.001). The calculated 1-year total and sudden death mortality rates after ablation and pacing therapy were 6.3% and 2.0%, respectively. CONCLUSIONS: Ablation and pacing therapy improves a broad range of clinical outcomes for patients with medically refractory atrial fibrillation. The calculated 1-year mortality rates after this therapy are low and comparable with medical therapy.

Aged↗

PubMed2004

Dose-response relationship of inhaled budesonide in adult asthma: a meta-analysis.

The aim of this study was to examine the dose-response relationship of inhaled budesonide in adolescents and adults with asthma. A meta-analysis was carried out on placebo-controlled, randomised clinical trials, presenting data on at least one outcome measure of asthma and using at least two doses of budesonide, delivered by turbuhaler or metered-dose inhaler + spacer twice daily. A total of six studies of 1,435 adolescents and adults, with mild to moderately severe asthma, met the inclusion criteria for the meta-analysis. A negative exponential model indicated that 80% of the benefit at 1,600 micrograms.day-1 was achieved at doses of approximately 200-400 micrograms.day-1 and 90% by 300-600 micrograms.day-1. Meta-regression with a quadratic term in dose showed that the maximum effect was obtained with doses of approximately 1,000 micrograms.day-1. In conclusion, the available published data indicate that, in adolescents and adults with mild to moderate asthma, most of the therapeutic benefit of budesonide delivered by turbuhaler or metered-dose inhaler + spacer is achieved with a dose of approximately 400 micrograms.day-1 and the maximum effect is achieved at approximately 1,000 micrograms.day-1. This conclusion is qualified by the recognition that there is considerable individual variability in the response to inhaled corticosteroids and that the subjects included in this meta-analysis had predominantly mild to moderate asthma.

Administration, Inhalation↗