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Avoiding serious infections associated with abdominal hysterectomy: a meta-analysis of antibiotic prophylaxis.

OBJECTIVE: Our objective was to determine whether the use of preoperative antibiotics prevents serious infections associated with total abdominal hysterectomy. STUDY DESIGN: We identified 25 randomized controlled trials of antibiotic prophylaxis that used rigorous protocols. We performed meta-analysis and cumulative meta-analyses for all of the trials, and then we performed separate meta-analysis for cefazolin, metronidazole, and tinidazole. RESULTS: Overall, 21.1% (373 of 1768) of the patients who did not receive antibiotic prophylaxis had serious infections after abdominal hysterectomy. Among patients who received any antibiotics, we found that 9.0% (166/1836) had serious postoperative infections; among those who received cefazolin, metronidazole, or tinidazole, 11.4% (70 of 615), 6.3% (17 of 269), and 5.0% (5 of 101), respectively, had serious postoperative morbidity. The differences in the prevalence of infection between women who received prophylaxis and women who did not receive prophylaxis were statistically significant (any antibiotics, p = 0.00001; cefazolin, p = 0.00021; metronidazole, p = 0.015; and tinidazole, p = 0.034). CONCLUSION: Because preoperative antibiotics are highly effective in the prevention of serious infections associated with total abdominal hysterectomy, we believe they should be used routinely. In addition, we believe that the use of controls who receive no treatment is no longer justified in trials of antibiotic prophylaxis for total abdominal hysterectomy.

Abdomen↗

A survey of current problems in meta-analysis. Discussion from the Agency for Health Care Policy and Research inter-PORT Work Group on Literature Review/Meta-Analysis.

The United States Agency for Health Care Policy and Research brought together representatives from each of the Patient Outcomes Research Teams (PORTs) as the Inter-PORT Meta-Analysis Work Group. The purpose of the meeting was to discuss a wide range of problems the panel had encountered in the area of meta-analysis. Several actual problems were presented, and tentative solutions to those problems were given. The PORTs had to consider issues such as quality assessment, survival analysis, rare events, sensitivity and specificity, and random effects models. The solutions presented represent the methods used by several researchers who are active in the area of meta-analysis.

Evaluation Studies as Topic↗

Meta-analysis of plethysmography and rheography in the diagnosis of deep vein thrombosis.

BACKGROUND: Plethysmography and rheography techniques have been widely studied as diagnostic tests for deep vein thrombosis (DVT). This study aimed to systematically review the accuracy of these tests for diagnosing clinically suspected DVT. METHODS: The following databases were searched: Medline, EMBASE, CINAHL, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, Database of Reviews of Effectiveness, the ACP Journal Club (1966 to 2004), and citation lists of retrieved articles. Studies that compared plethysmography or rheography to a reference standard of ultrasound or contrast venography were selected. Standardised data were extracted and study quality determined against validated criteria. Data were analysed by random effects meta-analysis and meta-regression. RESULTS: The meta-analysis included 78 studies, reporting 82 patient cohorts. Sensitivity and specificity (95% CI) were: 75% (73% to 77%) and 90% (89% to 91%) for impedance plethysmography, 83% (81% to 85%) and 81% (79% to 82%) for strain-gauge plethysmography, 85% (79% to 90%) and 91% (81% to 95%) for air plethysmography, 91% (87% to 94%) and 71% (66% to 75%) for light-reflex rheography, and 86% (83% to 89%) and 93% (91% to 95%) for phleborheography. Meta-regression was limited by poor reporting of studies. There was some evidence that diagnostic performance depended on the proportion of males in the cohort and reporting of study setting. CONCLUSIONS: Although plethysmography and rheography techniques add diagnostic value, they have inadequate diagnostic performance to act as a stand-alone test in DVT diagnosis. Evaluation of their role in combination with other tests, or standardised clinical assessment, is required.

Cohort Studies↗

Meta-analysis shows strong positive association of the neuregulin 1 (NRG1) gene with schizophrenia.

Chromosome 8p22-p11 has been identified as a locus for schizophrenia in several genome-wide scans and confirmed by meta-analysis of published linkage data. Systematic fine mapping using extended Icelandic pedigrees identified an associated haplotype in the gene neuregulin 1 (NRG1), also known as heuregulin, glial growth factor, NDF43 and ARIA. A 290 kb core at risk haplotype at the 5' end of the gene (HAP(ICE)), defined by five SNPs and two microsatellite polymorphisms was found to be associated with schizophrenia in the Icelandic and Scottish populations. A number of subsequent independent studies have attempted to replicate the association, and while some have been successful, the associated haplotype is not always HAP(ICE). Furthermore, no obviously functional or pathogenic variants have been identified, and the relationship between the gene and schizophrenia has remained inconclusive. To reconcile these conflicting findings and to give a comprehensive picture of the genetic architecture of this important gene, we performed a meta-analysis of 13 published population-based and family-based association studies up to November 2005. We analysed data from the SNP markers SNP8NRG241930, SNP8NRG243177, SNP8NRG221132 and SNP8NRG221533, and the microsatellite markers 478B14-848, 420M9-1395. Across these studies, strong positive association was found for all six polymorphisms. The haplotype analysis also showed significant association in the pooled international populations (OR=1.22, 95% CI 1.15-1.3, P=8 x 10(-10)). In Asian populations, the risk haplotype was focused around the two microsatellite markers, 478B14-848, 420M9-1395 (haplotype block B), and in Caucasian populations with the remaining four SNP markers (haplotype block A). This meta-analysis supports the involvement of NRG1 in the pathogenesis of schizophrenia, but with association between two different but adjacent haplotypes blocks in the Caucasian and Asian populations.

Asian People↗

Meta-analysis of genome-wide linkage studies for bone mineral density.

Genome-wide linkage studies have shown several chromosome loci that may harbor genes that regulate bone mineral density (BMD), but results have been inconsistent. A meta-analysis was performed to assess evidence for linkage of BMD across whole genome scan studies. Eleven whole-genome scans of BMD or osteoporosis containing 3,097 families with 12,685 individuals were included in this genome scan meta-analysis (GSMA). For each study, 120 genomic bins of approximately 30 cM were defined and ranked according to maximum evidence for linkage within each bin. Bin ranks were weighted and summed across all studies. The summed rank for each bin was assessed empirically for significance using permutation methods. A total of seven bins lie above the 95% confidence level (P=0.05) and one bin was above the 99% confidence level (P=0.01) in the GSMA of eleven linkage studies: bins 16.1 (16pter-16p12.3, Psumrnk <0.01), 3.3 (3p22.2-3p14.1), 1.1 (1pter-1p36.22), 18.2 (18p11.23-18q12.2), 6.3 (6p21.1-6q15), 20.1 (20pter-20p12.3), and 18.1 (18pter-18p11.23). GSMA was performed with seven studies with linkage scores of LOD >1-1.85 for sensitivity test, confirming the linkage on chromosome 16p and 3p and revealing evidence of new linkage in bins 10.2 (10p14-10q11.21) and 22.2 (22q12.3-22pter). In conclusion, the meta-analysis of whole-genome linkage studies of BMD has shown chromosome 16pter-16p12.3 to have the greatest evidence of linkage as well as revealing evidence of linkage in chromosomes 1p, 3p, 6, 10, 18, 20p, and 22q across studies. This data may provide a basis with which to carry out targeted linkage and candidate gene studies particularly in these regions.

Bone Density↗

Factors Associated With Menopause Symptoms: A Systematic Review and Meta-Analysis.

BACKGROUND: Menopause, marked by hormonal decline and menstrual cessation, is associated with various symptoms. Socio-demographic and behavioural factors may influence symptom type and severity. Understanding these associations can inform better symptom management. OBJECTIVES: To identify factors associated with the presence and severity of menopausal symptoms through systematic review and meta-analysis. SEARCH STRATEGY: We searched Medline, Embase, CINAHL and Cochrane for studies on demographic, behavioural, or health factors linked to vasomotor, vaginal dryness and joint symptoms in women aged 40-60. SELECTION CRITERIA: Studies reporting odds ratios or raw numbers for symptom presence or severity were included. DATA COLLECTION AND ANALYSIS: Studies were combined for meta-analysis, reporting odds ratios and 95% confidence intervals. Quality assessment was performed to quantify the risk of bias. RESULTS: Of 9228 screened articles, 61 were meta-analysed. Compared with White women, Black women had higher odds of vasomotor symptom presence (OR 1.65, 1.41-1.94) and severity (OR 1.91, 1.10-3.29), and vaginal dryness presence (OR 1.27, 1.10-1.47), while Asian had lower vasomotor symptom presence and severity (OR 0.40, 0.22-0.72; OR 0.55, 0.53-0.56). Higher education (OR 1.31, 1.09-1.56), high income (OR 1.41, 1.01-1.97) and depression (OR 2.36, 1.51-3.70) were associated with increased presence of vasomotor symptoms. Smoking and obesity were associated with both presence (OR 1.63, 1.30-2.04 and 1.35, 1.02-1.78) and severity (OR 1.56, 1.07-2.27 and 1.42, 1.11-1.83) of vasomotor symptoms. CONCLUSION: Socio-demographic and behavioural factors, including ethnicity, education, income, smoking, obesity and depression, influence menopausal symptoms, highlighting the need for personalised care. TRIAL REGISTRATION: PROSPERO number: CRD42023459154.

Humans↗

Meta-analysis of surgical outcome in adolescent idiopathic scoliosis. A 35-year English literature review of 11,000 patients.

STUDY DESIGN: Meta-analysis of the English literature on the surgical treatment of adolescent idiopathic scoliosis. OBJECTIVE: To gather comparable data from a number of different sources and combine the data to create a larger, more statistically significant pool of information for the analysis of surgical outcome. SUMMARY OF BACKGROUND DATA: Meta-analysis is a technique of scientific literature review used in outcome evaluation of medical treatment. This technique has been applied to the surgical outcome of adolescent idiopathic scoliosis. METHODS: A structured literature review was performed that cross-referenced English literature articles pertaining to the surgical treatment of adolescent idiopathic scoliosis with a focus on patient-based outcomes. Measures of patient satisfaction were compared with process measures of care. RESULTS: A number of patients (10,989) were reviewed in 139 patient populations. Unspecified curve types (9424) and King curve types (1565) were reviewed over a 35-year period from 1958 to 1993. Of the patients, 87.32% were studied retrospectively and 12.70% prospectively. Effect-weighted follow-up was 6.8 years. Only studies with complete process and patient data for unspecified or King curve types were included for satisfaction correlation calculations. Pearson product moment correlation for n = 33 studies, n' = 2926 patients revealed a positive r' = 0.628 correlation between degree of curve correction and percent satisfaction per study. To determine the degree of curvature correction resulting in patient satisfaction, a stepwise multiple linear regression analysis was performed with level of confidence (P < or = 0.05). Of significance was that the degree of curvature corrected accounted for all the satisfaction variance predicted. A significant correction exists between degree of curve correction and percent of patients satisfied. The percent of correction and the Group type (either unspecified or King classified), did not significantly alter this prediction. The best predictor of satisfaction appears to be degree of curve correction according to these data. CONCLUSION: Patients appear to be more satisfied by the magnitude of curve correction rather than the percent of curve correction. The degree of curvature before surgery did not predict patient satisfaction. Pearsons r' = 0.045. Satisfaction appears to be best predicted by the degree of correction only and not by the percent curve correction, the curve magnitude before surgery, nor the Group type (King, unspecified). Patient satisfaction is subjective. It does not reflect the benefits of surgery with respect to the future preservation of pulmonary function in thoracic curves nor the prevention of osteoarthritis in lumbar curves.

Adolescent↗

Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer.

BACKGROUND: Despite more than 70 randomised trials, the effect of chemotherapy on non-metastatic head and neck squamous-cell carcinoma remains uncertain. We did three meta-analyses of the impact of survival on chemotherapy added to locoregional treatment. METHODS: We updated data on all patients in randomised trials between 1965 and 1993. We included patients with carcinoma of the oropharynx, oral cavity, larynx, or hypopharynx. FINDINGS: The main meta-analysis of 63 trials (10,741 patients) of locoregional treatment with or without chemotherapy yielded a pooled hazard ratio of death of 0.90 (95% CI 0.85-0.94, p<0.0001), corresponding to an absolute survival benefit of 4% at 2 and 5 years in favour of chemotherapy. There was no significant benefit associated with adjuvant or neoadjuvant chemotherapy. Chemotherapy given concomitantly to radiotherapy gave significant benefits, but heterogeneity of the results prohibits firm conclusions. Meta-analysis of six trials (861 patients) comparing neoadjuvant chemotherapy plus radiotherapy with concomitant or alternating radiochemotherapy yielded a hazard ratio of 0.91 (0.79-1.06) in favour of concomitant or alternating radiochemotherapy. Three larynx-preservation trials (602 patients) compared radical surgery plus radiotherapy with neoadjuvant chemotherapy plus radiotherapy in responders or radical surgery and radiotherapy in non-responders. The hazard ratio of death in the chemotherapy arm as compared with the control arm was 1.19 (0.97-1.46). INTERPRETATION: Because the main meta-analysis showed only a small significant survival benefit in favour of chemotherapy, the routine use of chemotherapy is debatable. For larynx preservation, the non-significant negative effect of chemotherapy in the organ-preservation strategy indicates that this procedure must remain investigational.

Antineoplastic Agents↗

DNA repair gene XRCC3 polymorphisms and cancer risk: a meta-analysis of 48 case-control studies.

The X-ray repair cross-complementing group 3 (XRCC3) is a highly suspected candidate gene for cancer susceptibility. However, association studies on the XRCC3 polymorphisms (4541A>G, Thr(241)Met, 17893A>G) in cancer have shown conflicting results. Therefore, we performed a meta-analysis to better assess the purported associations. Forty eight eligible case-control studies including 24,975 cancer patients and 34, 209 controls were selected for our meta-analysis. Overall, individuals carrying the XRCC3 Met/Met genotype showed a small cancer risk under a recessive genetic model. The subgroup and meta-regression analysis demonstrated different scenarios concerning the XRCC3 Met/Met genotype's role in cancer susceptibility for different subgroups. Specially, there was a significantly increased risk of breast cancer (OR, 1.14; P=0.0004; 95% CI, 1.06-1.23; P=0.37 for heterogeneity), elevated but not significant risk of cancer for head and neck, bladder, surprisingly, a significantly decreased risk of non-melanoma skin cancer (OR, 0.76; P=0.007; 95% CI, 0.62-0.93; P=0.61 for heterogeneity). A significantly elevated risk of cancer was observed in population-based case-control studies but not in nested or hospital based studies. Similarly, we found a significantly increased risk of cancer for A4541G and a decreased risk for A17893G under dominant genetic models. Our meta-analysis results support that the XRCC3 might represent a low-penetrance susceptible gene especially for cancer of breast, bladder, head and neck, and non-melanoma skin cancer. A single larger study should be required to further evaluate gene-gene and gene-environment interactions on XRCC3 polymorphisms and tissue-specific cancer risk in an ethnicity specific population.

Amino Acid Substitution↗

Systematic review and meta-analysis of the association between complement factor H Y402H polymorphisms and age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world and complement factor H (CFH) polymorphism has been found to associated with the AMD. We performed a meta-analysis to estimate the magnitude of the gene effect and the possible mode of action. A meta-analysis of eight studies assessing association between the CFH Y402H polymorphism and AMD was performed. Data extraction and study quality assessment were performed in duplicate, and heterogeneity and publication bias were explored. There was strong evidence for association between CFH and AMD, with those having CC and TC genotypes being roughly six and 2.5 times more likely to have AMD than patients with TT genotype, suggesting a co-dominant, multiplicative genetic model. The population attributable risk for the CC/TC genotype is 58.9%, i.e. the CFH polymorphism is involved in over half of all AMD. This meta-analysis summarizes the strong evidence for an association between CFH and AMD and indicates a multiplicative model with each C allele increasing the odds of AMD by approximately 2.5-fold. This result is at least as important at the population level as ApoE4 and Alzheimer's disease, playing a role in almost 60% of AMD at the population level.

Aged↗

Nonparametric meta-analysis of published data on kidney-function dependence of pharmacokinetic parameters for the aminoglycoside netilmicin.

The distribution and elimination of various drugs depend on kidney function. This dependence is published either as a linear regression equation or as the discrete extreme values for normal kidney function and anuria. A meta-analysis of the published pharmacokinetic data is required to build up a knowledge-based computer system for dosage adjustment in renal failure. A sample comparison of 4 statistical methods for meta-analysis was performed by applying them to 13 publications about the aminoglycoside netilmicin. Parametric meta-analytical methods I and II are based on regression equations alone (Z-transformation, maximum likelihood) and yield unreliable data, especially with regard to extreme values for anuria. The parametric meta-analytical method III is based on means of extreme values (standard 2-stage approach) and does not permit a decision as to whether linear interpolation of a parameter (e.g. volume of distribution) can be used for all degrees of renal insufficiency. In contrast, the nonparametric median (meta-analytical method IV) is based on the extreme values calculated from regression equations and empirical extreme values combined into 1 group of data on normal kidney function and another on anuria. For netilmicin, the meta-analytical median with the 95% confidence interval (95% CI) yields a significant increase in the dominant elimination half-life from 2h (95% CI 1.9h, 2.6h) in patients with normal kidney function to 45h (95% CI 41h, 301h) in those with anuria (p = 0.001). For a normal bodyweight of 65kg, the volume of distribution also increases significantly from 13L (95% CI 9L, 15L) to 20L (95% CI 14L, 21L) in patients with anuria (p = 0.04). Thus, drug dosage adjustment according to therapeutic peak and trough concentrations requires knowledge of the distribution and elimination parameters, since they can both be independently altered in renal failure. We conclude that the most robust meta-analysis of these alterations is achieved with the nonparametric median of extreme values.

Creatinine↗

Prevalence of hepatitis C virus infection in B-cell non-Hodgkin's lymphoma: systematic review and meta-analysis.

BACKGROUND & AIMS: The aim of our study was to conduct a systematic review of studies evaluating prevalence of hepatitis C virus (HCV) infection in B-cell non-Hodgkin's lymphoma (B-NHL) and to perform a meta-analysis of case-control studies comparing this prevalence with that of a reference group. METHODS DATA SOURCES: Electronic databases and the Cochrane Controlled Trials Register. STUDY SELECTION: Studies evaluating prevalence of HCV infection in patients with B-NHL. Studies comparing HCV prevalence in B-NHL (cases) and in a reference group (controls) were included in the meta-analysis. DATA EXTRACTION: Author/country, diagnostic method (serology/PCR), control type, matching/design, and VHC prevalence. DATA SYNTHESIS: Prevalence of HCV infection and meta-analysis combining the odds ratios (OR). RESULTS: Forty-eight studies (5542 patients) were identified. Mean HCV infection prevalence was 13% (95% CI: 12%-14%), which was higher in Italy (20%) and Japan (14%). Ten studies compared HCV prevalence in B-NHL (17%) and healthy controls (1.5%) (OR: 10.8; 95% CI: 7.4-16), results being homogeneous; OR increased up to 14.1 when only Italian studies were considered. Sixteen studies compared HCV prevalence in B-NHL (13%) and in other hematologic malignancies (2.9%) (OR: 4.2; 95% CI: 2.5-7), also with homogeneous results; OR increased up to 7.8 when subanalysis included only Italian studies. CONCLUSIONS: HCV prevalence in patients with B-NHL is approximately 15%, higher than that reported not only in general population (1.5%) but also in patients with other hematologic malignancies (2.9%), suggesting a role of HCV in the etiology of B-NHL. The striking geographic variation in this association suggests that genetic and/or environmental factors are also involved in the pathogenesis of this disorder.

Hepatitis C↗

Meta-analysis models with group structure for pleiotropy detection at gene and variant level using summary statistics from multiple datasets.

Genome-wide association studies (GWASs) have highlighted the importance of pleiotropy in human diseases, where one gene can impact 2 or more unrelated traits. Examining shared genetic risk factors across multiple diseases can enhance our understanding of these conditions by pinpointing new genes and biological pathways involved. Furthermore, with an increasing wealth of GWAS summary statistics available to the scientific community, leveraging these findings across multiple phenotypes could unveil novel pleiotropic associations. Existing selection methods examine pleiotropic associations one by one at a scale of either the genetic variant or the gene, and thus cannot consider all the genetic information at the same time. To address this limitation, we propose a new approach called MPSG (Meta-analysis model adapted for Pleiotropy Selection with Group structure). This method performs a penalized multivariate meta-analysis method adapted for pleiotropy and takes into account the group structure information nested in the data to select relevant variants and genes (or pathways) from all the genetic information. To do so, we implemented an alternating direction method of multipliers algorithm. We compared the performance of the method with other benchmark meta-analysis approaches such as GCPBayes, PLACO, and ASSET by considering as inputs different kinds of summary statistics. We provide an application of our method to the identification of potential pleiotropic genes between breast and thyroid cancers.

Humans↗

Attributes of successful smoking cessation interventions in medical practice. A meta-analysis of 39 controlled trials.

Meta-analysis was used to examine 108 intervention comparisons in 39 controlled smoking cessation trials. Type of intervention (face-to-face advice being better than all others), type of intervenor (both physician and nonphysician counselors better than either alone), the number of reinforcing sessions, and the duration of reinforcing sessions were related to success six months after the initiation of intervention. The number of modalities used by the intervention predicted success with borderline statistical significance. Multivariate analysis predicted that a team of physicians and nonphysicians using multiple intervention modalities to deliver individualized advice on multiple occasions would produce the best result. Program success 12 months after the initiation of intervention was related to the type of intervention session (group and individual sessions combined better than either alone), the number of intervention modalities, and the number of reinforcing sessions. With multivariate adjustment for confounding, the number of intervention modalities alone had a positive association with intervention success.

Analysis of Variance↗

Heart rate level and antisocial behavior in children and adolescents: a meta-analysis.

OBJECTIVE: To assess whether antisocial children are characterized by low heart rate. METHOD: A meta-analysis was conducted on 45 independent effect sizes of the resting heart rate-antisocial behavior relationship obtained from 40 studies meeting inclusion and exclusion criteria. Studies were conducted between 1971 to 2002 using a total of 5,868 children. A secondary meta-analysis was also conducted on heart rate during a stressor. RESULTS: Significant overall effect sizes were found for both resting heart rate (d = -0.44, p <.0001) and heart during a stressor (d = -0.76, p <.0001). Gender, age, method of recording, use of psychiatric control group, recruitment source, concurrent versus prospective nature of testing, and source of behavioral rating all failed to moderate this relationship. CONCLUSIONS: Low resting heart rate appears to be the best-replicated biological correlate to date of antisocial behavior in children and adolescents. Several theoretical interpretations of this relationship are outlined that should be examined in future studies.

Adolescent↗

Intracytoplasmic sperm injection versus in vitro fertilization: a randomized controlled trial and a meta-analysis of the literature.

OBJECTIVE: To compare ICSI with IVF using two insemination concentrations in moderate male infertility and to compare these data with other randomized controlled trials (RCTs). DESIGN: Prospective, randomized, controlled trial and meta-analysis. SETTING: University-based tertiary referral center. PATIENT(S): Seventy-three couples undergoing ART. INTERVENTION(S): In one IVF group a standard insemination concentration of 0.2 x 10(6)/mL was used, whereas in the other group a high insemination concentration (HIC) of 0.8 x 10(6)/mL was used. Each protocol was compared with ICSI on sibling oocytes. MAIN OUTCOME MEASURE(S): Fertilization, fertilization failure, and embryonic development. RESULT(S): The overall fertilization rate was significantly lower after standard IVF than after ICSI: 37.4% vs. 64.3%. Where HIC IVF was used, the overall fertilization rate was not significantly different from that after ICSI: 59.6% vs. 67.6%. Eight randomized controlled trials were selected and reviewed together with the present randomized controlled trial by meta-analysis. The risk ratio for an oocyte to become fertilized was 1.9 (95% confidence interval of 1.4 to 2.5) in favor of ICSI, and 3.1 ICSI cycles may be needed to avoid one complete fertilization failure after conventional IVF (95% CI of 1.7 to 12.4). CONCLUSION(S): The data from this study and the meta-analysis show that ICSI is a more efficient technique in terms of fertilization, but not in comparison with HIC IVF.

Adult↗

Which SSRI? A meta-analysis of pharmacotherapy trials in pediatric obsessive-compulsive disorder.

OBJECTIVE: The authors conducted a meta-analysis of published randomized, controlled medication trials in children and adolescents with obsessive-compulsive disorder (OCD) to assess evidence for differential efficacy based on type of drug, study design, and outcome measure. METHOD: A systematic literature search was performed for articles pertaining to the pharmacological treatment of pediatric and/or adolescent OCD. All baseline, posttreatment, and change scores with standard deviations reported in each study were included in the analyses. Effect sizes for dependent measures were expressed as standardized mean differences. The analysis included data on efficacy for four selective serotonin reuptake inhibitors (SSRIs) (paroxetine, fluoxetine, fluvoxamine, and sertraline) and clomipramine, four study designs, four dependent outcome measures, and two types of outcome scores (change and posttreatment scores). Multivariate regression was performed to assess the degree to which the effect sizes varied with the methodological features of each study. RESULTS: Twelve studies with a total of 1,044 participants met all inclusion criteria for the analysis. The pooled standardized mean difference for the results of all studies was 0.46 and showed a highly significant difference between drug and placebo treatment. Only one of the four outcome measures evaluated was not sensitive to change with treatment. A multivariate regression analysis of drug effect with other variables controlled showed that clomipramine was significantly superior to each of the SSRIs but that the SSRIs were comparably effective. CONCLUSIONS: Although highly significant, the overall effect sizes for medication were modest. Similarities and differences between the variables studied that emerged in the meta-analysis may have implications for both clinical care and future research.

Adolescent↗

Cervical cerclage for prevention of preterm delivery: meta-analysis of randomized trials.

OBJECTIVE: To estimate the effectiveness of prophylactic and therapeutic cerclage by meta-analysis of randomized clinical trials. DATA SOURCES: We searched the Cochrane Pregnancy and Childbirth Group specialized register of clinical trials (May 2002). Congress proceedings of international society meetings of fetal-maternal and reproductive medicine were searched by hand. METHODS OF STUDY SELECTION: Meta-analysis of randomized clinical trials comparing cervical cerclage with expectant management during pregnancy was performed. Further clarification was sought from trial authors when required. TABULATION, INTEGRATION, AND RESULTS: Six trials describing a total of 2175 women were analyzed. Prophylactic cerclage was compared with no cerclage in four trials. Pooled results failed to show a statistically significant reduction in pregnancy loss and preterm delivery rates, although a small reduction in births less than 33 weeks' gestation was seen in the largest trial (relative risk [RR] 0.75; 95% confidence interval [CI] 0.58 to 0.98). Cervical cerclage was associated with mild pyrexia, increased use of tocolytic therapy, and hospital admission but no serious morbidity. Two trials examined the role of therapeutic cerclage when ultrasound examination revealed a short cervix. Pooled results failed to show a reduction in total pregnancy loss, early pregnancy loss, or preterm delivery before 28 and 34 weeks in women assigned to cervical cerclage. CONCLUSION: The effectiveness of prophylactic cerclage in preventing preterm delivery in women at low or medium risk for second-trimester pregnancy loss has not been proven. The role of cerclage in women whose ultrasound reveals short cervix remains uncertain.

Adult↗