Prophylactic antibiotics before cord clamping in cesarean delivery: a systematic review.

INTRODUCTION: The number of clinical trials investigating the optimal timing of prophylactic antibiotics in cesarean section has increased rapidly over the last few years. We conducted a systematic review to inform up-to-date evidence-based guidelines to prevent postpartum infectious morbidity in the mother and rule out any safety issues related to antepartum antibiotic exposure in infants. MATERIAL AND METHODS: Four bibliographic databases were searched for published reports of trials. Ongoing or unpublished studies were searched in Clinicaltrials.gov and the World Health Organization registry platform. Randomized controlled trials comparing antibiotic prophylaxis before and after cord clamping in cesarean section were eligible. Maternal and neonatal outcomes were assessed, and certainty of evidence graded. RESULTS: In total, 18 randomized controlled trials met the inclusion criteria. Those women who received antibiotics preoperatively were 28% (relative risk 0.72, 95% confidence interval 0.56-0.92, nine studies, 4342 women, high quality of evidence) less likely to show infectious morbidity as compared with those who received antibiotics after cord clamping. The risk of endomyometritis and/or endometritis was reduced by 43% (relative risk 0.57, 95% confidence interval 0.40-0.82, 13 studies, 6250 women, high quality of evidence) and the risk of wound infection by 38% (relative risk 0.62, 95% confidence interval 0.47-0.81, 14 studies, 6450 women, high quality of evidence) in those who received antibiotics preoperatively as compared to those who received antibiotics after cord clamping. For other maternal infections no significant differences were identified. The risk for neonatal outcomes, such as deaths attributed to infection, sepsis, neonatal antibiotic treatment, intensive care unit admission or antibiotic-related adverse events, was not found to be different, either clinically or statistically, when antibiotics were given before or after cord clamping (moderate to low quality of evidence). CONCLUSIONS: The evidence in favor of prophylactic antibiotic administration before, in comparison with after, cord clamping for major maternal infections was of high quality, meaning that further research would be unlikely to change the confidence in these findings. However, we recommend additional research reflecting the precision of the effect estimates for neonatal outcomes.

Systematic review finds that study data not published in full text articles have unclear impact on meta-analyses results in medical research.

BACKGROUND: A meta-analysis as part of a systematic review aims to provide a thorough, comprehensive and unbiased statistical summary of data from the literature. However, relevant study results could be missing from a meta-analysis because of selective publication and inadequate dissemination. If missing outcome data differ systematically from published ones, a meta-analysis will be biased with an inaccurate assessment of the intervention effect. As part of the EU-funded OPEN project (www.open-project.eu) we conducted a systematic review that assessed whether the inclusion of data that were not published at all and/or published only in the grey literature influences pooled effect estimates in meta-analyses and leads to different interpretation. METHODS AND FINDINGS: Systematic review of published literature (methodological research projects). Four bibliographic databases were searched up to February 2016 without restriction of publication year or language. Methodological research projects were considered eligible for inclusion if they reviewed a cohort of meta-analyses which (i) compared pooled effect estimates of meta-analyses of health care interventions according to publication status of data or (ii) examined whether the inclusion of unpublished or grey literature data impacts the result of a meta-analysis. Seven methodological research projects including 187 meta-analyses comparing pooled treatment effect estimates according to different publication status were identified. Two research projects showed that published data showed larger pooled treatment effects in favour of the intervention than unpublished or grey literature data (Ratio of ORs 1.15, 95% CI 1.04-1.28 and 1.34, 95% CI 1.09-1.66). In the remaining research projects pooled effect estimates and/or overall findings were not significantly changed by the inclusion of unpublished and/or grey literature data. The precision of the pooled estimate was increased with narrower 95% confidence interval. CONCLUSIONS: Although we may anticipate that systematic reviews and meta-analyses not including unpublished or grey literature study results are likely to overestimate the treatment effects, current empirical research shows that this is only the case in a minority of reviews. Therefore, currently, a meta-analyst should particularly consider time, effort and costs when adding such data to their analysis. Future research is needed to identify which reviews may benefit most from including unpublished or grey data.

Treatment as Required versus Regular Monthly Treatment in the Management of Neovascular Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis.

BACKGROUND: To investigate whether treatment as required 'pro re nata' (PRN) versus regular monthly treatment regimens lead to differences in outcomes in neovascular age-related macular degeneration (nAMD). Regular monthly administration of vascular endothelial growth factor (VEGF) inhibitors is an established gold standard treatment, but this approach is costly. Replacement of monthly by PRN treatment can only be justified if there is no difference in patient relevant outcomes. METHODS: Systematic review and meta-analysis. The intervention was PRN treatment and the comparator was monthly treatment with VEGF-inhibitors. Four bibliographic databases were searched for randomised controlled trials comparing both treatment regimens directly (head-to-head studies). The last literature search was conducted in December 2014. Risk of bias assessment was performed after the Cochrane Handbook for Systematic Reviews of Interventions. FINDINGS: We included 3 head-to-head studies (6 reports) involving more than 2000 patients. After 2 years, the weighted mean difference in best corrected visual acuity (BCVA) was 1.9 (95% CI 0.5 to 3.3) ETDRS letters in favour of monthly treatment. Systemic adverse events were higher in PRN treated patients, but these differences were not statistically significant. After 2 years, the total number of intravitreal injections required by the patients in the PRN arms were 8.4 (95% CI 7.9 to 8.9) fewer than those having monthly treatment. The studies were considered to have a moderate risk of bias. CONCLUSIONS: PRN treatment resulted in minor but statistically significant decrease in mean BCVA which may not be clinically meaningful. There is a small increase in risk of systemic adverse events for PRN treated patients. Overall, the results indicate that an individualized treatment approach with anti-VEGF using visual acuity and OCT-guided re-treatment criteria may be appropriate for most patients with nAMD.