Background Although pregnant women are a priority group for influenza vaccination, its effect on birth outcomes has long been debated. Numerous observational studies and a few randomized controlled studies have been conducted, with inconsistent results. Objectives To evaluate the association of influenza vaccination in pregnancy with adverse birth outcomes. Data source The Cochrane Library, PubMed, EMBASE, Web of Science, and Scopus were searched. Study eligibility criteria This analysis included randomized placebo-controlled studies, cohort studies, and case-control studies, in which inactivated influenza vaccination was given during pregnancy and fetal adverse birth outcomes were assessed. Participants & intervention Women who received inactivated influenza vaccine during pregnancy and their offspring. Study appraisal and synthesis Two independent reviewers and a third reviewer collaborated in study selection and data extraction. A Bayesian 3-level random-effects model was utilized to assess the impact of maternal influenza vaccination on birth outcomes, which were presented as odds ratios (ORs) with 95% credible interval (CrIs). Bayesian outcome probabilities (P) of an OR<1 were calculated, and values of at least 90% (0.9) were deemed to indicate a significant result. Results Among the 6,249 identified publications, 48 studies were eligible for the meta-analysis, including 2 randomized controlled trials, 41 cohort studies, and 5 case-control studies. The risk of none of the following adverse birth outcomes decreased significantly: preterm birth (OR = 0.945, 95% CrI: 0.736–1.345, P = 73.3%), low birth weight (OR = 0.928, 95% CrI: 0.432–2.112, P = 76.7%), small for gestational age (OR = 0.971, 95% CrI: 0.249–4.217,P = 63.3%), congenital malformation (OR = 1.026, 95% CrI: 0.687–1.600, P = 38.0%), and fetal death (OR = 0.942, 95% CrI: 0.560–1.954, P = 61.6%). Summary estimates including only cohort studies showed significantly decreased risks for preterm birth, small for gestational age and fetal death. However, after adjusting for season at the time of vaccination and countries’ income level, only fetal death remained significant. Conclusion This Bayesian meta-analysis did not find a protective effect of maternal influenza vaccination against adverse birth outcomes, as reported in previous studies. In fact, our results showed evidence of null associations between maternal influenza vaccination and adverse birth outcomes.

BackgroundAlthough exacerbation and mortality are the most important clinical outcomes of stable chronic obstructive pulmonary disease (COPD), the drug classes that are the most efficacious in reducing exacerbation and mortality among all possible inhaled drugs have not been determined.Methods and findingsWe performed a systematic review (SR) and Bayesian network meta-analysis (NMA). We searched Medline, EMBASE, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, the European Union Clinical Trials Register, and the official websites of pharmaceutical companies (from inception to July 9, 2019). The eligibility criteria were as follows: (1) parallel-design randomized controlled trials (RCTs); (2) adults with stable COPD; (3) comparisons among long-acting muscarinic antagonists (LAMAs), long-acting beta-agonists (LABAs), inhaled corticosteroids (ICSs), combined treatment (ICS/LAMA/LABA, LAMA/LABA, or ICS/LABA), or a placebo; and (4) study duration ≥ 12 weeks. This study was prospectively registered in International Prospective Register of Systematic Reviews (PROSPERO; CRD42017069087). In total, 219 trials involving 228,710 patients were included. Compared with placebo, all drug classes significantly reduced the total exacerbations and moderate to severe exacerbations. ICS/LAMA/LABA was the most efficacious treatment for reducing the exacerbation risk (odds ratio [OR] = 0.57; 95% credible interval [CrI] 0.50–0.64; posterior probability of OR > 1 [P(OR > 1)] < 0.001). In addition, in contrast to the other drug classes, ICS/LAMA/LABA and ICS/LABA were associated with a significantly higher probability of reducing mortality than placebo (OR = 0.74, 95% CrI 0.59–0.93, P[OR > 1] = 0.004; and OR = 0.86, 95% CrI 0.76–0.98, P[OR > 1] = 0.015, respectively). The results minimally changed, even in various sensitivity and covariate-adjusted meta-regression analyses. ICS/LAMA/LABA tended to lower the risk of cardiovascular mortality but did not show significant results. ICS/LAMA/LABA increased the probability of pneumonia (OR for triple therapy = 1.56; 95% CrI 1.19–2.03; P[OR > 1] = 1.000). The main limitation is that there were few RCTs including only less symptomatic patients or patients at a low risk.ConclusionsThese findings suggest that triple therapy can potentially be the best option for stable COPD patients in terms of reducing exacerbation and all-cause mortality.

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Background Although exacerbation and mortality are the most important clinical outcomes of stable chronic obstructive pulmonary disease (COPD), the drug classes that are the most efficacious in reducing exacerbation and mortality among all possible inhaled drugs have not been determined. Methods and findings We performed a systematic review (SR) and Bayesian network meta-analysis (NMA). We searched Medline, EMBASE, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, the European Union Clinical Trials Register, and the official websites of pharmaceutical companies (from inception to July 9, 2019). The eligibility criteria were as follows: (1) parallel-design randomized controlled trials (RCTs); (2) adults with stable COPD; (3) comparisons among long-acting muscarinic antagonists (LAMAs), long-acting beta-agonists (LABAs), inhaled corticosteroids (ICSs), combined treatment (ICS/LAMA/ LABA, LAMA/LABA, or ICS/LABA), or a placebo; and (4) study duration � 12 weeks. This study was prospectively registered in International Prospective Register of Systematic Reviews (PROSPERO; CRD42017069087). In total, 219 trials involving 228,710 patients were included. Compared with placebo, all drug classes significantly reduced the total exacerbations and moderate to severe exacerbations. ICS/LAMA/LABA was the most efficacious treatment for reducing the exacerbation risk (odds ratio [OR] = 0.57; 95% credible interval [CrI] 0.50-0.64; posterior probability of OR > 1 [P(OR > 1)] < 0.001). In addition, in contrast to the other drug classes, ICS/LAMA/LABA and ICS/LABA were associated with a significantly higher probability of reducing mortality than placebo (OR = 0.74, 95% CrI 0.

Background: Recent advances in esophageal cancer treatment require a reevaluation of the relationship between institutional case-volume and patient outcome. The aim of this study was to analyze and update the association between surgical case-volume and both in-hospital and long-term mortality after esophagectomy for esophageal cancer. Methods: Data of all adult patients who received esophageal cancer surgery in Korea between 2004 and 2017 were extracted from the database of the National Health Insurance Service. Hospitals were categorized into three groups according to the average annual number of esophageal cancer surgery: low-volume (<12 cases/year), medium-volume (12-48 cases/ year), and high-volume centers (>48 cases/year). Postoperative in-hospital and 1-, 3-, and 5-year mortality were analyzed according to the categorized groups using logistic regression. Results: In total, 11, 346 esophageal cancer surgeries in 122 hospitals were analyzed. In-hospital mortality in the high-, medium-, and low-volume centers were 3.4%, 6.4%, and 11.1%, respectively. In-hospital mortality was significantly higher in low-volume (adjusted odds ratio, 3.91; confidence interval, 3.18-4.80; p < 0.001) and medium volume (adjusted odds ratio, 2.21; confidence interval, 1.80-2.74, p < 0.001) centers compared to high-volume centers. Patients who received esophageal cancer surgery in a low-or medium-volume center also had higher 1-, 3-, and 5-year mortality compared to patients who received the surgery in a high-volume center. Conclusions Centers with lower case-volume showed higher in-hospital mortality and long-term mortality after esophageal cancer surgery.