Key Points• TSOACs are associated with less major bleeding, fatal bleeding, clinically relevant nonmajor bleeding, and total bleeding.• The meta-analysis does not show increased risk of major gastrointestinal bleeding in patients who received TSOACs compared with warfarin.Vitamin K antagonists (VKAs) have been the standard of care for treatment of thromboembolic diseases. Target-specific oral anticoagulants (TSOACs) have been developed and found to be at least noninferior to VKAs with regard to efficacy, but the risk of bleeding with TSOACs remains controversial. We performed a systematic review and meta-analysis of phase-3 randomized controlled trials (RCTs) to assess the bleeding side effects of TSOACs compared with VKAs in patients with venous thromboembolism or atrial fibrillation. We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials; conference abstracts; and www.clinicaltrials.gov with no language restriction. Two reviewers independently performed study selection, data extraction, and study quality assessment. Twelve RCTs involving 102 607 patients were retrieved. TSOACs significantly reduced the risk of overall major bleeding (relative risk [RR] 0.72, P < .01), fatal bleeding (RR 0.53, P < .01), intracranial bleeding (RR 0.43, P < .01), clinically relevant nonmajor bleeding (RR 0.78, P < .01), and total bleeding (RR 0.76, P < .01). There was no significant difference in major gastrointestinal bleeding between TSOACs and VKAs (RR 0.94, P 5 .62). When compared with VKAs, TSOACs are associated with less major bleeding, fatal bleeding, intracranial bleeding, clinically relevant nonmajor bleeding, and total bleeding. Additionally, TSOACs do not increase the risk of gastrointestinal bleeding. (Blood. 2014;124(15):2450-2458

IMPORTANCE Various noninvasive ventilation strategies are used to prevent bronchopulmonary dysplasia (BPD)of preterm infants; however, the best mode is uncertain.OBJECTIVE To compare 7 ventilation strategies for preterm infants including nasal continuous positive airway pressure (CPAP) alone, intubation and surfactant administration followed by immediate extubation (INSURE), less invasive surfactant administration (LISA), noninvasive intermittent positive pressure ventilation, nebulized surfactant administration, surfactant administration via laryngeal mask airway, and mechanical ventilation.DATA SOURCES MEDLINE, EMBASE, CINAHL, and Cochrane CENTRAL from their inceptions to June 2016. STUDY SELECTION Randomized clinical trials comparing ventilation strategies for infants younger than 33 weeks' gestational age within 24 hours of birth who had not been intubated.DATA EXTRACTION AND SYNTHESIS Data were independently extracted by 2 reviewers and synthesized with Bayesian random-effects network meta-analyses. MAIN OUTCOMES AND MEASURES A composite of death or BPD at 36 weeks' postmenstrual age was the primary outcome. Death, BPD, severe intraventricular hemorrhage, and air leak by discharge were the main secondary outcomes. RESULTSAmong 5598 infants involved in 30 trials, the incidence of the primary outcome was 33% (1665 of 4987; including 505 deaths and 1160 cases of BPD). The secondary outcomes ranged from 6% (314 of 5587) for air leak to 26% (1160 of 4455) for BPD . Compared with mechanical ventilation, LISA had a lower odds of the primary outcome (odds ratio [OR], 0.49; 95% credible interval [CrI], 0.30-0.79; absolute risk difference [RD], 164 fewer per 1000 infants; 57-253 fewer per 1000 infants; moderate quality of evidence), BPD(OR, 0.53; 95% CrI, 0.27-0.96; absolute RD, 133 fewer per 1000 infants; 95% CrI, 9-234 fewer per 1000 infants; moderate-quality), and severe intraventricular hemorrhage (OR, 0.44; 95% CrI, 0.19-0.99; absolute RD, 58 fewer per 1000 births; 95% CrI, 1-86 fewer per 1000 births; moderate-quality). Compared with nasal CPAP alone, LISA had a lower odds of the primary outcome (OR, 0.58; 95% CrI, 0.35-0.93; absolute RD, 112 fewer per 1000 births; 95% CrI, 16-190 fewer per 1000 births; moderate quality), and air leak (OR, 0.24; 95% CrI, 0.05-0.96; absolute RD, 47 fewer per 1000 births; 95% CrI, 2-59 fewer per 1000 births; very low quality). Ranking probabilities indicated that LISA was the best strategy with a surface under the cumulative ranking curve of 0.85 to 0.94, but this finding was not robust for death when limited to higher-quality evidence.CONCLUSIONS AND RELEVANCE Among preterm infants, the use of LISA was associated with the lowest likelihood of the composite outcome of death or BPD at 36 weeks' postmenstrual age. These findings were limited by the overall low quality of evidence and lack of robustness in higher-quality trials. INSURE intubation and surfactant administration followed by immediate extubation LISA less invasive surfactant administration NPPV noninvasive intermittent po...

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence to Decision Framework Highlights sections. The task forces also listed priority knowledge gaps for further research.

The network ranking of survival rates for very preterm infants remained largely unchanged as GA increased; however, survival rates showed marked variations at lower GAs. The median age at death also varied among networks. These findings warrant further assessment of the representativeness of the study populations, organization of perinatal services, national guidelines, philosophy of care at extreme GAs, and resources used for decision-making.

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence to Decision Framework Highlights sections. The task forces also listed priority knowledge gaps for further research.

Composite outcome of mortality or major morbidity was significantly lower in Japan than Canada for VLBW infants. However, there were significant differences in various individual outcomes identifying areas for improvement for both networks.

The use of different definitions for bronchopulmonary dysplasia (BPD) has been an ongoing challenge. We searched papers published in English from 2010 and 2015 reporting BPD as an outcome, together with studies that compared BPD definitions between 1978 and 2015. We found that the incidence of BPD ranged from 6% to 57%, depending on the definition chosen, and that studies that investigated correlations with long-term pulmonary and/or neurosensory outcomes reported moderate-to-low predictive values regardless of the BPD criteria. CONCLUSION A comprehensive and evidence-based definition for BPD needs to be developed for benchmarking and prognostic use. Accepted ArticleThis article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/apa.13672This article is protected by copyright. All rights reserved. Accepted ArticleThis article is protected by copyright. All rights reserved. Key Notes The use of different definitions for bronchopulmonary dysplasia (BPD) has been an ongoing challenge. We found that the incidence of BPD ranged from 6% to 57%, depending on the definition chosen, and studies investigating correlations with long-term pulmonary and, or, neurosensory outcomes reported moderate to low predictive values regardless of the BPD criteria. A comprehensive evidence-based definition for BPD needs to be developed for benchmarking and prognostic use.

To cite this article: Chai-Adisaksopha C, Hillis C, Isayama T, Lim W, Iorio A, Crowther M. Mortality outcomes in patients receiving direct oral anticoagulants: a systematic review and meta-analysis of randomized controlled trials. J Thromb Haemost 2015; 13: 2012-20.Summary. Background: Direct oral anticoagulants (DOACs) are widely used as an alternative for warfarin. However, the impact of DOACs on mortality outcomes compared with warfarin remains unclear. Objective: To estimate the mortality outcomes in patients treated with DOACs vs. warfarin (or another vitamin K antagonist). Methods: MEDLINE, EMBASE and CENTRAL databases (inception to September 2014), conference abstracts and www.-clinicaltrials.gov, were searched, without language restriction. Studies were selected if there were phase III, randomized trials comparing DOACs with warfarin in patients with non-valvular atrial fibrillation or venous thromboembolism. Results: Thirteen randomized controlled trials involving 102 707 adult patients were included in the analysis. The case-fatality rate of major bleeding was 7.57% (95% CI, 6.53-8.68; I 2 = 0%) in patients taking DOACs and 11.04% (95% CI, 9.16-13.07; I 2 = 33.3%) in patients taking warfarin. The rate of fatal bleeding in adult patients receiving DOACs was 0.16 per 100 patient-years (95% CI, 0.12-0.20; I 2 = 36.5%). When compared with warfarin, DOACs were associated with significant reductions in fatal bleeding (RR, 0.53; 95% CI, 0.43-0.64; I 2 = 0%), cardiovascular mortality (RR, 0.88; 95% CI, 0.82-0.94; I 2 = 0%) and all-cause mortality (RR, 0.91; 95% CI, 0.87-0.96; I 2 = 0%). Conclusions: The use of DOACs compared with warfarin is associated with a lower rate of fatal bleeding, case-fatality rate of major bleeding, cardiovascular mortality and all-cause mortality.