The panel formulated and provided a rationale for the direction as well as for the strength of each recommendation to establish the diagnosis of PCD.

ECPR is feasible for refractory OHCA of cardiac origin in adult patients. It may enable neurologically good survival in selected patients, who practically have no other alternative in order to save their lives with quality of life, and contribute to organ donation in those who die. Large, prospective studies are required to clarify patient selection, modifiable outcome variables, risk-benefit and cost-effectiveness.

Major depressive disorder (MDD) and bipolar disorder (BD) lack robust biomarkers useful for screening purposes in a clinical setting. A systematic review of the literature was conducted on metabolomic studies of patients with MDD or BD through the use of analytical platforms such as in vivo brain imaging, mass spectrometry, and nuclear magnetic resonance. Our search identified a total of 7,590 articles, of which 266 articles remained for full-text revision. Overall, 249 metabolites were found to be dysregulated with 122 of these metabolites being reported in two or more of the studies included. A list of biomarkers for MDD and BD established from metabolites found to be abnormal, along with the number of studies supporting each metabolite and a comparison of which biological fluids they were reported in, is provided. Metabolic pathways that may be important in the pathophysiology of MDD and BD were identified and predominantly center on glutamatergic metabolism, energy metabolism, and neurotransmission.Using online drug registries, we also illustrate how metabolomics can facilitate the discovery of novel candidate drug targets. K E Y W O R D Sbiochemical, biomarker panel, mood disorders, omics

BackgroundThe large burden of injuries falls disproportionately on low/middle-income countries (LMICs). Health system interventions improve outcomes in high-income countries. Assessing LMIC trauma systems supports their improvement. Evaluating systems using a Three Delays framework, considering barriers to seeking (Delay 1), reaching (Delay 2) and receiving care (Delay 3), has aided maternal health gains. Rapid assessments allow timely appraisal within resource and logistically constrained settings. We systematically reviewed existing literature on the assessment of LMIC trauma systems, applying the Three Delays framework and rapid assessment principles.MethodsWe conducted a systematic review and narrative synthesis of articles assessing LMIC trauma systems. We searched seven databases and grey literature for studies and reports published until October 2018. Inclusion criteria were an injury care focus and assessment of at least one defined system aspect. We mapped each study to the Three Delays framework and judged its suitability for rapid assessment.ResultsOf 14 677 articles identified, 111 studies and 8 documents were included. Sub-Saharan Africa was the most commonly included region (44.1%). Delay 3, either alone or in combination, was most commonly assessed (79.3%) followed by Delay 2 (46.8%) and Delay 1 (10.8%). Facility assessment was the most common method of assessment (36.0%). Only 2.7% of studies assessed all Three Delays. We judged 62.6% of study methodologies potentially suitable for rapid assessment.ConclusionsWhole health system injury research is needed as facility capacity assessments dominate. Future studies should consider novel or combined methods to study Delays 1 and 2, alongside care processes and outcomes.

a b s t r a c tAim: Extracorporeal resuscitation during cardiopulmonary resuscitation (ECPR) deploys rapid cardiopulmonary bypass to sustain oxygenated circulation until the return of spontaneous circulation (ROSC). The purpose of this systematic review is to address the defining elements and outcomes (quality survival and organ donation) of currently active protocols for ECPR in refractory out-of-hospital cardiac arrest (OHCA) of cardiac origin in adult patients. The results may inform policy and practices for ECPR and help clarify the corrresponding intersection with deceased organ donation. Methods: We searched Medline, Embase, Cochrane and seven other electronic databases from 2005 to 2015, with no language restrictions. Internal validity and the quality of the studies reporting outcomes and guidelines were assessed. The review was included in the international prospective register of systematic reviews (Prospero, CRD42014015259). Results: One guideline and 20 outcome studies were analyzed. Half of the studies were prospective observational studies assessed to be of fair to good methodological quality. The remainder were retrospective cohorts, case series, and case studies. Ages ranged from 16 to 75 years and initial shockable cardiac rhythms, witnessed events, and a reversible primary cause of cardiac arrest were considered favorable prognostic factors. CPR duration and time to hospital cannulation varied considerably. Coronary revascularization, hemodynamic interventions and targeted temperature management neuroprotection were variable. A total of 833 patients receiving this ECPR approach had an overall reported survival rate of Abbreviations: ECPR, extracorporeal resuscitation; ROSC, return of spontaneous circulation; OHCA, out-of-hospital cardiac arrest; CPC, cerebral performance category; GOS, Glasgow Outcome Scale; LOE, level of evidence; ILCOR, International Liaison Committee on Resuscitation; RCTs, randomized controlled trials; TTM, targeted temperature management; IABP, intra-aortic balloon pump; DBD, donation after brain death; cDCD, controlled donation after circulatory determination of death; ELSO, extracorporeal life support organization. I. Ortega-Deballon et al. / Resuscitation 101 (2016) 12-20 13 22%, including 13% with good neurological recovery. Additionally, 88 potential and 17 actual deceased organ donors were identified among the non-survivor population in 8 out of 20 included studies. Study heterogeneity precluded a meta-analysis preventing any meaningful comparison between protocols, interventions and outcomes. Conclusions: ECPR is feasible for refractory OHCA of cardiac origin in adult patients. It may enable neurologically good survival in selected patients, who practically have no other alternative in order to save their lives with quality of life, and contribute to organ donation in those who die. Large, prospective studies are required to clarify patient selection, modifiable outcome variables, risk-benefit and cost-effectiveness.

Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. MethodsWe did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. FindingsWe included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58•0%) were male. Median gestational age at birth was 38 weeks (IQR 36-39) and median bodyweight at presentation was 2•8 kg (2•3-3•3). Mortality among all patients was 37 (39•8%) of 93 in low-income countries, 583 (20•4%) of 2860 in middle-income countries, and 50 (5•6%) of 896 in high-income countries (p<0•0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90•0%] of ten in lowincome countries, 97 [31•9%] of 304 in middle-income countries, and two [1•4%] of 139 in high-income countries; p≤0•0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2•78 [95% CI 1•88-4•11], p<0•0001; middle-income vs high-income countries, 2•11 [1•59-2•79], p<0•0001), sepsis at presentation (1•20 [1•04-1•40], p=0•016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4-5 vs ASA 1-2, 1•82 [1•40-2•35], p<0•0001; ASA 3 vs ASA 1-2, 1•58, [1•30-1•92], p<0•0001]), surgical safety checklist not used (1•39 [1•02-1•90], p=0•035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1•96, [1•4...

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