Summary Background Sustainable Development Goal 3.2 has targeted elimination of preventable child mortality, reduction of neonatal death to less than 12 per 1000 livebirths, and reduction of death of children younger than 5 years to less than 25 per 1000 livebirths, for each country by 2030. To understand current rates, recent trends, and potential trajectories of child mortality for the next decade, we present the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 findings for all-cause mortality and cause-specific mortality in children younger than 5 years of age, with multiple scenarios for child mortality in 2030 that include the consideration of potential effects of COVID-19, and a novel framework for quantifying optimal child survival. Methods We completed all-cause mortality and cause-specific mortality analyses from 204 countries and territories for detailed age groups separately, with aggregated mortality probabilities per 1000 livebirths computed for neonatal mortality rate (NMR) and under-5 mortality rate (U5MR). Scenarios for 2030 represent different potential trajectories, notably including potential effects of the COVID-19 pandemic and the potential impact of improvements preferentially targeting neonatal survival. Optimal child survival metrics were developed by age, sex, and cause of death across all GBD location-years. The first metric is a global optimum and is based on the lowest observed mortality, and the second is a survival potential frontier that is based on stochastic frontier analysis of observed mortality and Healthcare Access and Quality Index. Findings Global U5MR decreased from 71·2 deaths per 1000 livebirths (95% uncertainty interval [UI] 68·3–74·0) in 2000 to 37·1 (33·2–41·7) in 2019 while global NMR correspondingly declined more slowly from 28·0 deaths per 1000 live births (26·8–29·5) in 2000 to 17·9 (16·3–19·8) in 2019. In 2019, 136 (67%) of 204 countries had a U5MR at or below the SDG 3.2 threshold and 133 (65%) had an NMR at or below the SDG 3.2 threshold, and the reference scenario suggests that by 2030, 154 (75%) of all countries could meet the U5MR targets, and 139 (68%) could meet the NMR targets. Deaths of children younger than 5 years totalled 9·65 million (95% UI 9·05–10·30) in 2000 and 5·05 million (4·27–6·02) in 2019, with the neonatal fraction of these deaths increasing from 39% (3·76 million [95% UI 3·53–4·02]) in 2000 to 48% (2·42 million; 2·06–2·86) in 2019. NMR and U5MR were generally higher in males than in females, although there was no statistically significant difference at the global level. Neonatal disorders remained the leading cause of death in children younger than 5 years in 2019, followed by lower respiratory infections, diarrhoeal diseases, congenital birth defects, and malaria. The global optimum analysis suggests NMR could be reduced to as low as 0·80 (95% UI 0·71–0·86) deaths per 1000 livebirths and U5MR to 1·44 (95% UI 1·27–1·58) deaths per 1...

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Our results support the finding that endoscopic biliary drainage for malignant biliary obstruction is a first-line intervention. Endoscopic drainage is superior to percutaneous drainage, in regard to adverse event rate, for patients with pancreatic cancer. For patients with cholangiocarcinoma, endoscopic drainage is superior in centers that perform a low volume of percutaneous biliary drainage procedures.

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Background and study aims The use of lumen apposing metal stents (LAMS) during EUS-guided transmural drainage (EUS-TD) of pancreatic walled-off necrosis (WON) has gained popularity. Data supporting their use in WON over plastic stents (PS), however, remain scarce. The aim of this study was to compare the clinical efficacy of LAMS (Axios, Boston Scientific) with PS in WON. Patients and methods This was a multicenter, retrospective study involving 14 centers. Consecutive patients who underwent EUS-TD of WON (2012 – 2016) were included. The primary end point was clinical success defined as WON size ≤ 3 cm within a 6-month period without need for percutaneous drainage (PCD) or surgery. Results A total of 189 patients (mean age 55.2 ± 15.6 years, 34.9 % female) were included (102 LAMS and 87 PS). Technical success rates were similar: 100 % in LAMS and 98.9 % in PS (P = 0.28). Clinical success was attained in 80.4 % of LAMS and 57.5 % of PS (P = 0.001). Rate of PCD was similar (13.7 % LAMS vs. 16.3 % PS, P = 0.62), while PS was associated with a greater need for surgery (16.1 % PS vs. 5.6 % LAMS, P = 0.02). Adverse events (AEs) were observed in 9.8 % of LAMS and 10.3 % of PS (P = 0.90) and were rated as severe in 2.0 % and 6.9 %, respectively (P = 0.93). After excluding patients with < 6 months follow-up, the rate of WON recurrence following initial clinical success was greater with PS (22.9 % PS vs. 5.6 % LAMS, P = 0.04). Conclusions When compared to PS, LAMS in WON is associated with higher clinical success, shorter procedure time, lower need for surgery, and lower rate of recurrence.

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Cannabis hyperemesis syndrome (CHS) is a form of functional gut-brain axis disorder characterized by bouts of episodic nausea and vomiting worsened by cannabis intake. It is considered as a variant of cyclical vomiting syndrome seen in cannabis users especially characterized by compulsive hot bathing/showers to relieve the symptoms. CHS was reported for the first time in 2004, and since then, an increasing number of cases have been reported. With cannabis use increasing throughout the world as the threshold for legalization becomes lower, its user numbers are expected to rise over time. Despite this trend, a strict criterion for the diagnosis of CHS is lacking. Early recognition of CHS is essential to prevent complications related to severe volume depletion. The recent body of research recognizes that patients with CHS impose a burden on the healthcare systems. Understanding the pathophysiology of the endocannabinoid system (ECS) remains central in explaining the clinical features and potential drug targets for the treatment of CHS. The frequency and prevalence of CHS change in accordance with the doses of tetrahydrocannabinol and other cannabinoids in various formulations of cannabis. CHS is unique in presentation, because of the cannabis’s biphasic effect as anti-emetic at low doses and pro-emetic at higher doses, and the association with pathological hot water bathing. In this narrative review, we elaborate on the role of the ECS, its management, and the identification of gaps in our current knowledge of CHS to further enhance its understanding in the future.