Background We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19. Methods In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov , NCT04501978 . Findings Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50–72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74–1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67–1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74–1·58]; BRII-196 plus BRII-198 1·00 [0·68–1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91–...

The Russian and Norwegian Arctic are gaining notoriety as an alternative maritime route connecting the Atlantic and Pacific Oceans and as sources of natural resources. The renewed interest in the Northeast Passage or the Northern Sea Route is fueled by a recession of Arctic sea ice coupled with the discovery of new natural resources at a time when emerging and global markets are in growing demand for them. Driven by the expectation of potential future economic importance of the region, political interest and governance has been rapidly developing, mostly within the Arctic Council. However, this paper argues that optimism regarding the potential of Arctic routes as an alternative to the Suez Canal is overstated. The route involves many challenges: jurisdictional disputes create political uncertainties; shallow waters limit ship size; lack of modern deepwater ports and search and rescue (SAR) capabilities requires ships to have higher standards of autonomy and safety; harsh weather conditions and free-floating ice make navigation more difficult and schedules more variable; and more expensive ship construction and operation costs lessen the economic viability of the route. Technological advances and infrastructure investments may ameliorate navigational challenges, enabling increased shipping of natural resources from the Arctic to global markets.

The management of vomiting and antiemetic therapy in young children with acute gastroenteritis (AGE) has not been standardized by any management guidelines. Antiemetic drugs including promethazine, prochlorperazine, metoclopramide, ondansetron, and domperidone are readily used in the emergency departments (EDs). The aim of this study was to compare the efficacy of ondansetron with domperidone in cessation of vomiting in pediatric AGE. Methods This open-label, two-arm trial was conducted in a pediatric ED in Pakistan. Children of age 1 to 60 months presenting with acute vomiting and no or mild-to-moderate dehydration associated with AGE were randomized into two groups. Group A children received ondansetron suspension orally at a dose of 0.15 mg/kg body weight. Group B received domperidone suspension orally at a dose of 0.5 mg/kg body weight. The primary outcome was the number of children in each group who did not have any episode of vomiting 24 hours posttreatment. The data were entered and analyzed using Statistical Package for the Social Sciences (SPSS) for Windows version 20.0 (IBM Corp., Armonk, NY). Results At 6 hours, 87% of children in the ondansetron group improved and their vomiting episodes ceased as compared to 81% of children in the domperidone group. The differences were statistically insignificant (p>0.05). At 24 hours, 95% in the ondansetron group had improved and only 85% in the domperidone group. The results were statistically significant favoring the end results of the ondansetron (p=0.01). Conclusions This study concluded that ondansetron is more efficacious than domperidone in cessation of vomiting associated with AGE and no or mild-to-moderate dehydration in children of age three months to five years.

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ACTIV-3/TICO Study Group* Background: Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection.Objective: To investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone.