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IMPORTANCEIn patients who require mechanical ventilation for acute hypoxemic respiratory failure, further reduction in tidal volumes, compared with conventional low tidal volume ventilation, may improve outcomes. OBJECTIVE To determine whether lower tidal volume mechanical ventilation using extracorporeal carbon dioxide removal improves outcomes in patients with acute hypoxemic respiratory failure. DESIGN, SETTING, AND PARTICIPANTS This multicenter, randomized, allocation-concealed, open-label, pragmatic clinical trial enrolled 412 adult patients receiving mechanical ventilation for acute hypoxemic respiratory failure, of a planned sample size of 1120, between May 2016 and December 2019 from 51 intensive care units in the UK. Follow-up ended on March 11, 2020. INTERVENTIONS Participants were randomized to receive lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal for at least 48 hours (n = 202) or standard care with conventional low tidal volume ventilation (n = 210). MAIN OUTCOMES AND MEASURESThe primary outcome was all-cause mortality 90 days after randomization. Prespecified secondary outcomes included ventilator-free days at day 28 and adverse event rates. RESULTS Among 412 patients who were randomized (mean age, 59 years; 143 [35%] women), 405 (98%) completed the trial. The trial was stopped early because of futility and feasibility following recommendations from the data monitoring and ethics committee. The 90-day mortality rate was 41.5% in the lower tidal volume ventilation with extracorporeal carbon dioxide removal group vs 39.5% in the standard care group (risk ratio, 1.05 [95% CI, 0.83-1.33]; difference, 2.0% [95% CI, −7.6% to 11.5%]; P = .68). There were significantly fewer mean ventilator-free days in the extracorporeal carbon dioxide removal group compared with the standard care group (7.1 [95% CI, 5.9-8.3] vs 9.2 [95% CI, 7.9-10.4] days; mean difference, −2.1 [95% CI, −3.8 to −0.3]; P = .02). Serious adverse events were reported for 62 patients (31%) in the extracorporeal carbon dioxide removal group and 18 (9%) in the standard care group, including intracranial hemorrhage in 9 patients (4.5%) vs 0 (0%) and bleeding at other sites in 6 (3.0%) vs 1 (0.5%) in the extracorporeal carbon dioxide removal group vs the control group. Overall, 21 patients experienced 22 serious adverse events related to the study device.CONCLUSIONS AND RELEVANCE Among patients with acute hypoxemic respiratory failure, the use of extracorporeal carbon dioxide removal to facilitate lower tidal volume mechanical ventilation, compared with conventional low tidal volume mechanical ventilation, did not significantly reduce 90-day mortality. However, due to early termination, the study may have been underpowered to detect a clinically important difference.

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The SARS-CoV-2 virus is primarily transmitted through virus-laden fluid particles ejected from the mouth of infected people. Face covers can mitigate the risk of virus transmission but their outward effectiveness is not fully ascertained. Objective: by using a background oriented schlieren technique, we aim to investigate the air flow ejected by a person while quietly and heavily breathing, while coughing, and with different face covers. Results: we found that all face covers without an outlet valve reduce the front flow through by at least 63% and perhaps as high as 86% if the unfiltered cough jet distance was resolved to the anticipated maximum distance of 2-3 m. However, surgical and handmade masks, and face shields, generate significant leakage jets that may present major hazards. Conclusions: the effectiveness of the masks should mostly be considered based on the generation of secondary jets rather than on the ability to mitigate the front throughflow. INDEX TERMS COVID-19 pandemic, face coverings, face masks, aerosol dispersal, aerosol generating procedures. IMPACT STATEMENT These results show the effectiveness of face coverings in mitigating aerosol dispersion and can aid policy makers to make informed decisions and PPE developers to improve their product effectiveness.

Objective: To describe the extent and nature of developmental delay at different stages in childhood in a community in South Africa, with a known high rate of Fetal Alcohol Spectrum Disorder (FASD). Method: A cohort of infants, clinically examined for FASD at two time periods, 7-12 months (N= 392; 45 FASD) and 17-21 months of age (N= 83, 35 FASD) were assessed using the Griffiths Mental Developmental Scales (GMDS). Results: Infants and children with FASD perform worse than their Non-FASD counterparts over all scales and total developmental quotients. Mean quotients for both groups decline between assessments across subscales with a particularly marked decline in the hearing and language scale at Time 2 (scores dropping from 110.6 to 83.1 in the Non-FASD group and 106.3 to 72.7 in the FASD group; P=0.004). By early childhood the developmental gap between the groups widens with low maternal education, maternal depression, high parity and previous loss of sibling/s influencing development during early childhood. Conclusion: The FASD group show more evidence of developmental delay over both time points compared to their Non-FASD counterparts. Demographic and socio-economic factors further impact early childhood. These findings are important in setting up primary level psycho-educational and national prevention programmes especially in periurban communities with a focus on early childhood development and FASD.