Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Surface materials and aspects of care: A study in modes of being in a visual art practice

Through creative practice and written research, this thesis explores the peculiar qualities of surface materials, revealing a broader ethos of practice which I identify as care. I propose that care arises as a mode of being between artist and work, work and beholder, and between the parts of the work. The thesis situates the art practice within an ethical framework, premised on, but extending, Heidegger's ontological equation of care with being. The original contribution is in the claim that the particular qualities of worldly matter generate the terms for care as a particular mode of engagement that is reciprocal and intransitive

Asking the right questions about secondhand smoke

INTRODUCTION: Despite knowledge about major health effects of secondhand smoke (SHS) exposure, systematic incorporation of SHS screening and counseling in clinical settings has not occurred. METHODS: A three-round modified Delphi Panel of tobacco control experts was convened to build consensus on the screening questions that should be asked and identify opportunities and barriers to SHS exposure screening and counseling. The panel considered four questions: 1) what questions should be asked about SHS exposure; 2) what are the top priorities to advance the goal of ensuring that these questions are asked; 3) what are the barriers to achieving these goals; and 4) how might these barriers be overcome. Each panel member submitted answers to the questions. Responses were summarized and successive rounds were reviewed by panel members for consolidation and prioritization. RESULTS: Panelists agreed that both adults and children should be screened during clinical encounters by asking if they are exposed or have ever been exposed to smoke from any tobacco products in their usual environment. The panel found that consistent clinician training, quality measurement or other accountability, and policy and electronic health records interventions were needed to successfully implement consistent screening. CONCLUSIONS: The panel successfully generated screening questions and identified priorities to improve SHS exposure screening. Policy interventions and stakeholder engagement are needed to overcome barriers to implementing effective secondhand smoke screening. IMPLICATIONS: In a modified Delphi panel, tobacco control and clinical prevention experts agreed that all adults and children should be screened during clinical encounters by asking if they are exposed or have ever been exposed to smoke from tobacco products. Consistent training, accountability, and policy and electronic health records interventions are needed to implement consistent screening. Increasing secondhand smoke screening will have a significant impact on public health and costs

Which Spreading Depolarizations Are Deleterious To Brain Tissue?

Spreading depolarizations (SDs) are profound disruptions of cellular homeostasis that slowly propagate through gray matter and present an extraordinary metabolic challenge to brain tissue. Recent work has shown that SDs occur commonly in human patients in the neurointensive care setting and have established a compelling case for their importance in the pathophysiology of acute brain injury. The International Conference on Spreading Depolarizations (iCSD) held in Boca Raton, Florida, in September of 2018 included a discussion session focused on the question of "Which SDs are deleterious to brain tissue?" iCSD is attended by investigators studying various animal species including invertebrates, in vivo and in vitro preparations, diseases of acute brain injury and migraine, computational modeling, and clinical brain injury, among other topics. The discussion included general agreement on many key issues, but also revealed divergent views on some topics that are relevant to the design of clinical interventions targeting SDs. A draft summary of viewpoints offered was then written by a multidisciplinary writing group of iCSD members, based on a transcript of the session. Feedback of all discussants was then formally collated, reviewed and incorporated into the final document. It is hoped that this report will stimulate collection of data that are needed to develop a more nuanced understanding of SD in different pathophysiological states, as the field continues to move toward effective clinical interventions