Background In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov ( NCT04381936 ). Findings Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding UK Research and Innovation (Medical Research Council) and National Institute of Health Research.

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In spite of their precipitous encounter with the environment, newborn infants cannot readily mount T helper type 1 (TH1) cell antibacterial and antiviral responses. Instead, they show skewing toward TH2 responses, which, together with immunoregulatory functions, are thought to limit the potential for inflammatory damage, while simultaneously permitting intestinal colonization by commensals. However, these collective capabilities account for relatively few T cells. Here we demonstrate that a major T cell effector function in human newborns is interleukin-8 (CXCL8) production, which has the potential to activate antimicrobial neutrophils and γδ T cells. CXCL8 production was provoked by antigen receptor engagement of T cells that are distinct from those few cells producing TH1, TH2 and TH17 cytokines, was co-stimulated by Toll-like receptor signaling, and was readily apparent in preterm babies, particularly those experiencing neonatal infections and severe pathology. By contrast, CXCL8-producing T cells were rare in adults, and no equivalent function was evident in neonatal mice. CXCL8 production counters the widely held view that T lymphocytes in very early life are intrinsically anti-inflammatory, with implications for immune monitoring, immune interventions (including vaccination) and immunopathologies. It also emphasizes qualitative distinctions between infants' and adults' immune systems.

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Female sex workers (FSW) living with HIV in sub-Saharan Africa have poor engagement to HIV care and treatment. Understanding the HIV care and treatment engagement experiences of FSW has important implications for interventions to enhance care and treatment outcomes. We conducted a systematic review to examine the HIV care experiences and determinants of linkage and retention in care, antiretroviral therapy (ART) initiation, and ART adherence and viral suppression among FSW living with HIV in sub-Saharan Africa. The databases PubMed, Embase, Web of Science, SCOPUS, CINAHL, Global Health, Psycinfo, Sociological Abstracts, and Popline were searched for variations of search terms related to sex work and HIV care and treatment among sub-Saharan African populations. Ten peer-reviewed articles published between January 2000 and August 2015 met inclusion criteria and were included in this review. Despite expanded ART access, FSW in sub-Saharan Africa have sub-optimal HIV care and treatment engagement outcomes. Stigma, discrimination, poor nutrition, food insecurity, and substance use were commonly reported and associated with poor linkage to care, retention in care, and ART initiation. Included studies suggest that interventions with FSW should focus on multilevel barriers to engagement in HIV care and treatment and explore the involvement of social support from intimate male partners. Our results emphasise several critical points of intervention for FSW living with HIV, which are urgently needed to enhance linkage to HIV care, retention in care, and treatment initiation, particularly where the HIV prevalence among FSW is greatest.

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This review demonstrated that use of nasal prong CPAP to transport infants with bronchiolitis was a safe management strategy in those with moderate to severe disease severity.

Does the clinical trials' evidence of benefit justify the routine use of probiotics in the preterm infant? There are many uncertainties surrounding the use of probiotics in the preterm, including the mechanism(s) of action of probiotics, knowledge of who benefits and who might not, whether it is placement of large numbers of bacteria into the small intestine or colonisation that determines efficacy, the forms of microbial adaptation(s) and ecological consequences. There is also a current lack of defined products with associated evidence of safety in the preterm infant. It is argued that one cannot assume safety because of a lack of evidence of harm and that one should take a precautionary approach to the introduction of probiotics into routine neonatal practice. One should also consider how best one might monitor microbiological and ecological consequences and longer-term health outcomes before the introduction of this novel intervention into routine practice.