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.

Writing Committee for the REMAP-CAP Investigators IMPORTANCE The evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive.OBJECTIVE To determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19. DESIGN, SETTING, AND PARTICIPANTSThe ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) enrolled and randomized 4763 adults with suspected or confirmed COVID-19 between March 9, 2020, and January 18, 2021, within at least 1 domain; 2011 critically ill adults were randomized to open-label interventions in the immunoglobulin domain at 129 sites in 4 countries. Follow-up ended on April 19, 2021. INTERVENTIONSThe immunoglobulin domain randomized participants to receive 2 units of high-titer, ABO-compatible convalescent plasma (total volume of 550 mL ± 150 mL) within 48 hours of randomization (n = 1084) or no convalescent plasma (n = 916). MAIN OUTCOMES AND MEASURESThe primary ordinal end point was organ support-free days (days alive and free of intensive care unit-based organ support) up to day 21 (range, −1 to 21 days; patients who died were assigned -1 day). The primary analysis was an adjusted bayesian cumulative logistic model. Superiority was defined as the posterior probability of an odds ratio (OR) greater than 1 (threshold for trial conclusion of superiority >99%). Futility was defined as the posterior probability of an OR less than 1.2 (threshold for trial conclusion of futility >95%). An OR greater than 1 represented improved survival, more organ support-free days, or both. The prespecified secondary outcomes included in-hospital survival; 28-day survival; 90-day survival; respiratory support-free days; cardiovascular support-free days; progression to invasive mechanical ventilation, extracorporeal mechanical oxygenation, or death; intensive care unit length of stay; hospital length of stay; World Health Organization ordinal scale score at day 14; venous thromboembolic events at 90 days; and serious adverse events. RESULTS Among the 2011 participants who were randomized (median age, 61 [IQR, 52 to 70] years and 645/1998 [32.3%] women), 1990 (99%) completed the trial. The convalescent plasma intervention was stopped after the prespecified criterion for futility was met. The median number of organ support-free days was 0 (IQR, -1 to 16) in the convalescent plasma group and 3 (IQR, -1 to 16) in the no convalescent plasma group. The in-hospital mortality rate was 37.3% (401/1075) for the convalescent plasma group and 38.4% (347/904) for the no convalescent plasma group and the median number of days alive and free of organ support was 14 (IQR, 3 to 18) and 14 (IQR, 7 to 18), respectively. The median-adjusted OR was 0.97 (95% credible interval, 0.83 to 1.15) and the posterior probability of futility (OR <1.2) was 99.4% for the convalescent plasma group compared with the no convalescent plasma group. The treatment effects were consistent across the primary outcome and the 11...

Purpose The COVID-19 pandemic is unprecedented for young people within the UK. The pandemic has presented particular challenges for vulnerable children and young people. For example, a recent study in the UK indicated that 83% of young people with existing mental health conditions said the pandemic had made their condition worse (Young Minds, 2020). To date, the impact upon populations such as young people in Secure Children’s Homes (SCHs) is unknown. This study aims to elucidate this area. Design/methodology/approach SCHs provide a safe, supportive environment for vulnerable young people who frequently present with multiple and complex needs. Young people residing within a SCH may be residing at the setting because of a Secure Accommodation Order under a Section 25 Order of the Children’s Act (1989) or for criminal justice reasons, i.e. serving a Remand period or custodial sentence. Preliminary research compared a baseline period to a follow-up period after the commencement of COVID-19 national lockdown measures within a SCH in the North of England to develop understanding of the impact for young people. Findings A significant decrease in overall incidents (t (5) = −6.88, p < 0.001), restraints (t (5) = −9.07, p < 0.001) and other incidents including assaults occurred during follow-up. The SECURE STAIRS framework supports trauma-informed care and enhances support within the setting. Consistent with the framework, provision of formulation meetings was significantly increased within the follow-up period (Welsh’s t (74) = −2.74, p < 0.001). Reflections and future recommendations are outlined. Originality/value The unanticipated results highlight the value of examining incident data within secure environments and could lead to effective practice changes for practitioners working within this domain. This research also demonstrates how frameworks such as SECURE STAIRS can be beneficial for vulnerable young people during periods of change and stress in mitigating some of the potential negative effects. The implementation of such frameworks within SCHs is still novel and thus evaluative research is valuable.

Purpose The SECURE STAIRS framework for integrated care is a trauma-informed approach to supporting staff and young people within the Children and Young People’s Secure Estate (CYPSE) in the UK. Within secure settings, therapeutic climate is a concept that encapsulates an individual’s perception of safety, connectedness with others and level of support within the environment. To support evaluation of the SECURE STAIRS framework, a Secure Children’s Home (SCH) within the North East of England examined therapeutic climate for staff and young people annually using the Essen Climate Evaluation Schema (EssenCES) over a three-year period. This paper aims to present the findings. Design/methodology/approach Over the three years, a total of 71 young people and 214 staff EssenCES questionnaires were administered. Between 2020 and 2021, the setting also experienced significant changes resulting from the COVID-19 pandemic. Numbers of young people also decreased within the setting over the three-year period. Findings Results indicated a positive trend for therapeutic climate sub-scores. For example, Experienced Safety for young people significantly increased from 2020 to 2021. Additionally, therapeutic hold for staff was significantly higher in 2020 and 2021 in comparison to 2018. Originality/value Findings are discussed in relation to implementation of the SECURE STAIRS framework and providing trauma-informed care for vulnerable young people within secure settings. Implications for practice are explored.

cases are the response of the tissues (anergy or allergy) to a tuberCulous invader, but it is more than likely that the second stage in infection is a non-specific one, and that the appearances of disease of a common sort are only produLced when the balance between attack and defence is so disturbed as to allow of the development of the proliferative lesions of the third stage of' disease, with the characteristic tissuie immunity. Summary An unusLual case of sarcoidosis is described, with visceralization" in the nervous system, producing Adie's syndrome.Episcleritis and Luveo-parotitis oCCLerred later in the same patient.A general discussion of the possible mechanisms of infection is attempted, and it is maintained that conditions such as sarcoiditis represent a non-specific second stage of disease. REFERENCESGarland, H. G., and Thomson. J. G. (1934). Lancet, 2, 743. Heerfordt, C. F. (1909). v. Graeles A-ch. Oplihtal., 70, 254. Ingram, J. Fr. (1938). British Medical Jourcnal, 1, 872. Lemming, R. (1940. Acia ned. wsand., 103, 400 (quoted in British Mle(dical Jourtial, 1941, 1, 92 1from the mains of the near-by town, was chlorinated duLring the period of investigation.Among a very large number of troops about 150 reported sick, and some 30 of these had to be admitted to hospital. In addition many had'had similar symptoms. buLt of suLch mild degree that they did not seek medical advice. In those cases admitted to hospital every effort was made to obtain a careful history of the illness and its opening phases, and thorough bacteriological examinations were made of the faeces and the blood in the acuLte phase and during the convalescent stage ten days after the onset and later. All bloods sent to the laboratory were culttLred. It may be noted at once that the bacteriological examination of both blood and faeces was entirely negative. Blood counts were not done, and as we were unable to obtain specimens the vomit was not subnmitted to laboratory examination. The history of the illness was not constant, though 60% conformed very closely to what we can call the typical case. In such a case the patient retired to bed feeling perfectly fit. In the early hoturs of the morning he or she would wake up with intense and urgent vomiting, followed by diarrhoea of a very watery type. There was little malaise, and the most prominent symptoms apart from diarrhoea and vomiting were mild backache and a feeling of heaviness in the abdomen. The diarrhoea varied from a few motions a day to, in, one case, twenty-six motions. The stools contained no blood or mucus; they were offensive, ol the typical small-intestine type, and usually chocolatecoloured. The course of the illness in its acute stage was short. Most patients had a temperature varying from 990 to 1000 for from twenty-four to thirty-six hours. A few had a higher temperature, but none over 1010, and in a few cases the pyrexia persisted for seventy-two hours. There was no prostration in any case, and imniediately after the 'acute phase all patients complained ol hunger and as...