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Purpose: The aim of this study was to conduct a process evaluation of a whole‐genome sequence report form (SRF) used to reduce nosocomial SARS‐CoV‐2 through changing infection prevention and control (IPC) behaviours within the COVID‐19 pandemic. Methods: We used a three‐staged design. Firstly, we described and theorized the purported content of the SRF using the behaviour change wheel (BCW). Secondly, we used inductive thematic analysis of one‐to‐one interviews (n = 39) to explore contextual accounts of using the SRF. Thirdly, further deductive analysis gauged support for the intervention working as earlier anticipated. Results: It was possible to theorize the SRF using the BCW approach and visualize it within a simple logic model. Inductive thematic analyses identified the SRF's acceptability, ease of use and perceived effectiveness. However, major challenges to embedding it in routine practice during the unfolding COVID‐19 crisis were reported. Notwithstanding this insight, deductive analysis showed support for the putative intervention functions 'Education', 'Persuasion' and 'Enablement'; behaviour change techniques '1.2 Problem solving', '2.6 Biofeedback', '2.7 Feedback on outcomes of behaviour' and '7.1 Prompts and cues'; and theoretical domains framework domains 'Knowledge' and 'Behavioural regulation'. Conclusions: Our process evaluation of the SRF, using the BCW approach to describe and theorize its content, provided granular support for the SRF working to change IPC behaviours as anticipated. However, our complementary inductive thematic analysis highlighted the importance of the local context in constraining its routine use. For SRFs to reach their full potential in reducing nosocomial infections, further implementation research is needed. [ABSTRACT FROM AUTHOR]

Plasma exchange is a highly efficient technique to remove circulating autoantibodies and other humoral factors rapidly from the vascular compartment. It was the first effective acute treatment for peripheral disorders such as Guillain- Barré syndrome and myasthenia gravis before intravenous immunoglobulin became available. The recent recognition of rapidly progressive severe antibody- mediated central nervous system disorders, such as neuromyelitis optica spectrum disorders and anti- N- methyl- D- aspartate- receptor encephalitis, has renewed interest in using plasma exchange for their acute treatment also. In this review we explain the principles and technical aspects of plasma exchange, review its current indications, and discuss the implications for its provision in the UK. [ABSTRACT FROM AUTHOR]

Background: Aspirin has been proposed as a treatment for COVID-19 on the basis of its anti-thrombotic properties. We aimed to evaluate the efficacy and safety of aspirin in patients admitted to hospital with COVID-19., Methods: In this randomised, controlled, open-label, platform trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19. The trial took place at 177 hospitals in the UK, two hospitals in Indonesia, and two hospitals in Nepal. Eligible and consenting adults were randomly allocated in a 1:1 ratio to either usual standard of care plus 150 mg aspirin once per day until discharge or usual standard of care alone using web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was 28 day mortality. All analyses were done by intention to treat. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936)., Findings: Between Nov 1, 2020, and March 21, 2021, 14 892 (66%) of 22 560 patients enrolled into the RECOVERY trial were eligible to be randomly allocated to aspirin. 7351 patients were randomly allocated (1:1) to receive aspirin and 7541 patients to receive usual care alone. Overall, 1222 (17%) of 7351 patients allocated to aspirin and 1299 (17%) of 7541 patients allocated to usual care died within 28 days (rate ratio 0·96, 95% CI 0·89-1·04; p=0·35). Consistent results were seen in all prespecified subgroups of patients. Patients allocated to aspirin had a slightly shorter duration of hospitalisation (median 8 days, IQR 5 to >28, vs 9 days, IQR 5 to >28) and a higher proportion were discharged from hospital alive within 28 days (75% vs 74%; rate ratio 1·06, 95% CI 1·02-1·10; p=0·0062). Among patients not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (21% vs 22%; risk ratio 0·96, 95% CI 0·90-1·03; p=0·23). Aspirin use was associated with a reduction in thrombotic events (4·6% vs 5·3%; absolute reduction 0·6%, SE 0·4%) and an increase in major bleeding events (1·6% vs 1·0%; absolute increase 0·6%, SE 0·2%)., Interpretation: In patients hospitalised with COVID-19, aspirin was not associated with reductions in 28 day mortality or in the risk of progressing to invasive mechanical ventilation or death, but was associated with a small increase in the rate of being discharged alive within 28 days., Funding: UK Research and Innovation (Medical Research Council), National Institute of Health Research, and the Wellcome Trust through the COVID-19 Therapeutics Accelerator., Competing Interests: Declaration of interests The authors declare no competing interests or financial relationships relevant to the submitted work. No form of payment was given to anyone to produce the manuscript. The Nuffield Department of Population Health at the University of Oxford has a staff policy of not accepting honoraria or consultancy fees directly or indirectly from industry., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19., 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. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936., Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93-1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94-1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93-1·05; p=0·79)., Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes., Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Coronavirus disease 2019 (Covid-19) is associated with diffuse lung damage. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death., Methods: In this controlled, open-label trial comparing a range of possible treatments in patients who were hospitalized with Covid-19, we randomly assigned patients to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days or to receive usual care alone. The primary outcome was 28-day mortality. Here, we report the final results of this assessment., Results: A total of 2104 patients were assigned to receive dexamethasone and 4321 to receive usual care. Overall, 482 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomization (age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P<0.001). The proportional and absolute between-group differences in mortality varied considerably according to the level of respiratory support that the patients were receiving at the time of randomization. In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among those who were receiving no respiratory support at randomization (17.8% vs. 14.0%; rate ratio, 1.19; 95% CI, 0.92 to 1.55)., Conclusions: In patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support. (Funded by the Medical Research Council and National Institute for Health Research and others; RECOVERY ClinicalTrials.gov number, NCT04381936; ISRCTN number, 50189673.)., (Copyright © 2020 Massachusetts Medical Society.)

Background: Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatory actions. 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-19 Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospital with COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once per day by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatment groups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment and were twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants and local study staff were not masked to the allocated treatment, but all others involved in the trial were masked to the outcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treat population. 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%) were eligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was 65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomly allocated 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 (median 10 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, no significant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilation or 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 other prespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restricted to patients in whom there is a clear antimicrobial indication., Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Influenced by Orientalist assumptions and Utilitarian ideals, and needing to enforce a system of adjudication that responded to their interests, the East India Company's officers selected among varied religious texts a set of norms and tried to apply them consistently. The decision to rely on texts rather than practice, the choice of certain precepts at the expense of others, and their rigid application ran counter to the traditional administration of justice, which had been fluid, contextual, and plural. They also distorted the meaning of Hanafi fiḳh, turning what had been an instrument of legitimation, a moral reference, and a source of social standing into a system of organized dispute settlement. The emphasis on religious textual sources and the attempt to use them as a basis for codification coincided with the idea, which gained ground in the nineteenth century among Muslim reformist movements, that political weakness could be countered by returning to a pristine scripturalist Islam, focused on its legal aspects and seen as a systematic doctrine devoid of ambiguities. These ideas can be also found in the Islamist thought that subsequently spread among urban reformist movements and in legal reforms adopted in Pakistan. A review of case studies, however, suggests that the flexibility and contextuality that characterized the enforcement of Islamic law in precolonial Islam is still to be found in legal practice. [ABSTRACT FROM AUTHOR]

Objective An international, non-randomised study evaluated efficacy and safety of risperidone long-acting injectable (RLAI) compared to previous treatment. To investigate generisability of the European data set to the UK subset safety and switching data are reported here. Methods Patients with schizophrenia or other psychotic disorder, symptomatically stable on antipsychotic medication, received intramuscular injections of RLAI 25 mg (to a maximum of 50 mg) every 2 weeks for 6 months. Results Of 182 UK patients enrolled, 79% had schizophrenia, 21% other psychotic disorders. Insufficient efficacy (43%), side effects (45%), and non-compliance (25%) were the most common reasons for switching. Sixty-nine per cent of patients completed the trial; 8% discontinued due to adverse events (AEs). Most frequent treatment-emergent AEs were headache (8.2%), relapse (7.7%) and insomnia (7.1%); 8 (4.4%) patients reported injection-related AEs. There were significant improvements in extrapyramidal symptom rating scale total and subscale (particularly Parkinsonism) scores, regardless of previous medication (total cohort, p≤0.0001). There was a small but significant increase in body weight at endpoint (1.2kg, p = 0.0023). One patient suffered a myocardial infarction and died (not treatment-related). There were no substantial differences between the full data set and the UK sub-population Conclusion Switch to RLAI was well-tolerated in stable patients over 6 months. The European data set is generalisable to the UK patient population. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]