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.

ObjectivesStudy objectives were to investigate the prevalence and causes of prescribing errors amongst foundation doctors (i.e. junior doctors in their first (F1) or second (F2) year of post-graduate training), describe their knowledge and experience of prescribing errors, and explore their self-efficacy (i.e. confidence) in prescribing.MethodA three-part mixed-methods design was used, comprising: prospective observational study; semi-structured interviews and cross-sectional survey. All doctors prescribing in eight purposively selected hospitals in Scotland participated. All foundation doctors throughout Scotland participated in the survey. The number of prescribing errors per patient, doctor, ward and hospital, perceived causes of errors and a measure of doctors' self-efficacy were established.Results4710 patient charts and 44,726 prescribed medicines were reviewed. There were 3364 errors, affecting 1700 (36.1%) charts (overall error rate: 7.5%; F1:7.4%; F2:8.6%; consultants:6.3%). Higher error rates were associated with : teaching hospitals (p<0.001), surgical (p = <0.001) or mixed wards (0.008) rather thanmedical ward, higher patient turnover wards (p<0.001), a greater number of prescribed medicines (p<0.001) and the months December and June (p<0.001). One hundred errors were discussed in 40 interviews. Error causation was multi-factorial; work environment and team factors were particularly noted. Of 548 completed questionnaires (national response rate of 35.4%), 508 (92.7% of respondents) reported errors, most of which (328 (64.6%) did not reach the patient. Pressure from other staff, workload and interruptions were cited as the main causes of errors. Foundation year 2 doctors reported greater confidence than year 1 doctors in deciding the most appropriate medication regimen.ConclusionsPrescribing errors are frequent and of complex causation. Foundation doctors made more errors than other doctors, but undertook the majority of prescribing, making them a key target for intervention. Contributing causes included work environment, team, task, individual and patient factors. Further work is needed to develop and assess interventions that address these.

BackgroundPrescribing errors are a major source of morbidity and mortality and represent a significant patient safety concern. Evidence suggests that trainee doctors are responsible for most prescribing errors. Understanding the factors that influence prescribing behavior may lead to effective interventions to reduce errors. Existing investigations of prescribing errors have been based on Human Error Theory but not on other relevant behavioral theories. The aim of this study was to apply a broad theory-based approach using the Theoretical Domains Framework (TDF) to investigate prescribing in the hospital context among a sample of trainee doctors.MethodSemistructured interviews, based on 12 theoretical domains, were conducted with 22 trainee doctors to explore views, opinions, and experiences of prescribing and prescribing errors. Content analysis was conducted, followed by applying relevance criteria and a novel stage of critical appraisal, to identify which theoretical domains could be targeted in interventions to improve prescribing.ResultsSeven theoretical domains met the criteria of relevance: “social professional role and identity,” “environmental context and resources,” “social influences,” “knowledge,” “skills,” “memory, attention, and decision making,” and “behavioral regulation.” From critical appraisal of the interview data, “beliefs about consequences” and “beliefs about capabilities” were also identified as potentially important domains. Interrelationships between domains were evident. Additionally, the data supported theoretical elaboration of the domain behavioral regulation.ConclusionsIn this investigation of hospital-based prescribing, participants’ attributions about causes of errors were used to identify domains that could be targeted in interventions to improve prescribing. In a departure from previous TDF practice, critical appraisal was used to identify additional domains that should also be targeted, despite participants’ perceptions that they were not relevant to prescribing errors. These were beliefs about consequences and beliefs about capabilities. Specifically, in the light of the documented high error rate, beliefs that prescribing errors were not likely to have consequences for patients and that trainee doctors are capable of prescribing without error should also be targeted in an intervention. This study is the first to suggest critical appraisal for domain identification and to use interview data to propose theoretical elaborations and interrelationships between domains.

Introduction

No abstract

What is already known about this subject • In the UK prescribing-related errors are common.• Poor prescribing and prescribing errors result in significant patient morbidity and mortality.• In hospital, junior doctors are responsible for a significant number of prescribing errors. AimsTo determine whether, in retrospect, first year foundation (FY1) programme doctors believe that their undergraduate education in Clinical Pharmacology and Therapeutics (CPT) has prepared them to prescribe safely and rationally. MethodsThis was a prospective questionnaire survey. Ninety FY1 doctors, employed in the Aberdeen Teaching Hospitals, participated. ResultsSeventy-one percent of FY1 doctors completed the survey. Thirty percent of respondents rated their knowledge of CPT as poor or worse and only 8% as good; 74% reported having witnessed an adverse drug reaction (ADR) and 55% a drug-drug interaction, a number of which had resulted in patient morbidity or mortality. Many of these events were reported to have been avoidable or predictable with more extensive undergraduate and postgraduate training. Forty-two percent of respondents stated that they had not been taught enough about avoiding ADRs and 60% about avoiding drug-drug interactions during their undergraduate years. Over 75% of respondents reported high levels of confidence for the unsupervised use of warfarin, nonsteroidal analgesics and opiate analgesics. In retrospect, FY1 doctors would like more undergraduate teaching in prescribing for special patient groups, ADRs, drug interactions, together with CPT in their postgraduate teaching programme. ConclusionsFY1 doctors believe that their undergraduate and postgraduate training in CPT is insufficient to prescribe safely and rationally. This study adds further weight to the call for an increase in the training of junior doctors in the rational and safe use of medicines.

No abstract

AimTo identify experience with and attitudes towards paediatric off-label prescribing in primary care. MethodA prospective questionnaire survey was sent to a sample of Scottish primary care practices (346 doctors in 80 general practices located throughout Scotland). ResultsTwo hundred and two (58%) completed questionnaires were returned. Over 70% of GPs admitted to being familiar with the concept, and 40% to knowingly prescribing off-label. The most important sources of paediatric prescribing information were the British National Formulary (81%), personal experience (71%) and previous prescription notes (45%). The most common reason given by GPs for off-label prescribing was prescribing for a younger age than recommended, although prescribing data confirm that age is the least important and dose the most important reason for such prescribing. When asked to comment upon different causes for off-label prescribing, 80% of respondents expressed appropriate awareness of and concern for the described scenarios. Over 97% of GPs ranked development of paediatric formulations and clearer dosage information more highly than clinical trials as a means to reducing off-label prescribing. ConclusionsDespite high levels of off-label prescribing in primary care in the U K, the majority of GPs claimed to be familiar with the concept, although less than half were aware of this common practice. A clear disparity between perceived and actual reasons for offlabel prescribing was noted, possibly due to a reliance on personal experience, colleague experience or previous patient prescription notes as a guide to prescribing.