Genomic characteristics and clinical effect of the emergent SARS-CoV-2 B.1.1.7 lineage in London, UK: a whole-genome sequencing and hospital-based cohort study.

BACKGROUND: Emergence of variants with specific mutations in key epitopes in the spike protein of SARS-CoV-2 raises concerns pertinent to mass vaccination campaigns and use of monoclonal antibodies. We aimed to describe the emergence of the B.1.1.7 variant of concern (VOC), including virological characteristics and clinical severity in contemporaneous patients with and without the variant. METHODS: In this cohort study, samples positive for SARS-CoV-2 on PCR that were collected from Nov 9, 2020, for patients acutely admitted to one of two hospitals on or before Dec 20, 2020, in London, UK, were sequenced and analysed for the presence of VOC-defining mutations. We fitted Poisson regression models to investigate the association between B.1.1.7 infection and severe disease (defined as point 6 or higher on the WHO ordinal scale within 14 days of symptoms or positive test) and death within 28 days of a positive test and did supplementary genomic analyses in a cohort of chronically shedding patients and in a cohort of remdesivir-treated patients. Viral load was compared by proxy, using PCR cycle threshold values and sequencing read depths. FINDINGS: Of 496 patients with samples positive for SARS-CoV-2 on PCR and who met inclusion criteria, 341 had samples that could be sequenced. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. We found no evidence of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio [PR] 0·97 [95% CI 0·72-1·31]), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 [0·76-1·38]). We detected no B.1.1.7 VOC-defining mutations in 123 chronically shedding immunocompromised patients or in 32 remdesivir-treated patients. Viral load by proxy was higher in B.1.1.7 samples than in non-B.1.1.7 samples, as measured by cycle threshold value (mean 28·8 [SD 4·7] vs 32·0 [4·8]; p=0·0085) and genomic read depth (1280 [1004] vs 831 [682]; p=0·0011). INTERPRETATION: Emerging evidence exists of increased transmissibility of B.1.1.7, and we found increased virus load by proxy for B.1.1.7 in our data. We did not identify an association of the variant with severe disease in this hospitalised cohort. FUNDING: University College London Hospitals NHS Trust, University College London/University College London Hospitals NIHR Biomedical Research Centre, Engineering and Physical Sciences Research Council.

Online patient simulation training to improve clinical reasoning: a feasibility randomised controlled trial.

BACKGROUND: Online patient simulations (OPS) are a novel method for teaching clinical reasoning skills to students and could contribute to reducing diagnostic errors. However, little is known about how best to implement and evaluate OPS in medical curricula. The aim of this study was to assess the feasibility, acceptability and potential effects of eCREST - the electronic Clinical Reasoning Educational Simulation Tool. METHODS: A feasibility randomised controlled trial was conducted with final year undergraduate students from three UK medical schools in academic year 2016/2017 (cohort one) and 2017/2018 (cohort two). Student volunteers were recruited in cohort one via email and on teaching days, and in cohort two eCREST was also integrated into a relevant module in the curriculum. The intervention group received three patient cases and the control group received teaching as usual; allocation ratio was 1:1. Researchers were blind to allocation. Clinical reasoning skills were measured using a survey after 1 week and a patient case after 1 month. RESULTS: Across schools, 264 students participated (18.2% of all eligible). Cohort two had greater uptake (183/833, 22%) than cohort one (81/621, 13%). After 1 week, 99/137 (72%) of the intervention and 86/127 (68%) of the control group remained in the study. eCREST improved students' ability to gather essential information from patients over controls (OR = 1.4; 95% CI 1.1-1.7, n = 148). Of the intervention group, most (80/98, 82%) agreed eCREST helped them to learn clinical reasoning skills. CONCLUSIONS: eCREST was highly acceptable and improved data gathering skills that could reduce diagnostic errors. Uptake was low but improved when integrated into course delivery. A summative trial is needed to estimate effectiveness.

The GP tests of competence assessment: which part best predicts fitness to practise decisions?

BACKGROUND: The General Medical Council (GMC) conducts Tests of Competence (ToC) for doctors referred for Fitness to Practise (FtP) issues. GPs take a single best answer knowledge test, an Objective Structured Clinical Examination (OSCE), and a Simulated Surgery (SimSurg) assessment which is a simulated GP consultation. The aim of this study was to examine the similarities between OSCEs and SimSurg to determine whether each assessment contributed something unique to GP ToCs. METHODS: A mixed methods approach was used. Data were collated on 153 GPs who were required to undertake a ToC as a part of being investigated for FtP issues between February 2010 and October 2016. Using correlation analysis, we examined to what degree performance on the knowledge test, OSCE, and SimSurg related to case examiner recommendations and FtP outcomes, including the unique predictive power of these three assessments. The outcome measures were case examiner recommendations (i) not fit to practise; ii) fit to practise on a limited basis; or iii) fit to practise) as well as FtP outcomes (i) erased/removed from the register; ii) having restrictions/conditions; or iii) be in good standing). For the qualitative component, 45 GP assessors were asked to rate whether they assess the same competencies and which assessment provides better feedback about candidates. RESULTS: There was significant overlap between OSCEs and SimSurg, p < 0.001. SimSurg had additional predictive power in the presence of OSCEs and the knowledge test (p = 0.030) in distinguishing doctors from different FtP categories, while OSCEs did not (p = 0.080). Both the OSCEs (p = 0.004) and SimSurg (p < 0.001) had significant negative correlations with case examiner recommendations when accounting for the effects of the other two assessments. Inductive thematic analysis of the responses to the questionnaire showed that assessors perceived OSCEs to be better suited to target specific knowledge and skills. SimSurg was thought to produce a more global picture as the scenarios more accurately portray a patient consultation. CONCLUSION: While all three assessments are strong predictors of both case examiner recommendations and FtP outcomes, our findings suggest that the efficiency of GP ToCs can be improved by removing some of this overlapping content.