Effect of Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Initiation on Organ Support-Free Days in Patients Hospitalized With COVID-19: A Randomized Clinical Trial.

IMPORTANCE: Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective: To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS: In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non-critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS: Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES: The primary outcome was organ support-free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS: On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support-free days among critically ill patients was 10 (-1 to 16) in the ACE inhibitor group (n = 231), 8 (-1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support-free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE: In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02735707.

Pandemic Proof Property Companies

Using a sample of 163 U.S. based equity real estate investment trusts (REITs), this paper explores the consequences of COVID-19 on securitized commercial property markets. More specifically, we first map the geographic location of each firm’s investment property holdings to gauge the degree of exposure of each REIT’s asset base to the pandemic. We next demonstrate these firm level exposure metrics are directly related to the negative returns encountered by REITs in the early months of the pandemic and explore what firm specific characteristics and attributes (notably financial flexibility and financing constraints) may moderate this relation and enhance the resiliency of their equity returns. Finally, we examine the impact of the Federal Reserve’s late-March intervention designed to address and soften the economic fallout of the pandemic and ensure the liquidity and stability of capital markets. After this intervention, previously observed relations and patterns between firm specific COVID-exposure levels and operating characteristics fail to retain their prior signs and significance. In sum, the magnitude of the government’s response to the economic challenges brought about by the coronavirus pandemic is shown to outweigh the importance of firm specific factors in predicting the resiliency of REIT returns during this crisis period.

Incidence and factors related to SARS-CoV-2 infection in a cohort of patients with rheumatoid arthritis from a health service provider in Colombia during the COVID-19 pandemic.

Background: Patients with rheumatoid arthritis (RA) have an increased risk of SARS-CoV-2 infection due to intrinsic characteristics of the pathology and the medications used to treat it. The aim was to evaluate the incidence of and factors related to SARS-CoV-2 infection in patients with RA in Colombia. Methods: This was an observational study of patients diagnosed with RA who were treated at a health care institution in Colombia. The study evaluated whether the patients presented SARS-CoV-2 infection and other clinical variables. Variables associated with the risk of SARS-CoV-2 infection were identified. Results: A total of 2566 patients with RA were identified. They had a median age of 61.9 years, and 81.1% were women. They were mainly treated with synthetic disease-modifying antirheumatic drugs (DMARDs) (85.3%), glucocorticoids (52.2%), and biological DMARDs (26.8%). The incidence of SARS-CoV-2 infection was 5.1%, and the factors that increased the risk included treatment with synthetic DMARDs with or without biological DMARDs but with concomitant systemic glucocorticoids [odds ratio (OR): 2.18, 95% confidence interval (CI): 1.21-3.93 and OR: 1.69, 95% CI: 1.05-2.74, respectively] and receiving antidiabetic drugs (OR: 2.24, 95% CI: 1.27-3.94). A total of 20.8% of patients with COVID-19 required hospitalization and 3.8% died. Conclusion: The incidence of COVID-19 is higher among patients with RA who receive DMARDs and glucocorticoids simultaneously or who have diabetes mellitus than among patients with RA not receiving these drug combinations, which should guide treatment strategies.

Exploring Perceptions of a Fresh Food Prescription Program during COVID-19.

This qualitative study aimed to elicit the perspectives of individuals with food insecurity (FI) who were enrolled in a Fresh Food Prescription (FFRx) delivery program through a collaboration between an academic medical center and multiple community partners in the southeastern United States. Semi-structured interviews and open-ended survey responses explored the experiences of participants enrolled in a FFRx delivery program during the COVID-19 pandemic. The interviews probed the shopping habits, food security, experience, and impact of the program on nutrition, health, and well-being; the surveys explored the perceptions of and satisfaction with the program. A coding scheme was developed inductively, and a thematic analysis was conducted on raw narrative data using Atlas.ti 8.4 to sort and manage the data. The themes included that the program promoted healthy dietary habits, improved access to high-quality foods, improved well-being, enhanced financial well-being, and alleviated logistical barriers to accessing food and cooking. Participants provided suggestions for FFRx improvement. Future studies may facilitate improved clinical-community partnerships to address FI.

Strategies and Lessons Learned from a Home Delivery Food Prescription Program for Older Adults.

Food insecurity (FI) is a growing health problem, worsening during the COVID-19 pandemic. Fresh food prescription programs (FFRx) have been shown to increase healthy eating and decrease FI, but few FFRx are community-informed, or theory based. Our FFRx was a delivery program developed to alleviate FI for older adults. It was implemented in an academic medical center and guided by the Capabilities, Opportunities, Motivations, and Behaviors and Theoretical Domains Framework. We tested impacts of the program on FI, Fruit and Vegetable (FV) intake, depression, and loneliness at six-month intervals. During the FFRx, 31 people completed surveys every six months. FI decreased by an average of 2.03 points (p = <.001) while FV intake increased from a mean of 2.8 servings per day to 2.9 servings per day (p = .53). Depression and loneliness scores stayed stable. Preliminary data from this FFRx program, a partnership between an academic medical center and community partners, had positive impacts on FI.

Risk of severe COVID-19 outcomes associated with immune-mediated inflammatory diseases and immune-modifying therapies: a nationwide cohort study in the OpenSAFELY platform.

Background: The risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases and on immune-modifying drugs might not be fully mediated by comorbidities and might vary by factors such as ethnicity. We aimed to assess the risk of severe COVID-19 in adults with immune-mediated inflammatory diseases and in those on immune-modifying therapies. Methods: We did a cohort study, using OpenSAFELY (an analytics platform for electronic health records) and TPP (a software provider for general practitioners), analysing routinely collected primary care data linked to hospital admission, death, and previously unavailable hospital prescription data. We included people aged 18 years or older on March 1, 2020, who were registered with TPP practices with at least 12 months of primary care records before March, 2020. We used Cox regression (adjusting for confounders and mediators) to estimate hazard ratios (HRs) comparing the risk of COVID-19-related death, critical care admission or death, and hospital admission (from March 1 to Sept 30, 2020) in people with immune-mediated inflammatory diseases compared with the general population, and in people with immune-mediated inflammatory diseases on targeted immune-modifying drugs (eg, biologics) compared with those on standard systemic treatment (eg, methotrexate). Findings: We identified 17 672 065 adults; 1 163 438 adults (640 164 [55·0%] women and 523 274 [45·0%] men, and 827 457 [71·1%] of White ethnicity) had immune-mediated inflammatory diseases, and 16 508 627 people (8 215 020 [49·8%] women and 8 293 607 [50·2%] men, and 10 614 096 [64·3%] of White ethnicity) were included as the general population. Of 1 163 438 adults with immune-mediated inflammatory diseases, 19 119 (1·6%) received targeted immune-modifying therapy and 181 694 (15·6%) received standard systemic therapy. Compared with the general population, adults with immune-mediated inflammatory diseases had an increased risk of COVID-19-related death after adjusting for confounders (age, sex, deprivation, and smoking status; HR 1·23, 95% CI 1·20-1·27) and further adjusting for mediators (body-mass index [BMI], cardiovascular disease, diabetes, and current glucocorticoid use; 1·15, 1·11-1·18). Adults with immune-mediated inflammatory diseases also had an increased risk of COVID-19-related critical care admission or death (confounder-adjusted HR 1·24, 95% CI 1·21-1·28; mediator-adjusted 1·16, 1·12-1·19) and hospital admission (confounder-adjusted 1·32, 1·29-1·35; mediator-adjusted 1·20, 1·17-1·23). In post-hoc analyses, the risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases was higher in non-White ethnic groups than in White ethnic groups (as it was in the general population). We saw no evidence of increased COVID-19-related death in adults on targeted, compared with those on standard systemic, therapy after adjusting for confounders (age, sex, deprivation, BMI, immune-mediated inflammatory diseases [bowel, joint, and skin], cardiovascular disease, cancer [excluding non-melanoma skin cancer], stroke, and diabetes (HR 1·03, 95% CI 0·80-1·33), and after additionally adjusting for current glucocorticoid use (1·01, 0·78-1·30). There was no evidence of increased COVID-19-related death in adults prescribed tumour necrosis factor inhibitors, interleukin (IL)-12/IL­23 inhibitors, IL-17 inhibitors, IL-6 inhibitors, or Janus kinase inhibitors compared with those on standard systemic therapy. Rituximab was associated with increased COVID-19-related death (HR 1·68, 95% CI 1·11-2·56), with some attenuation after excluding people with haematological malignancies or organ transplants (1·54, 0·95-2·49). Interpretation: COVID-19 deaths and hospital admissions were higher in people with immune-mediated inflammatory diseases. We saw no increased risk of adverse COVID-19 outcomes in those on most targeted immune-modifying drugs for immune-mediated inflammatory diseases compared with those on standard systemic therapy. Funding: UK Medical Research Council, NIHR Biomedical Research Centre at King's College London and Guy's and St Thomas' NHS Foundation Trust, and Wellcome Trust.

Exploring and Addressing the User Acceptance Issues Embedded in the Adoption of Reusable Packaging Systems

Plastic in the linear consumption model is frequently manufactured and disposed of, leading to the creation of excessive plastic waste, which has significant consequences for the environment. Single-use food packaging waste is a large constituent of plastic waste that needs to be addressed urgently. The implementation of reusable packaging systems (RPSs) to close the loop of consumption appears to be promising, but the insights into consumers’ willingness to accept them are limited. This research investigates the aspect of consumers’ adoption of RPSs by identifying the particular user acceptance issues and eventually providing a set of design recommendations to address them. The data collection methods are remote interviews, engaging with 42 participants in three iterations, to evaluate three user experiences of RPSs in order to identify the user acceptance issues. After the user acceptance issues are identified in each iteration, the Theory of Attitude-Behaviour-Context is employed to advance the understanding of the acceptance issues. In order to continuously refine the user experiences, insights from design for sustainable behaviour are applied to address the user acceptance issues. The research results include three refined user experiences, four user acceptance issues—namely hygiene, usability, finance and motivation—and design recommendations to address those user acceptance issues. This research may be of interest to packaging professionals, and could be used to design and refine the RPSs to induce consumers’ adoption.

Understanding crisis resilience in manufacturing firms in the DACH region during the COVID-19 pandemic

Purpose>This paper describes the impact of COVID-19 on manufacturing firms in the DACH region of Europe (DACH is an acronym used to describe Germany, Austria and Switzerland). The purpose of the study was threefold: first to describe crisis resilience empirically through the actions taken by the firms using the elements of resilience;the paper then goes on to compare the DACH region with Northern Italy;finally, based on the findings, an existing crisis management model is expanded.Design/methodology/approach>A mixed method of quantitative research based on survey data and qualitative interviews was applied for data collection. The findings are based on 57 survey results and 13 interviews from December 2020 to March 2021. The findings are presented based on the resilience elements and are discussed based on processes, technologies and people. The findings are compared with those from an Italian study made 6–9 months before this study. The comparison provides the basis for the adaptations to the crisis management model.Findings>The findings describe the actions taken by firms in the DACH region to overcome the challenges posed by COVID-19. The findings were, in most cases, very similar to those from the Italian study. The most resilient firms had well-defined processes in place, adaptable employees who were well-led, and had (digital) technologies that could be quickly implemented.Originality/value>The timing for the crisis was later in the DACH region and firms were able to learn from Italy. The crisis management model based on the Italian study was refined;the resulting model will support managers to face future crises. This model needs testing and extending to link to past and future events.

DNA-PK(cs) Regulates Stability of Egr1 During T Cell Activation

IMPACT: This work provides supporting evidence for the development of a novel immunosuppression therapy for transplant patients. OBJECTIVES/GOALS: Our laboratory reported that inhibition of the kinase DNA-PK(cs) in mice delays allogeneic graft rejection in part by mitigating the induction of certain cytokines. We hypothesized that this was due to an inhibition of intracellular signaling programs in T cells and designed studies to identify the mechanism(s) by which this occurs. METHODS/STUDY POPULATION: The immortalized Jurkat T cell line was used to evaluate the effect of the DNA-PK(cs) inhibitor NU7441 on T cell activation by PMA/Ionomycin or PMA/PHA. Mouse primary splenocytes also were used to demonstrate the universality and reproducibility of our observations. Initially, protein mass spectrometry of lysates from untreated and NU7441-treated Jurkat cells identified proteins of interest regulated by DNA-PK(cs) that play a role in T cell activation and cytokine production. CRISPR genome editing was used to validate a potential downstream target of DNA-PK(cs). Western blot, ELISA, and flow cytometry were used to document changes in protein levels with respect to treatments. RESULTS/ANTICIPATED RESULTS: We observed that expression of the transcription factor Egr1 was highly induced after activation but attenuated after treatment with NU7441 in both Jurkat T cells and mouse splenocytes. Phosphorylated serine 301 of Egr1 was identified by mass spectrometry in stimulated cells and fits the kinase consensus sequence for DNA-PK(cs). Both an endogenous CRISPR-generated serine 301 to alanine mutant and expression of a plasmid-based S301A mutant resulted in an unstable form of Egr1 that was barely detectable. In contrast, expression of either a S301 to D or E phospho-mimetic mutant resulted in a stable form of the protein detectable by Western blot. Further evaluation of these mutants and Egr1 phosphorylation is underway to determine the mechanism by which DNA-PK(cs) kinase regulates protein stability. DISCUSSION/SIGNIFICANCE OF FINDINGS: We previously reported a role for DNA-PK(cs) in immunomodulation. We now have evidence that this occurs in part through stabilization of Egr1. We believe this novel finding will lead to uncovering a broader role for DNA-PK(cs) as a mediator of protein stability in T cells and provide support for targeting DNA-PK(cs) in immunosuppression therapy.

Association between smoking, e-cigarette use and severe COVID-19: a cohort study.

BACKGROUND: Smoking is a risk factor for most respiratory infections, but it may protect against SARS-CoV-2 infection. The objective was to assess whether smoking and e-cigarette use were associated with severe COVID-19. METHODS: This cohort ran from 24 January 2020 until 30 April 2020 at the height of the first wave of the SARS-CoV-2 epidemic in England. It comprised 7 869 534 people representative of the population of England with smoking status, demographic factors and diseases recorded by general practitioners in the medical records, which were linked to hospital and death data. The outcomes were COVID-19-associated hospitalization, intensive care unit (ICU) admission and death. The associations between smoking and the outcomes were assessed with Cox proportional hazards models, with sequential adjustment for confounding variables and indirect causal factors (body mass index and smoking-related disease). RESULTS: Compared with never smokers, people currently smoking were at lower risk of COVID-19 hospitalization, adjusted hazard ratios (HRs) were 0.64 (95% confidence intervals 0.60 to 0.69) for <10 cigarettes/day, 0.49 (0.41 to 0.59) for 10-19 cigarettes/day, and 0.61 (0.49 to 0.74) for ≥20 cigarettes/day. For ICU admission, the corresponding HRs were 0.31 (0.24 to 0.40), 0.15 (0.06 to 0.36), and 0.35 (0.17 to 0.74) and death were: 0.79 (0.70 to 0.89), 0.66 (0.48 to 0.90), and 0.77 (0.54 to 1.09) respectively. Former smokers were at higher risk of severe COVID-19: HRs: 1.07 (1.03 to 1.11) for hospitalization, 1.17 (1.04 to 1.31) for ICU admission, and 1.17 (1.10 to 1.24) for death. All-cause mortality was higher for current smoking than never smoking, HR 1.42 (1.36 to 1.48). Among e-cigarette users, the adjusted HR for e-cigarette use and hospitalization with COVID-19 was 1.06 (0.88 to 1.28), for ICU admission was 1.04 (0.57 to 1.89, and for death was 1.12 (0.81 to 1.55). CONCLUSIONS: Current smoking was associated with a reduced risk of severe COVID-19 but the association with e-cigarette use was unclear. All-cause mortality remained higher despite this possible reduction in death from COVID-19 during an epidemic of SARS-CoV-2. Findings support investigating possible protective mechanisms of smoking for SARS-CoV-2 infection, including the ongoing trials of nicotine to treat COVID-19.

Does Unprecedented ICU Capacity Strain, As Experienced During the COVID-19 Pandemic, Impact Patient Outcome?

OBJECTIVES: To determine whether patients admitted to an ICU during times of unprecedented ICU capacity strain, during the COVID-19 pandemic in the United Kingdom, experienced a higher risk of death. DESIGN: Multicenter, observational cohort study using routine clinical audit data. SETTING: Adult general ICUs participating the Intensive Care National Audit & Research Centre Case Mix Programme in England, Wales, and Northern Ireland. PATIENTS: One-hundred thirty-thousand six-hundred eighty-nine patients admitted to 210 adult general ICUs in 207 hospitals. INTERVENTIONS: Multilevel, mixed effects, logistic regression models were used to examine the relationship between levels of ICU capacity strain on the day of admission (typical low, typical, typical high, pandemic high, and pandemic extreme) and risk-adjusted hospital mortality. MEASUREMENTS AND MAIN RESULTS: In adjusted analyses, compared with patients admitted during periods of typical ICU capacity strain, we found that COVID-19 patients admitted during periods of pandemic high or pandemic extreme ICU capacity strain during the first wave had no difference in hospital mortality, whereas those admitted during the pandemic high or pandemic extreme ICU capacity strain in the second wave had a 17% (odds ratio [OR], 1.17; 95% CI, 1.05-1.30) and 15% (OR, 1.15; 95% CI, 1.00-1.31) higher odds of hospital mortality, respectively. For non-COVID-19 patients, there was little difference in trend between waves, with those admitted during periods of pandemic high and pandemic extreme ICU capacity strain having 16% (OR, 1.16; 95% CI, 1.08-1.25) and 30% (OR, 1.30; 95% CI, 1.14-1.48) higher overall odds of acute hospital mortality, respectively. CONCLUSIONS: For patients admitted to ICU during the pandemic, unprecedented levels of ICU capacity strain were significantly associated with higher acute hospital mortality, after accounting for differences in baseline characteristics. Further study into possible differences in the provision of care and outcome for COVID-19 and non-COVID-19 patients is needed.

Impact of the COVID-19 pandemic on in-hospital cardiac arrests in the UK.

AIMS: To compare in-hospital cardiac arrest (IHCA) rates and patient outcomes during the first COVID-19 wave in the United Kingdom (UK) in 2020 with the same period in previous years. METHODS: A retrospective, multicentre cohort study of 154 UK hospitals that participate in the National Cardiac Arrest Audit and have intensive care units participating in the Case Mix Programme national audit of intensive care. Hospital burden of COVID-19 was defined by the number of patients with confirmed SARS-CoV2 infection admitted to critical care per 10,000 hospital admissions. RESULTS: 16,474 patients with IHCA where a resuscitation team attended were included. Patients admitted to hospital during 2020 were younger, more often male, and of non-white ethnicity compared with 2016-2019. A decreasing trend in IHCA rates between 2016 and 2019 was reversed in 2020. Hospitals with higher burden of COVID-19 had the greatest difference in IHCA rates (21.8 per 10,000 admissions in April 2020 vs 14.9 per 10,000 in April 2019). The proportions of patients achieving ROSC ≥ 20 min and surviving to hospital discharge were lower in 2020 compared with 2016-19 (46.2% vs 51.2%; and 21.9% vs 22.9%, respectively). Among patients with IHCA, higher hospital burden of COVID-19 was associated with reduced survival to hospital discharge (OR = 0.95; 95% CI 0.93 to 0.98; p < 0.001). CONCLUSIONS: In comparison with 2016-2019, the first COVID-19 wave in 2020 was associated with a higher rate of IHCA and decreased survival among patients attended by resuscitation teams. These changes were greatest in hospitals with the highest COVID-19 burden.

Mortality and critical care unit admission associated with the SARS-CoV-2 lineage B.1.1.7 in England: an observational cohort study.

BACKGROUND: A more transmissible variant of SARS-CoV-2, the variant of concern 202012/01 or lineage B.1.1.7, has emerged in the UK. We aimed to estimate the risk of critical care admission, mortality in patients who are critically ill, and overall mortality associated with lineage B.1.1.7 compared with non-B.1.1.7. We also compared clinical outcomes between these two groups. METHODS: For this observational cohort study, we linked large primary care (QResearch), national critical care (Intensive Care National Audit & Research Centre Case Mix Programme), and national COVID-19 testing (Public Health England) databases. We used SARS-CoV-2 positive samples with S-gene molecular diagnostic assay failure (SGTF) as a proxy for the presence of lineage B.1.1.7. We extracted two cohorts from the data: the primary care cohort, comprising patients in primary care with a positive community COVID-19 test reported between Nov 1, 2020, and Jan 26, 2021, and known SGTF status; and the critical care cohort, comprising patients admitted for critical care with a positive community COVID-19 test reported between Nov 1, 2020, and Jan 27, 2021, and known SGTF status. We explored the associations between SARS-CoV-2 infection with and without lineage B.1.1.7 and admission to a critical care unit (CCU), 28-day mortality, and 28-day mortality following CCU admission. We used Royston-Parmar models adjusted for age, sex, geographical region, other sociodemographic factors (deprivation index, ethnicity, household housing category, and smoking status for the primary care cohort; and ethnicity, body-mass index, deprivation index, and dependency before admission to acute hospital for the CCU cohort), and comorbidities (asthma, chronic obstructive pulmonary disease, type 1 and 2 diabetes, and hypertension for the primary care cohort; and cardiovascular disease, respiratory disease, metastatic disease, and immunocompromised conditions for the CCU cohort). We reported information on types and duration of organ support for the B.1.1.7 and non-B.1.1.7 groups. FINDINGS: The primary care cohort included 198 420 patients with SARS-CoV-2 infection. Of these, 117 926 (59·4%) had lineage B.1.1.7, 836 (0·4%) were admitted to CCU, and 899 (0·4%) died within 28 days. The critical care cohort included 4272 patients admitted to CCU. Of these, 2685 (62·8%) had lineage B.1.1.7 and 662 (15·5%) died at the end of critical care. In the primary care cohort, we estimated adjusted hazard ratios (HRs) of 2·15 (95% CI 1·75-2·65) for CCU admission and 1·65 (1·36-2·01) for 28-day mortality for patients with lineage B.1.1.7 compared with the non-B.1.1.7 group. The adjusted HR for mortality in critical care, estimated with the critical care cohort, was 0·91 (0·76-1·09) for patients with lineage B.1.1.7 compared with those with non-B.1.1.7 infection. INTERPRETATION: Patients with lineage B.1.1.7 were at increased risk of CCU admission and 28-day mortality compared with patients with non-B.1.1.7 SARS-CoV-2. For patients receiving critical care, mortality appeared to be independent of virus strain. Our findings emphasise the importance of measures to control exposure to and infection with COVID-19. FUNDING: Wellcome Trust, National Institute for Health Research Oxford Biomedical Research Centre, and the Medical Sciences Division of the University of Oxford.

Predictive validity of A-level grades and teacher-predicted grades in UK medical school applicants: a retrospective analysis of administrative data in a time of COVID-19.

OBJECTIVES: To compare in UK medical students the predictive validity of attained A-level grades and teacher-predicted A levels for undergraduate and postgraduate outcomes. Teacher-predicted A-level grades are a plausible proxy for the teacher-estimated grades that replaced UK examinations in 2020 as a result of the COVID-19 pandemic. The study also models the likely future consequences for UK medical schools of replacing public A-level examination grades with teacher-predicted grades. DESIGN: Longitudinal observational study using UK Medical Education Database data. SETTING: UK medical education and training. PARTICIPANTS: Dataset 1: 81 202 medical school applicants in 2010-2018 with predicted and attained A-level grades. Dataset 2: 22 150 18-year-old medical school applicants in 2010-2014 with predicted and attained A-level grades, of whom 12 600 had medical school assessment outcomes and 1340 had postgraduate outcomes available. OUTCOME MEASURES: Undergraduate and postgraduate medical examination results in relation to attained and teacher-predicted A-level results. RESULTS: Dataset 1: teacher-predicted grades were accurate for 48.8% of A levels, overpredicted in 44.7% of cases and underpredicted in 6.5% of cases. Dataset 2: undergraduate and postgraduate outcomes correlated significantly better with attained than with teacher-predicted A-level grades. Modelling suggests that using teacher-estimated grades instead of attained grades will mean that 2020 entrants are more likely to underattain compared with previous years, 13% more gaining the equivalent of the lowest performance decile and 16% fewer reaching the equivalent of the current top decile, with knock-on effects for postgraduate training. CONCLUSIONS: The replacement of attained A-level examination grades with teacher-estimated grades as a result of the COVID-19 pandemic may result in 2020 medical school entrants having somewhat lower academic performance compared with previous years. Medical schools may need to consider additional teaching for entrants who are struggling or who might need extra support for missed aspects of A-level teaching.

Exploration of Psychological Resilience during a 25-Day Endurance Challenge in an Extreme Environment.

Psychological resilience is the ability to use personal qualities to withstand pressure, consisting of the interaction between the individual and the environment over time. It is essential when operating in extreme environments which are typically characterised by a complex combination of stressors with increased elements of risk and adversity. Psychological resilience has never been investigated "live" (e.g., in the moment) throughout the duration of an extreme endurance challenge, despite anecdotal accounts of the need for resilience to successfully function in such environments. The aim of the study was to explore psychological resilience with challenge team members (n = 4, mean age = 46.0 years) involved in a 25-day extreme endurance challenge. The object of the challenge was to 'TAB' (Tactical Advance to Battle, fast marching with weighted packs) 100 peaks in the UK in 25 days and complete long-distance bike rides between base camps. A mixed-methods approach with a focus on qualitative methods was utilised. Specifically, individual reflective video diaries (n = 47) and focus groups (n = 4) were completed and analysed using interpretative phenomenological analysis (IPA). At the same time, the 10-item Connor Davidson Resilience Scale was employed to measure resilience, which highlighted the individualised and dynamic nature of resilience. Two superordinate themes were identified from the video diaries and focus groups, namely, the identification of the stressors within extreme environments and strategies to maintain functioning. Stressors were split into subordinate themes of significant and every day, and collectively, they created a cluster effect which contributed to pressure associated with operating in these environments. Challenge team members employed various strategies to maintain functioning, including using a challenge mindset to positively appraise pressure as a challenging learning experience. Further research should continue to develop an understanding of how participants completing challenges within extreme environments utilise and develop personal qualities to maintain functioning.