The Covid-19 pandemic has placed unprecedented pressure on healthcare systems and workers around the world. Such pressures may impact on working conditions, psychological wellbeing and perception of safety. In spite of this, no study has assessed the relationship between safety attitudes and psychological outcomes. Moreover, only limited studies have examined the relationship between personal characteristics and psychological outcomes during Covid-19. From 22nd March 2020 to 18th June 2020, healthcare workers from the United Kingdom, Poland, and Singapore were invited to participate using a self-administered questionnaire comprising the Safety Attitudes Questionnaire (SAQ), Oldenburg Burnout Inventory (OLBI) and Hospital Anxiety and Depression Scale (HADS) to evaluate safety culture, burnout and anxiety/depression. Multivariate logistic regression was used to determine predictors of burnout, anxiety and depression. Of 3,537 healthcare workers who participated in the study, 2,364 (67%) screened positive for burnout, 701 (20%) for anxiety, and 389 (11%) for depression. Significant predictors of burnout included patient-facing roles: doctor (OR 2.10; 95% CI 1.49–2.95), nurse (OR 1.38; 95% CI 1.04–1.84), and ‘other clinical’ (OR 2.02; 95% CI 1.45–2.82); being redeployed (OR 1.27; 95% CI 1.02–1.58), bottom quartile SAQ score (OR 2.43; 95% CI 1.98–2.99), anxiety (OR 4.87; 95% CI 3.92–6.06) and depression (OR 4.06; 95% CI 3.04–5.42). Significant factors inversely correlated with burnout included being tested for SARS-CoV-2 (OR 0.64; 95% CI 0.51–0.82) and top quartile SAQ score (OR 0.30; 95% CI 0.22–0.40). Significant factors associated with anxiety and depression, included burnout, gender, safety attitudes and job role. Our findings demonstrate a significant burden of burnout, anxiety, and depression amongst healthcare workers. A strong association was seen between SARS-CoV-2 testing, safety attitudes, gender, job role, redeployment and psychological state. These findings highlight the importance of targeted support services for at risk groups and proactive SARS-CoV-2 testing of healthcare workers.

Covid-19 has placed an unprecedented demand on healthcare systems worldwide. A positive safety culture is associated with improved patient safety and, in turn, with patient outcomes. To date, no study has evaluated the impact of Covid-19 on safety culture. The Safety Attitudes Questionnaire (SAQ) was used to investigate safety culture at a large UK healthcare trust during Covid-19. Findings were compared with baseline data from 2017. Incident reporting from the year preceding the pandemic was also examined. SAQ scores of doctors and “other clinical staff”, were relatively higher than the nursing group. During Covid-19, on univariate regression analysis, female gender, age 40–49 years, non-White ethnicity, and nursing job role were all associated with lower SAQ scores. Training and support for redeployment were associated with higher SAQ scores. On multivariate analysis, non-disclosed gender (−0.13), non-disclosed ethnicity (−0.11), nursing role (−0.15), and support (0.29) persisted to a level of significance. A significant decrease (p < 0.003) was seen in error reporting after the onset of the Covid-19 pandemic. This is the first study to investigate SAQ during Covid-19. Differences in SAQ scores were observed during Covid-19 between professional groups when compared to baseline. Reductions in incident reporting were also seen. These changes may reflect perception of risk, changes in volume or nature of work. High-quality support for redeployed staff may be associated with improved safety perception during future pandemics.

Monitoring real-time apoptosis in-vivo is an unmet need of neurodegeneration science, both in clinical and research settings. For patients, earlier diagnosis before the onset of symptoms provides a window of time in which to instigate treatment. For researchers, being able to objectively monitor the rates of underlying degenerative processes at a cellular level provides a biomarker with which to test novel therapeutics. The DARC (Detection of Apoptosing Retinal Cells) project has developed a minimally invasive method using fluorescent annexin A5 to detect rates of apoptosis in retinal ganglion cells, the key pathological process in glaucoma. Numerous animal studies have used DARC to show efficacy of novel, pressure-independent treatment strategies in models of glaucoma and other conditions where retinal apoptosis is reported, including Alzheimer’s disease. This may forge exciting new links in the clinical science of treating both cognitive and visual decline. Human trials are now underway, successfully demonstrating the safety and efficacy of the technique to differentiate patients with progressive neurodegeneration from healthy individuals. We review the current perspectives on retinal ganglion cell apoptosis, the way in which this can be imaged, and the exciting advantages that these future methods hold in store.

Introduction: Covid-19 has placed an unprecedented demand on healthcare systems worldwide. A positive safety culture is associated with improved patient safety and in turn patient outcomes. To date, no study has evaluated the impact of Covid-19 on safety culture. Methods: The Safety Attitudes Questionnaire (SAQ) was used to investigate safety culture at a large UK teaching hospital during Covid-19. Findings were compared with baseline data from 2017. Incident reporting from the year preceding the pandemic was also examined. Results: Significant increased were seen in SAQ scores of doctors and ‘other clinical staff’, there was no change in the nursing group. During Covid-19, on univariate regression analysis, female gender, age 40-49 years, non-white ethnicity, and nursing job role were all associated with lower SAQ scores. Training and support for redeployment were associated with higher SAQ scores. On multivariate analysis, non-disclosed gender (−0.13), non-disclosed ethnicity (−0.11), nursing role (−0.15), and support (0.29) persisted to significance. A significant decrease (p<0.003) was seen in error reporting after the onset of the Covid-19 pandemic. Discussion: This is the first study to report SAQ during Covid-19 and compare with baseline. Differences in SAQ scores were observed during Covid-19 between professional groups and compared to baseline. Reductions in incident reporting were also seen. These changes may reflect perception of risk, changes in volume or nature of work. High-quality support for redeployed staff may be associated with improved safety perception during future pandemics. WHAT IS ALREADY KNOWN ON THE SUBJECT: Safety culture is associated with patient safety and outcomes This is the first study to investigate safety culture during the Covid-19 pandemic This study uses the Safety Attitudes Questionnaire (SAQ) and Datix incident reporting data to investigate determinants of safety climate during the Covid-19 pandemic. Safety climate is context specific, this study is strengthened by the availability of benchmarking data from before the onset of the Covid-19 pandemic. Significant differences in SAQ scores between professional groups were observed during Covid-19. Gender, ethnicity and job role were significant determinants of safety attitudes. Support during redeployment was associated with improved safety attitudes. The number of incidents that were reported reduced significantly during Covid-19, although the number of events leading to harm remained constant.

Objectives: The primary objective of MATIS is to determine the efficacy of ruxolitinib (RUX) or fostamatinib (FOS) compared to standard of care (SOC) with respect to reducing the proportion of hospitalised patients progressing from mild or moderate to severe COVID-19 pneumonia. Secondary objectives, at 14 and 28 days, are to: Determine the efficacy of RUX or FOS to reduce mortality Determine the efficacy of RUX or FOS to reduce the need for invasive ventilation or ECMO Determine the efficacy of RUX or FOS to reduce the need for non-invasive ventilation Determine the efficacy of RUX or FOS to reduce the proportion of participants suffering significant oxygen desaturation Determine the efficacy of RUX or FOS to reduce the need for renal replacement therapy Determine the efficacy of RUX and FOS to reduce the incidence of venous thromboembolism Determine the efficacy of RUX and FOS to reduce the severity of COVID-19 pneumonia [graded by a 9-point modified WHO Ordinal Scale* Determine the efficacy of RUX or FOS to reduce systemic inflammation Determine the efficacy of RUX or FOS to the incidence of renal impairment Determine the efficacy of RUX or FOS to reduce duration of hospital stay Evaluate the safety of RUX and FOS for treatment of COVID-19 pneumonia. Trial design: A multi-arm, multi-stage (3-arm parallel-group, 2-stage) randomised controlled trial that allocates participants 1:1:1 and tests for superiority in experimental arms versus standard of care. Participants: Patients will be recruited while inpatients during hospitalisation for COVID-19 in multiple centres throughout the UK including Imperial College Healthcare NHS Trust. INCLUSION: Patients age ≥ 18 years at screening Patients with mild or moderate COVID-19 pneumonia, defined as Grade 3 or 4 severity by the WHO COVID-19 Ordinal Scale Patients meeting criteria: Hospitalization AND SARS-CoV2 infection (clinically suspected or laboratory confirmed) AND Radiological change consistent with COVID-19 disease CRP ≥ 30mg/L at any time point Informed consent from patient or personal or professional representative Agreement to abstain from sexual intercourse or use contraception that is >99% effective for all participants of childbearing potential for 42 days after the last dose of study drug. For male participants, agreement to abstain from sperm donation for 42 days after the last dose of study drug. EXCLUSION: Requiring either invasive or non-invasive ventilation including CPAP or high flow nasal oxygen at any point after hospital admission but before baseline, not related to a pre-existing condition (e.g., obstructive sleep apnoea) Grade ≥ 5 severity on the modified WHO COVID-19 Ordinal Scale, i.e. SpO₂ < 90% on ≥ 60% inspired oxygen by facemask at baseline; non-invasive ventilation; or invasive mechanical ventilation In the opinion of the investigator, progression to death is inevitable within the next 24 hours, irrespective of the provision of therapy Known severe allergic reactions to the investigational agents Child-Pugh B or C grade hepatic dysfunction Use of drugs within the preceding 14 days that are known to interact with any study treatment (FOS or RUX), as listed in the Summary of Product Characteristics Pregnant or breastfeeding Any medical condition or concomitant medication that in the opinion of the investigator would compromise subjects’ safety or compliance with study procedures. Any medical condition which in the opinion of the principal investigator would compromise the scientific integrity of the study Non-English speakers will be able to join the study. If participants are unable to understand verbal or written information in English, then hospital translation services will be requested at the participating site for the participant where possible. Intervention and comparator: RUXOLITINIB (RUX) (14 days): An oral selective and potent inhibitor of Janus Associated Kinases (JAK1 and JAK2) and cell proliferation (Verstovek, 2010). It is approved for the treatment of disease-related splenomegaly or constitutional symptoms in myelofibrosis, polycythaemia vera and graft-versus-host-disease. RUX will be administered orally 10mg bd Day 1-7 and 5mg bd Day 8-14. FOSTAMATINIB (FOS) (14 days): An oral spleen tyrosine kinase inhibitor approved for the treatment of thrombocytopenia in adult participants with chronic immune thrombocytopenia. FOS will be administered orally 150mg bd Day 1-7 and 100mg bd Day 8-14. Please see protocol for recommended dose modifications where required. COMPARATOR (Standard of Care, SOC): experimental arms will be compared to participants receiving standard of care. It is accepted that SOC may change during a rapidly evolving pandemic. Co-enrolment to other trials and rescue therapy, either pre- or post-randomisation, is permitted and will be accounted for in the statistical analysis. Main outcomes: Pairwise comparison (RUX vs SOC and FOS vs SOC) of the proportion of participants diagnosed with severe COVID-19 pneumonia within 14 days. Severe COVID-19 pneumonia is defined by a score ≥ 5 on a modified WHO COVID-19 Ordinal Scale, comprising the following indicators of disease severity: Death OR Requirement for invasive ventilation OR Requirement for non-invasive ventilation including CPAP or high flow oxygen OR O₂ saturation < 90% on ≥60% inspired oxygen Randomisation: Participants will be allocated to interventions using a central web-based randomisation service that generates random sequences using random permuted blocks (1:1:1), with stratification by age (<65 and ≥65 years) and site. Blinding (masking): No participants or caregivers are blinded to group assignment. Clinical outcomes will be compared blind to group assignment. Numbers to be randomised (sample size): For an early informal dose examination by the Data Monitoring Committee a minimum of 30 participants will be recruited. For Stage 1 of this multi-arm multi-stage study, 171 participants will be randomised, with 57 participants in each arm. If at least one experimental intervention shows promise, then Stage 2 will recruit a further 95 participants per arm. Sample size calculations are given in the protocol. Trial Status: Recruitment is ongoing and started 2^nd October 2020. We anticipate completion of Stage 1 by July 2021 and Stage 2 by April 2022. The current protocol version 2.0 of 11^th February 2021 is appended. Trial registration: EudraCT: 2020-001750-22, 9^th July 2020 ClinicalTrials.gov: NCT04581954, 9^th October 2020 Full protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Aims: Artificial intelligence (AI) applied to a single-lead electrocardiogram (AI-ECG) can detect impaired left ventricular systolic dysfunction [LVSD: left ventricular ejection fraction (LVEF) ≤ 40%]. This study aimed to determine if AI-ECG can also predict the two-year risk of major adverse cardiovascular events (MACE) and all-cause mortality independent of LVSD. Methods and results: Clinical outcomes after two-year follow-up were collected on patients who attended for routine echocardiography and received simultaneous single-lead-ECG recording for AI-ECG analysis. MACE and all-cause mortality were compared by Cox regression, measured against the classification of LVEF > or ≤40%. A subgroup analysis was performed on patients with echocardiographic LVEF ≥ 50%. With previously established thresholds, ‘positive’ AI-ECG was defined as an LVEF-predicted ≤40%, and negative AI-ECG signified an LVEF-predicted >40%; 1007 patients were included for analysis (mean age, 62.3 years; 52.4% male). 339 (33.7%) had an AI-ECG-predicted LVEF ≤ 40% and had a higher MACE rate (LVEF ≤ 40% vs. >40%: 34.2% vs.11.9%; adjusted hazard ratio (aHR) 1.93; 95% CI, 1.39–2.69; P < 0.001), primarily driven by increased mortality (23% vs. 9.6%; P < 0.001; aHR 1.56; 95% CI, 1.06–2.29; P = 0.0239). In patients with echocardiographic LVEF ≥ 50%, there was a higher incidence of MACE in those with an AI-ECG ‘false positive’ prediction of LVEF ≤ 40% (27.2% vs.11.9%; P < 0.001; aHR 1.71 and 95% CI, 1.11–2.47) and all-cause mortality (20.4% vs. 9.6%; P < 0.001; aHR 1.59, 95% CI, 1.09–2.42). Conclusion: An AI-ECG algorithm designed to detect LVEF ≤ 40% can also identify patients at risk of MACE and all-cause mortality from single-lead ECG recording—independent of actual LVEF on echo. This requires further evaluation as a point-of-care risk stratification tool.