Limitation of life-sustaining treatment and patient involvement in decision-making: a retrospective study of a Danish COVID-19 patient cohort.

BACKGROUND: The coronavirus (COVID-19) pandemic and the risk of an extensive overload of the healthcare systems have elucidated the need to make decisions on the level of life-sustaining treatment for patients requiring hospitalisation. The purpose of the study was to investigate the proportion and characteristics of COVID-19 patients with limitation of life-sustaining treatment decisions and the degree of patient involvement in the decisions. METHODS: A retrospective observational descriptive study was conducted in three Danish regional hospitals, looking at all patients ≥ 18 years of age admitted in 2020 with COVID-19 as the primary diagnosis. Lists of hospitalised patients admitted due to COVID-19 were extracted. The data registration included age, gender, comorbidities, including mental state, body mass index, frailty, recent hospital admissions, COVID-19 life-sustaining treatment, ICU admission, decisions on limitations of life-sustaining treatment before and during current hospitalisation, hospital length of stay, and hospital mortality. RESULTS: A total of 476 patients were included. For 7% (33/476), a decision about limitation of life-sustaining treatment had been made prior to hospital admission. At the time of admission, one or more limitations of life-sustaining treatment were registered for 16% (75/476) of patients. During the admission, limitation decisions were made for an additional 11 patients, totaling 18% (86/476). For 40% (34/86), the decisions were either made by or discussed with the patient. The decisions not made by patients were made by physicians. For 36% (31/86), no information was disclosed about patient involvement. CONCLUSIONS: Life-sustaining treatment limitation decisions were made for 18% of a COVID-19 patient cohort. Hereof, more than a third of the decisions had been made before hospital admission. Many records lacked information on patient involvement in the decisions.

SARS-CoV-2 seroprevalence among 7950 healthcare workers in the Region of Southern Denmark.

OBJECTIVE: Healthcare workers (HCWs) carry a pronounced risk of acquiring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The aim of this study was to determine the seroprevalence and potential risk factors of SARS-CoV-2 infection among HCWs in the Region of Southern Denmark after the first pandemic wave in the spring of 2020. METHODS: This was an observational study conducted between May and June 2020. SARS-CoV-2 IgG and IgM antibodies were measured in plasma. Participants were asked to complete a questionnaire consisting of demographic information, risk factors, and COVID-19-related symptoms. RESULTS: A total of 7950 HCWs participated. The seroprevalence of SARS-CoV-2 antibodies was 2.1% (95% confidence interval (CI) 1.8-2.4%). Seropositive participants were significantly older (mean age 48.9 years vs 46.7 years in seronegative participants, P = 0.022) and a higher percentage had experienced at least one symptom of COVID-19 (P < 0.001). The seroprevalence was significantly higher among HCWs working on dedicated COVID-19 wards (3.5%; OR 2.02, 95% CI 1.44-2.84). Seroprevalence was significantly related to 11-50 close physical contacts per day outside work (OR 1.54, 95% CI 1.07-2.22). CONCLUSIONS: The prevalence of SARS-CoV-2 antibodies was low in HCWs. However, the occupational risk of contracting the infection was found to be higher for those working on dedicated COVID-19 wards. Further, the results imply that attention should be paid to occupational risk factors in planning pandemic preparedness.

Improved diagnostics of infectious diseases in emergency departments: a protocol of a multifaceted multicentre diagnostic study.

BACKGROUND: The major obstacle in prescribing an appropriate and targeted antibiotic treatment is insufficient knowledge concerning whether the patient has a bacterial infection, where the focus of infection is and which bacteria are the agents of the infection. A prerequisite for the appropriate use of antibiotics is timely access to accurate diagnostics such as point-of-care (POC) testing.The study aims to evaluate diagnostic tools and working methods that support a prompt and accurate diagnosis of hospitalised patients suspected of an acute infection. We will focus on the most common acute infections: community-acquired pneumonia (CAP) and acute pyelonephritis (APN). The objectives are to investigate (1) patient characteristics and treatment trajectory of the different acute infections, (2) diagnostic and prognostic accuracy of infection markers, (3) diagnostic accuracy of POC urine flow cytometry on diagnosing and excluding bacteriuria, (4) how effective the addition of POC analysis of sputum to the diagnostic set-up for CAP is on antibiotic prescriptions, (5) diagnostic accuracy of POC ultrasound and ultralow dose (ULD) computerized tomography (CT) on diagnosing CAP, (6) diagnostic accuracy of specialist ultrasound on diagnosing APN, (7) diagnostic accuracy of POC ultrasound in diagnosing hydronephrosis in patients suspected of APN. METHODS AND ANALYSIS: It is a multifaceted multicentre diagnostic study, including 1000 adults admitted with suspicion of an acute infection. Participants will, within the first 24 hours of admission, undergo additional diagnostic tests including infection markers, POC urine flow cytometry, POC analysis of sputum, POC and specialist ultrasound, and ULDCT. The primary reference standard is an assigned diagnosis determined by a panel of experts. ETHICS, DISSEMINATION AND REGISTRATION: Approved by Regional Committees on Health Research Ethics for Southern Denmark, Danish Data Protection Agency and clinicaltrials.gov. Results will be presented in peer-reviewed journals, and positive, negative and inconclusive results will be published. TRIAL REGISTRATION NUMBERS: NCT04661085, NCT04681963, NCT04667195, NCT04652167, NCT04686318, NCT04686292, NCT04651712, NCT04645030, NCT04651244.

Using BCG vaccine to enhance non-specific protection of health care workers during the COVID-19 pandemic: A structured summary of a study protocol for a randomised controlled trial in Denmark.

OBJECTIVES: The Bacille Calmette-Guérin (BCG) vaccine against tuberculosis is associated with non- specific protective effects against other infections, and significant reductions in all-cause morbidity and mortality have been reported. We aim to test whether BCG vaccination may reduce susceptibility to and/or the severity of COVID-19 and other infectious diseases in health care workers (HCW) and thus prevent work absenteeism.The primary objective is to reduce absenteeism due to illness among HCW during the COVID-19 pandemic. The secondary objectives are to reduce the number of HCW that are infected with SARS-CoV-2, and to reduce the number of hospital admissions among HCW during the COVID-19 pandemic. HYPOTHESIS: BCG vaccination of HCW will reduce absenteeism by 20% over a period of 6 months. TRIAL DESIGN: Placebo-controlled, single-blinded, randomised controlled trial, recruiting study participants at several geographic locations. The BCG vaccine is used in this study on a different indication than the one it has been approved for by the Danish Medicines Agency, therefore this is classified as a phase III study. PARTICIPANTS: The trial will recruit 1,500 HCW at Danish hospitals.To be eligible for participation, a subject must meet the following criteria: Adult (≥18 years); Hospital personnel working at a participating hospital for more than 22 hours per week.A potential subject who meets any of the following criteria will be excluded from participation in this study: Known allergy to components of the BCG vaccine or serious adverse events to prior BCG administration Known prior active or latent infection with Mycobacterium tuberculosis (M. tuberculosis) or other mycobacterial species Previous confirmed COVID-19 Fever (>38 C) within the past 24 hours Suspicion of active viral or bacterial infection Pregnancy Breastfeeding Vaccination with other live attenuated vaccine within the last 4 weeks Severely immunocompromised subjects. This exclusion category comprises: a) subjects with known infection by the human immunodeficiency virus (HIV-1) b) subjects with solid organ transplantation c) subjects with bone marrow transplantation d) subjects under chemotherapy e) subjects with primary immunodeficiency f) subjects under treatment with any anti-cytokine therapy within the last year g) subjects under treatment with oral or intravenous steroids defined as daily doses of 10 mg prednisone or equivalent for longer than 3 months h) Active solid or non-solid malignancy or lymphoma within the prior two years Direct involvement in the design or the execution of the BCG-DENMARK-COVID trial Intervention and comparator: Participants will be randomised to BCG vaccine (BCG-Denmark, AJ Vaccines, Copenhagen, Denmark) or placebo (saline). An adult dose of 0.1 ml of resuspended BCG vaccine (intervention) or 0.1 ml of sterile 0.9% NaCl solution (control) is administered intradermally in the upper deltoid area of the right arm. All participants will receive one injection at inclusion, and no further treatment of study participants will take place. MAIN OUTCOMES: Main study endpoint: Days of unplanned absenteeism due to illness within 180 days of randomisation.Secondary study endpoints: The cumulative incidence of documented COVID-19 and the cumulative incidence of hospital admission for any reason within 180 days of randomisation.Randomisation: Randomisation will be done centrally using the REDCap tool with stratification by hospital, sex and age groups (+/- 45 years of age) in random blocks of 4 and 6. The allocation ratio is 1:1.Blinding (masking): Participants will be blinded to treatment. The participant will be asked to leave the room while the allocated treatment is prepared. Once ready for injection, vaccine and placebo will look similar, and the participant will not be able to tell the difference.The physicians administering the treatment are not blinded.Numbers to be randomised (sample size): Sample size: N=1,500. The 1,500 participants will be randomised 1:1 to BCG or placebo with 750 participants in each group.Trial Status: Current protocol version 5.1, from July 6, 2020.Recruitment of study participants started on May 18, 2020 and we anticipate having finished recruiting by the end of December 2020. TRIAL REGISTRATION: The trial was registered with EudraCT on April 16, 2020, EudraCT number: 2020-001888-90, and with ClinicalTrials.gov on May 1, 2020, registration number NCT04373291.Full protocol: The full protocol is attached as an additional file, accessible from the Trialswebsite (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.