Personal historical perspective of HIV: part 11.

All animal life on earth is thought to have a common origin and have common genetic mechanisms. Evolution has enabled differentiation of species. Pathogens likewise have evolved within various species and mostly come to a settled dynamic equilibrium such that co-existence results (pathogens ideally should not kill their hosts). Problems arise when pathogens jump species because the new host had not developed any resistance. These infections from related species are known as zoonoses. COVID-19 is the latest example of a virus entering another species but HIV (and various strains of influenza) were previous examples. HIV entered the human population from monkeys in Africa. These two papers outline the underlying principle of HIV and the differing epidemiologies in Africa, the USA and in Edinburgh. The underlying immunosuppression of HIV in Africa was initially hidden behind common infections and HIV first came to world awareness in focal areas of the USA as a disease seemingly limited to gay males. The epidemic of intravenous drug abuse in Edinburgh was associated with overlapping epidemics of bloodborne viruses like hepatitis B, hepatitis C and HIV.

Rheumatoid Vasculitis Complicated With Acute Inflammatory Demyelinating Polyneuropathy in an Older Female: A Case Report.

Rheumatoid vasculitis (RV) causes various complications in the heart, lungs, kidneys, and nerves that require intensive treatment. Rapid RV-related peripheral nerve involvement progression is critical and requires prompt treatment. We report the case of a 73-year-old female with RV, with a chief complaint of difficulty walking without any infectious symptoms for several months. We diagnosed Guillain-Barré syndrome (GBS) accompanied by RV and treated the patient with intravenous immunoglobulin and cyclophosphamide. Previous impairments of activities of daily living (ADLs) were resolved. Diagnosing the neurological manifestations of RV and GBS in older patients with an active RV is challenging because of the various patterns of the progression. For effective management, considering both diseases and implementing immunosuppressive and modulatory treatments is critical to stop the progression of neurological symptoms and prevent the deterioration of ADLs.

How Media Literacy, Trust of Experts and Flu Vaccine Behaviors Associated with COVID-19 Vaccine Intentions.

PURPOSE: To assess how previous experiences and new information contributed to COVID-19 vaccine intentions. DESIGN: Online survey (N = 1264) with quality checks. SETTING: Cross-sectional U.S. survey fielded June 22-July 18, 2020. SAMPLE: U.S. residents 18+; quotas reflecting U.S. Census, limited to English speakers participating in internet panels. MEASURES: Media literacy for news content and sources, COVID-19 knowledge; perceived usefulness of health experts; if received flu vaccine in past 12 months; vaccine willingness scale; demographics. ANALYSIS: Structural equation modelling. RESULTS: Perceived usefulness of health experts (b = .422, P < .001) and media literacy (b = .162, P < .003) predicted most variance in vaccine intentions (R-squared=31.5%). A significant interaction (b = .163, P < .001) between knowledge (b = -.132, P = .052) and getting flu shot (b = .185, P < .001) predicted additional 3.5% of the variance in future vaccine intentions. An increase in knowledge of COVID-19 associated with a decrease in vaccine intention among those declining the flu shot. CONCLUSION: The interaction result suggests COVID-19 knowledge had a positive association with vaccine intention for flu shot recipients but a counter-productive association for those declining it. Media literacy and trust in health experts provided strong counterbalancing influences. Survey-based findings are correlational; thus, predictions are based on theory. Future research should study these relationships with panel data or experimental designs.

Nurse-led virtual interventions in managing chronic diseases: a protocol for a systematic review of randomised controlled trials.

INTRODUCTION: Technological advances are changing nursing practice; however, nurse-led virtual care for chronic disease management has not yet been adequately explored and described. This study will review and analyse the effects of nurse-led virtual services and describe the virtual intervention characteristics relevant to the scope of nursing practice in chronic disease management. METHODS AND ANALYSIS: This study will systematically review randomised controlled trials evaluating the effects of nurse-led virtual care interventions on patients with chronic conditions. Databases including PubMed, Embase, Web of Science, CINAHL, Chinese National Knowledge Infrastructure, Wanfang (Chinese) and VIP Chinese Science and Technology Periodicals will be searched. All studies will be screened and selected using the criteria described in 'population, intervention, comparison, outcome and study design' format. Relevant studies will be searched using the reference lists of eligible studies and review articles. The risk of bias will be assessed using the Joanna Briggs Institute Quality Appraisal Form. Two reviewers will independently extract data from all the included studies using a standardised data extraction form on the Covidence platform. RevMan V.5.3 software will be used to perform the meta-analysis. Data synthesis will be conducted with descriptive synthesis by summarising and tabulating the data and presenting them according to the research questions. ETHICS AND DISSEMINATION: Formal ethical approval is not required as the data used in this systematic review are abstracted from the pre-existing literature. The results of this study will be disseminated through peer-reviewed journals and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42022361260.

Comprehensive Management of Vasculitis and Suspected Polyarteritis Nodosa in an Older Patient.

Polyarteritis nodosa (PAN) is a rare autoimmune disease that affects medium-sized arteries and causes inflammation and damage to the blood vessel walls. Testicular pain is an uncommon symptom of PAN but can occur in rare cases. This specific symptom may be useful in diagnosing older patients with limited tissue access because of their vulnerability and high risk for biopsy complications. We report the case of a 78-year-old male patient with progressive fatigue and walking difficulty. After ruling out various forms of vasculitis and malignancy, we diagnosed the patient with PAN and intensively treated him with rituximab, which successfully cured his symptoms. This case report highlights the importance of intensively ruling out possible diagnoses mimicking vasculitis and treating vasculitis with a tentative diagnosis of PAN in older patients in rural hospitals. The progressive clinical course of vasculitis may devastate older patients' activities of daily living (ADLs). PAN may particularly affect older patients with possible hepatitis B infections. Thus, shared decision-making and prompt intensive treatment should be considered.

Timing of Treatment for Cytomegalovirus Infection in an Immunocompetent Middle-Aged Woman With Fulminant Ulcerative Colitis: A Case Report.

Viral infections, such as cytomegalovirus (CMV) infection, may affect the clinical course of ulcerative colitis (UC). CMV can cause chronic inflammation of the intestinal mucosa. In inflammatory bowel disease, chronic inflammation caused by CMV can deter the regeneration of the mucosa of the colon. However, the relationship between CMV and inflammatory bowel disease still needs to be clarified, especially in immunocompetent patients, such as younger patients not treated with immunosuppressants. Herein, we describe our experience with a middle-aged immunocompetent female patient diagnosed with fulminant UC positive for myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA). Her initial response to high-dose prednisolone was favorable; however, remission was not achieved. Immunohistochemical staining revealed the presence of CMV. Subsequently, the patient was successfully treated with prednisolone, adalimumab, and azathioprine, along with the anti-CMV treatment comprising valganciclovir. This case shows that the presence of CMV in the mucosa and blood may make patients with UC refractory to immunosuppression; furthermore, the positivity of MPO-ANCA in patients with UC can necessitate the administration of high-dose immunosuppressants to taper the dose of prednisolone.

What is the role of primary care in the COVID-19 vaccine roll-out and the barriers and facilitators to an equitable vaccine roll-out? A rapid scoping review of nine jurisdictions.

OBJECTIVES: This study aimed to: (1) examine the experience of nine global jurisdictions that engaged primary care providers (PCPs) to administer COVID-19 vaccines during the pandemic; (2) describe how vaccine hesitancy and principles of equity were incorporated in the COVID-19 vaccine roll-out strategies and (3) identify the barriers and facilitators to the vaccine roll-out. DESIGN: Rapid scoping review. DATA SOURCES: Searches took place in MEDLINE, CINAHL, Embase, the Cochrane Library, SCOPUS and PsycINFO, Google, and the websites of national health departments. Searches and analyses took place from May 2021 to July 2021. RESULTS: Sixty-two documents met the inclusion criteria (35=grey literature; 56% and 27=peer reviewed; 44%). This review found that the vaccine distribution approach started at hospitals in almost all jurisdictions. In some jurisdictions, PCPs were engaged at the beginning, and the majority included PCPs over time. In many jurisdictions, equity was considered in the prioritisation policies for various marginalised communities. However, vaccine hesitancy was not explicitly considered in the design of vaccine distribution approaches. The barriers to the roll-out of vaccines included personal, organisational and contextual factors. The vaccine roll-out strategy was facilitated by establishing policies and processes for pandemic preparedness, well-established and coordinated information systems, primary care interventions, adequate supply of providers, education and training of providers, and effective communications strategy. CONCLUSIONS: Empirical evidence is lacking on the impact of a primary care-led vaccine distribution approach on vaccine hesitancy, adoption and equity. Future vaccine distribution approaches need to be informed by further research evaluating vaccine distribution approaches and their impact on patient and population outcomes.

Pneumomediastinum in patients with COVID-19 undergoing CT pulmonary angiography: a retrospective cohort study.

BACKGROUND: Various complications have been reported in patients with COVID-19 including pneumomediastinum. METHODS: The primary objective of the study was to determine the incidence of pneumomediastinum in COVID-19 positive patients who underwent CT pulmonary angiography (CTPA). The secondary objectives were to analyse if the incidence of pneumomediastinum changed between March and May 2020 (peak of the first wave in the UK) and January 2021 (peak of the second wave in the UK) and to determine the mortality rate in patients with pneumomediastinum. We undertook an observational, retrospective, single-centre, cohort study of patients with COVID-19 admitted to Northwick Park Hospital. RESULTS: 74 patients in the first wave and 220 patients in the second wave met the study criteria. Two patients during the first wave and eleven patients during the second wave developed pneumomediastinum. CONCLUSIONS: The incidence of pneumomediastinum changed from 2.7% during the first wave to 5% during the second wave and this change was not statistically significant (p value 0.4057). The difference in mortality rates of patients with pneumomediastinum in both waves of COVID-19 (69.23%) versus patients without pneumomediastinum in both waves of COVID-19 (25.62%) was statistically significant (p value 0.0005). Many patients with pneumomediastinum were ventilated, which could be a confounding factor. When controlling for ventilation, there was no statistically significant difference in the mortality rates of ventilated patients with pneumomediastinum (81.81%) versus ventilated patients without pneumomediastinum (59.30%) (p value 0.14).

Statistical Analysis and Logistic Regression to Assess How COVID-19 Has Changed Department of General Medicine Patients' Management: A Bicentric Study

The purpose of the present work was to assess the impact of the Covid-19 epidemic on the activity of the Department of General Medicine in the University Hospital "San Giovanni di Dio and Ruggi d'Aragona” of Salerno and the hospital "A.O.R.N. A. Cardarelli” of Naples (Italy). COVID-19 is a specific disease affecting subject respiratory system is a respiratory infection that changed the health context. Because of the pandemic hospitals had to reorganize departments to better manage resources. In order to make a comparison with and without Covid-19, the data for the year 2019 (in the absence of Covid-19) and in the year of the pandemic 2020 have been collected. In the work was used the logistic regression technique to study the following variables: age, sex, LOS, weight of DRG, mode of discharge and type of hospitalization. In addition, the results of the two hospitals were used to make a comparison. For both hospitals in the year 2020 the number of patients admitted is lower than the previous year, and this shows that there has been appropriate management and control to establish patients who really needed hospitalization. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Heyde Syndrome Complicated by Essential Thrombocythemia: A Case Report.

Heyde syndrome is a multisystem disorder characterized by the triad of aortic stenosis (AS), gastrointestinal bleeding, and acquired von Willebrand syndrome. Age-related degeneration is the most common cause of aortic stenosis and is frequently encountered in today's aging society. Approximately 20% of patients with severe aortic stenosis have Heyde syndrome. We encountered an older patient with primary thrombocytosis who was brought to a rural community hospital with bloody stools and was diagnosed with bleeding from an intestinal arteriovenous malformation. A final diagnosis of Heyde syndrome was made based on the presence of severe aortic stenosis and the presence of schistocytes in peripheral blood smears. Valvular diseases can complicate chronic hematological diseases. When the rapid progression of anemia and segmented red blood cells in the peripheral blood are observed in patients with severe aortic stenosis, Heyde syndrome should be considered based on peripheral blood smears and clinical course.

Relevance of prediction scores derived from the SARS-CoV-2 first wave, in the evolving UK COVID-19 second wave, for safe early discharge and mortality: a PREDICT COVID-19 UK prospective observational cohort study.

OBJECTIVE: Prospectively validate prognostication scores, SOARS and 4C Mortality Score, derived from the COVID-19 first wave, for mortality and safe early discharge in the evolving pandemic with SARS-CoV-2 variants (B.1.1.7 replacing D614) and healthcare responses altering patient demographic and mortality. DESIGN: Protocol-based prospective observational cohort study. SETTING: Single site PREDICT and multisite ISARIC (International Severe Acute Respiratory and Emerging Infections Consortium) cohorts in UK COVID-19 second wave, October 2020 to January 2021. PARTICIPANTS: 1383 PREDICT and 20 595 ISARIC SARS-CoV-2 patients. PRIMARY OUTCOME MEASURES: Relevance of SOARS and 4C Mortality Score determining in-hospital mortality and safe early discharge in the evolving UK COVID-19 second wave. RESULTS: 1383 (median age 67 years, IQR 52-82; mortality 24.7%) PREDICT and 20 595 (mortality 19.4%) ISARIC patient cohorts showed SOARS had area under the curve (AUC) of 0.8 and 0.74, while 4C Mortality Score had AUC of 0.83 and 0.91 for hospital mortality, in the PREDICT and ISARIC cohorts respectively, therefore, effective in evaluating safe discharge and in-hospital mortality. 19.3% (231/1195, PREDICT cohort) and 16.7% (2550/14992, ISARIC cohort) with SOARS of 0-1 were candidates for safe discharge to a virtual hospital (VH) model. SOARS implementation in the VH pathway resulted in low readmission, 11.8% (27/229) and low mortality, 0.9% (2/229). Use to prevent admission is still suboptimal, as 8.1% in the PREDICT cohort and 9.5% in the ISARIC cohort were admitted despite SOARS score of 0-1. CONCLUSIONS: SOARS and 4C Mortality Score remains valid, transforming complex clinical presentations into tangible numbers, aiding objective decision making, despite SARS-CoV-2 variants and healthcare responses altering patient demographic and mortality. Both scores, easily implemented within urgent care pathways for safe early discharge, allocate hospital resources appropriately to the pandemic's needs while enabling normal healthcare services resumption.

Global evidence of gender equity in academic health research: a scoping review.

OBJECTIVES: To chart the global literature on gender equity in academic health research. DESIGN: Scoping review. PARTICIPANTS: Quantitative studies were eligible if they examined gender equity within academic institutions including health researchers. PRIMARY AND SECONDARY OUTCOME MEASURES: Outcomes related to equity across gender and other social identities in academia: (1) faculty workforce: representation of all genders in university/faculty departments, academic rank or position and salary; (2) service: teaching obligations and administrative/non-teaching activities; (3) recruitment and hiring data: number of applicants by gender, interviews and new hires for various rank; (4) promotion: opportunities for promotion and time to progress through academic ranks; (5) academic leadership: type of leadership positions, opportunities for leadership promotion or training, opportunities to supervise/mentor and support for leadership bids; (6) scholarly output or productivity: number/type of publications and presentations, position of authorship, number/value of grants or awards and intellectual property ownership; (7) contextual factors of universities; (8) infrastructure; (9) knowledge and technology translation activities; (10) availability of maternity/paternity/parental/family leave; (11) collaboration activities/opportunities for collaboration; (12) qualitative considerations: perceptions around promotion, finances and support. RESULTS: Literature search yielded 94 798 citations; 4753 full-text articles were screened, and 562 studies were included. Most studies originated from North America (462/562, 82.2%). Few studies (27/562, 4.8%) reported race and fewer reported sex/gender (which were used interchangeably in most studies) other than male/female (11/562, 2.0%). Only one study provided data on religion. No other PROGRESS-PLUS variables were reported. A total of 2996 outcomes were reported, with most studies examining academic output (371/562, 66.0%). CONCLUSIONS: Reviewed literature suggest a lack in analytic approaches that consider genders beyond the binary categories of man and woman, additional social identities (race, religion, social capital and disability) and an intersectionality lens examining the interconnection of multiple social identities in understanding discrimination and disadvantage. All of these are necessary to tailor strategies that promote gender equity. TRIAL REGISTRATION NUMBER: Open Science Framework: https://osf.io/8wk7e/.

Metabolism-Mediated Thrombotic Microangiopathy in an Older Patient Without Malnutrition.

Vitamin B12 deficiency can cause thrombotic microangiopathy (TMA)-like symptoms such as purpura caused by platelet reduction, general fatigue caused by anemia, and renal and hepatic abnormalities caused by malnutrition. TMA-like symptoms are known as metabolism-mediated TMA (MM-TMA). In MM-TMA, blood cell production is altered, and both pancytopenia and schistocytes appear. The initial presentation of MM-TMA makes it challenging to distinguish between primary and secondary TMA when patients do not present risk factors for malnutrition. We encountered an older female patient with a chief complaint of unconsciousness and loss of appetite for two days. Laboratory tests revealed pancytopenia with schistocytes. Moreover, the laboratory data revealed low serum levels of vitamin B12, indicating MM-TMA. The patient was successfully treated with intravenous vitamin B12 supplementation and discharged home. The patient had atrophic gastritis, which could have impeded the absorption of vitamin B12 from food. Among older patients without prolonged appetite loss, TMA-like symptoms should be investigated as MM-TMA induced by vitamin B12 deficiency, and prompt initiation of appropriate treatment is essential to differentiate between MM-TMA and true TMA.

Appearance of Ankylosing Spondylitis in a Middle-Aged Female Patient With a Long History of Rheumatoid Arthritis.

Ankylosing spondylitis (AS) is a chronic inflammatory disease of the axial bones, primarily affecting the spine. AS is classified as spondyloarthritis because it affects the spine and other joints. AS has several presentations and, in some cases, can be insidious, making it difficult to diagnose. We encountered a patient on long-term follow-up for rheumatoid arthritis with an appearance of AS. This case suggests that patients with long-term rheumatoid arthritis can develop AS during follow-up and that the seropositivity of rheumatoid factors and anti-cyclic citrullinated peptide antibodies cannot rule out AS. Therefore, the possibility of AS should be considered, even in patients diagnosed with rheumatoid arthritis.

Validity and reliability of the Spanish version of the ACE tool for assessing competencies in evidence-based medicine in medical students.

OBJECTIVE: To translate and culturally adapt the tool 'Assessing Competency in evidence-based medicine (EBM)' (ACE) to Spanish and to implement it in a cohort of medical students for the evaluation of the instrument's psychometric properties. DESIGN: Bilingual translators produced a translation and backtranslation of the original instrument, with interim consensus in each stage with oversight and input by a group of experts. We then performed cognitive interviews to adapt the wording of the tool culturally. Finally, we implemented the final version in a cohort of medical students on a virtual general practice course with EBM modules. SETTING: Medical School in Buenos Aires, Argentina. Due to restrictions to in-person teaching during the COVID-19 pandemic, we conducted this study in the context of virtual learning. PARTICIPANTS: We included 125 fourth and fifth-year medical students. MAIN OUTCOME MEASURES: We measured internal consistency with the Kuder-Richardson coefficient (>0.6 as a threshold for reliability) and construct validity through a Pearson's correlation between the examinations carried out with the translated instrument and the results of the regular examinations of EBM in the same students (expected values of at least 0.3 to 0.7). We also compared the total score of the instrument of fifth-year students to fourth-year students. RESULTS: As for measurements for internal consistency, the coefficient Kuder-Richardson resulted in a value of 0.268, below our prespecified threshold. For construct validity, the Pearson correlation between the sum of the items and regular examinations was 0.139, also below our prespecified threshold. However, fifth-year students averaged 0.94 points more than fourth-year students (95% CI 0.24 more to 1.65 more). CONCLUSION: The translated and cross-culturally adapted version of the ACE tool into Spanish had low reliability and validity in an MBE course taught and evaluated in a virtual environment. TRIAL REGISTRATION: Not applicable.

Relationship between COVID-19 care and burnout among postgraduate clinical residents in Japan: a nationwide cross-sectional study.

OBJECTIVE: The relationship between the care of patients with COVID-19 and mental health among resident physicians in Japan is imperative for ensuring appropriate care of patients with COVID-19 and should be clarified. We herein assessed the relationship between the care of patients with COVID-19 and mental health among postgraduate year 1 (PGY-1) and PGY-2 resident physicians and factors associated with mental health. DESIGN: This nationwide cross-sectional study analysed data obtained using the clinical training environment self-reported questionnaire. SETTING: An observational study across Japan among resident physicians (PGY-1 and PGY-2) from 583 teaching hospitals. PARTICIPANTS: Examinees who took the general medicine in-training examination of academic year 2020. PRIMARY AND SECONDARY OUTCOME MEASURES: The Patient Health Questionnaire and Mini-Z 2.0 were used to assess mental health, and experience of caring for patients with COVID-19 was divided into three groups (none, 1-10 and ≥11). The prevalence of mental conditions in the three groups was compared using the 'modified' Poisson generalised estimating equations by adjusting for prefecture-level, hospital-level and resident-level variables. RESULTS: Of the 5976 participants analysed, 50.9% were PGY-1. The prevalence of burnout was 21.4%. Moreover, 47.0% of all resident physicians had no experience in the care of patients with COVID-19. The well-experienced group accounted for only 7.9% of the total participants. A positive association was found between the number of caring patients with COVID-19 and burnout (prevalence ratio 1.25; 95% CI 1.02 to 1.53). Moreover, the shortage of personal protective equipment was identified as a major contributor to burnout (prevalence ratio 1.60; 95% CI 1.36 to 1.88). CONCLUSIONS: Resident physicians who experienced more care of patients with COVID-19 had slightly greater burnout prevalence than those who did not. Approximately half of resident physicians did not participate in the care of patients with COVID-19, which posed a challenge from an educational perspective.

Standardised treatment and monitoring protocol to assess safety and tolerability of bacteriophage therapy for adult and paediatric patients (STAMP study): protocol for an open-label, single-arm trial.

INTRODUCTION: There has been renewed interest in the therapeutic use of bacteriophages (phages); however, standardised therapeutic protocols are lacking, and there is a paucity of rigorous clinical trial data assessing efficacy. METHODS AND ANALYSIS: We propose an open-label, single-arm trial investigating a standardised treatment and monitoring protocol for phage therapy. Patients included will have exhausted other therapeutic options for control of their infection and phage therapy will be administered under Australia's Therapeutic Goods Administration Special Access Scheme. A phage product with high in vitro activity against the targeted pathogen(s) must be available in line with relevant regulatory requirements. We aim to recruit 50-100 patients over 5 years, from any public or private hospitals in Australia. The standardised protocol will specify clinical assessments and biological sampling at scheduled time points. The primary outcome is safety at day 29, assessed by the frequency of adverse events, and overseen by an independent Data Safety Monitoring Board. Secondary outcomes include long-term safety (frequency of adverse events until at least 6 months following phage therapy), and feasibility, measured as the proportion of participants with>80% of minimum data available for analysis. Additional endpoints assessed include clinical response, patient/guardian reported quality of life measures, phage pharmacokinetics, human host immune responses and microbiome analysis. All trial outcomes will be summarised and presented using standard descriptive statistics. ETHICS AND DISSEMINATION: Participant inclusion will be dependent on obtaining written informed consent from the patient or guardian. The trial protocol was approved by the Sydney Children's Hospitals Network Human Research Ethics Committee in December 2021 (Reference 2021/ETH11861). In addition to publication in a peer-reviewed scientific journal, a lay summary of study outcomes will be made available for participants and the public on the Phage Australia website (https://www.phageaustralia.org/). TRIAL REGISTRATION NUMBER: Registered on ANZCTR, 10 November 2021 (ACTRN12621001526864; WHO Universal Trial Number: U1111-1269-6000).

Goals of Care, Critical Care Utilization and Clinical Outcomes in Obese Patients Admitted under General Medicine.

Obesity is associated with long-term morbidity and mortality, but it is unclear if obesity affects goals of care determination and intensive care unit (ICU) resource utilization during hospitalization under a general medicine service. In a cohort of 5113 adult patients admitted under general medicine, 15.3% were obese. Patients with obesity were younger and had a different comorbidity profile than patients who were not obese. In age-adjusted regression analysis, the distribution of goals of care categories for patients with obesity was not different to patients who were not obese (odds ratio for a lower category with more limitations, 0.94; 95% confidence interval [CI]: 0.79-1.12). Patients with obesity were more likely to be directly admitted to ICU from the Emergency Department, require more ICU admissions, and stayed longer in ICU once admitted. Hypercapnic respiratory failure and heart failure were more common in patients with obesity, but they were less likely to receive mechanical ventilation in favor of non-invasive ventilation. The COVID-19 pandemic was associated with 16% higher odds of receiving a lower goals of care category, which was independent of obesity. Overall hospital length of stay was not affected by obesity. Patients with obesity had a crude mortality of 3.8 per 1000 bed-days, and age-adjusted mortality rate ratio of 0.75 (95% CI: 0.49-1.14) compared to patients who were not obese. In conclusion, there was no evidence to suggest biased goals of care determination in patients with obesity despite greater ICU resource utilization.

Protocol for a 30-day randomised, parallel-group, non-inferiority, controlled trial investigating the effects of discontinuing renin-angiotensin system inhibitors in patients with and without COVID-19: the RASCOVID-19 trial.

INTRODUCTION: The COVID-19 pandemic caused by the virus SARS-CoV has spread rapidly and caused damage worldwide. Data suggest a major overrepresentation of hypertension and diabetes among patients experiencing severe courses of COVID-19 including COVID-19-related deaths. Many of these patients receive renin-angiotensin system (RAS) inhibiting therapy, and evidence suggests that treatment with angiotensin II receptor blockers (ARBs) could attenuate SARS-CoV-induced acute respiratory distress syndrome, and ACE inhibitors and ARBs have been suggested to alleviate COVID-19 pulmonary manifestations. This randomised clinical trial will address whether RAS inhibiting therapy should be continued or discontinued in hospitalised patients with COVID-19. METHODS AND ANALYSIS: This trial is a 30-day randomised parallel-group non-inferiority clinical trial with an embedded mechanistic substudy. In the main trial, 215 patients treated with a RAS inhibitor will be included. The participants will be randomly assigned in a 1:1 ratio to either discontinue or continue their RAS inhibiting therapy in addition to standard care. The patients are included during hospitalisation and followed for a period of 30 days. The primary end point is number of days alive and out of hospital within 14 days after recruitment. In a mechanistic substudy, 40 patients treated with RAS inhibition, who are not in hospital and not infected with COVID-19 will be randomly assigned to discontinue or continue their RAS inhibiting therapy with the primary end point of serum ACE2 activity. ETHICS AND DISSEMINATION: This trial has been approved by the Scientific-Ethical Committee of the Capital Region of Denmark (identification no. H-20026484), the Danish Medicines Agency (identification no. 2020040883) and by the Danish Data Protection Agency (P-2020-366). The results of this project will be compiled into one or more manuscripts for publication in international peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: 2020-001544-26; NCT04351581.