Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

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: NCT0273570

CAPE TOWN WATER AND SANITATION DESIGN

Monwabisi Park is an informal settlement in Cape Town, South Africa. Poor water and sanitation services in the area cause diarrheal diseases and negatively impact the quality of life. A facility was designed to expand access to clean water and toilet services in Monwabisi Park and also provide community interaction through public washing stations and gardening. The facility conserves water through waterless toilets, rainwater collection and recycling. The design is easily modified and can be replicated across Monwabisi Park

Traffic and Its Impacts

This project contributed to the ongoing development of an autonomous agent model of Venetian boat traffic by collecting detailed turning-movement counts at 17 intersections and updated indices for boat produced noise and wake pollution. These intersections had never before been studied nor had any of their traffic-related environmental concerns been assessed. The team identified the major contributors of each pollution type and recommended speed limit enforcement and more efficient traffic regulation as methods by which to mitigate potential environmental concerns

Patient Views on Advance Care Planning in Cirrhosis: A Qualitative Analysis

Aim. To investigate patient experiences and perceptions of advance care planning (ACP) process in cirrhosis. Methods. Purposive sampling was used to identify and recruit participants (N = 17) from discrete patient groups: compensated with no prior decompensation, decompensated and not yet listed for transplant, transplant wait listed, medical contraindications for transplant, and low socioeconomic status. Review and discussion of local ACP videos, documents, and experiences with ACP occurred in two individual interviews and four focus groups. Data were analyzed using inductive content analysis including iterative processes of open coding, categorization, and abstraction. Results. Three overarching categories emerged: (1) lack of understanding about disease trajectories and ACP processes, (2) roles of alternate decision makers, and (3) preferences for receiving ACP information. Most patients desired advanced care-planning conversations before the onset of decompensation (specifically hepatic encephalopathy) with a care provider with whom they had a trusting, preexisting relationship. Involvement of the alternate decision makers was of critical importance to participants, as was the use of direct, easy to understand patient education tools that address practical issues. Conclusion. Our findings support the need for early advance care planning in the outpatient setting. Outpatient clinicians may play a key role in facilitating these discussions

Collaborating with patients and caregivers to create web-based educational resources for people affected by cirrhosis

Objective: To describe the development of multimodal, web-based educational resources about cirrhosis alongside patients and caregivers. Methods: We used an iterative process that was guided by the Strategy for Patient Oriented Research (SPOR) patient engagement framework in describing patient engagement activities to partner with a team of 16 patients and caregivers (Patient Advisory Team (PAT)). This process included five phases: a) Prioritize and gather content, b) design and build the website and videos, c) gather and integrate feedback, d) improve user accessibility, and e) assess usability and knowledge uptake for users. Results: This 2-year process resulted in a 55-page website and 78 animated and live-action videos on cirrhosis complications, procedures, nutrition, and exercise. We implemented usability testing through pre-defined tasks and a think-aloud method from individuals with no previous exposure to the website to assess navigation, appearance, and content issues. Following usability testing, we have been gathering quantitative data from each unique page about relevance and ease of use, as well as qualitative data on the value of the content itself. Conclusions: Collaboration between clinicians, patients, and caregivers is key to developing high-quality digital educational resources. Lessons from our process may help other organizations looking to address disease-specific knowledge gaps. Next steps with www.cirrhosiscare.ca will be continued iterative refinement and structured impact evaluation. Innovation: This project used a patient-centered approach to develop a comprehensive online educational resource for patients with cirrhosis. By having patients with cirrhosis as a key part of our team, we ensured that the site met the needs of this unique population

Challenging identity: development of a measure of veterinary career motivations

BackgroundWhile little is known about the motivations underpinning veterinary work, previous literature has suggested that the main influences on veterinary career choice are early/formative exposure to animals or veterinary role models. The aim of this study was to develop and provisionally validate a veterinary career motivations questionnaire to assess the strength of various types of career motivations in graduating and experienced veterinarians.MethodsA cross-sectional sample of experienced veterinarians (n=305) and a smaller cohort of newly graduated veterinarians (n=53) were surveyed online using a long-form questionnaire. Exploratory factor analysis (EFA) was used to iteratively derive a final, short-form questionnaire for survey of a second cross-sectional sample of experienced veterinarians (n=751).ResultsEFA derived a final questionnaire with 22 items loading onto six factors (social purpose, animal orientation, vocational identity, challenge and learning, career affordances, and people orientation). While motivations based on animal orientation were predictably strong, those based on vocational identity were not universal and were weaker in younger and graduate veterinarians; both of these motivations were rated lower by male veterinarians. Motivations based on challenge and learning emerged as some of the strongest, most universal and most influential; people orientation and social purpose were also important, particularly for older veterinarians.ConclusionThe major motivations for pursuing a veterinary career may best be represented as an intrinsic passion for animal care and for learning through solving varied challenges. These motivations are largely intrinsically oriented and autonomously regulated, thus likely to be supportive of work satisfaction and wellbeing

Effects of the Mediterranean Diet before and after Weight Loss on Eating Behavioral Traits in Men with Metabolic Syndrome

The objective of this study was to investigate the impact of the Mediterranean diet (MedDiet) consumed before and after weight loss on eating behavioral traits as measured by the Three-Factor Eating Questionnaire (TFEQ) in men with metabolic syndrome (MetS). In this fixed sequence study, 19 men with MetS (National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) criteria), aged between 24 and 62 years, first consumed a five-week standardized North American control diet followed by a five-week MedDiet, both under weight-maintaining controlled-feeding conditions. This was followed by a 20-week caloric restriction weight loss period in free-living conditions, without specific recommendations towards adhering to the principles of the MedDiet. Participants were finally subjected to a final five-week MedDiet phase under isoenergetic controlled-feeding conditions. The MedDiet before weight loss had no impact on eating behavioral traits. Body weight reduction by caloric restriction (−10.2% of initial weight) was associated with increased cognitive restraint (p < 0.0001) and with reduced disinhibition (p = 0.02) and susceptibility to hunger (p = 0.01). Feeding the MedDiet for five weeks under isoenergetic conditions after the weight loss phase had no further impact on eating behavioral traits. Results of this controlled-feeding study suggest that consumption of the MedDiet per se has no effect on eating behavioral traits as measured by TFEQ, unless it is combined with significant weight loss

Third-Generation Cephalosporin-Resistant Spontaneous Bacterial Peritonitis: A single-Centre Experience and Summary of Existing Studies

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is the most prevalent bacterial infection in patients with cirrhosis. Although studies from Europe have reported significant rates of resistance to third-generation cephalosporins, there are limited SBP-specific data from centres in North America