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

AJR The Australian Journal of Rural Health 1038-5282 © 2001 National Rural Health Alliance Inc

ABSTRACT: Evidence shows that Aboriginal and Torres Strai

Diabetic foot care: developing culturally appropriate educational tools for Aboriginal and Torres Strait Islander peoples in the Northern Territory, Australia

Evidence shows that Aboriginal and Torres Strait Islander people have the highest national percentage of morbidity in relation to diabetes. Aboriginal and Torres Strait Islander people also suffer the greatest risk of amputation as a complication of diabetes. This participatory action research project sought to discover the opinions of a range of people, including registered nurses, general practitioners, Aboriginal health workers, cross-cultural liaison officers and Aboriginal and Torres Strait Islander people with diabetes. Focus groups provided valuable information regarding relevant issues of foot care education in the Northern Territory. The emergent themes included communication issues, educational resources, changing behaviour and other practical resources required for health education. The themes provided evidence of the inherent issues of foot care for Aboriginal and Torres Strait Islander people and guidance for the development of a visual educational tool. The results have lead to the development of a foot care educational tool that will be used by health-care professionals and clients in urban, community, rural and remote areas. The use of a participant action research process will ensure that the educational tool will be owned by Aboriginal and Torres Strait Islander People and health-care professionals

Iodine Excretion and Intake in Women of Reproductive Age in South Australia Eating Plant-Based and Omnivore Diets: A Pilot Study

Women consuming a strictly vegan/plant-based diet may be at increased risk of low iodine intake due to avoidance of animal products containing iodine. The aim of this pilot study was to determine the iodine excretion and intake in women consuming vegan/plant based diets compared with women consuming omnivore diets. Fifty-seven women (n = 31 plant-based, n = 26 omnivores), provided two spot urine samples to assess urinary iodine concentration (UIC). Two days of dietary intake were also recorded by participants. As the data were not normally distributed results are reported as median (IQR). UIC was significantly different between groups, 44 (26–66) µg/L in the vegan/plant-based group versus 64 (40–88) µg/L in omnivores (p &lt; 0.05). UIC did not meet the &gt;100 µg/L level recommended by the World Health Organization. Iodine intake was also significantly different, 78 (62–91) µg/day in the vegan/plant-based group and 125 (86–175) µg/day in the omnivores (p = 0.000). Iodine intake and bread intake were correlated with iodine excretion (CC 0.410–4.11, p = 0.003). These data indicate iodine insufficiency in both groups of women as the median values were below the minimum WHO recommendation. A larger study assessing iodine excretion in the Australian women of reproductive age who are not pregnant or breastfeeding is needed to confirm these findings.</jats:p

The Effect of a Peanut-Enriched Weight Loss Diet Compared to a Low-Fat Weight Loss Diet on Body Weight, Blood Pressure, and Glycemic Control: A Randomized Controlled Trial

The objective of this study was to examine the effect of consuming 35 g of peanuts prior to two main meals per day as part of a weight loss diet, compared to a traditional low-fat weight loss diet, on body weight, markers of glycemic control, and blood pressure in adults at risk of type 2 diabetes over 6 months. A two-arm randomized controlled trial was conducted. Adults (age > 18 years) with a BMI of >26 kg/m2 at risk of type 2 diabetes were randomized to the peanut group or the traditional low-fat-diet group (control). The peanut group was advised to consume 35 g of lightly salted dry-roasted peanuts prior to two main meals per day. Participants in the control group were given education to follow a low-fat diet. Both groups had dietetic counseling to restrict energy intake (women: 2, waist circumference 109 ± 13 cm, AUSDRISK score 15 ± 5 points), and 76 participants completed the study. No between-group difference in body weight (primary outcome) was observed at 6 months (mean difference, −0.12 kg; 95% CI, −2.42, 2.18; p = 0.92). The mean weight loss at 6 months was 6.7 ± 5.1 kg in the cohort (visit p p = 0.008). Intake of 35 g of peanuts prior to two main meals per day, in the context of an energy-restricted diet, resulted in weight loss comparable to a traditional low-fat weight loss diet without preloads. Greater systolic blood pressure reductions were observed with peanut intake, which may lower cardiovascular disease risk