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

Operative management of common forefoot deformities: a representative survey of Australian orthopaedic surgeons

BACKGROUND: Hallux valgus and hallux rigidus are common conditions for which numerous operative interventions have been described in the literature. Various clinical and radiological measurements have been used to help grade severity and to guide treatment. MATERIALS AND METHODS: A survey was e-mailed to all members of the Australian Orthopaedic Association. Questions were asked regarding respondents' demographics as well as their preferred treatment for 3 separate cases of hallux valgus and hallux rigidus of varying severity. They were specifically asked about type of deformity correction and type of fixation. The responses were collected and statistically analyzed. RESULTS: The authors collected the answers of 454 respondents with a response rate of 36%. There was a disproportionately large percentage of respondents who were members of the Australian Orthopaedic Foot and Ankle Society. Preferred treatments were different for the 3 different cases. Older surgeons were more likely to use Chevron osteotomies, and Australian Orthopaedic Foot and Ankle Society members were more likely to use a scarf. Scarf osteotomy was preferred by more than 50% for the cases of moderate and severe hallux valgus, whereas first metatarsophalangeal joint fusion was preferred for the case with significant arthritic changes. CONCLUSIONS: There are significant associations between the surgeons' age and expertise and their training and their preferred operative intervention. Considerable differences were found in the practice of the general orthopaedic surgeons and the foot and ankle specialists. Despite the large number of surgical options available for hallux valgus, only a small number were preferred by the majority of surgeons. Although anecdotally aware that lesser deformity is treated with distal osteotomies and more severe deformity with a proximal osteotomy, the authors are unaware of any current literature that verifies this

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

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