Oral Sabizabulin for High-Risk, Hospitalized Adults with Covid-19: Interim Analysis.

BACKGROUND: Sabizabulin is an oral, novel microtubule disruptor that has dual antiviral and anti-inflammatory activities in preclinical models. METHODS: A randomized, multicenter placebo-controlled phase 3 clinical trial was conducted with hospitalized patients with moderate to severe Covid-19 who were at high risk for acute respiratory distress syndrome (ARDS) and death. Patients were randomly assigned (2:1) to 9 mg of oral sabizabulin or placebo daily (up to 21 days). The primary end point was all-cause mortality up to day 60. Key secondary end points were days in the intensive care unit (ICU), days on mechanical ventilation, and days in the hospital. RESULTS: A total of 204 patients were randomly assigned to treatment: 134 to sabizabulin and 70 to placebo. Baseline characteristics were similar. Sabizabulin superiority was demonstrated by a planned interim analysis for the first 150 randomized patients. Sabizabulin treatment resulted in a 24.9 percentage point absolute reduction and a 55.2% relative reduction in deaths compared with placebo (odds ratio, 3.23; 95% CI confidence interval, 1.45 to 7.22; P=0.0042). The mortality rate was 20.2% (19 of 94) for sabizabulin versus 45.1% (23 of 51) for placebo. For the key secondary end points, sabizabulin treatment resulted in a 43% relative reduction in ICU days (P=0.0013), a 49% relative reduction in days on mechanical ventilation (P=0.0013), and a 26% relative reduction in days in the hospital (P=0.0277) versus placebo. Adverse and serious adverse events were lower in the sabizabulin group compared with the placebo group. CONCLUSIONS: Sabizabulin treatment resulted in a 24.9% absolute reduction in deaths compared with placebo in hospitalized patients with moderate to severe Covid-19 at high risk for ARDS and death, with a lower incidence of adverse and serious adverse events compared with placebo. (Funded by Veru, Inc.; ClinicalTrials.gov number, NCT04842747.)

Auxora versus standard of care for the treatment of severe or critical COVID-19 pneumonia: results from a randomized controlled trial.

BACKGROUND: Calcium release-activated calcium (CRAC) channel inhibitors stabilize the pulmonary endothelium and block proinflammatory cytokine release, potentially mitigating respiratory complications observed in patients with COVID-19. This study aimed to investigate the safety and efficacy of Auxora, a novel, intravenously administered CRAC channel inhibitor, in adults with severe or critical COVID-19 pneumonia. METHODS: A randomized, controlled, open-label study of Auxora was conducted in adults with severe or critical COVID-19 pneumonia. Patients were randomized 2:1 to receive three doses of once-daily Auxora versus standard of care (SOC) alone. The primary objective was to assess the safety and tolerability of Auxora. Following FDA guidance, study enrollment was halted early to allow for transition to a randomized, blinded, placebo-controlled study. RESULTS: In total, 17 patients with severe and three with critical COVID-19 pneumonia were randomized to Auxora and nine with severe and one with critical COVID-19 pneumonia to SOC. Similar proportions of patients receiving Auxora and SOC experienced ≥ 1 adverse event (75% versus 80%, respectively). Fewer patients receiving Auxora experienced serious adverse events versus SOC (30% versus 50%, respectively). Two patients (10%) receiving Auxora and two (20%) receiving SOC died during the 30 days after randomization. Among patients with severe COVID-19 pneumonia, the median time to recovery with Auxora was 5 days versus 12 days with SOC; the recovery rate ratio was 1.87 (95% CI, 0.72, 4.89). Invasive mechanical ventilation was needed in 18% of patients with severe COVID-19 pneumonia receiving Auxora versus 50% receiving SOC (absolute risk reduction = 32%; 95% CI, - 0.07, 0.71). Outcomes measured by an 8-point ordinal scale were significantly improved for patients receiving Auxora, especially for patients with a baseline PaO2/FiO2 = 101-200. CONCLUSIONS: Auxora demonstrated a favorable safety profile in patients with severe or critical COVID-19 pneumonia and improved outcomes in patients with severe COVID-19 pneumonia. These results, however, are limited by the open-label study design and small patient population resulting from the early cessation of enrollment in response to regulatory guidance. The impact of Auxora on respiratory complications in patients with severe COVID-19 pneumonia will be further assessed in a planned randomized, blinded, placebo-controlled study. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04345614 . Submitted on 7 April 2020.

Medical student quality-of-life in the clerkships: a scale validation study.

Many aspects of medical school are stressful for students. To empirically assess student reactions to clerkship programs, or to assess efforts to improve such programs, educators must measure the overall well-being of the students reliably and validly. The purpose of the study was to develop and validate a measure designed to achieve these goals. The authors developed a measure of quality of life for medical students by sampling (public domain) items tapping general happiness, fatigue, and anxiety. A quality-of-life scale was developed by factor analyzing responses to the items from students in two different clerkships from 2005 to 2008. Reliability was assessed using Cronbach's alpha. Validity was assessed by factor analysis, convergence with additional theoretically relevant scales, and sensitivity to change over time. The refined nine-item measure is a Likert scaled survey of quality-of-life items comprised of two domains: exhaustion and general happiness. The resulting scale demonstrated good reliability and factorial validity at two time points for each of the two samples. The quality-of-life measure also correlated with measures of depression and the amount of sleep reported during the clerkships. The quality-of-life measure appeared more sensitive to changes over time than did the depression measure. The measure is short and can be easily administered in a survey. The scale appears useful for program evaluation and more generally as an outcome variable in medical educational research.

FLS skill acquisition: a comparison of blocked vs interleaved practice.

INTRODUCTION: Fundamentals of Laparoscopic Surgery (FLS) certification is required for general surgery. The recommended practice for learning FLS is to practice tasks one at a time until proficient (blocked practice). Learning theory suggests that interleaved practice, a method in which tasks are rotated rather than learned one at a time, may result in superior learning. METHOD: Residents were randomized into 1 of 2 groups: blocked practice or interleaved practice. We compared the performance of residents across groups over 20 trials of each of 4 FLS tasks (peg transfer, pattern cut, extracorporeal suture, and intracorporeal suture). Four weeks later, participants returned to the laboratory and completed 2 additional trials of each of the 4 tasks. RESULTS: Performance on each of the tasks improved with increased practice. The interleaved group showed significantly better performance on the peg transfer task; trends favoring the interleaved group resulted for the other tasks. Standardized mean differences in favor of the interleaved group were substantial both at the end of practice and at follow-up (with the exception of the pattern cut). CONCLUSION: Interleaved practice appears to have advantages over blocked practice in developing and retaining FLS skills. We encourage others to experiment with the method to confirm our findings.

Surgical interest and surgical match for third-year students: results of a prospective multivariate longitudinal cohort study.

BACKGROUND: Numerous factors have been linked to surgical career choice, including the quality of third-year surgical clerkship. The vast majority of studies also selectively evaluate one or only a few variables that link to surgical career choice, so relative impact cannot be assessed. This study simultaneously evaluates the majority of variables linked to surgical career choice in previous research so that the relative contributions of each of these variables with respect to surgical career choice can be determined. STUDY DESIGN: Surveys before, during, and after the third-year surgical clerkship included student demographics, background, and values (eg, importance of money, controllable lifestyle), and student reactions to the third-year surgical clerkship. The dependent variables in this study included interest in surgery at the beginning and end of the clerkship and matching into a surgical residency. RESULTS: Both univariate and multivariate analyses generally supported findings in the literature, but the strengths of these associations reported previously might not have been accurate. In this study, the surgical resident match odds ratio for students starting the clerkship already knowing they wanted to be a surgeon was 22.46; the next highest associations were 4.65 and 3.37, which corresponded to earlier exposure to a surgical specialty and earlier exposure to general surgery, respectively. Differences in career choice for general surgeons and surgical specialists were also explored. CONCLUSIONS: Although the experience of the clerkship is related to career choice, the largest impact of the clerkship is for those already interested in a surgical career. Interest in a surgical career largely develops before the third-year clerkship. Implications of the results for recruiting greater numbers of students into surgical careers are discussed.

Laparoscopic drainage of a hepatic echinococcal cyst: a case report.

The Echinococcus granulosus tapeworm causes hepatic echinococcosis. It is endemic in the Mediterranean region, Middle East, and South America. Human infection is secondary to accidental consumption of ova in feces. Absorption through the bowel wall and entrance into the portal circulation leads to liver infection. This case involves a 34 y/o Moroccan male with an echinococcal liver cyst. His chief complaint was RUQ pain. The patient was treated with albendazole and praziquantel. His PMH and PSH was noncontributory. Patient was not on any other medications. ROS was otherwise unremarkable. The patient was AF VSS. He was tender to palpation in RUQ. Liver function tests were normal. Echinococcal titers were positive. CT demonstrated a large cystic lesion in the right lobe of the liver measuring 13.5 cm in diameter. The patient underwent successful laparoscopic drainage and excision of echinococcal cyst. Final pathology demonstrated degenerating parasites (E. granulosus) of echinococcal cyst.