Randomized Phase 3 Trial of Ruxolitinib for COVID-19-Associated Acute Respiratory Distress Syndrome.

OBJECTIVES: Evaluate the safety and efficacy of the Janus kinase (JAK)1/JAK2 inhibitor ruxolitinib in COVID-19-associated acute respiratory distress syndrome requiring mechanical ventilation. DESIGN: Phase 3 randomized, double-blind, placebo-controlled trial Ruxolitinib in Participants With COVID-19-Associated Acute Respiratory Distress Syndrome Who Require Mechanical Ventilation (RUXCOVID-DEVENT; NCT04377620). SETTING: Hospitals and community-based private or group practices in the United States (29 sites) and Russia (4 sites). PATIENTS: Eligible patients were greater than or equal to 12 years old, hospitalized with severe acute respiratory syndrome coronavirus 2 infection, and mechanically ventilated with a Pa o2 /F io2 of less than or equal to 300 mm Hg within 6 hours of randomization. INTERVENTIONS: Patients were randomized 2:2:1 to receive twice-daily ruxolitinib 15 mg, ruxolitinib 5 mg, or placebo, each plus standard therapy. MEASUREMENTS AND MAIN RESULTS: The primary endpoint, 28-day mortality, was tested for each ruxolitinib group versus placebo using a mixed-effects logistic regression model and one-tailed significance test (significance threshold: p < 0.025); no type 1 error was allocated to secondary endpoints. Between May 24, 2020 and December 15, 2020, 211 patients (age range, 24-87 yr) were randomized (ruxolitinib 15/5 mg, n = 77/87; placebo, n = 47). Acute respiratory distress syndrome was categorized as severe in 27% of patients (58/211) at randomization; 90% (190/211) received concomitant steroids. Day-28 mortality was 51% (39/77; 95% CI, 39-62%) for ruxolitinib 15 mg, 53% (45/85; 95% CI, 42-64%) for ruxolitinib 5 mg, and 70% (33/47; 95% CI, 55-83%) for placebo. Neither ruxolitinib 15 mg (odds ratio, 0.46 [95% CI, 0.201-1.028]; one-sided p = 0.029) nor 5 mg (odds ratio, 0.42 [95% CI, 0.171-1.023]; one-sided p = 0.028) significantly reduced 28-day mortality versus placebo. Numerical improvements with ruxolitinib 15 mg versus placebo were observed in secondary outcomes including ventilator-, ICU-, and vasopressor-free days. Rates of overall and serious treatment-emergent adverse events were similar across treatments. CONCLUSIONS: The observed reduction in 28-day mortality rate between ruxolitinib and placebo in mechanically ventilated patients with COVID-19-associated acute respiratory distress syndrome was not statistically significant; however, the trial was underpowered owing to early termination.

Aesthetics in Thyroid Surgery: The Patient Perspective.

Objectives To define characteristics that influence patient perceptions of thyroidectomy scar cosmesis. Study Design Prospective cohort study. Setting Tertiary endocrine surgery practice in an academic medical center. Subjects and Methods Institutional review board-approved trial in which 136 subjects were recruited from a population of patients being seen for either thyroid or sinus surgery and evaluated standardized photographs, superimposed with computer-generated thyroidectomy scars of varying lengths (2, 4, and 6 cm) and widths (1 and 2 mm), and graded their perception of the scars using the observer scar assessment scale (OSAS) domains of the patient and observer scar assessment scale. Results There were 69 subjects in the thyroid group and 67 in the nonthyroid group. Controlling for width, longer scars were perceived as worse than shorter scars; controlling for length, thicker scars were perceived as worse than thinner scars ( P < .01). Beyond 2 cm, thick scars were judged to be worse than thin scars, even when they were shorter. There was no difference in the mean overall OSAS scores between surgery, sex, or age groups. Nonwhites tended to judge scars as being worse than whites did ( P < .01). Conclusion As expected, patients of all demographics prefer shorter scars compared with longer scars and thinner scars over thick scars. Ethnic differences in scar perception were identified and deserve additional study. Surgeons should endeavor to perform thyroid surgery through the smallest incision that allows the operation to be performed safely to minimize the cosmetic impact of the operation.