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

The Impact of Word Processing on the Written Expression of Students with Learning Disabilities in the Area of Written Expression

The purpose of this study was to investigate the effect of word processing on the quality of written expression of students with learning disabilities identified in the area of written expression. A examination of existing research revealed that most studies do not focus on word processing independent of writing instruction. Therefore, the consensus among researchers that word processors make a difference is limited by the influence of instruction within the research setting. Therefore, this study sought to determine the impact made solely by word processing by controlling for instruction. The 75 students who participated in the study represented three groups--students with learning disabilities identified in the area of written expression (LD-W), students with learning disabilities identified in an area other than written expression (LD-O), and general education students (NA). Each student completed four writing samples: (a) descriptive - handwritten, (b) informative - handwritten, (c) descriptive - word processed, and (d) informative - word processed. The writing samples were scored according to the TOWL-3 on the three Spontaneous Composite subtests (e.g., Contextual Conventions, Contextual Language, and Story Construction). In addition, Word Perfect 6.1- Grammatik was used to determine the number of syllables, words, and sentences in each writing sample. A multivariate analysis of variance (MANOVA) was used in the analysis in conjunction with univariate F-Tests and Tukey's Honestly Significant Difference (HSD) test. General education students scored consistently higher than LD-W on all subtests even when handwriting and word processing were considered. They also generated more syllables, words, and sentences than students with learning disabilities. In addition, all students scored higher on subtests when writing descriptive samples rather than writing informative samples. No practically significant results were determined for the effect of word processing. Therefore, word processing alone does not have an impact on students' quality of writing. It is simply a tool in the writing process. These results do not suggest that schools disregard the use of technology. Rather, teachers must continue to use word processors during writing instruction but should focus on providing good writing instruction

The Sizes and Albedos of Centaurs 2014 YY 49_{49} and 2013 NL 24_{24} from Stellar Occultation Measurements by RECON

In 2019, the Research and Education Collaborative Occultation Network (RECON) obtained multiple-chord occultation measurements of two centaur objects: 2014 YY$_{49}$ on 2019 January 28 and 2013 NL$_{24}$ on 2019 September 4. RECON is a citizen-science telescope network designed to observe high-uncertainty occultations by outer solar system objects. Adopting circular models for the object profiles, we derive a radius $r=16^{+2}_{-1}$km and a geometric albedo $p_V=0.13^{+0.015}_{-0.024}$ for 2014 YY$_{49}$, and a radius $r=66 ^{+5}_{-5}$km and geometric albedo $p_V = 0.045^{+0.006}_{-0.008}$ for 2013 NL$_{24}$. To the precision of these measurements, no atmosphere or rings are detected for either object. The two objects measured here are among the smallest distant objects measured with the stellar occultation technique. In addition to these geometric constraints, the occultation measurements provide astrometric constraints for these two centaurs at a higher precision than has been feasible by direct imaging. To supplement the occultation results, we also present an analysis of color photometry from the Pan-STARRS surveys to constrain the rotational light curve amplitudes and spectral colors of these two centaurs. We recommend that future work focus on photometry to more deliberately constrain the objects' colors and light curve amplitudes, and on follow-on occultation efforts informed by this astrometry