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

Student, Teacher, and Observer Perceptions of the Classroom Environment Before and after the Transition to Junior High School

Student and teacher perceptions of the classroom environment were assessed during mathematics instruction in 117 sixth grade elementary school classrooms and the following year in 138 seventh grade junior high school classrooms. Observer perceptions were collected in a subset of these classrooms. As hypothesized, after the transition students were given fewer opportunities for input, interaction and cooperation; whole class task organization and the use of social comparison increased; and student/teacher relationships deteriorated. Contrary to predictions, competition was more prevalent before than after the transition and the frequency of grading did not change. It is suggested that a "developmental mismatch" may exist between maturing children and the classroom environments they experience before and after the transition to junior high school.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67243/2/10.1177_0272431688082003.pd

Hungarian pronominal case and the dichotomy of content and form in inflectional morphology

Hungarian nouns take some seventeen or so suffixal case inflections, e.g. ház ‘house (nominative)’ ∼ ház-ban ‘in a house (inessive)’. Personal pronouns have corresponding case-marked forms but these are not formed by means of suffixal case inflections. Instead, postposition-like stems expressing the individual cases are inflected for each pronoun’s person and number in exactly the same way that nouns inflect for possessor agreement or true postpositions inflect for a pronominal complement (inessive benn-e ‘in him’, benn-ük ‘in them; cf. könyv-e ‘his book’, könyv-ük ‘their book’ from the noun könyv; mögött-e ‘behind him’, mögött-ük ‘behind them’ from the postposition mögött). This manner of case marking embodies a highly unusual pattern of ‘functor-argument reversal’, which is problematic for many models of morphosyntax. In our account of this phenomenon, we adopt the modification of Stump’s (2001) Paradigm Function Morphology proposed by Stump (2002); this modification (‘PFM2’) distinguishes form paradigms (expressing morphological properties) from content paradigms (expressing syntactic properties). We also distinguish absolute forms from (bound) conjunct forms of the case postpositions. Pronominal case forms are built on the case postpositions’ absolute forms and a rule of paradigm linkage that effects functor-argument reversal guarantees that their person-number inflection realizes the content of each pronoun