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

Referral order placement decreases time to transfer to adult congenital heart disease care.

Abstract Background Pediatric patients with moderate and great complexity congenital heart disease (CHD) may benefit from coordinated transfer to adult congenital heart disease (ACHD) centers to reduce the risk of complications; however, there are a variety of transfer practices. We examined the impact of referral order placement at the last pediatric cardiology visit on time to transfer to an ACHD center. Methods We analyzed data collected from pediatric patients with moderate and great complexity CHD who were eligible to transfer to our tertiary center’s accredited ACHD center. We examined transfer outcomes and time-to-transfer between those with a referral order placed at the last pediatric cardiology visit and those without using Cox proportional hazards modeling. Results The sample (n = 65) was 44.6% female and mean age at study start was 19.5 years (± 2.2). Referral orders were placed for 32.3% of patients at the last pediatric cardiology visit. Those who had a referral order placed at the last visit had significantly higher number of successful transfers to the ACHD center compared to those who did not (95% vs 25%, p &lt; 0.001). In a Cox regression model, placement of a referral order at the last pediatric cardiology visit was associated significantly with a sooner time to transfer (HR 6.0; 95% CI 2.2–16.2, p &gt; 0.001), adjusting for age, sex, complexity, living location, and pediatric cardiology visit location. Conclusions Placement of a referral order at the last pediatric cardiology visit may improve transfer occurrence and time to transfer to accredited ACHD centers.</jats:p

A medical assistant-facilitated transition activity in a pediatric cardiology clinic

Background: Formal transition programs prepare pediatric patients with congenital heart disease (CHD) for successful lifelong management of their disease. Conducting transition program activities in pediatric cardiology clinics can be a challenge if there are limited resources. The purpose of this study was to test the effectiveness of a medical assistant (MA)-facilitated transition activity in increasing documentation of transition discussions and characterize staff acceptability of this intervention. Method: We performed a prospective exploratory study over a five-week period. CHD patients aged 13 and older presenting for routine pediatric cardiology follow-up appointments received a prompt from the MA to view a list of 17 transition topics from which to choose topics for discussion with the pediatric cardiologist during the clinic visit. Historical control group data were collected from the same period, two years prior. We compared the presence of documentation of transition discussions between the transition activity and control group using comparative statistics. Staff acceptability was assessed using the revised Treatment Acceptability and Preference Questionnaire. Results: A total of 14 staff members participated in the transition activity involving 29 patients. Significantly more transition discussions were documented in the transition activity group compared with the historic control group (p < 0.001). Patients discussed more transition topics (median = 5, Interquartile range 2–7) than what was requested (median = 2, Interquartile range 1–4). All staff rated the activity as acceptable (ranging from ‘somewhat acceptable’ to ‘very much acceptable’) and were willing to continue after the study ended. Conclusion: Having an MA-facilitated transition activity increased documentation of transition discussions in the pediatric cardiology clinic. Staff were accepting and in favor of continuing this low-resource activity

Three Types Of Polarity

There can be no doubt that the phenomenon of polarity, though usually the subject of syntactic and semantic study, is essentially of a purely lexical nature.' This is evident to anyone who is familiar with the distribution of so-called negative polarity items. The fact that expressions such as hoeven and ook maar iets in Dutch, brauchen and auch nur irgendetwas in German, or the English cognates need and anything (at all) require the presence of a negative element somewhere in the sentence, is a property which is intrinsic to the items in question and must therefore be accounted for in the lexicon. If there is any doubt as to the lexical nature of this phenomenon, it is completely eradicated by the distinction between negative polarity items of the weak and those of the strong type. In order to get a clear view of the content of this distinction, one does well to take the following Dutch examples into consideration.

Additional file 1: of Evaluation of a risk-stratification strategy to improve primary care for low back pain: the MATCH cluster randomized trial protocol

Non-specific Back Pain Assessment, Management, and Follow-up Guideline. (DOCX 176 kb