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

Patterns of stressful life events: distinguishing suicide ideators from suicide attempters

Background Suicidal ideation is an important indicator for subsequent suicidal behaviour, yet only a proportion of ideators transit from thought to action. This has led to interest surrounding the factors that distinguish ideators who attempt from non-attempters. The study aimed to identify distinct classes of life event categories amongst a sample of ideators and assess the ability of the classes to predict the risk of a suicide attempt. Methods A subsample of ideators was extracted based on responses to the suicidality section of the Adult Psychiatric Morbidity Survey (N=7403). Fifteen stressful life events (SLEs) were grouped into six broad categories. Results Using Latent Class Analysis (LCA), three distinct classes emerged; class 1 had a high probability of encountering interpersonal conflict, class 2 reported a low probability of experiencing any of the SLE categories with the exception of minor life stressors, whereas class 3 had a high probability of endorsing multiple SLE categories. The Odds Ratio for attempted suicide were highest among members of Class 3. Limitations The use of broad event categories as opposed to discrete life events may have led to an underestimation of the true exposure to SLEs. Conclusions The findings suggest the experience of multiple types of SLEs may predict the risk of transitioning towards suicidal behaviour for those individuals who have contemplated suicide. In application, this re-emphasises the need for a routine appraisal of risk amongst this vulnerable group and an assessment of the variety of events which may signal the individuals who may be at immediate risk

Association between mental disorders and subsequent adult onset asthma

Associations between asthma and anxiety and mood disorders are well established, but little is known about their temporal sequence. We examined associations between a wide range of DSM-IV mental disorders with adult onset of asthma and whether observed associations remain after mental comorbidity adjustments. METHODS: During face-to-face household surveys in community-dwelling adults (n = 52,095) of 19 countries, the WHO Composite International Diagnostic Interview retrospectively assessed lifetime prevalence and age at onset of 16 DSM-IV mental disorders. Asthma was assessed by self-report of physician's diagnosis together with age of onset. Survival analyses estimated associations between first onset of mental disorders and subsequent adult onset asthma, without and with comorbidity adjustment. RESULTS: 1860 adult onset (21 years+) asthma cases were identified, representing a total of 2,096,486 person-years of follow up. After adjustment for comorbid mental disorders several mental disorders were associated with subsequent adult asthma onset: bipolar (OR = 1.8; 95%CI 1.3-2.5), panic (OR = 1.4; 95%CI 1.0-2.0), generalized anxiety (OR = 1.3; 95%CI 1.1-1.7), specific phobia (OR = 1.3; 95%CI 1.1-1.6); post-traumatic stress (OR = 1.5; 95%CI 1.1-1.9); binge eating (OR = 1.8; 95%CI 1.2-2.9) and alcohol abuse (OR = 1.5; 95%CI 1.1-2.0). Mental comorbidity linearly increased the association with adult asthma. The association with subsequent asthma was stronger for mental disorders with an early onset (before age 21). CONCLUSIONS: A wide range of temporally prior mental disorders are significantly associated with subsequent onset of asthma in adulthood. The extent to which asthma can be avoided or improved among those with early mental disorders deserves study

Cross-national epidemiology of panic disorder and panic attacks in the world mental health surveys

CONTEXT: The scarcity of cross-national reports and the changes in Diagnostic and Statistical Manual version 5 (DSM-5) regarding panic disorder (PD) and panic attacks (PAs) call for new epidemiological data on PD and PAs and its subtypes in the general population. OBJECTIVE: To present representative data about the cross-national epidemiology of PD and PAs in accordance with DSM-5 definitions. DESIGN AND SETTING: Nationally representative cross-sectional surveys using the World Health Organization Composite International Diagnostic Interview version 3.0. PARTICIPANTS: Respondents (n = 142,949) from 25 high, middle, and lower-middle income countries across the world aged 18 years or older. MAIN OUTCOME MEASURES: PD and presence of single and recurrent PAs. RESULTS: Lifetime prevalence of PAs was 13.2% (SE 0.1%). Among persons that ever had a PA, the majority had recurrent PAs (66.5%; SE 0.5%), while only 12.8% fulfilled DSM-5 criteria for PD. Recurrent PAs were associated with a subsequent onset of a variety of mental disorders (OR 2.0; 95% CI 1.8-2.2) and their course (OR 1.3; 95% CI 1.2-2.4) whereas single PAs were not (OR 1.1; 95% CI 0.9-1.3 and OR 0.7; 95% CI 0.6-0.8). Cross-national lifetime prevalence estimates were 1.7% (SE 0.0%) for PD with a median age of onset of 32 (IQR 20-47). Some 80.4% of persons with lifetime PD had a lifetime comorbid mental disorder. CONCLUSIONS: We extended previous epidemiological data to a cross-national context. The presence of recurrent PAs in particular is associated with subsequent onset and course of mental disorders beyond agoraphobia and PD, and might serve as a generic risk marker for psychopathology