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

Ramelteon for Insomnia Symptoms in a Community Sample of Adults with Generalized Anxiety Disorder: An Open Label Study

OBJECTIVE: Prior research confirms the relationship between insomnia and psychiatric disorders, particularly anxiety and depression. The effectiveness and tolerability of ramelteon was examined in adult generalized anxiety disorder (GAD) patients with insomnia symptoms. METHODS: Twenty-seven adults with sleep disturbance meeting DSM-IV diagnostic criteria for GAD and partially responsive on an SSRI or SNRI by randomization visit (as signified by a Hamilton Anxiety scale [HAMA] maximum score of 15 and minimum of 8, Clinical Global Impressions Severity of Illness [CGI-S] scale of \u3c or = 4 and \u3e or = 2 [measuring anxiety symptoms], CGI-S of 4 [measuring insomnia symptoms], \u3e or = 5 on the Pittsburgh Sleep Quality Index [PSQI], and \u3e or = 10 on the Epworth Sleepiness Scale [ESS]) were treated openly for 10 weeks on ramelteon 8 mg at bedtime. Analysis was conducted using repeated measures methodology. Patient reported sleep diaries were maintained throughout the study. RESULTS: Significant symptom reduction was observed on all scales (HAMA, ESS, CGI-I, CGI-S), with subjects falling asleep faster and sleeping longer. Headache upon stopping ramelteon, daytime tiredness, agitation, and depression were the most commonly reported side effects and were cited as transient. CONCLUSION: Data from this 12-week open-label study suggests ramelteon is an effective and generally well tolerated treatment for insomnia symptoms in this community sample of adults with GAD

Safety and Efficacy of Bupropion Extended Release in Treating a Community Sample of Hispanic and African American Adults With Major Depressive Disorder: An Open-Label Study

Objectives: Many publications and federal agencies call for more trials and research on the effectiveness of medications and treatment needs in diverse patient populations with psychiatric disorders. This study investigates the effectiveness of bupropion extended release (XL) on a community sample of men and women of either Hispanic or African American heritage with major depressive disorder (MDD)

Effects of Paroxetine CR on Depressive and Anxiety Symptoms: In a Community Sample of Adult Hispanic Women with Major Depression or Generalized Anxiety Disorder.

OBJECTIVE: Previous research reports higher rates of depression in Hispanic women than Caucasian or African American women. The effectiveness and tolerability of paroxetine CR (controlled release) was examined in women of Hispanic heritage with depression or anxiety. METHODS: Thirty-six Hispanic female patients 18 years or older meeting DSM-IV criteria for major depression or generalized anxiety disorder diagnosis with an initial Hamilton Depression Rating scale (17 item) Ž20 or Hamilton Anxiety Rating scale Ž18 measuring no less than 4 on the Clinical Global Impression Severity scale received paroxetine CR (12.5-50mg/day) for 29 weeks of open label treatment. Analysis was conducted using repeated measures methodology. RESULTS: Significant symptom reduction was observed on all scales. Mean dose was 31.7mg. The side effect of sexual dysfunction (17%) appeared most frequently but did not cause any patients to cease study participation. CONCLUSIONS: Paroxetine CR was an effective and generally well tolerated treatment in this population