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

Psychometric Performance and Responsiveness of the Functional Outcomes of Sleep Questionnaire and Sleep Apnea Quality of Life Index in a Randomized Trial: The HomePAP Study

Study objectivesMeasures of health-related quality of life (HRQL) specific for sleep disorders have had limited psychometric evaluation in the context of randomized controlled trials (RCTs). We investigated the psychometric properties of the Functional Outcomes of Sleep Questionnaire (FOSQ) and Sleep Apnea Quality of Life Instrument (SAQLI). We evaluated the FOSQ and SAQLI construct and criterion validity, determined a minimally important difference, and assessed for associations of responsiveness to baseline subject characteristics and continuous positive airway pressure (CPAP) adherence in a RCT population.DesignSecondary analysis of data collected in a multisite RCT of home versus laboratory-based diagnosis and treatment of obstructive sleep apnea (HomePAP trial).ParticipantsIndividuals enrolled in the HomePAP trial (n = 335).InterventionsN/A.Measurement and resultsThe FOSQ and SAQLI subscores demonstrated high reliability and criterion validity, correlating with Medical Outcomes Study 36-Item Short Form Survey domains. Correlations were weaker with the Epworth Sleepiness Scale (ESS). Both the FOSQ and SAQLI scores improved after 3 mo with CPAP therapy. Averaging 4 h or more of CPAP use was associated with an increase in the FOSQ beyond the minimally important difference. Baseline depressive symptoms and sleepiness predicted FOSQ and SAQLI responsiveness; demographic, objective obstructive sleep apnea (OSA) severity and sleep habits were not predictive in linear regression.ConclusionsThe FOSQ and SAQLI are responsive to CPAP intervention, with the FOSQ being more sensitive to differences in CPAP adherence than the SAQLI. These instruments provide unique information about health outcomes beyond that provided by changes in physiological measures of OSA severity (apnea-hypopnea index).Clinical trial informationPortable Monitoring for Diagnosis and Management of Sleep Apnea (HomePAP) URL: http://clinicaltrials.gov/show/NCT00642486. NIH clinical trials registry number: NCT00642486

A dozen years of American Academy of Sleep Medicine (AASM) International Mini-Fellowship: program evaluation and future directions.

UNLABELLED: Sleep medicine remains an underrepresented medical specialty worldwide, with significant geographic disparities with regard to training, number of available sleep specialists, sleep laboratory or clinic infrastructures, and evidence-based clinical practices. The American Academy of Sleep Medicine (AASM) is committed to facilitating the education of sleep medicine professionals to ensure high-quality, evidence-based clinical care and improve access to sleep centers around the world, particularly in developing countries. In 2002, the AASM launched an annual 4-week training program called Mini-Fellowship for International Scholars, designed to support the establishment of sleep medicine in developing countries. The participating fellows were generally chosen from areas that lacked a clinical infrastructure in this specialty and provided with training in AASM Accredited sleep centers. This manuscript presents an overview of the program, summarizes the outcomes, successes, and lessons learned during the first 12 years, and describes a set of programmatic changes for the near-future, as assembled and proposed by the AASM Education Committee and recently approved by the AASM Board of Directors. CITATION: Ioachimescu OC; Wickwire EM; Harrington J; Kristo D; Arnedt JT; Ramar K; Won C; Billings ME; DelRosso L; Williams S; Paruthi S; Morgenthaler TI. A dozen years of American Academy of Sleep Medicine (AASM) international mini-fellowship: program evaluation and future directions

A Dozen Years of American Academy of Sleep Medicine (AASM) International Mini-Fellowship: Program Evaluation and Future Directions

Sleep medicine remains an underrepresented medical specialty worldwide, with significant geographic disparities with regard to training, number of available sleep specialists, sleep laboratory or clinic infrastructures, and evidence-based clinical practices. The American Academy of Sleep Medicine (AASM) is committed to facilitating the education of sleep medicine professionals to ensure high-quality, evidence-based clinical care and improve access to sleep centers around the world, particularly in developing countries. In 2002, the AASM launched an annual 4-week training program called Mini-Fellowship for International Scholars, designed to support the establishment of sleep medicine in developing countries. The participating fellows were generally chosen from areas that lacked a clinical infrastructure in this specialty and provided with training in AASM Accredited sleep centers. This manuscript presents an overview of the program, summarizes the outcomes, successes, and lessons learned during the first 12 years, and describes a set of programmatic changes for the near-future, as assembled and proposed by the AASM Education Committee and recently approved by the AASM Board of Directors. CITATION: Ioachimescu OC; Wickwire EM; Harrington J; Kristo D; Arnedt JT; Ramar K; Won C; Billings ME; DelRosso L; Williams S; Paruthi S; Morgenthaler TI. A dozen years of American Academy of Sleep Medicine (AASM) international mini-fellowship: program evaluation and future directions. J Clin Sleep Med 2014;10(3):331-334

Dose-response relationship between positive airway pressure therapy and excessive daytime sleepiness: the HomePAP study.

Study objectivesThe clinical benefits of positive airway pressure (PAP) therapy for obstructive sleep apnea are assumed to require adherent PAP usage, defined by the Centers for Medicare & Medicaid Services as ≥ 4 hours of use ≥ 70% of nights. However, this definition is based on early data and does not necessarily capture improvements at subthreshold adherence. We explored dose-response relationships between PAP adherence measures and excessive daytime sleepiness from the HomePAP randomized controlled trial.MethodsParticipants aged ≥ 18 years with an apnea-hypopnea index ≥ 15 events/h and baseline sleepiness (Epworth Sleepiness Scale [ESS] ≥ 12) received PAP therapy. Data were collected at baseline, 1-month follow-up, and 3-months follow-up. Regression models and receiver operating characteristic curves evaluated PAP measures as predictors of ESS change and normalization (ESS < 10).ResultsIn 119 participants (aged 49.4 ± 12.6 years, 66.4% male, 72.3% White), > 50% were PAP nonadherent per Centers for Medicare & Medicaid Services criteria at 3 months. The percentage of nights with PAP use ≥ 4 hours predicted ESS change (P = .023), but not when controlling for the apnea-hypopnea index. The percentage of nights with ≥ 4 hours and average PAP use provided the best discrimination for predicting ESS normalization; each 10% increase in PAP use ≥ 4 hours increased the odds of ESS normalization by 22% (P = .007); those using PAP ≥ 4 hours had a nearly 3-fold greater odds of ESS normalization (P = .025). PAP use for at least 4 hours and on 70% of nights provided the best balance between specificity (0.50) and sensitivity (0.73).ConclusionsAlthough subadherent PAP usage may still confer some benefit for patients with obstructive sleep apnea, adherence to current criteria confers the highest likelihood for ESS change and normalization.Clinical trial registrationRegistry: ClinicalTrials.gov; Name: Portable Monitoring for Diagnosis and Management of Sleep Apnea (HomePAP); URL: https://clinicaltrials.gov/ct2/show/NCT00642486; Identifier: NCT00642486.CitationPascoe M, Bena J, Andrews ND, et al. Dose-response relationship between positive airway pressure therapy and excessive daytime sleepiness: the HomePAP study. J Clin Sleep Med. 2022;18(4):1027-1034