American journal of respiratory and critical care medicine
-
Am. J. Respir. Crit. Care Med. · Mar 2022
Observational StudyAlveolar, Endothelial, and Organ Injury Marker Dynamics in Severe COVID-19.
Rationale: Alveolar and endothelial injury may be differentially associated with coronavirus disease (COVID-19) severity over time. Objectives: To describe alveolar and endothelial injury dynamics and associations with COVID-19 severity, cardiorenovascular injury, and outcomes. Methods: This single-center observational study enrolled patients with COVID-19 requiring respiratory support at emergency department presentation. ⋯ Conclusions: Alveolar injury markers increase early. Endothelial injury markers increase later and are associated with cardiorenovascular injury and 28-day outcome. Alveolar and endothelial injury likely contribute at different times to disease progression in severe COVID-19.
-
Am. J. Respir. Crit. Care Med. · Mar 2022
Multi-night Prevalence, Variability, and Diagnostic Misclassification of Obstructive Sleep Apnea.
Rationale: Recent studies suggest that obstructive sleep apnea (OSA) severity can vary markedly from night to night, which may have important implications for diagnosis and management. Objectives: This study aimed to assess OSA prevalence from multinight in-home recordings and the impact of night-to-night variability in OSA severity on diagnostic classification in a large, global, nonrandomly selected community sample from a consumer database of people that purchased a novel, validated, under-mattress sleep analyzer. Methods: A total of 67,278 individuals aged between 18 and 90 years underwent in-home nightly monitoring over an average of approximately 170 nights per participant between July 2020 and March 2021. ⋯ Misdiagnosis error rates decreased with increased monitoring nights (e.g., 1-night F1-score = 0.77 vs. 0.94 for 14 nights) and remained stable after 14 nights of monitoring. Conclusions: Multinight in-home monitoring using novel, noninvasive under-mattress sensor technology indicates a global prevalence of moderate to severe OSA of approximately 20%, and that approximately 20% of people diagnosed with a single-night study may be misclassified. These findings highlight the need to consider night-to-night variation in OSA diagnosis and management.
-
Am. J. Respir. Crit. Care Med. · Mar 2022
Efficacy of Long-Acting Bedaquiline Regimens in a Mouse Model of Tuberculosis Preventive Therapy.
Rationale: Completion of preventive therapy is a major bottleneck in global tuberculosis control. Long-acting injectable drug formulations would shorten therapy administration and may thereby improve completion rates. Recently, a long-acting formulation of bedaquiline demonstrated antituberculosis activity for up to 12 weeks after injection in a validated mouse model of preventive therapy. ⋯ Measurements and Main Results: One injection of long-acting bedaquiline at 160 mg/kg exerted antituberculosis activity for 12 weeks. Compared with the positive control (daily isoniazid-rifapentine for 4 wk), six regimens had equivalent bactericidal activity (including two all-oral comparator regimens), and two regimens had superior sterilizing activity: one injection with 2 weeks of oral bedaquiline and high-dose rifapentine; and two injections with 4 weeks of oral bedaquiline. Conclusions: Long-acting injectable bedaquiline has significant potential for shortening tuberculosis preventive therapy.