American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Mar 2022
Association of Intensive Care Unit Admission and Outcomes in Sepsis and Acute Respiratory Failure.
Rationale: Many decisions to admit patients to the ICU are not grounded in evidence regarding who benefits from such triage, straining ICU capacity and limiting its cost-effectiveness. Objectives: To measure the benefits of ICU admission for patients with sepsis or acute respiratory failure. Methods: At 27 United States hospitals across two health systems from 2013 to 2018, we performed a retrospective cohort study using two-stage instrumental variable quantile regression with a strong instrument (hospital capacity strain) governing ICU versus ward admission among high-acuity patients (i.e., laboratory-based acute physiology score v2 ⩾ 100) with sepsis and/or acute respiratory failure who did not require mechanical ventilation or vasopressors in the emergency department. ⋯ In sensitivity analyses of length of stay, excluding, ignoring, or censoring death, results were similar in sepsis but not in respiratory failure. In subgroup analyses, harms of ICU admission for patients with sepsis were concentrated among older patients and those with fewer comorbidities, and the benefits of ICU admission for patients with respiratory failure were concentrated among older patients, highest-acuity patients, and those with more comorbidities. Conclusions: Among high-acuity patients with sepsis who did not require life support in the emergency department, initial admission to the ward, compared with the ICU, was associated with shorter length of stay and improved survival, whereas among patients with acute respiratory failure, triage to the ICU compared with the ward was associated with improved survival.
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Am. J. Respir. Crit. Care Med. · Mar 2022
Multicenter Study Observational StudyEffects of Elexacaftor/Tezacaftor/Ivacaftor Therapy on CFTR Function in Patients with Cystic Fibrosis and One or Two F508del Alleles.
Rationale: The CFTR (cystic fibrosis transmembrane conductance regulator) modulator combination elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to improve clinical outcomes and sweat chloride concentration in patients with cystic fibrosis (CF) and one or two F508del alleles. However, the effect of ELX/TEZ/IVA on CFTR function in the airways and intestine has not been studied. Objectives: To assess the effect of ELX/TEZ/IVA on CFTR function in airway and intestinal epithelia in patients with CF and one or two F508del alleles aged 12 years and older. ⋯ In F508del homozygous patients, ELX/TEZ/IVA exceeded improvement of CFTR function observed with TEZ/IVA and increased CFTR-mediated Cl- secretion to a level of 47.4% of normal (IQR, 19.3-69.2; P < 0.001) in nasal and 45.9% (IQR, 19.7-66.6; P < 0.001) in intestinal epithelia. Conclusions: Treatment with ELX/TEZ/IVA results in effective improvement of CFTR function in airway and intestinal epithelia in patients with CF and one or two F508del alleles. Clinical trial registered with www.clinicaltrials.gov (NCT04732910).
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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.