American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Mar 2021
Inflammation and Coagulation during Critical Illness and Long-Term Cognitive Impairment and Disability.
Rationale: The biological mechanisms of long-term cognitive impairment and disability after critical illness are unclear. Objectives: To test the hypothesis that markers of acute inflammation and coagulation are associated with subsequent long-term cognitive impairment and disability. Methods: We obtained plasma samples from adults with respiratory failure or shock on Study Days 1, 3, and 5 and measured concentrations of CRP (C-reactive protein), IFN-γ, IL-1β, IL-6, IL-8, IL-10, IL-12, MMP-9 (matrix metalloproteinase-9), TNF-α (tumor necrosis factor-α), soluble TNF receptor 1, and protein C. ⋯ No other markers were consistently associated with disability outcomes. Conclusions: Markers of systemic inflammation and coagulation measured early during critical illness are not associated with long-term cognitive outcomes and demonstrate inconsistent associations with disability outcomes. Future studies that pair longitudinal measurement of inflammation and related pathways throughout the course of critical illness and during recovery with long-term outcomes are needed.
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Am. J. Respir. Crit. Care Med. · Mar 2021
Editorial Comparative StudyRisk Stratification in PAH: Do Not Forget the Patient Perspective!
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Am. J. Respir. Crit. Care Med. · Mar 2021
Comparative StudyEnrichment Benefits of Risk Algorithms for Pulmonary Arterial Hypertension Clinical Trials.
Rationale: Event-driven primary endpoints are increasingly used in pulmonary arterial hypertension clinical trials, substantially increasing required sample sizes and trial lengths. The U. S. ⋯ The REVEAL 2.0's risk grouping provided the greatest time and sample size savings in AMBITION and GRIPHON for all enrichment strategies but lacked appropriate inputs (i.e., N-terminal-proB-type natriuretic peptide) to perform as well in SERAPHIN. Cost analysis applied to GRIPHON demonstrated the greatest financial benefit by enrolling patients with a REVEAL score ≥8. Conclusions: This preliminary study demonstrates the feasibility of risk algorithms for pulmonary arterial hypertension trial enrichment and a need for further investigation.
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Am. J. Respir. Crit. Care Med. · Mar 2021
Development and Validation of SDBeasy Score as a Predictor of Behavioral Outcomes in Childhood.
Rationale: There are limited tools to identify which children are at greatest risk for developing sleep-disordered breathing (SDB)-associated behavioral morbidity. Objectives: To examine associations between age of onset and duration of parent-reported symptoms of SDB and behavioral problems at the age of 5 years. Methods: Data were collected and analyses were completed for participants in the CHILD (Canadian Healthy Infant Longitudinal Development) cohort at the Edmonton and Toronto sites. ⋯ Children had a 0.35-point-higher CBCL total behavioral score at 5 years for each 1-point increase in their SDBeasy score (95% confidence interval, 0.24-0. 5; P < 0.01). We found consistent results among CHILD-Toronto participants; children had a 0.26-point-higher CBCL total behavioral score at 5 years for each 1-point increase in their SDBeasy score (95% confidence interval, 0.08-0.44; P = 0.005). Conclusions: The SDBeasy score, based on the Pediatric Sleep Questionnaire, enables identification of children with higher behavioral-problem scores.
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Am. J. Respir. Crit. Care Med. · Mar 2021
Comparative StudyEndotypic Mechanisms of Successful Hypoglossal Nerve Stimulation for Obstructive Sleep Apnea.
Rationale: Approximately one-third of patients with obstructive sleep apnea (OSA) treated with hypoglossal nerve stimulation (HGNS) therapy are incomplete responders, despite careful patient selection based on baseline characteristics and drug-induced sleep endoscopy. Objectives: Here we use polysomnographic endotyping to assess the pathophysiological mechanisms underlying favorable versus incomplete responses to HGNS therapy. Methods: Baseline polysomnography data of the STAR (Stimulation Therapy for Apnea Reduction) trial were included. ⋯ Conclusions: Favorable responses to HGNS therapy are associated with the pathophysiological traits causing OSA, particularly a higher arousal threshold. Along with established criteria, individuals with favorable traits could potentially be prioritized for precision HGNS therapy. This analysis was a secondary analysis of the STAR trial registered with clinicaltrials.gov (NCT01161420).