American journal of respiratory and critical care medicine
-
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.
-
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.
-
Am. J. Respir. Crit. Care Med. · Mar 2021
Editorial Comparative StudyRisk Stratification in PAH: Do Not Forget the Patient Perspective!