American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Dec 2024
Randomized Controlled TrialPyrazinamide Safety, Efficacy, and Dosing for Treating Drug-Susceptible Pulmonary Tuberculosis: A Phase 3, Randomized, Controlled Clinical Trial.
Rationale: Optimizing pyrazinamide dosing is critical to improve treatment efficacy while minimizing toxicity during tuberculosis treatment. Study 31/AIDS Clinical Trials Group A5349 represents the largest phase 3 randomized controlled therapeutic trial to date for such an investigation. Objectives: We sought to report pyrazinamide pharmacokinetic parameters, risk factors for lower pyrazinamide exposure, and relationships between pyrazinamide exposure and efficacy and safety outcomes. ⋯ Flat dosing of pyrazinamide at 1,000 mg would have permitted an additional 13.1% (n = 96) of participants allocated to the control and 9.2% (n = 70) to the rifapentine-moxifloxacin regimen dosed within the therapeutic window, compared with the current weight-banded dosing. Conclusions: Flat dosing of pyrazinamide at 1,000 mg/d would be readily implementable and could optimize treatment outcomes in drug-susceptible tuberculosis. Clinical trial registered with www.clinicaltrials.gov (NCT02410772).
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Am. J. Respir. Crit. Care Med. · Dec 2024
Association Between Baseline Driving Pressure and Mortality in Very Old Patients with ARDS.
Rationale: Because of the effects of aging on the respiratory system, it is conceivable that the association between driving pressure and mortality depends on age. Objectives: We endeavored to evaluate whether the association between driving pressure and mortality of patients with acute respiratory distress syndrome (ARDS) varies across the adult lifespan, hypothesizing that it is stronger in older, including very old (⩾80 yr), patients. Methods: We performed a secondary analysis of individual patient-level data from seven ARDS Network and PETAL Network randomized controlled trials ("ARDSNet cohort"). ⋯ In both cohorts, a driving pressure threshold of 11 cm H2O was associated with mortality in very old patients. Conclusions: Data from randomized controlled trials with strict inclusion criteria suggest that the effect of driving pressure on the mortality of patients with ARDS may depend on age. These results may advocate for a personalized age-dependent mechanical ventilation approach.
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Am. J. Respir. Crit. Care Med. · Dec 2024
Concordance and Prognostic Relevance of Different Definitions of Systemic Sclerosis Interstitial Lung Disease Progression.
Rationale: Interstitial lung disease (ILD) in systemic sclerosis (SSc) is a common complication that has a varied progression rate and prognosis. Different progression definitions are available, including minimal clinically important worsening of FVC, EUSTAR (European Scleroderma Trials and Research Group) progression, OMERACT (Outcome Measures in Rheumatology Clinical Trials) progression, and Erice ILD working group progression. Pulmonary function and symptom changes may act as specific confounding factors when applying these definitions in SSc. ⋯ Erice criteria appeared superior in patients with duration ≥3 years, limited cutaneous variant, and pulmonary artery systolic pressure <40 mm Hg. OMERACT criteria performed better in diffuse cutaneous variant patients with severe functional impairment. Conclusions: The four evaluated definitions of progression in SSc-ILD are not interchangeable, resulting in up to one-third of cases being classified differently on the basis of adopted criteria and presenting different prognostic values, particularly within specific clinical groups.