American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · May 2023
Clinical TrialA Standardized Approach for Collection of Objective Data to Support Outcome Determination for Late-Phase TB Trials.
Rationale: We developed a standardized method, possible poor treatment response (PPTR), to help ascertain efficacy endpoints in Study S31/A5349 (NCT02410772), an open-label trial comparing two 4-month rifapentine-based regimens with a standard 6-month regimen for the treatment of pulmonary tuberculosis (TB). Objectives: We describe the use of the PPTR process and evaluate whether the goals of minimizing bias in efficacy endpoint assessment and attainment of relevant data to determine outcomes for all participants were achieved. Methods: A PPTR event was defined as the occurrence of one or more prespecified triggers. ⋯ At least one PPTR event was experienced by 92.4% (133 of 144) of participants with TB-related unfavorable outcome and between 13.8% and 14.7% of participants with favorable and not-assessable outcomes. A total of 75% of participants with TB-related unfavorable outcomes had microbiological confirmation of failure to achieve a disease-free cure. Conclusions: Standardized methodologies, such as our PPTR approach, could facilitate unbiased efficacy outcome determinations, improve discrimination between outcomes that are related and unrelated to regimen efficacy, and enhance the ability to conduct pooled analyses of contemporary trials.
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Am. J. Respir. Crit. Care Med. · May 2023
Temperature Trajectory Subphenotypes in Oncology Patients with Neutropenia and Suspected Infection.
Rationale: Despite etiologic and severity heterogeneity in neutropenic sepsis, management is often uniform. Understanding host response clinical subphenotypes might inform treatment strategies for neutropenic sepsis. Objectives: In this retrospective two-hospital study, we analyzed whether temperature trajectory modeling could identify distinct, clinically relevant subphenotypes among oncology patients with neutropenia and suspected infection. ⋯ Bloodstream infections were more common among hyperthermic slow resolvers (n = 248 [21.8%]) and hyperthermic fast resolvers (n = 240 [18.3%]) than among hypothermic (n = 188 [11.7%]) or normothermic (n = 418 [11.5%]) encounters (P < 0.001). Adjusted for confounders, hyperthermic slow resolvers had increased adjusted odds for mortality (primary cohort odds ratio, 1.91 [P = 0.03]; validation cohort odds ratio, 2.19 [P < 0.001]) and bloodstream infection (primary odds ratio, 1.54 [P = 0.04]; validation cohort odds ratio, 2.15 [P < 0.001]). Conclusions: Temperature trajectory subphenotypes were independently associated with important outcomes among hospitalized patients with neutropenia in two independent cohorts.
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Am. J. Respir. Crit. Care Med. · May 2023
Randomized Controlled TrialRespective Effects of Helmet Pressure Support, Continuous Positive Airway Pressure and Nasal High-Flow in Hypoxemic Respiratory Failure: A Randomized Crossover Clinical Trial.
Rationale: The respective effects of positive end-expiratory pressure (PEEP) and pressure support delivered through the helmet interface in patients with hypoxemia need to be better understood. Objectives: To assess the respective effects of helmet pressure support (noninvasive ventilation [NIV]) and continuous positive airway pressure (CPAP) compared with high-flow nasal oxygen (HFNO) on effort to breathe, lung inflation, and gas exchange in patients with hypoxemia (PaO2/FiO2 ⩽ 200). Methods: Fifteen patients underwent 1-hour phases (constant FiO2) of HFNO (60 L/min), helmet NIV (PEEP = 14 cm H2O, pressure support = 12 cm H2O), and CPAP (PEEP = 14 cm H2O) in randomized sequence. ⋯ CPAP and NIV similarly increased oxygenation, end-expiratory lung volume, and Vt, without affecting ΔPL. NIV, and to a lesser extent CPAP, mitigated pendelluft. Clinical trial registered with clinicaltrials.gov (NCT04241861).