American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · May 2022
Randomized Controlled Trial Multicenter StudyAn All-Oral 6-Month Regimen for Multidrug-Resistant TB (the NExT Study): A Multicenter, Randomized Controlled Trial.
Rationale: Improving treatment outcomes while reducing drug toxicity and shortening the treatment duration to ∼6 months remains an aspirational goal for the treatment of multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB). Objectives: To conduct a multicenter randomized controlled trial in adults with MDR/RR-TB (i.e., without resistance to fluoroquinolones or aminoglycosides). Methods: Participants were randomly assigned (1:1 ratio) to a ∼6-month all-oral regimen that included levofloxacin, bedaquiline, and linezolid, or the standard-of-care (SOC) ⩾9-month World Health Organization (WHO)-approved injectable-based regimen. ⋯ However, drug toxicity occurred frequently in both arms. These findings inform strategies to develop future regimens for MDR/RR-TB. Clinical trial registered with www.clinicaltrials.gov (NCT02454205).
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Am. J. Respir. Crit. Care Med. · May 2022
Randomized Controlled TrialEarly Bactericidal Activity of Meropenem Plus Clavulanate (+/-Rifampin) For TB: The COMRADE Randomized, Phase 2 Trial.
Rationale: Carbapenems are recommended for treatment of drug-resistant tuberculosis. Optimal dosing remains uncertain. Objectives: To evaluate the 14-day bactericidal activity of meropenem, at different doses, with or without rifampin. ⋯ This difference was only detectable with solid culture. Tolerability of intravenous meropenem, with amoxicillin/clavulanate, though, was poor at all doses, calling into question the utility of this drug in second-line regimens. Clinical trial registered with www.clinicaltrials.gov (NCT03174184).
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Am. J. Respir. Crit. Care Med. · May 2022
Historical ArticleFiftieth Anniversary of Uncovering the Tuskegee Syphilis Study: The Story and Timeless Lessons.
This year marks the 50th anniversary of the uncovering of the Tuskegee syphilis study, when the public learned that the Public Health Service (precursor of the CDC) for 40 years intentionally withheld effective therapy against a life-threatening illness in 400 African American men. In 2010, we learned that the same research group had deliberately infected hundreds of Guatemalans with syphilis and gonorrhea in the 1940s, with the goal of developing better methods for preventing these infections. Despite 15 journal articles detailing the results, no physician published a letter criticizing the Tuskegee study. ⋯ Lack of imagination, rationalization, and institutional constraints are formidable obstacles. The central lessons from the study are the need to pause and think, reflect, and examine one's conscience; the courage to speak; and above all the willpower to act. History, although about the past, is our best defense against future errors and transgressions.
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Am. J. Respir. Crit. Care Med. · May 2022
Observational StudyComparison of 6-Month Outcomes of COVID-19 vs Non-COVID-19 Survivors of Critical Illness.
Rationale: The outcomes of survivors of critical illness due to coronavirus disease (COVID-19) compared with non-COVID-19 are yet to be established. Objectives: We aimed to investigate new disability at 6 months in mechanically ventilated patients admitted to Australian ICUs with COVID-19 compared with non-COVID-19. Methods: We included critically ill patients with COVID-19 and non-COVID-19 from two prospective observational studies. ⋯ The incidence of death or new disability at 180 days was similar (58/93 [62.4%] vs. 99/150 [66/0%]; P = 0.583). Conclusions: At 6 months, there was no difference in new disability for patients requiring mechanical ventilation for acute respiratory failure due to COVID-19 compared with non-COVID-19. Clinical trial registered with www.clinicaltrials.gov (NCT04401254).