American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Sep 2020
Rifapentine Population Pharmacokinetics and Dosing Recommendations for Latent Tuberculosis Infection.
Rationale: Rifapentine has been investigated at various doses, frequencies, and dosing algorithms, but clarity on the optimal dosing approach is lacking. Objectives: To characterize rifapentine population pharmacokinetics, including autoinduction, and determine optimal dosing strategies for short-course rifapentine-based regimens for latent tuberculosis infection. Methods: Rifapentine pharmacokinetic studies were identified though a systematic review of literature. ⋯ Pharmacokinetic simulations showed that current weight-based dosing leads to lower exposures in individuals with low weight, which can be overcome with flat dosing. In HIV-positive patients, 30% higher doses are required to match drug exposure in HIV-negative patients. Conclusions: Weight-based dosing of rifapentine should be removed from clinical guidelines, and higher doses for HIV-positive patients should be considered to provide equivalent efficacy.
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Am. J. Respir. Crit. Care Med. · Sep 2020
Editorial CommentSub-Clinical AKI is AKI and Should not be Ignored.
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Am. J. Respir. Crit. Care Med. · Sep 2020
Comment Randomized Controlled Trial Multicenter StudyRecommended Reading from Boston University School of Medicine Fellows.
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Am. J. Respir. Crit. Care Med. · Sep 2020
Comparative StudyPathological Comparisons of Paraseptal and Centrilobular Emphysema in COPD.
Rationale: Although centrilobular emphysema (CLE) and paraseptal emphysema (PSE) are commonly identified on multidetector computed tomography (MDCT), little is known about the pathology associated with PSE compared with that of CLE. Objectives: To assess the pathological differences between PSE and CLE in chronic obstructive pulmonary disease (COPD). Methods: Air-inflated frozen lung specimens (n = 6) obtained from patients with severe COPD treated by lung transplantation were scanned with MDCT. ⋯ The number of terminal bronchioles per milliliter of lung and cross-sectional lumen area were significantly lower and wall area percentage was significantly higher in CLE-dominant regions compared with mild emphysema and PSE-dominant regions (all P < 0.05), whereas no difference was found between PSE-dominant and mild emphysema samples (all P > 0.5). Immunohistochemistry showed significantly higher infiltration of neutrophils (P = 0.002), but not of macrophages, CD4, CD8, or B cells, in PSE compared with CLE regions. Conclusions: The terminal bronchioles are relatively preserved, whereas neutrophilic inflammation is increased in PSE-dominant regions compared with CLE-dominant regions in patients with COPD.