Annals of the American Thoracic Society
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Randomized Controlled Trial Multicenter Study
A Phase II Clinical Trial of an Aromatase Inhibitor for Postmenopausal Women with Lymphangioleiomyomatosis.
Lymphangioleiomyomatosis (LAM) is a progressive cystic lung disease that predominantly affects women and can worsen with pregnancy, estrogen treatment, and the menstrual cycle, suggesting an important role for estrogen in disease pathogenesis. ⋯ Letrozole treatment appears to be safe and well tolerated in postmenopausal patients with LAM, including those taking sirolimus. Enrollment in this trial was compromised by the publication of an effective treatment (sirolimus) in the same month as the study opened, resulting in limited power to detect treatment effects. Post hoc matched pairs exploration studies provide tentative support for additional studies of letrozole in LAM. Considering the reduced rate of lung function decline in postmenopausal patients, future studies will likely require enhanced study designs, such as selective enrollment of those with prognostic biomarkers predictive of decline. Clinical trial registered with www.clinicaltrials.gov (NCT01353209).
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Multicenter Study Observational Study
Assessing the Usefulness and Validity of Frailty Markers in Critically Ill Adults.
Identifying frailty by the presence of a critical number of frailty markers has been difficult to operationalize in the intensive care unit (ICU), where patients often cannot complete performance measures or answer complex questions. ⋯ Asking patients or surrogates about frailty markers may be a valid approach to identifying critically ill adults with a frailty phenotype associated with increased risk of adverse outcomes. Larger studies measuring frailty markers may provide insight into factors that impact short- and long-term outcomes after ICU admission.
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Acute respiratory distress syndrome (ARDS) is a major clinical problem with high morbidity and mortality. Diffuse alveolar damage (DAD) is considered the histological hallmark for the acute phase of ARDS. DAD is characterized by an acute phase with edema, hyaline membranes, and inflammation, followed by an organizing phase with alveolar septal fibrosis and type II pneumocyte hyperplasia. ⋯ A predictive model for DAD based on noninvasive measurements has been developed in an autopsy cohort but must be validated. It would be ideal to identify biomarkers or imaging techniques that help determine which patients with ARDS have DAD. We conclude that additional studies are needed to determine the effect of DAD on outcomes in ARDS, and whether noninvasive techniques to identify DAD should be developed with the goal of determining whether this population responds differently to specific therapies targeting the molecular mechanisms of ARDS.
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Multicenter Study
Patients with Chronic Obstructive Pulmonary Disease Walk with Altered Step Time and Step Width Variability as Compared with Healthy Control Subjects.
Compared with control subjects, patients with chronic obstructive pulmonary disease (COPD) have an increased incidence of falls and demonstrate balance deficits and alterations in mediolateral trunk acceleration while walking. Measures of gait variability have been implicated as indicators of fall risk, fear of falling, and future falls. ⋯ Patients with COPD walk with increased duration of time between steps, and this timing is more variable than that of control subjects. They also walk with a narrower step width in which the variability of the step widths from step to step is decreased. Changes in these parameters have been related to increased risk of falling in aging research. This provides a mechanism that could explain the increased prevalence of falls in patients with COPD.