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Rationale: Two distinct subphenotypes have been identified in acute respiratory distress syndrome (ARDS), but the presence of subgroups in ARDS associated with coronavirus disease (COVID-19) is unknown. Objectives: To identify clinically relevant, novel subgroups in COVID-19-related ARDS and compare them with previously described ARDS subphenotypes. Methods: Eligible participants were adults with COVID-19 and ARDS at Columbia University Irving Medical Center. Latent class analysis was used to identify subgroups with baseline clinical, respiratory, and laboratory data serving as partitioning variables. A previously developed machine learning model was used to classify patients as the hypoinflammatory and hyperinflammatory subphenotypes. Baseline characteristics and clinical outcomes were compared between subgroups. Heterogeneity of treatment effect for corticosteroid use in subgroups was tested. Measurements and Main Results: From March 2, 2020, to April 30, 2020, 483 patients with COVID-19-related ARDS met study criteria. A two-class latent class analysis model best fit the population (P = 0.0075). Class 2 (23%) had higher proinflammatory markers, troponin, creatinine, and lactate, lower bicarbonate, and lower blood pressure than class 1 (77%). Ninety-day mortality was higher in class 2 versus class 1 (75% vs. 48%; P

BackgroundMoral distress is a reason for burnout in healthcare professionals, but the clinical settings in which moral distress is most often experienced by medical students, and whether moral distress is associated with burnout and career choices in medical students is unknown. We assessed moral distress in medical students while caring for older patients, and examined associations with burnout and interest in geriatrics.MethodsA cross-sectional survey study of second-, third-, and fourth-year medical students at an American medical school. The survey described 12 potentially morally distressing clinical scenarios involving older adult patients. Students reported if they encountered each scenario, and whether they experienced moral distress, graded on a 1-10 scale. We conducted a principal axis factor analysis to assess the dimensionality of the survey scenarios. A composite moral distress score was calculated as the sum of moral distress scores across all 12 scenarios. Burnout was assessed using the Maslach Abbreviated Burnout Inventory, and interest in geriatrics was rated on a 7-point Likert scale.ResultsTwo-hundred and nine students responded (47%), of whom 90% (188/209) reported moral distress in response to ≥1 scenario with a median (IQR) score of 6 (4-7). Factor analysis suggested a unidimensional factor structure of the 12 survey questions that reliably measured individual distress (Cronbach alpha = 0.78). Those in the highest tertile of composite moral distress scores were more likely to be burnt out (51%) than those in the middle tertile of scores (34%), or lowest tertile of scores (31%) (p = 0.02). There was a trend towards greater interest in geriatrics among those in the higher tertiles of composite moral distress scores (16% lowest tertile, 20% middle tertile, 25% highest tertile, p-for-tend = 0.21). Respondents suggested that moral distress might be mitigated with didactic sessions in inpatient geriatric care, and debriefing sessions with peers and faculty on the inpatient clerkships on medicine, neurology, and surgery, where students most often reported experiencing moral distress.ConclusionsMoral distress is highly prevalent among medical students while caring for older patients, and associated with burnout. Incorporating geriatrics education and debriefing sessions into inpatient clerkships could alleviate medical student moral distress and burnout.

CT measurement of body composition may improve lung transplant candidate selection. We assessed whether skeletal muscle adipose deposition on abdominal and thigh CT scans was associated with 6 min walk distance (6MWD) and wait-list survival in lung transplant candidates. Each ½-SD decrease in abdominal muscle attenuation (indicating greater lipid content) was associated with 14 m decrease in 6MWD (95% CI -20 to -8) and 20% increased risk of death or delisting (95% CI 10% to 40%). Each ½-standard deviation decrease in thigh muscle attenuation was associated with 15 m decrease in 6MWD (95% CI -21 to -10). CT imaging may improve candidate risk stratification.

RationaleThe frail phenotype has gained popularity as a clinically relevant measure in adults with advanced lung disease and in critical illness survivors. Because respiratory disease and chronic illness can greatly limit physical activity, the measurement of participation in traditional leisure time activities as a frailty component may lead to substantial misclassification of frailty in pulmonary and critical care patients.ObjectivesTo test and validate substituting the Duke Activity Status Index (DASI), a simple 12-item questionnaire, for the Minnesota Leisure Time Physical Activity (MLTA) questionnaire, a detailed questionnaire covering 18 leisure time activities, as the measure of low activity in the Fried frailty phenotype (FFP) instrument.MethodsIn separate multicenter prospective cohort studies of adults with advanced lung disease who were candidates for lung transplant and older survivors of acute respiratory failure, we assessed the FFP using either the MLTA or the DASI. For both the DASI and MLTA, we evaluated content validity by testing floor effects and construct validity through comparisons with conceptually related factors. We tested the predictive validity of substituting the DASI for the MLTA in the FFP assessment using Cox models to estimate associations between the FFP and delisting/death before transplant in those with advanced lung disease and 6-month mortality in older intensive care unit (ICU) survivors.ResultsAmong 618 adults with advanced lung disease and 130 older ICU survivors, the MLTA had a substantially greater floor effect than the DASI (42% vs. 1%, and 49% vs. 12%, respectively). The DASI correlated more strongly with strength and function measures than did the MLTA in both cohorts. In models adjusting for age, sex, comorbidities, and illness severity, substitution of the DASI for the MLTA led to stronger associations of the FFP with delisting/death in lung transplant candidates (FFP-MLTA hazard ratio [HR], 1.42; 95% confidence interval [CI], 0.55-3.65; FFP-DASI HR, 2.99; 95% CI, 1.03-8.65) and with mortality in older ICU survivors (FFP-MLTA HR, 2.68; 95% CI, 0.62-11.6; FFP-DASI HR, 5.71; 95% CI, 1.34-24.3).ConclusionsThe DASI improves the construct and predictive validity of frailty assessment in adults with advanced lung disease or recent critical illness. This simple questionnaire should replace the more complex MLTA in assessing the frailty phenotype in these populations.

Conceptualized first in the field of geriatrics, frailty is a syndrome characterized by a generalized vulnerability to stressors resulting from an accumulation of physiologic deficits across multiple interrelated systems. This accumulation of deficits results in poorer functional status and disability. Frailty is a "state of risk" for subsequent disproportionate declines in health status following new exposure to a physiologic stressor. Two predominant models have emerged to operationalize the measurement of frailty. The phenotype model defines frailty as a distinct clinical syndrome that includes conceptual domains such as strength, activity, wasting, and mobility. The cumulative deficit model defines frailty by enumerating the number of age-related things wrong with a person. The biological pathways driving frailty include chronic systemic inflammation, sarcopenia, and neuroendocrine dysregulation, among others. In adults with chronic lung disease, frailty is independently associated with more frequent exacerbations of lung disease, all-cause hospitalization, declines in functional status, and all-cause mortality. In addition, frail adults who become critically ill are more likely develop chronic critical illness or severe disability and have higher in-hospital and long-term mortality rates. The evaluation of frailty appears to provide important prognostic information above and beyond routinely collected measures in adults with chronic lung disease and the critically ill. The study of frailty in these populations, however, requires multipronged efforts aimed at refining clinical assessments, understanding the mechanisms, and developing therapeutic interventions.