Associations of a plant-centered diet and lung function across early to mid-adulthood: The CARDIA Lung Study.

BACKGROUND: Lung function throughout adulthood predicts morbidity and mortality even among adults without chronic respiratory disease. Diet quality may represent a modifiable risk factor for lung function impairment later in life. We investigated associations between nutritionally-rich plant-centered diet and lung function across early and middle adulthood from the Coronary Artery Risk Development in Young Adults (CARDIA) Study. METHODS: Diet was assessed at baseline and years 7 and 20 of follow-up using the validated CARDIA diet history questionnaire. Plant-centered diet quality was scored using the validated A Priori Diet Quality Score (APDQS), which weights food groups to measure adherence to a nutritionally-rich plant-centered diet for 20 beneficially rated foods and 13 adversely rated foods. Scores were cumulatively averaged over follow-up and categorized into quintiles. The primary outcome was lung function decline, including forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), measured at years 0, 2, 5, 10, 20, and 30. We estimated the association of APDQS with annual pulmonary function changes and cross-sectional differences in a repeated measures regression model, adjusting for clinically relevant covariates. RESULTS: The study included 3,787 Black and White men and women aged 18-30 in 1985-86 and followed for 30 years. In multivariable repeated measures regression models, individuals in the lowest APDQS quintile (poorest diet) had declines in FEV1 that were 1.6 ml/year greater than individuals in the highest quintile (35.0 vs. 33.4 ml/year, ß ± SE per 1 SD change APDQS 0.94 ± 0.36, p = 0.009). Additionally, declines in FVC were 2.4 ml/year greater in the lowest APDQS quintile than those in the highest quintile (37.0 vs 34.6 ml/year, ß ± SE per 1 SD change APDQS 1.71 ± 0.46, p < 0.001). The association was not different between never and ever smokers (pint = 0.07 for FVC and 0.32 for FEV1). In sensitivity analyses where current asthma diagnosis and cardiorespiratory fitness were further adjusted, results remained similar. Cross-sectional analysis at each exam year also showed significant differences in lung function according to diet after covariate adjustment. CONCLUSIONS: In this 30-year longitudinal cohort study, long-term adherence to a nutritionally-rich plant-centered diet was associated with cross-sectional differences in lung function as well as slower decline in lung function, highlighting diet quality as a potential treatable trait supporting long-term lung health.

A Plant-Centered Diet is Inversely Associated with Radiographic Emphysema: Findings from the CARDIA Lung Study.

Chronic obstructive pulmonary disease (COPD) is a significant public health concern and intercepting the development of emphysema is vital for COPD prevention. Smokers are a high-risk population for emphysema with limited prevention strategies. We aimed to determine if adherence to a nutritionally rich plant-centered diet among young ever-smokers is associated with reduced risk of future radiographic emphysema. We studied participants from the Coronary Artery Risk Development in Young Adults (CARDIA) Lung Prospective Cohort Study who were 18-30 years old at enrollment and followed for 30 years. We analyzed 1,706 adults who reported current or former smoking by year 20. Repeated measures of diet history were used to calculate A Priori Diet Quality Scores (APDQS), and categorized into quintiles, with higher quintiles representing higher nutritionally rich plant-centered food intake. Emphysema was assessed at year 25 (n=1,351) by computed tomography (CT). Critical covariates were selected, acknowledging potential residual confounding. Emphysema was observed in 13.0% of the cohort, with a mean age of 50.4 ± 3.5 years. The prevalence of emphysema was 4.5% in the highest APDQS quintile (nutritionally rich), compared with 25.4% in the lowest quintile. After adjustment for multiple covariates, including smoking, greater adherence to a plant-centered diet was inversely associated with emphysema (highest vs lowest quintile odds ratio: 0.44, 95% CI 0.19-0.99, ptrend=0.008). To conclude, longitudinal adherence to a nutritionally rich plant-centered diet was associated with decreased risk of emphysema development in middle adulthood, warranting further examination of diet as a strategy for emphysema prevention in a high-risk smoking population.

Caregiver Perceived Stress and Child Sleep Health: An Item-Level Individual Participant Data Meta-Analysis.

Up to 50% of children and adolescents in the United States (U.S.) experience sleep problems. While existing research suggests that perceived stress in caregivers is associated with poorer sleep outcomes in children, research on this relationship is often limited to infant and early childhood populations; therefore, we investigated this association in school-age children and adolescents. We used cross-sectional caregiver-reported surveys and applied item response theory (IRT) followed by meta-analysis to assess the relationship between caregiver perceived stress and child sleep disturbance, and moderation of this relationship by child age and the presence of a child mental or physical health condition. We analyzed data from the National Institutes of Health (NIH) Environmental influences on Child Health Outcomes (ECHO) Program, a collaboration of existing pediatric longitudinal cohort studies that collectively contribute a diverse and large sample size ideal for addressing questions related to children's health and consolidating results across population studies. Participants included caregivers of children ages 8 to 16 years from four ECHO cohorts. Caregiver perceived stress was measured using the Perceived Stress Scale (PSS), and child sleep disturbance was assessed using five sleep-related items from the School-Age version of the Child Behavior Checklist (CBCL). Increases in caregiver perceived stress and child mental or physical health condition were independently associated with greater sleep disturbance among children. The findings reinforce the importance of accounting for, and potentially intervening on, the broader family context and children's mental and physical health in the interest of improving sleep health.

Functional imaging for assessing regional lung ventilation in preclinical and clinical research.

Dynamic heterogeneity in lung ventilation is an important measure of pulmonary function and may be characteristic of early pulmonary disease. While standard indices like spirometry, body plethysmography, and blood gases have been utilized to assess lung function, they do not provide adequate information on regional ventilatory distribution nor function assessments of ventilation during the respiratory cycle. Emerging technologies such as xenon CT, volumetric CT, functional MRI and X-ray velocimetry can assess regional ventilation using non-invasive radiographic methods that may complement current methods of assessing lung function. As a supplement to current modalities of pulmonary function assessment, functional lung imaging has the potential to identify respiratory disease phenotypes with distinct natural histories. Moreover, these novel technologies may offer an optimal strategy to evaluate the effectiveness of novel therapies and therapies targeting localized small airways disease in preclinical and clinical research. In this review, we aim to discuss the features of functional lung imaging, as well as its potential application and limitations to adoption in research.

Associations of a Plant-centered Diet and Lung Function Decline across Early to Mid-Adulthood: The CARDIA Lung Study.

Background: Lung function throughout adulthood predicts morbidity and mortality even among adults without chronic respiratory disease. Diet quality may represent a modifiable risk factor for lung function impairment later in life. We investigated associations between nutritionally-rich plant-centered diet and lung function decline across early and middle adulthood from the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Methods: Diet was assessed at baseline and years 7 and 20 of follow-up using the validated CARDIA diet history questionnaire. Plant-centered diet quality was scored using the validated A Priori Diet Quality Score (APDQS), which weights food groups to measure adherence to a nutritionally-rich plant-centered diet 1 to 5 points for 20 beneficially rated foods and 5 to 1 points for 13 adversely rated foods. Scores were cumulatively averaged over follow-up and categorized into quintiles. The primary outcome was lung function decline, including forced expiratory volume in 1 second (FEV1) and functional vital capacity (FVC), measured at years 0, 2, 5, 10, 20, and 30. We estimated the association of APDQS with annual pulmonary function changes in a repeated measures regression model, adjusting for clinically relevant covariates. Results: The study included 3,787 Black and White men and women aged 18-30 in 1985-86 and followed for 30 years. In multivariable repeated measures regression models, individuals in the lowest APDQS quintile (poorest diet) had declines in FEV1 that were 1.6 ml/year greater than individuals in the highest quintile (35.0 vs. 33.4 ml/year, ß±SE per 1 SD change APDQS 0.94 ± 0.36, p = 0.009). Additionally, declines in FVC were 2.4 ml/year greater in the lowest APDQS quintile than those in the highest quintile (37.0 vs 34.6 ml/year, ß±SE per 1 SD change APDQS 1.71 ± 0.46, p < 0.001). The association was not different between never and ever smokers (pint = 0.07 for FVC and 0.32 for FEV1). In sensitivity analyses where current asthma diagnosis and cardiorespiratory fitness were further adjusted, results remained similar. Conclusions: In this 30-year longitudinal cohort study, long-term adherence to a nutritionally-rich plant-centered diet was associated with slower decline in lung function, highlighting diet quality as a potential treatable trait supporting long-term lung health.

Association between Diet Quality and Adolescent Wheezing: Effect Modification by Environmental Tobacco Smoke Exposure.

Rationale: Protective effects of a high-quality diet on respiratory health, particularly among youths exposed to environmental tobacco smoke (ETS), are unknown. Objectives: To assess if a higher-quality diet is associated with improved respiratory symptoms and lung function among adolescents and if these associations are modified by ETS exposure. Methods: This was a cross-sectional study on 7,026 nonsmoking adolescents of the 2003-2012 National Health and Nutrition Examination Survey. Diet quality was assessed using the Healthy Eating Index-2010 score (HEI-2010), categorized into quintiles. ETS exposure was measured using serum cotinine, dichotomized as high (>2.99 ng/ml) or low (⩽2.99 ng/ml). Outcomes included the presence of wheezing and cough symptoms in the past 12 months and, in a subgroup, spirometric lung function. Survey design-adjusted logistic and linear models evaluated associations between diet and 1) respiratory symptoms, and 2) lung function, respectively, and assessed the interaction between HEI-2010 and serum cotinine. Results: Although there were no significant associations between diet quality and respiratory symptoms, there was a significant interaction between HEI-2010 and serum cotinine on wheezing (Pint = 0.011). In models stratified by serum cotinine, adolescents with high serum cotinine and the healthiest diet (fifth quintile HEI-2010) experienced lower wheezing odds (odds ratio, 0.10; 95% confidence interval, 0.02-0.61) than those with the poorest diet (first quintile HEI-2010). In contrast, among adolescents with low serum cotinine, there were no significant differences in any respiratory symptoms between those with the highest compared with the lowest diet quality. Of the subgroup with spirometry data (n = 3,166), there was a trend toward better lung function with improving diet quality, although this did not achieve statistical significance. There was no effect modification by ETS exposure on the relationship between diet quality and lung function. Conclusions: Consuming a higher-quality diet was associated with lower wheezing odds in adolescents with substantial ETS exposure. Although longitudinal studies are needed, public health interventions to improve diet quality in vulnerable, environmentally exposed populations merit consideration.

Knowledge Gaps, Challenges, and Opportunities in Health and Prevention Research for Asian Americans, Native Hawaiians, and Pacific Islanders: A Report From the 2021 National Institutes of Health Workshop.

Asian Americans (AsA), Native Hawaiians, and Pacific Islanders (NHPI) comprise 7.7% of the U.S. population, and AsA have had the fastest growth rate since 2010. Yet the National Institutes of Health (NIH) has invested only 0.17% of its budget on AsA and NHPI research between 1992 and 2018. More than 40 ethnic subgroups are included within AsA and NHPI (with no majority subpopulation), which are highly diverse culturally, demographically, linguistically, and socioeconomically. However, data for these groups are often aggregated, masking critical health disparities and their drivers. To address these issues, in March 2021, the National Heart, Lung, and Blood Institute, in partnership with 8 other NIH institutes, convened a multidisciplinary workshop to review current research, knowledge gaps, opportunities, barriers, and approaches for prevention research for AsA and NHPI populations. The workshop covered 5 domains: 1) sociocultural, environmental, psychological health, and lifestyle dimensions; 2) metabolic disorders; 3) cardiovascular and lung diseases; 4) cancer; and 5) cognitive function and healthy aging. Two recurring themes emerged: Very limited data on the epidemiology, risk factors, and outcomes for most conditions are available, and most existing data are not disaggregated by subgroup, masking variation in risk factors, disease occurrence, and trajectories. Leveraging the vast phenotypic differences among AsA and NHPI groups was identified as a key opportunity to yield novel clues into etiologic and prognostic factors to inform prevention efforts and intervention strategies. Promising approaches for future research include developing collaborations with community partners, investing in infrastructure support for cohort studies, enhancing existing data sources to enable data disaggregation, and incorporating novel technology for objective measurement. Research on AsA and NHPI subgroups is urgently needed to eliminate disparities and promote health equity in these populations.

Study protocol for a national cohort of adults focused on respiratory health: the American Lung Association Lung Health Cohort (ALA-LHC) Study.

INTRODUCTION: The current framework for investigating respiratory diseases is based on defining lung health as the absence of lung disease. In order to develop a comprehensive approach to prevent the development of lung disease, there is a need to evaluate the full spectrum of lung health spanning from ideal to impaired lung health. The American Lung Association (ALA) Lung Health Cohort is a new, population-based, cohort study focused primarily on characterising lung health in members of the millennial generation without diagnosed severe respiratory disease. Participants will be enrolled for the baseline study visit starting in 2021, and funding will be sought to support future study exams as part of a longitudinal cohort study. This study will be crucial for developing a novel paradigm of lung health throughout the adult life course. METHODS AND ANALYSIS: This study will leverage the existing infrastructure of the ALA Airways Clinical Research Centers network to enrol 4000 participants between ages 25 and 35 years old at 39 sites across the USA between April 2021 and December 2024. Study procedures will include physical assessment, spirometry, chest CT scan, accelerometry and collection of nasal epithelial lining fluid, nasal epithelial cells, blood and urine. Participants will complete questionnaires about their sociodemographic characteristics, home address histories and exposures, work history and exposure, medical histories, lung health and health behaviours and activity. ETHICS AND DISSEMINATION: The study was approved by the Johns Hopkins Medicine Institutional Review Board. Findings will be disseminated to the scientific community through peer-reviewed journals and at professional conferences. The lay public will receive scientific findings directly through the ALA infrastructure including the official public website. Deidentified datasets will be deposited to BioLINCC, and deidentified biospecimens may be made available to qualified investigators along with a limited-use datasets.

Impact of corticosteroids in hospitalised COVID-19 patients.

BACKGROUND: Corticosteroids are a potential therapeutic agent for patients with COVID-19 pneumonia. The RECOVERY (Randomised Trials in COVID-19 Therapy) trial provided data on the mortality benefits of corticosteroids. The study aimed to determine the association between corticosteroid use on mortality and infection rates and to define subgroups who may benefit from corticosteroids in a real-world setting. METHODS: Clinical data were extracted that included demographic, laboratory data and details of the therapy, including the administration of corticosteroids, azithromycin, hydroxychloroquine, tocilizumab and anticoagulation. The primary outcome was in-hospital mortality. Secondary outcomes included intensive care unit (ICU) admission and invasive mechanical ventilation. Outcomes were compared in patients who did and did not receive corticosteroids using the multivariate Cox regression model. RESULTS: 4313 patients were hospitalised with COVID-19 during the study period, of whom 1270 died (29.4%). When administered within the first 7 days after admission, corticosteroids were associated with reduced mortality (OR 0.73, 95% CI 0.55 to 0.97, p=0.03) and decreased transfers to the ICU (OR 0.72, 95% CI 0.47 to 1.11, p=0.02). This mortality benefit was particularly impressive in younger patients (<65 years of age), females and those with elevated inflammatory markers, defined as C reactive protein ≥150 mg/L (p≤0.05), interleukin-6 ≥20 pg/mL (p≤0.05) or D-dimer ≥2.0 µg/L (p≤0.05). Therapy was safe with similar rates of bacteraemia and fungaemia in corticosteroid-treated and non-corticosteroid-treated patients. CONCLUSION: In patients hospitalised with COVID-19 pneumonia, corticosteroid use within the first 7 days of admission decreased mortality and ICU admissions with no associated increase in bacteraemia or fungaemia.

Cardiovascular Disease and Severe Hypoxemia Are Associated With Higher Rates of Noninvasive Respiratory Support Failure in Coronavirus Disease 2019 Pneumonia.

Acute hypoxemic respiratory failure is the major complication of coronavirus disease 2019, yet optimal respiratory support strategies are uncertain. We aimed to describe outcomes with high-flow oxygen delivered through nasal cannula and noninvasive positive pressure ventilation in coronavirus disease 2019 acute hypoxemic respiratory failure and identify individual factors associated with noninvasive respiratory support failure. DESIGN: Retrospective cohort study to describe rates of high-flow oxygen delivered through nasal cannula and/or noninvasive positive pressure ventilation success (live discharge without endotracheal intubation). Fine-Gray subdistribution hazard models were used to identify patient characteristics associated with high-flow oxygen delivered through nasal cannula and/or noninvasive positive pressure ventilation failure (endotracheal intubation and/or in-hospital mortality). SETTING: One large academic health system, including five hospitals (one quaternary referral center, a tertiary hospital, and three community hospitals), in New York City. PATIENTS: All hospitalized adults 18-100 years old with coronavirus disease 2019 admitted between March 1, 2020, and April 28, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 331 and 747 patients received high-flow oxygen delivered through nasal cannula and noninvasive positive pressure ventilation as the highest level of noninvasive respiratory support, respectively; 154 (46.5%) in the high-flow oxygen delivered through nasal cannula cohort and 167 (22.4%) in the noninvasive positive pressure ventilation cohort were successfully discharged without requiring endotracheal intubation. In adjusted models, significantly increased risk of high-flow oxygen delivered through nasal cannula and noninvasive positive pressure ventilation failure was seen among patients with cardiovascular disease (subdistribution hazard ratio, 1.82; 95% CI, 1.17-2.83 and subdistribution hazard ratio, 1.40; 95% CI, 1.06-1.84, respectively). Conversely, a higher peripheral blood oxygen saturation to Fio2 ratio at high-flow oxygen delivered through nasal cannula and noninvasive positive pressure ventilation initiation was associated with reduced risk of failure (subdistribution hazard ratio, 0.32; 95% CI, 0.19-0.54, and subdistribution hazard ratio 0.34; 95% CI, 0.21-0.55, respectively). CONCLUSIONS: A significant proportion of patients receiving noninvasive respiratory modalities for coronavirus disease 2019 acute hypoxemic respiratory failure achieved successful hospital discharge without requiring endotracheal intubation, with lower success rates among those with comorbid cardiovascular disease or more severe hypoxemia. The role of high-flow oxygen delivered through nasal cannula and noninvasive positive pressure ventilation in coronavirus disease 2019-related acute hypoxemic respiratory failure warrants further consideration.

Prone Positioning and Survival in Mechanically Ventilated Patients With Coronavirus Disease 2019-Related Respiratory Failure.

OBJECTIVES: Therapies for patients with respiratory failure from coronavirus disease 2019 are urgently needed. Early implementation of prone positioning ventilation improves survival in patients with acute respiratory distress syndrome, but studies examining the effect of proning on survival in patients with coronavirus disease 2019 are lacking. Our objective was to estimate the effect of early proning initiation on survival in patients with coronavirus disease 2019-associated respiratory failure. DESIGN: Data were derived from the Study of the Treatment and Outcomes in Critically Ill Patients with coronavirus disease 2019, a multicenter cohort study of critically ill adults with coronavirus disease 2019 admitted to 68 U.S. hospitals. Using these data, we emulated a target trial of prone positioning ventilation by categorizing mechanically ventilated hypoxemic (ratio of Pao2 over the corresponding Fio2 ≤ 200 mm Hg) patients as having been initiated on proning or not within 2 days of ICU admission. We fit an inverse probability-weighted Cox model to estimate the mortality hazard ratio for early proning versus no early proning. Patients were followed until death, hospital discharge, or end of follow-up. SETTING: ICUs at 68 U.S. sites. PATIENTS: Critically ill adults with laboratory-confirmed coronavirus disease 2019 receiving invasive mechanical ventilation with ratio of Pao2 over the corresponding Fio2 less than or equal to 200 mm Hg. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 2,338 eligible patients, 702 (30.0%) were proned within the first 2 days of ICU admission. After inverse probability weighting, baseline and severity of illness characteristics were well-balanced between groups. A total of 1,017 (43.5%) of the 2,338 patients were discharged alive, 1,101 (47.1%) died, and 220 (9.4%) were still hospitalized at last follow-up. Patients proned within the first 2 days of ICU admission had a lower adjusted risk of death compared with nonproned patients (hazard ratio, 0.84; 95% CI, 0.73-0.97). CONCLUSIONS: In-hospital mortality was lower in mechanically ventilated hypoxemic patients with coronavirus disease 2019 treated with early proning compared with patients whose treatment did not include early proning.

Hyperglycemia is Associated With Increased Mortality in Critically Ill Patients With COVID-19.

OBJECTIVE: To explore the relationship between hyperglycemia in the presence and absence of diabetes mellitus (DM) and adverse outcomes in critically ill patients with coronavirus disease 2019 (COVID-19). METHODS: The study included 133 patients with COVID-19 admitted to an intensive care unit (ICU) at an urban academic quaternary-care center between March 10 and April 8, 2020. Patients were categorized based on the presence or absence of DM and early-onset hyperglycemia (EHG), defined as a blood glucose >180 mg/dL during the first 2 days after ICU admission. The primary outcome was 14-day all-cause in-hospital mortality; also examined were 60-day all-cause in-hospital mortality and the levels of C-reactive protein, interleukin 6, procalcitonin, and lactate. RESULTS: Compared to non-DM patients without EHG, non-DM patients with EHG exhibited higher adjusted hazard ratios (HRs) for mortality at 14 days (HR 7.51, CI 1.70-33.24) and 60 days (HR 6.97, CI 1.86-26.13). Non-DM patients with EHG also featured higher levels of median C-reactive protein (306.3 mg/L, P = .036), procalcitonin (1.26 ng/mL, P = .028), and lactate (2.2 mmol/L, P = .023). CONCLUSION: Among critically ill COVID-19 patients, those without DM with EHG were at greatest risk of 14-day and 60-day in-hospital mortality. Our study was limited by its retrospective design and relatively small cohort. However, our results suggest the combination of elevated glucose and lactate may identify a specific cohort of individuals at high risk for mortality from COVID-19. Glucose testing and control are important in individuals with COVID-19, even those without preexisting diabetes.

Sex differences in M2 polarization, chemokine and IL-4 receptors in monocytes and macrophages from asthmatics.

Allergic asthma affects more women than men. It is mediated partially by IL-4/IL-13-driven polarization of monocyte-derived macrophages in the lung. We tested whether sex differences in asthma are due to differential IL-4 responsiveness and/or chemokine receptor expression in monocytes and monocyte-derived macrophages from healthy and allergic asthmatic men and women. We found female cells expressed M2 genes more robustly following IL-4 stimulation than male cells, as did cells from asthmatics than those from healthy controls. This likely resulted from increased expression ofγC, part of the type I IL-4 receptor, and reduced IL-4-induced SOCS1, a negative regulator of IL-4 signaling, in asthmatic compared to healthy macrophages. Monocytes from asthmatic women expressed more CX3CR1, which enhances macrophage survival. Our findings highlight how sex differences in IL-4 responsiveness and chemokine receptor expression may affect monocyte recruitment and macrophage polarization in asthma, potentially leading to new sex-specific therapies to manage the disease.

Increased advanced glycation end product and meat consumption is associated with childhood wheeze: analysis of the National Health and Nutrition Examination Survey.

We examined 4388 children from the 2003 to 2006 National Health and Nutrition Examination Survey and used survey-design-adjusted multivariable logistic regression to evaluate associations between dietary advanced glycation end product (AGE) and meat consumption frequencies and respiratory symptoms. Higher AGE intake was significantly associated with increased odds of wheezing (adjusted OR 1.18; 95% CI 1.02 to 1.36), wheeze-disrupted sleep (1.26; 95% CI 1.05 to 1.51) and exercise (1.34; 95% CI 1.08 to 1.67) and wheezing requiring prescription medication (1.35; 95% CI 1.13 to 1.63). Higher intake of non-seafood meats was associated with wheeze-disrupted sleep (2.32; 95% CI 1.11 to 4.82) and wheezing requiring prescription medication (2.23; 95% CI 1.10 to 4.54).

Clinical features of COVID-19 mortality: development and validation of a clinical prediction model.

Background: The COVID-19 pandemic has affected millions of individuals and caused hundreds of thousands of deaths worldwide. Predicting mortality among patients with COVID-19 who present with a spectrum of complications is very difficult, hindering the prognostication and management of the disease. We aimed to develop an accurate prediction model of COVID-19 mortality using unbiased computational methods, and identify the clinical features most predictive of this outcome. Methods: In this prediction model development and validation study, we applied machine learning techniques to clinical data from a large cohort of patients with COVID-19 treated at the Mount Sinai Health System in New York City, NY, USA, to predict mortality. We analysed patient-level data captured in the Mount Sinai Data Warehouse database for individuals with a confirmed diagnosis of COVID-19 who had a health system encounter between March 9 and April 6, 2020. For initial analyses, we used patient data from March 9 to April 5, and randomly assigned (80:20) the patients to the development dataset or test dataset 1 (retrospective). Patient data for those with encounters on April 6, 2020, were used in test dataset 2 (prospective). We designed prediction models based on clinical features and patient characteristics during health system encounters to predict mortality using the development dataset. We assessed the resultant models in terms of the area under the receiver operating characteristic curve (AUC) score in the test datasets. Findings: Using the development dataset (n=3841) and a systematic machine learning framework, we developed a COVID-19 mortality prediction model that showed high accuracy (AUC=0·91) when applied to test datasets of retrospective (n=961) and prospective (n=249) patients. This model was based on three clinical features: patient's age, minimum oxygen saturation over the course of their medical encounter, and type of patient encounter (inpatient vs outpatient and telehealth visits). Interpretation: An accurate and parsimonious COVID-19 mortality prediction model based on three features might have utility in clinical settings to guide the management and prognostication of patients affected by this disease. External validation of this prediction model in other populations is needed. Funding: National Institutes of Health.

Anticoagulation, Bleeding, Mortality, and Pathology in Hospitalized Patients With COVID-19.

BACKGROUND: Thromboembolic disease is common in coronavirus disease-2019 (COVID-19). There is limited evidence on the association of in-hospital anticoagulation (AC) with outcomes and postmortem findings. OBJECTIVES: The purpose of this study was to examine association of AC with in-hospital outcomes and describe thromboembolic findings on autopsies. METHODS: This retrospective analysis examined the association of AC with mortality, intubation, and major bleeding. Subanalyses were also conducted on the association of therapeutic versus prophylactic AC initiated ≤48 h from admission. Thromboembolic disease was contextualized by premortem AC among consecutive autopsies. RESULTS: Among 4,389 patients, median age was 65 years with 44% women. Compared with no AC (n = 1,530; 34.9%), therapeutic AC (n = 900; 20.5%) and prophylactic AC (n = 1,959; 44.6%) were associated with lower in-hospital mortality (adjusted hazard ratio [aHR]: 0.53; 95% confidence interval [CI]: 0.45 to 0.62 and aHR: 0.50; 95% CI: 0.45 to 0.57, respectively), and intubation (aHR: 0.69; 95% CI: 0.51 to 0.94 and aHR: 0.72; 95% CI: 0.58 to 0.89, respectively). When initiated ≤48 h from admission, there was no statistically significant difference between therapeutic (n = 766) versus prophylactic AC (n = 1,860) (aHR: 0.86; 95% CI: 0.73 to 1.02; p = 0.08). Overall, 89 patients (2%) had major bleeding adjudicated by clinician review, with 27 of 900 (3.0%) on therapeutic, 33 of 1,959 (1.7%) on prophylactic, and 29 of 1,530 (1.9%) on no AC. Of 26 autopsies, 11 (42%) had thromboembolic disease not clinically suspected and 3 of 11 (27%) were on therapeutic AC. CONCLUSIONS: AC was associated with lower mortality and intubation among hospitalized COVID-19 patients. Compared with prophylactic AC, therapeutic AC was associated with lower mortality, although not statistically significant. Autopsies revealed frequent thromboembolic disease. These data may inform trials to determine optimal AC regimens.