Faculty Bibliography

BACKGROUND:Little is known about long-term recovery from severe COVID-19 disease. Here, we characterize overall health, physical health, and mental health of patients 1 month after discharge for severe COVID-19. METHODS:This was a prospective single health system observational cohort study of patients ≥ 18 years hospitalized with laboratory-confirmed COVID-19 disease who required at least 6 l of oxygen during admission, had intact baseline cognitive and functional status, and were discharged alive. Participants were enrolled between 30 and 40 days after discharge. Outcomes were elicited through validated survey instruments: the PROMIS® Dyspnea Characteristics and PROMIS® Global Health-10. RESULTS:A total of 161 patients (40.6% of eligible) were enrolled; 152 (38.3%) completed the survey. Median age was 62 years (interquartile range [IQR], 50-67); 57 (37%) were female. Overall, 113/152 (74%) participants reported shortness of breath within the prior week (median score 3 out of 10 [IQR 0-5]), vs 47/152 (31%) pre-COVID-19 infection (0, IQR 0-1), p < 0.001. Participants also rated their physical health and mental health as worse in their post-COVID state (43.8, standard deviation 9.3; mental health 47.3, SD 9.3) compared to their pre-COVID state, (54.3, SD 9.3; 54.3, SD 7.8, respectively), both p < 0.001. Physical and mental health means in the general US population are 50 (SD 10). A total of 52/148 (35.1%) patients without pre-COVID oxygen requirements needed home oxygen after hospital discharge; 20/148 (13.5%) reported still using oxygen at time of survey. CONCLUSIONS:Patients with severe COVID-19 disease typically experience sequelae affecting their respiratory status, physical health, and mental health for at least several weeks after hospital discharge.

OBJECTIVES/OBJECTIVE:The aim of this study was to evaluate whether machine learning (ML) of noncontrast computed tomographic (CT) and clinical variables improves the prediction of atherosclerotic cardiovascular disease (ASCVD) and coronary heart disease (CHD) deaths compared with coronary artery calcium (CAC) Agatston scoring and clinical data. BACKGROUND:The CAC score provides a measure of the global burden of coronary atherosclerosis, and its long-term prognostic utility has been consistently shown to have incremental value over clinical risk assessment. However, current approaches fail to integrate all available CT and clinical variables for comprehensive risk assessment. METHODS:The study included data from 66,636 asymptomatic subjects (mean age 54 ± 11 years, 67% men) without established ASCVD undergoing CAC scanning and followed for cardiovascular disease (CVD) and CHD deaths at 10 years. Clinical risk assessment incorporated the ASCVD risk score. For ML, an ensemble boosting approach was used to fit a predictive classifier for outcomes, followed by automated feature selection using information gain ratio. The model-building process incorporated all available clinical and CT data, including the CAC score; the number, volume, and density of CAC plaques; and extracoronary scores; comprising a total of 77 variables. The overall proposed model (ML all) was evaluated using a 10-fold cross-validation framework on the population data and area under the curve (AUC) as metrics. The prediction performance was also compared with 2 traditional scores (ASCVD risk and CAC score) and 2 additional models that were trained using all the clinical data (ML clinical) and CT variables (ML CT). RESULTS:The AUC by ML all (0.845) for predicting CVD death was superior compared with those obtained by ASCVD risk alone (0.821), CAC score alone (0.781), and ML CT alone (0.804) (p < 0.001 for all). Similarly, for predicting CHD death, AUC by ML all (0.860) was superior to the other analyses (0.835 for ASCVD risk, 0.816 for CAC, and 0.827 for ML CT; p < 0.001). CONCLUSIONS:The comprehensive ML model was superior to ASCVD risk, CAC score, and an ML model fitted using CT variables alone in the prediction of both CVD and CHD death.

Objectives/UNASSIGNED:The aim of this study was to test the mediating role of perceived discrimination and stress on associations between perceived neighborhood social environment (PNSE) and TV viewing. Methods/UNASSIGNED:Baseline data were used for 4716 participants (mean age = 55.1 y; 63.4% female) in the Jackson Heart Study (JHS), a large prospective cohort study of African Americans in Jackson, Mississippi. One binary TV viewing outcome was created: ≥4 h/day versus <4 h/day. PNSE variables included neighborhood violence, problems (higher value = more violence/problems), and social cohesion (higher value = more cohesion). Mediators included perceived lifetime discrimination, daily discrimination, and chronic stress (higher value = greater discrimination/stress). Multivariable regression was used with bootstrap-generated 95% bias-corrected confidence intervals (BC CIs) to test for mediation adjusting for demographics, health-related and psychosocial factors, and population density. Results/UNASSIGNED: = 1.01, 1.10, respectively). Daily discrimination was neither directly nor indirectly associated with TV viewing. Conclusions/UNASSIGNED:Each PNSE variable was indirectly associated with TV viewing via lifetime discrimination and perceived stress, but not with daily discrimination among JHS participants. Unexpected directionality of mediating effects of lifetime discrimination and chronic stress should be replicated in future studies. Further research is also needed to pinpoint effective community efforts and physical environmental policies (e.g., installing bright street lights, community policing) to reduce adverse neighborhood conditions and psychosocial factors, and decrease TV viewing and subsequent cardiovascular disease risk.

BACKGROUND:There are specific issues regarding sexual orientation (SO) collection and analysis among transgender and nonbinary patients. A limitation to meaningful SO and gender identity (GI) data collection is their consideration as a fixed trait or demographic data point. METHODS:A de-identified patient database from a single electronic health record (EHR) that allows for searching any discrete data point in the EHR was used to query demographic data (sex assigned at birth and current GI) for transgender individuals from January 2011 to March 2020 at a large urban tertiary care academic health center. RESULTS: = 232). CONCLUSION:Current SO categories do not fully capture transgender individuals' identities and experiences, and limit the clinical and epidemiological utility of collecting this data in the current form. Anatomical assumptions based on SO should be seen as a potential shortcoming in over-reliance on SO as an indicator of screening needs and risk factors.

New therapies offer hope for a cure to millions of persons living with hepatitis C virus (HCV) infection. HCV elimination is a global goal that will be difficult to achieve using the traditional paradigms of diagnosis and care. The current standard has evolved toward universal HCV screening and treatment, to achieve elimination goals. There are several steps between HCV diagnosis and cure with major barriers along the way. Innovative models of care can address barriers to better serve hardly reached populations and scale national efforts in the United States and abroad. Herein, we highlight innovative models of HCV care that aid in our progress toward HCV elimination.

BACKGROUND & AIMS:Chronic liver disease (CLD) and cirrhosis are associated with immune dysregulation, leading to concerns that affected patients may be at risk of adverse outcomes following SARS-CoV-2 infection. We aimed to determine the impact of COVID-19 on patients with pre-existing liver disease, which currently remains ill-defined. METHODS:Between 25th March and 8th July 2020, data on 745 patients with CLD and SARS-CoV-2 (including 386 with and 359 without cirrhosis) were collected by 2 international registries and compared to data on non-CLD patients with SARS-CoV-2 from a UK hospital network. RESULTS:Mortality was 32% in patients with cirrhosis compared to 8% in those without (p <0.001). Mortality in patients with cirrhosis increased according to Child-Pugh class (A [19%], B [35%], C [51%]) and the main cause of death was from respiratory failure (71%). After adjusting for baseline characteristics, factors associated with death in the total CLD cohort were age (odds ratio [OR] 1.02; 1.01-1.04), Child-Pugh A (OR 1.90; 1.03-3.52), B (OR 4.14; 2.4-7.65), or C (OR 9.32; 4.80-18.08) cirrhosis and alcohol-related liver disease (OR 1.79; 1.03-3.13). Compared to patients without CLD (n = 620), propensity-score-matched analysis revealed significant increases in mortality in those with Child-Pugh B (+20.0% [8.8%-31.3%]) and C (+38.1% [27.1%-49.2%]) cirrhosis. Acute hepatic decompensation occurred in 46% of patients with cirrhosis, of whom 21% had no respiratory symptoms. Half of those with hepatic decompensation had acute-on-chronic liver failure. CONCLUSIONS:In the largest such cohort to date, we demonstrate that baseline liver disease stage and alcohol-related liver disease are independent risk factors for death from COVID-19. These data have important implications for the risk stratification of patients with CLD across the globe during the COVID-19 pandemic. LAY SUMMARY:This international registry study demonstrates that patients with cirrhosis are at increased risk of death from COVID-19. Mortality from COVID-19 was particularly high among patients with more advanced cirrhosis and those with alcohol-related liver disease.

BACKGROUND:Effective prevention against coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently limited to nonpharmaceutical strategies. Laboratory and observational data suggested that hydroxychloroquine had biological activity against SARS-CoV-2, potentially permitting its use for prevention. OBJECTIVE:To test hydroxychloroquine as postexposure prophylaxis for SARS-CoV-2 infection. DESIGN:Household-randomized, double-blind, controlled trial of hydroxychloroquine postexposure prophylaxis. (ClinicalTrials.gov: NCT04328961). SETTING:National U.S. multicenter study. PARTICIPANTS:Close contacts recently exposed (<96 hours) to persons with diagnosed SARS-CoV-2 infection. INTERVENTION:Hydroxychloroquine (400 mg/d for 3 days followed by 200 mg/d for 11 days) or ascorbic acid (500 mg/d followed by 250 mg/d) as a placebo-equivalent control. MEASUREMENTS:Participants self-collected mid-turbinate swabs daily (days 1 to 14) for SARS-CoV-2 polymerase chain reaction (PCR) testing. The primary outcome was PCR-confirmed incident SARS-CoV-2 infection among persons who were SARS-CoV-2 negative at enrollment. RESULTS: = 0.026). LIMITATION:The delay between exposure, and then baseline testing and the first dose of hydroxychloroquine or ascorbic acid, was a median of 2 days. CONCLUSION:This rigorous randomized controlled trial among persons with recent exposure excluded a clinically meaningful effect of hydroxychloroquine as postexposure prophylaxis to prevent SARS-CoV-2 infection. PRIMARY FUNDING SOURCE:Bill & Melinda Gates Foundation.

BACKGROUND:Evidence-based preventive care in the USA is underutilized, diminishing population health and worsening health disparities. We developed Project ACTIVE, a program to improve adherence with preventive care goals through personalized and patient-centered care. OBJECTIVE:To determine whether Project ACTIVE improved utilization of preventive care and/or estimated life expectancy compared to usual care. DESIGN/METHODS:Single-site randomized controlled trial. PARTICIPANTS/METHODS:Cluster-randomized 140 English or Spanish speaking adult patients in primary care with at least one of twelve unfulfilled preventive care goals based on USPSTF grade A and B recommendations. INTERVENTION/METHODS:Project ACTIVE employs a validated mathematical model to predict and rank individualized estimates of health benefit that would arise from improved adherence to different preventive care guidelines. Clinical staff engaged the participant in a shared medical decision-making (SMD) process to identify highest priority unfulfilled clinical goals, and health coaching staff engaged the participant to develop and monitor action steps to reach those goals. MAIN MEASURES/METHODS:Change in number of unfulfilled preventive care goals from USPSTF grade A and B recommendations and change in overall gain in estimated life expectancy. KEY RESULTS/RESULTS:In an intent-to-treat analysis, Project ACTIVE increased the average number of fulfilled preventive care goals out of 12 by 0.68 in the intervention arm compared with 0.15 in the control arm (mean difference [95% CI] 0.53 [0.19-0.86]), yielding a gain in estimated life expectancy of 8.8 months (3.8, 14.2). In a per-protocol analysis, Project ACTIVE increased fulfilled preventive care goals by 0.80 in the intervention arm compared with 0.16 in the control arm (mean difference [95% CI], 0.65 [0.25-1.04]), yielding a gain in estimated life expectancy of 13.7 months (6.2, 21.2). Among the 12 preventive care goals, more improvement occurred for alcohol use, hypertension, hyperlipidemia, depression, and smoking. CONCLUSIONS:Project ACTIVE improved unfulfilled preventive care goals and improved estimated life expectancy. CLINICAL TRIAL REGISTRATION NUMBER/BACKGROUND:NCT04211883.

OBJECTIVE:We previously found that antibiotic use at <24 months of age was associated with slightly higher body weight at 5 years of age. In this study, we examine associations of early life antibiotic prescriptions with weight outcomes at 108 to 132 months of age ("10 years"). METHODS:We used electronic health record data from 2009 through 2016 from 10 health systems in PCORnet, a national distributed clinical research network. We examined associations of any (vs no) antibiotics at <24 months of age with body mass index z-score (BMI-z) at 10 years adjusted for confounders selected a priori. We further examined dose response (number of antibiotic episodes) and antibiotic spectrum (narrow and broad). RESULTS:Among 56,727 included children, 57% received any antibiotics at <24 months; at 10 years, mean (standard deviation) BMI-z was 0.54 (1.14), and 36% had overweight or obesity. Any versus no antibiotic use at <24 months was associated with a slightly higher BMI-z at 10 years among children without a complex chronic condition (β 0.03; 95% confidence interval [CI] 0.01, 0.05) or with a complex chronic condition (β 0.09; 95% CI 0.03, 0.15). Any versus no antibiotic use was not associated with odds of overweight or obesity at 10 years among children without (odds ratio 1.02; 95% CI 0.97, 1.07) or with a complex chronic condition (odds ratio 1.07; 95% CI 0.96, 1.19). CONCLUSIONS:The small and likely clinically insignificant associations in this study are consistent with our previous 5-year follow-up results, suggesting that, if this relationship is indeed causal, early increases in weight are small but maintained over time.