The COVID-19 (Coronavirus disease-2019) pandemic, caused by the SARS-CoV-2 coronavirus, is a significant threat to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and MERS-CoV. Here, we have carried out comparative viral-human protein-protein interaction and viral protein localization analysis for all three viruses. Subsequent functional genetic screening identified host factors that functionally impinge on coronavirus proliferation, including Tom70, a mitochondrial chaperone protein that interacts with both SARS-CoV-1 and SARS-CoV-2 Orf9b, an interaction we structurally characterized using cryo-EM. Combining genetically-validated host factors with both COVID-19 patient genetic data and medical billing records identified important molecular mechanisms and potential drug treatments that merit further molecular and clinical study.

IMPORTANCEStrategies that enhance self-care of patients with heart failure reduce mortality and health care use. OBJECTIVE To examine whether an empowerment-based self-care education program was more effective and cost-effective to improve self-care, health status, and hospital service use than a didactic education program in patients with heart failure. DESIGN, SETTING, AND PARTICIPANTS In this double-blind randomized clinical trial, a consecutive sample of 988 patients with heart failure from the cardiac clinics of 2 regional hospitals underwent eligibility screening from February 1, 2017, to May 31, 2019, using the criteria of age of 55 years or older, heart failure diagnosed 6 months before screening, and New York Heart Association class II to IV. A total of 236 participants were randomized to the empowerment (n = 118) or education (n = 118) group. INTERVENTIONS The 12-week, group-based, empowerment-based education program included self-care assessment, goal-orientated actions in symptom recognition and response, fluid and dietary modification, and lifestyle management. Didactic education covered the same topics without empowerment strategies. MAIN OUTCOMES AND MEASURESThe primary outcome was self-care measured by the Self-care Heart Failure Index (SCHFI) maintenance, management, and symptom perception subscales at posttest and 3-month end points. Secondary outcomes included measures of knowledge, confidence, health-related quality of life, and health service use. Direct, indirect, and social costs of the 2 programs were collected for cost-effectiveness analysis. RESULTSA total of 236 Chinese patients (mean [SD] age, 70 [8.0] years; 149 [63.1%] men) were included in the study. The empowerment group reported significantly greater improvement in SCHFI management scores (mean difference, 13.76; 95% CI, 5.89-21.62; Cohen d = 0.46 at posttest and Cohen d = 0.35 at 3 months) and symptom perception scores (mean difference, 20.36; 95% CI, 13.98-26.75; Cohen d = 0.84 at posttest and Cohen d = 0.61 at 3 months). The empowerment group had lower risks of emergency department attendance (incidence rate ratio, 0.55; 95% CI, 0.31-0.95; P = .03) and hospital admission (incidence rate ratio, 0.38; 95% CI, 0.21-0.68; P = .001) and better improved self-care knowledge (change in score [empowerment minus education], 1.29; 95% CI, 0.48-2.09) and confidence (change in score [empowerment minus education], 7.98; 95% CI, 1.91-14.05). Empowerment was cost-saving and cost-effective at T2 compared with the education group for quality-adjusted life-years, with an incremental cost-effectiveness ratio of −114 485.(continued) Key Points Question What are the effectiveness and cost-effectiveness of a 12-week, empowerment-based self-care intervention on health outcomes and health care use among patients with heart failure? Findings In this randomized clinical trial of 236 patients with heart failure, when compared with didactic education, an empowerment-based self-care intervention was effective and costeffective, resulting in improvement in s...

The relative effects of various cardiovascular diseases (CVD) and varying severity of chronic kidney disease (CKD) on mortality risk, direct medical cost and life expectancy in patients with diabetes mellitus (DM) are unclear. The aim of this study was to evaluate these associations. Research Design and Methods This was a retrospective cohort study that included 208,792 adults with diabetes stratified into 12 disease status groups with varying combinations of heart disease, stroke, moderate CKD (eGFR:30-59ml/min/1.73m 2) and severe CKD (eGFR: <30ml/min/1.73m 2) in 2008-2010. The effect of risk mortality, annual direct medical costs and life expectancy were assessed using Cox regression, Gamma generalized linear with log link function, and flexible parametric survival models. Results Over a median follow-up of 8.5 years (1.6 million patient-years), 50,154 deaths were recorded. Mortality risks for patients with only a single condition among heart disease, stroke and moderate CKD were similar. The mortality risks were 1.75 times, 2.63 times and 3.58 times greater for patients with one, two and all three conditions (consisting of stroke, heart disease and moderate CKD), compared with patients without these diseases, suggesting an independent and individually additive effect for any combination. A similar trend was observed in annual public healthcare costs with 2.91, 3.90 and 3.88 fold increased costs for patients with one, two and three conditions, respectively. Increases in the number of conditions reduced life expectancy greatly, particularly in younger patients. Reduction in life expectancy for a 40-year-Page 4 of 28 old with one, two and three conditions were 20, 25, 30 years for men and 25, 30, 35 years for women. A similar trend of greater magnitude was observed for severe CKD. Conclusion The effect of heart diseases, stroke, CKD and the combination of these conditions on all-cause mortality and direct medical costs are independent and cumulative. CKD, especially severe CKD, appears to have a particularly significant impact on life expectancy and direct medical costs in patients with diabetes. These finding supports the importance of preventing both CVD and CKD in patients with DM.