Background: The novel Severe Acute Respiratory Syndrome Coronavirus-2 has led to a global pandemic in which case fatality rate (CFR) has varied from country to country. This study aims to identify factors that may explain the variation in CFR across countries. Methods: We identified 24 potential risk factors affecting CFR. For all countries with over 5000 reported COVID-19 cases, we used country-specific datasets from the WHO, the OECD, and the United Nations to quantify each of these factors. We examined univariable relationships of each variable with CFR, as well as correlations among predictors and potential interaction terms. Our final multivariable negative binomial model included univariable predictors of significance and all significant interaction terms. Results: Across the 39 countries under consideration, our model shows COVID-19 case fatality rate was best predicted by time to implementation of social distancing measures, hospital beds per 1000 individuals, percent population over 70 years, CT scanners per 1 million individuals, and (in countries with high population density) smoking prevalence. Conclusion: Our model predicted an increased CFR for countries that waited over 14 days to implement social distancing interventions after the 100th reported case. Smoking prevalence and percentage population over the age of 70 years were also associated with higher CFR. Hospital beds per 1000 and CT scanners per million were identified as possible protective factors associated with decreased CFR.

Hepatocellular carcinoma is 1 of few cancers with rising incidence and mortality in the United States. Little is known about disease presentation and outcomes across the rural-urban continuum. Using the population-based Surveillance, Epidemiology, and End Results registry, we identified adults with incident hepatocellular carcinoma between 2000 and 2016. Urban, suburban, and rural residence at time of cancer diagnosis were categorized by the Census Bureau’s percent of the population living in nonurban areas. We examined association between place of residence and overall survival. Secondary outcomes were late tumor stage and receipt of therapy. Of 83 368 incident cases of hepatocellular carcinoma, 75.8%, 20.4%, and 3.8% lived in urban, suburban, and rural communities, respectively. Median survival was 7 months (interquartile range = 2-24). All stage and stage-specific survival differed by place of residence, except for distant stage. In adjusted models, rural and suburban residents had a respective 1.09-fold (95% confidence interval [CI] = 1.04 to 1.14; P < .001) and 1.08-fold (95% CI = 1.05 to 1.10; P < .001) increased hazard of overall mortality as compared with urban residents. Furthermore, rural and suburban residents had 18% (odds ratio [OR] = 1.18, 95% CI = 1.10 to 1.27; P < .001) and 5% (OR = 1.05, 95% CI = 1.02 to 1.09; P = .003) higher odds of diagnosis at late stage and were 12% (OR = 0.88, 95% CI = 0.80 to 0.94; P < .001) and 8% (OR = 0.92, 95% CI = 0.88 to 0.95; P < .001) less likely to receive treatment, respectively, compared with urban residents. Residence in a suburban and rural community at time of diagnosis was independently associated with worse indicators across the cancer continuum for liver cancer. Further research is needed to elucidate the primary drivers of these rural-urban disparities.

Nonalcoholic fatty liver disease (NAFLD) among Latinos is partially attributed to a prevalent C>G polymorphism in the patatin-like phospholipase 3 (PNPLA3) gene. Cross-sectional analyses in Latino children showed the association between dietary sugar and liver fat was exacerbated by GG genotype. Pediatric feeding studies show extreme sugar restriction improves liver fat, but no prior trial has examined the impact of a clinical intervention or whether effects differ by PNPLA3 genotype. We aimed to test effects of a clinical intervention to reduce dietary sugar compared with standard dietary advice on change in liver fat, and secondary-endpoint changes in liver fibrosis, liver enzymes, and anthropometrics; and whether effects differ by PNPLA3 genotype (assessed retrospectively) in Latino youth with obesity (BMI ≥ 95^th percentile). This parallel-design trial randomly assigned participants (n = 105; mean baseline liver fat: 12.7%; mean age: 14.8 y) to control or sugar reduction (goal of ≤10% of calories from free sugar) for 12 wk. Intervention participants met with a dietitian monthly and received delivery of bottled water. Changes in liver fat, by MRI, were assessed by intervention group via general linear models. Mean free sugar intake decreased in intervention compared with control [11.5% to 7.3% compared with 13.9% to 10.7% (% energy), respectively; P = 0.02], but there were no significant effects on liver outcomes or anthropometrics (P_all > 0.10), and no PNPLA3 interactions (P_all > 0.10). In exploratory analyses, participants with whole-body fat mass (FM) reduction (mean ± SD: −1.9 ± 2.4 kg), irrespective of randomization, had significant reductions in liver fat compared with participants without FM reduction (median: −2.1%; IQR: −6.5% to −0.8% compared with 0.3%; IQR: −1.0% to 1.1%; P < 0.001). In Latino youth with obesity, a dietitian-led sugar reduction intervention did not improve liver outcomes compared with control, regardless of PNPLA3 genotype. Results suggest FM reduction is important for liver fat reduction, confirming clinical recommendations of weight loss and a healthy diet for pediatric NAFLD. This trial was registered at clinicaltrials.gov as NCT02948647.

U.S. military suicides are increasing and disrupted relationships frequently precede them. Group-level interventions are needed that reduce future suicide vulnerability among healthy members and also ameliorate risk among those already suicidal. We examined whether our Wingman-Connect Program (W-CP) strengthened Air Force relationship networks and socially integrated at-risk members. Air Force personnel classes in training were randomized to W-CP or active control (cluster RCT), followed up at 1 and 6 months (94% and 84% retention). Data were collected in 2017-2019 and analyzed in 2020-2021. Participants were 1485 male and female Airmen in 215 technical training classes. W-CP training involved strengthening group bonds, skills for managing career and personal stressors, and diffusion of healthy norms. Active control was stress management training. Primary outcomes were social network metrics based on Airmen nominations of valued classmates after 1 month. Baseline CAT-SS >34 defined elevated suicide risk. W-CP increased social network integration, with largest impact for Airmen already at elevated suicide risk (n = 114, 7.7%). For elevated risk Airmen, W-CP improved all network integration metrics, including 53% average gain in valued connection nominations received from other Airmen (RR = 1.53, 95% CI = 1.12, 2.08) and eliminated isolation. No elevated risk Airmen in W-CP were isolates with no valued connections after 1-month vs. 10% among controls (P < .035). In contrast to at-risk controls, at-risk W-CP Airmen increased connections after intervention. W-CP's effect on a key indicator, ≥2 connections, was still greater 2-4 months after classes disbanded (6-months). Wingman-Connect Program built enhanced suicide protection into unit relationship networks and counteracted standard drift towards disconnection for at-risk Airmen, despite no explicit content targeting connections specifically to at-risk Airmen. Findings support a growing case for the unique contribution of group-level interventions to improve social health of broader military populations while also ameliorating risk among individuals already at elevated suicide risk.