Estimation of COVID-19 risk-stratified epidemiological parameters and policy implications for Los Angeles County through an integrated risk and stochastic epidemiological model.

Background: Health disparities have emerged with the COVID-19 epidemic because the risk of exposure to infection and the prevalence of risk factors for severe outcomes given infection vary within and between populations. However, estimated epidemic quantities such as rates of severe illness and death, the case fatality rate (CFR), and infection fatality rate (IFR), are often expressed in terms of aggregated population-level estimates due to the lack of epidemiological data at the refined subpopulation level. For public health policy makers to better address the pandemic, stratified estimates are necessary to investigate the potential outcomes of policy scenarios targeting specific subpopulations. Methods: We develop a framework for using available data on the prevalence of COVID-19 risk factors (age, comorbidities, BMI, smoking status) in subpopulations, and epidemic dynamics at the population level and stratified by age, to estimate subpopulation-stratified probabilities of severe illness and the CFR (as deaths over observed infections) and IFR (as deaths over estimated total infections) across risk profiles representing all combinations of risk factors including age, comorbidities, obesity class, and smoking status. A dynamic epidemic model is integrated with a relative risk model to produce time-varying subpopulation-stratified estimates. The integrated model is used to analyze dynamic outcomes and parameters by population and subpopulation, and to simulate alternate policy scenarios that protect specific at-risk subpopulations or modify the population-wide transmission rate. The model is calibrated to data from the Los Angeles County population during the period March 1 - October 15 2020. Findings: We estimate a rate of 0.23 (95% CI: 0.13,0.33) of infections observed before April 15, which increased over the epidemic course to 0.41 (0.11,0.69). Overall population-average IFR( t ) estimates for LAC peaked at 0.77% (0.38%,1.15%) on May 15 and decreased to 0.55% (0.24%,0.90%) by October 15. The population-average IFR( t ) stratified by age group varied extensively across subprofiles representing each combination of the additional risk factors considered (comorbidities, BMI, smoking). We found median IFRs ranging from 0.009%-0.04% in the youngest age group (0-19), from 0.1%-1.8% for those aged 20-44, 0.36%-4.3% for those aged 45-64, and 1.02%-5.42% for those aged 65+. In the group aged 65+ for which the rate of unobserved infections is likely much lower, we find median CFRs in the range 4.4%-23.45%. The initial societal lockdown period avoided overwhelming healthcare capacity and greatly reduced the observed death count. In comparative scenario analysis, alternative policies in which the population-wide transmission rate is reduced to a moderate and sustainable level of non-pharmaceutical interventions (NPIs) would not have been sufficient to avoid overwhelming healthcare capacity, and additionally would have exceeded the observed death count. Combining the moderate NPI policy with stringent protection of the at-risk subpopulation of individuals 65+ would have resulted in a death count similar to observed levels, but hospital counts would have approached capacity limits. Interpretation: The risk of severe illness and death of COVID-19 varies tremendously across subpopulations and over time, suggesting that it is inappropriate to summarize epidemiological parameters for the entire population and epidemic time period. This includes variation not only across age groups, but also within age categories combined with other risk factors analyzed in this study (comorbidities, obesity status, smoking). In the policy analysis accounting for differences in IFR across risk groups in comparing the control of infections and protection of higher risk groups, we find that the strict initial lockdown period in LAC was effective because it both reduced overall transmission and protected individuals at greater risk, resulting in preventing both healthcare overload and deaths. While similar numbers of deaths as observed in LAC could have been achieved with a more moderate NPI policy combined with greater protection of individuals 65+, this would have come at the expense of overwhelming the healthcare system. In anticipation of a continued rise in cases in LAC this winter, policy makers need to consider the trade offs of various policy options on the numbers of the overall population that may become infected, severely ill, and that die when considering policies targeted at subpopulations at greatest risk of transmitting infection and at greatest risk for developing severe outcomes.

Assessment of vocal cord movement by ultrasound in the ICU.

PURPOSE: Ultrasound can be used to non-invasively and rapidly examine airway conditions, but vocal cord visualization with the traditional approaches is poor. Our aim was to compare the accuracies of front-side transverse-axis ultrasound (FTU), lateral-side longitudinal-axis ultrasound (LLU), and the combination of both approaches for vocal cord movement disorder diagnoses (e.g., vocal cord paralysis or arytenoid cartilage dislocation). METHODS: We compared FTU, LLU, and the combination of both methods for patients in the intensive care unit (ICU). We used nasal fiber-optic endoscopy to confirm vocal cord injury. RESULTS: Among the 120 patients examined, 24 (20%) had vocal cord paralysis. The visualization rate of vocal cords for FTU was 71.7% (assessable, 86; non-assessable, 34), that for LLU was 88.3% (assessable, 106; non-assessable, 14), and that for the combined approach was 96.7% (assessable, 116; non-assessable, 4). The sensitivities and specificities were 58.3% (14/24) and 75% (72/96) for FTU, 91.7% (22/24) and 87.5% (84/96) for LLU, and 100% (24/24) and 95.8% (92/96) for the combined approach. Visualization rates for LLU were significantly higher than for FTU (P = 0.002); FTU + LLU rates were higher than those for FTU (P = 0.001). The difference between LLU and FTU + LLU was not statistically significant (P = 0.025). CONCLUSION: LLU can be used to evaluate arytenoid cartilage activity in ICUs, and the results are highly correlated with the diagnosis of nasal fiber-optic endoscopy. The combination of FTU and LLU shows promise as a rapid primary screening method for vocal cord injury.

CpG-set association assessment of lipid concentration changes and DNA methylation.

Epigenome association studies that test a large number of methylation sites suffer from stringent multiple-testing corrections. This study's goals were to investigate region-based associations between DNA methylation sites and lipid-level changes in response to the treatment with fenofibrate in the GAW20 data and to investigate whether improvements in power could be obtained by taking into account correlations between DNA methylation at neighboring cytosine-phosphate-guanine (CpG) sites. To this end, we applied both a recently developed block-based data-dimension-reduction approach and a region-based variance-component (VC) linear mixed model to GAW20 data. We compared analyses of unrelated individuals with familial data. The region-based VC approach using unrelated (independent) individuals identified the gene LGALS9C as significantly associated with changes in triglycerides. However, univariate tests of individual CpG sites yielded no valid statistically significant results.

A genome-wide association study of energy intake and expenditure.

Excessive energy intake or insufficient energy expenditure, which result in energy imbalance, contribute to the development of obesity. Obesity-related genes, such as FTO, are associated with energy traits. No genome-wide association studies (GWAS) have been conducted to detect the genetic associations with energy-related traits, including energy intake and energy expenditure, among European-ancestry populations. In this study, we conducted a genome-wide study using pooled GWAS including 12,030 European-ancestry women and 6,743 European-ancestry men to identify genetic variants associated with these two energy traits. We observed a statistically significant genome-wide SNP heritability for energy intake of 6.05% (95%CI = (1.76, 10.34), P = 0.006); the SNP heritability for expenditure was not statistically significantly greater than zero. We discovered three SNPs on chromosome 12q13 near gene ANKRD33 that were genome-wide significantly associated with increased total energy intake among all men. We also identified signals on region 2q22 that were associated with energy expenditure among lean people. Body mass index related SNPs were found to be significantly associated with energy intake and expenditure through SNP set analyses. Larger GWAS studies of total energy traits are warranted to explore the genetic basis of energy intake, including possible differences between men and women, and the association between total energy intake and other downstream phenotypes, such as diabetes and chronic diseases.

Analysis of multi drug resistant tuberculosis (MDR-TB) financial protection policy: MDR-TB health insurance schemes, in Chhattisgarh state, India.

INTRODUCTION: There are significant financial barriers to access treatment for multi drug resistant tuberculosis (MDR-TB) in India. To address these challenges, Chhattisgarh state in India has established a MDR-TB financial protection policy by creating MDR-TB benefit packages as part of the universal health insurance scheme that the state has rolled out in their effort towards attaining Universal Health Coverage for all its residents. In these schemes the state purchases health insurance against set packages of services from third party health insurance agencies on behalf of all its residents. Provider payment reform by strategic purchasing through output based payments (lump sum fee is reimbursed as per the MDR-TB benefit package rates) to the providers - both public and private health facilities empanelled under the insurance scheme was the key intervention. AIM: To understand the implementation gap between policy and practice of the benefit packages with respect to equity in utilization of package claims by the poor patients in public and private sector. METHODS: Data from primary health insurance claims from January 2013 to December 2015, were analysed using an extension of 'Kingdon's multiple streams for policy implementation framework' to explain the implementation gap between policy and practice of the MDR-TB benefit packages. RESULTS: The total number of claims for MDR-TB benefit packages increased over the study period mainly from poor patients treated in public facilities, particularly for the pre-treatment evaluation and hospital stay packages. Variations and inequities in utilizing the packages were observed between poor and non-poor beneficiaries in public and private sector. Private providers participation in the new MDR-TB financial protection mechanism through the universal health insurance scheme was observed to be much lower than might be expected given their share of healthcare provision overall in India. CONCLUSION: Our findings suggest that there may be an implementation gap due to weak coupling between the problem and the policy streams, reflecting weak coordination between state nodal agency and the state TB department. There is a pressing need to build strong institutional capacity of the public and private sector for improving service delivery to MDR-TB patients through this new health insurance mechanism.