Determining the Influence of Clinicodemographic, Biologic and SDOH Factors in Racial and Ethnic Disparities in the Prognosis of Alcohol-Associated Liver Disease

确定临床人口统计学、生物和 SDOH 因素对酒精相关性肝病预后中种族和民族差异的影响

• 批准号: 10785492
• 负责人: Thomas Gerard Cotter
• 金额: $ 19.33万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-20 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10785492
• 关键词: AODR mortality; Accounting; Address; Affect; Age; Alcohol consumption; Alcoholic Hepatitis; Alcoholic Liver Diseases; Alcohols; American Indians; Award; Bilirubin; Biological; Black Populations; Black race; Case/Control Studies; Cause of Death; Cessation of life; Cirrhosis; Clinical; Clinical Research; Data; Development; Disease Outcome; Disease Progression; Disparity; Electronic Health Record; Ethnic Origin; Ethnic Population; Europe; European; Fibrosis; Funding; Future; Genes; Genetic; Genetic Diseases; Genetic Risk; Goals; Health; Health Services; Hispanic; Hispanic Populations; International; Intervention; Knowledge; Liver diseases; Logistic Regressions; Machine Learning; Mediation; Mediator; Mentors; Mentorship; Metabolic syndrome; Modeling; Monitor; Morbidity - disease rate; Natural History; Not Hispanic or Latino; Organ; Outcome; Patient Care; Patient-Focused Outcomes; Patients; Pattern; Population; Population Heterogeneity; Prevalence; Prognosis; Prognostic Factor; Prospective cohort; Psychological Impact; Psychosocial Factor; Public Health; Race; Regression Analysis; Research; Research Personnel; Risk; Risk Factors; Role; Sampling; Severity of illness; Single Nucleotide Polymorphism; Social Values; Socioeconomic Status; Steatohepatitis; Survey Methodology; Surveys; Talents; Time; Training; alcohol abstinence; alcohol use disorder; barrier to care; burden of illness; career; cohort; cultural values; disease natural history; disease prognosis; disparity reduction; ethnic difference; ethnic disparity; ethnic diversity; ethnic health disparity; ethnic minority; experience; genetic epidemiology; health disparity; improved; improved outcome; interest; liver transplantation; machine learning method; mortality; patient prognosis; prognostic; prospective; protective factors; racial difference; racial disparity; racial diversity; racial health disparity; racial minority; racial population; research study; risk prediction; risk stratification; sex; skills; social health determinants; socioeconomics; statistics; therapy development

PROJECT SUMMARY / ABSTRACT Alcohol-associated liver disease (ALD) is a major public health problem and the most common cause of death from cirrhosis in the US. ALD disproportionately impacts racial/ethnic minorities, with Hispanic and American Indian patients having increased morbidity and mortality compared with non-Hispanic White patients. Our understanding of these disparities is limited as most data on ALD natural history comes from Europe, while most prognostic studies focus on either risk of developing ALD among drinkers or short-term prognosis in severe ALD. Moreover, few studies have examined how clinicodemographic (e.g., metabolic syndrome) and social determinants of health (SDOH) factors impact patient prognosis in established ALD. Although the association of genetics (e.g., PNPLA3) with risk of developing ALD continues to garner interest, few studies have examined how genetics impact ALD prognosis. My central hypothesis is that unique clinicodemographic, biologic and SDOH factors drive differences in the prognosis and natural history of ALD among racial and ethnic groups, including risk factors leading to progression of ALD among Hispanics and AIs. Guided by an adapted Warnecke conceptual model, I will disentangle direct and indirect effects of clinicodemographic (e.g, Race/ethnicity), biologic (e.g., genetics), and SDOH (e.g. barriers to care) factors on ALD prognostication through the following specific aims in a racially, ethnically, and socioeconomically diverse cohort: 1) Define the role of clinicodemographic and SDOH factors with racial and ethnic differences in ALD severity; 2) Examine the association of genetic factors and ALD severity; 3) Derive a multilevel risk stratification model for ALD prognostication. These data will inform the most impactful interventions to reduce disparities in ALD. The PI is a clinical researcher and hepatologist at UT Southwestern, with a long-term vision of improving care for patients with ALD, including tackling disparities. The proposed training plan is integrated with the research aims and builds on his existing knowledge in clinical research whereby he will acquire new, advanced skills in advanced quantitative analysis, health disparities, genetics, cohort building, survey methods, machine learning in risk prediction. He has assembled an exceptionally talented interdisciplinary team of mentors with complementary expertise: Dr. Mack Mitchell, an experienced researcher and ALD content expert; Dr. Amit Singal, a world- renowned health services and disparities researcher; Dr. Helen Hobbs, an international expert in genetics and liver disease; Dr. King, an expert in AUD; Dr. Zhang, an expert statistician in quantitative analyses; Dr. Kozlitina, an expert in genetic statistics; and Dr. Sandikçi, an expert statistician in machine learning in risk prediction. The research studies in this proposal have significant public health impact as they will fill gaps in our understanding of the prognosis of ALD among racial/ethnic minorities. This award and training plan will provide the PI with the protected time, training, and mentorship, to build an independently-funded research career focused on improving ALD outcomes.

项目摘要 /摘要 酒精相关肝病（ALD）是一个主要的公共卫生问题，也是最常见的死亡原因 来自美国的肝硬化。与西班牙裔和美国人，ALD不成比例地影响种族/民族 与非西班牙裔白人患者相比，印度患者发病率和死亡率增加。我们的 对这些分布的理解是有限的，因为大多数关于ALD自然历史的数据来自欧洲，而大多数数据 预后研究的重点是饮酒者中发展ALD的风险或严重ALD的短期预后。 此外，很少有研究研究临床代码人口统计学（例如代谢综合征）和社会如何 健康的决定因素（SDOH）因素会影响既定ALD的患者预后。虽然是 遗传学（例如PNPLA3）有发展ALD的风险继续引起人们的兴趣，很少有研究检查 遗传学如何影响ALD预后。我的中心假设是独特的临床代码人口表，生物学和 SDOH因素推动了种族和族裔中ALD的预后和自然历史的差异， 包括导致西班牙裔和AIS中ALD发展的风险因素。在改编的Warnecke的指导下 概念模型，我将解散临床代码人口统计学（例如种族/种族）的直接和间接影响， 生物学（例如遗传学）和SDOH（例如，护理障碍）ALD编程的因素 具体的目的是在大致，种族和社会经济上多样化的队列中：1）定义的作用 ALD严重程度的种族和种族差异的临床代码人口表和SDOH因素； 2）检查 遗传因素和ALD严重程度的关联； 3）得出ALD的多层次风险分层模型 预测。这些数据将为减少ALD分布的最有影响力的干预措施提供信息。 PI是一个 UT Southwestern的临床研究人员和肝病学家，长期愿景可以改善患者的护理 与ALD一起，包括解决差异。拟议的培训计划与研究目的和 基于他在临床研究中的现有知识，从而获得高级高级技能 定量分析，健康分布，遗传学，队列建筑，调查方法，机器学习风险 预言。他已经组建了一个非常有才华的跨学科导师团队 专业知识：经验丰富的研究员和ALD内容专家Mack Mitchell博士；阿米特·辛纳尔（Amit Singal）博士，世界 - 著名的卫生服务和差异研究员；海伦·霍布斯（Helen Hobbs）博士，遗传学和国际专家 肝病； King博士，AUD专家；张博士，定量分析的专业统计学家； Kozlitina博士， 遗传统计专家；以及Sandikçi博士，他是风险预测的机器学习专业统计学家。这 该提案中的研究具有重大的公共卫生影响，因为它们将在我们的理解中填补空白 种族/族裔少数民族中ALD的预后。该奖项和培训计划将为PI提供 受保护的时间，培训和精神制，以建立一个专注于改进的独立资助研究职业 ALD结果。