Investigating the role of frailty on outcomes in acutely ill patients with cirrhosis undergoing liver transplantation in the acute care setting

调查虚弱对在急症护理环境中接受肝移植的急性肝硬化患者的结局的作用

• 批准号: 10658726
• 负责人: Jennifer C. Lai
• 金额: $ 83.12万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-15 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10658726
• 关键词: Acute; Address; American; Biological; Chronic; Cirrhosis; Clinical; Data; Decision Making; Equilibrium; Evaluation; Event; Extrahepatic; Eye; Goals; Hand; Hand Strength; Health; Healthcare Systems; Hepatology; Hospitalization; Hour; Individual; Inpatients; Intercept; Length of Stay; Liver; Machine Learning; Malnutrition; Measures; Modeling; Muscular Atrophy; Operative Surgical Procedures; Outcome; Outpatients; Patients; Personal Satisfaction; Physiological; Population; Population Dynamics; Portal Hypertension; Predictive Value; Recovery; Research; Role; Severities; Societies; Standardization; Surveys; Testing; Time; Transplant Recipients; Transplantation; Transplantation Surgery; Validation; acute care; clinical practice; clinical predictive model; cost; disability; frailty; functional disability; functional status; health care service utilization; health related quality of life; improved; indexing; liver function; liver transplantation; model building; mortality; novel; outcome prediction; post-transplant; recruit; stressor; theories; tool

PROJECT SUMMARY For patients with cirrhosis, liver transplantation is a well-established therapy, restoring liver function and reversing portal hypertension within days to weeks of the surgery itself. But cirrhosis also leads to insidious extra-hepatic effects such as muscle wasting, malnutrition, and functional impairment that may take months to reverse, if at all, which can compromise health and wellbeing (“global functional health”) after transplantation. In the ambulatory setting, these chronic cirrhosis manifestations can be captured by measures of “frailty”, the chronic biological state of decreased physiological reserve and increased vulnerability to health stressors, and operationalized using the Liver Frailty Index (LFI)—which our team developed from grip strength, chair stands, and balance. When assessed in the ambulatory setting, LFI predicts adverse health outcomes including hospitalizations and mortality. Frailty is now a well-accepted construct in hepatology/transplantation: in 2019, the American Society of Transplantation (AST) endorsed the use of standardized frailty metrics, including the LFI, for ambulatory liver transplant evaluation. However, approximately 1/3 of cirrhosis patients are hospitalized with acute illness immediately prior to transplant, in whom pre-morbid, ambulatory, frailty metrics may not be available. In this setting, transplant clinicians have, in many instances, been applying this construct in the acute care setting to inform transplant decisions—often informally through an “eyeball test”—despite a lack of studies evaluating the construct of frailty or tools to measure frailty in acutely ill patients. Unlike in the ambulatory setting where frailty represents factors that would not reverse with liver transplantation, a single frailty assessment in the acute setting may simply reflect the severity of acute liver-related decompensation, which, in theory, could reverse with a new liver. On the other hand, frailty trajectories may be informative of a patient’s ability to recovery a major stressor such as transplant surgery, so application of frailty as a trajectory may be more clinically appropriate. But testing of these hypotheses has not yet been done. In this proposal, we will leverage our 9-center research network to develop and validate a novel inpatient frailty index optimized for this acutely ill population, investigate models incorporating single and longitudinal assessments of frailty for the prediction of 1-year post-transplant global functional health, and associate inpatient frailty assessments with 1- year post-transplant healthcare utilization. Impact: Our proposal will result in a pragmatic, objective tool to standardize assessment of frailty in acutely ill patients with cirrhosis undergoing liver transplantation and clinical prediction models to guide use of single and longitudinal assessments of frailty for transplant decision- making in this clinically dynamic population. Understanding the precise relationship between acute care frailty and outcomes is essential to facilitate appropriate and systematic implementation of frailty in transplantation.

项目摘要 对于肝硬化患者，肝移植是一种完善的疗法，恢复肝功能和 在手术本身的几天内逆转门户高血压。但是肝硬化也导致阴险 诸如肌肉浪费，营养不良和功能障碍之类的外脑外影响，可能需要几个月的时间才能 反向（如果有的话），这可能会损害移植后的健康和福祉（“全球功能健康”）。 在门诊环境中，这些慢性肝硬化表现可以通过“脆弱”的措施来捕获 慢性生物学状态减少了物理储备和增加对健康压力源的脆弱性，以及 使用肝脏脆弱指数（LFI）进行操作 - 我们的团队从握把力量，椅子摊上发展， 和平衡。当在门诊环境中进行评估时，LFI预测了不良健康结果 住院和死亡率。现在，脆弱的是肝病/移植中的一个良好接受的结构：2019年， 美国移植学会（AST）认可使用标准化的脆弱指标，包括 LFI，用于门诊肝移植评估。但是，大约1/3的肝硬化患者是 在移植前立即患有急性疾病，其中室前，卧床，脆弱的指标 可能无法使用。在这种情况下，移植临床医生在许多情况下都应用了这种结构 在急性护理环境中，以告知移植决策（通常是通过“眼球测试”） 缺乏评估脆弱患者中脆弱或工具的结构的研究。与 脆弱的卧床环境代表不会随着肝移植而逆转的因素，一个单一的因素 急性环境中的脆弱评估可能只是反映了与急性肝相关的代偿作用的严重程度， 从理论上讲，这可以用新的肝脏逆转。另一方面，脆弱的轨迹可能是 患者能够恢复主要压力源（例如移植手术）的能力，因此将脆弱的应用于轨迹 可能在临床上更合适。但是对这些假设的检验尚未进行。在这个建议中，我们 将利用我们的9个中心研究网络来开发和验证针对 这个急性疾病的人调查了进口单一和纵向评估的模型 预测1年移植后全球功能健康，并以1-的相关住院脆弱评估 移植后医疗保健保健使用年度。影响：我们的建议将导致务实的客观工具 标准化急性病肝硬化患者的虚弱的评估，接受肝移植和 临床预测模型，以指导使用单一和纵向评估的脆弱和纵向评估用于移植决策 - 在这个临床动态的人群中。了解急性护理脆弱之间的精确关系 结果对于促进移植中脆弱的适当和系统地实施至关重要。