Improving Surgical Risk Prediction and Decision Making among Patients with Cirrhosis

项目总结 与普通人群相比，肝硬变患者的手术风险增加了几个危险因素 已被建立用于预测肝硬变手术风险。这些都反映在用于风险的主要临床工具中。 预测-终末期肝病的模型-钠(MELD-Na)、Child-Turcotte-Pugh(CTP)评分和 Mayo手术风险评分-取决于年龄、肝硬变严重程度、ASA身体状况评分和 肝病。然而，按手术类型划分的术后死亡率显著不同(例如，心脏 与整形外科的对比)表明，这些工具是不够的。关于肝硬变手术风险预测的文献 进一步受到以下因素的限制：1)样本量小的单中心设计；2)缺乏针对风险的细粒度数据 预测，3)预测得分校准不佳的证据，4)缺乏关键利益相关者的参与以提供信息 预测工具的现实实施，以及5)没有纳入决策分析方法进行比较 从外科到非手术的管理。这些缺陷的影响是许多肝硬变患者 由于对风险的高估而被拒绝接受必要的手术，其他人接受手术的方式不准确 预后咨询或对非手术选择考虑不足。人口级别的细粒度数据 要弥补上述差距，就需要采取必要的措施。通过使用国家退伍军人健康管理局(VHA)和大学 对于宾夕法尼亚州医院系统(UPHS)数据，我们假设我们将能够创建和实施 一种准确的、校准良好的肝硬化手术风险计算器，具有广泛的临床实用价值。这样做的主要目的是 建议如下：目标1-推导、内部验证和外部验证肝硬变手术风险 不同类型的肝硬变患者手术后短期和中期死亡率模型；目标2 -创建一个Web应用程序，用于根据关键利益相关者的输入进行手术风险预测。目标3-使用马尔科夫 建模以比较手术和非手术管理路径并确定最佳临床 一个常见的临床场景的决策：急性胆囊炎。这项提议将促进纳迪姆·马哈茂德博士 发展为独立的、由NIH资助的临床研究人员，专注于改善对 慢性肝病患者，以及高级预测建模方面的特定专业知识，定性 方法和决策分析。这将通过一项全面的指导计划来促进，该计划包括： 1)每两周至每月与他的指导团队举行一次会议，2)高级预测的正式课程 通过临床流行病学中心进行建模、定性研究方法和决策分析 和生物统计学(CCEB)，沃顿商学院，卫生政策研究(HPR)，运营， 信息和决策系(OIDD)和统计系(STAT) 宾夕法尼亚州，3)有组织的研究研讨会和国家会议，以及4)概念、开发、 并在授标期后期提交未来赠款，以进一步探讨与以下方面有关的问题 肝硬变患者的手术风险预测。

PROJECT SUMMARY Patients with cirrhosis have increased surgical risk relative to the general population Several risk factors have been established to predict cirrhosis surgical risk. These are reflected in the primary clinical tools used for risk prediction—the Model for End-stage Liver Disease-sodium (MELD-Na), Child-Turcotte-Pugh (CTP) score, and the Mayo surgical risk score—which rely on age, cirrhosis severity, ASA physical status score, and etiology of liver disease. However, significant heterogeneity in post-operative mortality by surgery type (e.g., cardiac versus orthopedic) suggests that these tools are inadequate. The literature on cirrhosis surgical risk prediction is further limited by: 1) single-center designs with small sample sizes, 2) lack of granular data for risk prediction, 3) evidence of poor prediction score calibration, 4) lack of key stakeholder involvement to inform real-world implementation of prediction tools, and 5) no incorporation of decision analysis methods to compare surgery to non-operative management. The impact of these shortcomings is that many patients with cirrhosis are denied necessary surgery due to overestimates of risk, and others receive surgery with inaccurate prognostic counseling or inadequate consideration of non-operative options. Granular, population-level data are needed to address the above gaps. By using national Veterans Health Administration (VHA) and University of Pennsylvania Hospital System (UPHS) data, we hypothesize that we will be able to create and implement an accurate, well-calibrated cirrhosis surgical risk calculator with broad clinical utility. The primary aims of this proposal are as follows: Aim 1 – derive, internally validate, and externally validate cirrhosis surgical risk models for short- and intermediate-term post-operative mortality among diverse patients with cirrhosis.; Aim 2 – create a web application for surgical risk prediction informed by key stakeholder input.; Aim 3 – use Markov modeling to compare operative to non-operative management pathways and determine optimal clinical decisions for a common clinical scenario: acute cholecystitis. This proposal will foster Dr. Nadim Mahmud's development as an independent, NIH-funded clinical researcher with a focus on improving risk prediction for patients with chronic liver diseases, as well as specific expertise in advanced prediction modeling, qualitative methods, and decision analysis. This will be facilitated through a comprehensive mentorship plan consisting of: 1) biweekly to monthly meetings with his mentorship team, 2) formal coursework in advanced prediction modeling, qualitative research methods, and decision analysis through the Center for Clinical Epidemiology and Biostatistics (CCEB), Wharton School, Department of Health Policy Research (HPR), Operations, Information, and Decisions Department (OIDD), and Department of Statistics (STAT) at the University of Pennsylvania, 3) structured research workshops and national conferences, and 4) conception, development, and submission of future grants during the latter portion of the award period to further explore issues related to surgical risk prediction among patients with cirrhosis.