用可解释的反事实分析,预测新冠后心衰患者住院风险并找出干预路径。
A Hybrid Enumeration Framework for Optimal Counterfactual Generation in Post-Acute COVID-19 Heart Failure
- 结合精确枚举与优化算法,搜索高维干预空间中的最优反事实路径。
- 在2700名患者上实现AUROC 0.88,精准预测新冠后心衰住院风险。
- 适合临床研究者与医学AI开发者,用于个性化风险干预决策支持。
反事实推断为在不同干预下推理假设结果提供了数学框架,连接因果推理与预测建模。本文提出一种针对既往心衰患者中新冠后遗症(PASC)相关心衰住院风险的个体化风险评估与干预分析框架。基于大规模医疗系统队列的纵向诊断、检验及用药数据,将正则化预测模型与反事实搜索相结合,识别出可操作的预防路径。框架融合精确枚举与基于优化的方法,包括最近实例反事实解释(NICE)和多目标反事实(MOC)算法,高效探索高维干预空间。应用于超过2700名确诊感染SARS-CoV-2且有既往心衰的个体,模型表现优异(AUROC: 0.88,95% CI: 0.84–0.91),生成可解释、患者特异的反事实,量化改变共病模式或治疗因素如何影响预测结果。本研究证明反事实推理可形式化为预测函数上的优化问题,提供一种严谨、可解释且计算高效的复杂生物医学系统个性化推断方法。
原文摘要 · Abstract (English)
Counterfactual inference provides a mathematical framework for reasoning about hypothetical outcomes under alternative interventions, bridging causal reasoning and predictive modeling. We present a counterfactual inference framework for individualized risk estimation and intervention analysis, illustrated through a clinical application to post-acute sequelae of COVID-19 (PASC) among patients with pre-existing heart failure (HF). Using longitudinal diagnosis, laboratory, and medication data from a large health-system cohort, we integrate regularized predictive modeling with counterfactual search to identify actionable pathways to PASC-related HF hospital admissions. The framework combines exact enumeration with optimization-based methods, including the Nearest Instance Counterfactual Explanations (NICE) and Multi-Objective Counterfactuals (MOC) algorithms, to efficiently explore high-dimensional intervention spaces. Applied to more than 2700 individuals with confirmed SARS-CoV-2 infection and prior HF, the model achieved strong discriminative performance (AUROC: 0.88, 95% CI: 0.84-0.91) and generated interpretable, patient-specific counterfactuals that quantify how modifying comorbidity patterns or treatment factors could alter predicted outcomes. This work demonstrates how counterfactual reasoning can be formalized as an optimization problem over predictive functions, offering a rigorous, interpretable, and computationally efficient approach to personalized inference in complex biomedical systems.
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