DINIRS：用于无创呼吸支持策略个体化治疗效应的数字孪生模型

中文摘要 AI 辅助

目的：为急性呼吸衰竭患者选择无创呼吸支持（NIRS）与有创机械通气（IMV）是一项复杂且时间敏感的决策，不同患者亚组的治疗效应存在异质性。尽管临床试验和指南提供了人群层面的指导，但仍不清楚哪些患者从NIRS中获益多于IMV。我们开发并验证了一种考虑删失的无创呼吸支持个体化治疗效应数字孪生框架（DINIRS），用于估计涵盖死亡率和通气时长的个体化治疗效应（ITEs）。材料与方法：我们在MIMIC-IV数据库中5336名急性呼吸衰竭患者的ICU入住前24小时内的23项基线临床变量上训练DINIRS。我们使用带生存注意力门的Transformer编码器将28天无呼吸机天数（VFD-28）分解为生存概率和条件通气时长。采用交叉拟合的双重鲁棒学习器估计ITEs。我们在多中心eICU-CRD数据集的2540名患者中对DINIRS进行外部验证。结果：与实际临床实践相比，DINIRS策略实现了每名患者平均2.07天的无呼吸机天数获益（每100名患者对应207天）。在器官功能障碍较轻的患者中，预测的NIRS获益比例更高（88.4%对比49.0%），且在不同低氧血症严重程度患者中均存在。外部验证无需重新训练即可复现该模式。讨论：我们的分析显示，NIRS的获益源于幸存者的通气时长更短，而非死亡率降低，提示避免插管相关并发症是主要机制。结论：本研究利用ICU数据实现了NIRS获益的个体化估计，但这些估计值在用于指导治疗决策前仍需前瞻性验证。

英文摘要

Objective: Choosing between noninvasive respiratory support (NIRS) and invasive mechanical ventilation (IMV) for acute respiratory failure is a time-sensitive decision. Although guidelines provide population-level guidance, it remains unclear who benefits more from NIRS than IMV. The standard outcome, ventilator-free days at 28 days (VFD-28), scores death and prolonged ventilation equally, and current estimators do not distinguish between them. We developed and validated a censoring-aware Digital Twin framework for Individualized Treatment Effects of Non-Invasive Respiratory Support (DINIRS) to estimate individualized treatment effects (ITEs) that capture both mortality and ventilation duration. Materials and Methods: We emulated a target trial in 5,336 MIMIC-IV patients and trained DINIRS on 23 baseline clinical variables measured during the first 24 ICU hours. A transformer encoder with a survival attention gate decomposed VFD-28 into survival probability and conditional ventilation duration. A cross-fitted, doubly robust learner estimated ITEs. We externally validated DINIRS in 2,540 patients from the multi-site eICU-CRD dataset without retraining. Results: The DINIRS policy achieved a mean benefit of 2.07 ventilator-free days per patient (207 per 100 patients) compared with observed practice. Predicted NIRS benefit was higher among patients with less organ dysfunction (88.4% versus 49.0%) and persisted across hypoxemia severity. External validation reproduced this pattern. Discussion: The NIRS benefit stemmed from shorter ventilation among survivors rather than from reduced mortality, indicating that avoiding intubation-associated complications was the primary mechanism. Conclusion: Prospective validation is needed before these estimates inform treatment decisions. The decomposition framework can be extended beyond respiratory support to any zero-inflated composite outcome.

发表机构

• College of Engineering, The University of Arizona（亚利桑那大学工程学院）
• College of Medicine - Tucson, The University of Arizona（亚利桑那大学图森医学院）

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