Corticosteroids for infectious critical illness: A multicenter target trial emulation stratified by predicted organ dysfunction trajectory.
Corticosteroids for infectious critical illness: A multicenter target trial emulation stratified by predicted organ dysfunction trajectory.
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皮质类固醇治疗传染性危重疾病：按预测的器官功能障碍轨迹分层的多中心目标试验模拟。
DOI：
10.1101/2024.03.07.24303926
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Wang,Fei
中科院分区：
文献类型：
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作者：
Rajendran,Suraj;Xu,Zhenxing;Pan,Weishen;Zang,Chengxi;Siempos,Ilias;Torres,Lisa;Xu,Jie;Bian,Jiang;Schenck,EdwardJ;Wang,Fei
皮质类固醇减少了一系列传染性危重病的器官功能障碍的持续时间，但其风险和益处并没有完全确定使用这个结构。本回顾性多中心研究旨在通过模拟目标试验框架，评价皮质类固醇的使用与感染性危重病患者死亡率之间的相关性。该研究采用了一种新的分层方法，基于器官功能障碍轨迹预测机器学习（ML）亚表型。我们的分析显示，皮质类固醇的有效性取决于分层方法。基于ML的方法确定了四种不同的亚表型，其中两种在我们的患者队列中具有足够大的样本量以进行进一步评估：“快速改善”（RI）和“快速恶化”（RW），其显示对皮质类固醇治疗的不同反应。具体而言，RW组受益于或不受皮质类固醇的损害，而RI组似乎受到损害。在由eICU和MIMIC-IV数据集的患者组合组成的开发队列中，RW组的主要结局（28天死亡率）的风险比估计值为1.05（95% CI：0.96 - 1.04），而RW组为1.40（95% CI：1.28 - 1.54）。对于验证队列，包括来自高级研究危重病数据库的患者，RW和RI组的28天死亡率估计值分别为1.24（95% CI：1.05 - 1.46）和1.34（95% CI：1.14 - 1.59）。对于次要结局，RW组的ICU出院时间和皮质类固醇治疗的机械通气停止时间较短，RI组再次显示出伤害。研究结果支持匹配的治疗策略，以经验观察的病理生物学，并提供了一个更细致入微的了解皮质类固醇的效用。我们的研究结果对观察性研究和随机对照试验（RCT）的设计和解释都有影响，这表明需要分层方法来解释对标准治疗的不同反应。
Corticosteroids decrease the duration of organ dysfunction in a range of infectious critical illnesses, but their risk and benefit are not fully defined using this construct. This retrospective multicenter study aimed to evaluate the association between usage of corticosteroids and mortality of patients with infectious critical illness by emulating a target trial framework. The study employed a novel stratification method with predictive machine learning (ML) subphenotyping based on organ dysfunction trajectory. Our analysis revealed that corticosteroids’ effectiveness varied depending on the stratification method. The ML-based approach identified four distinct subphenotypes, two of which had a large enough sample size in our patient cohorts for further evaluation: “Rapidly Improving” (RI) and “Rapidly Worsening,” (RW) which showed divergent responses to corticosteroid treatment. Specifically, the RW group either benefited or were not harmed from corticosteroids, whereas the RI group appeared to derive harm. In the development cohort, which comprised of a combination of patients from the eICU and MIMIC-IV datasets, hazard ratio estimates for the primary outcome, 28-day mortality, in the RW group was 1.05 (95% CI: 0.96 – 1.04) whereas for the RW group, it was 1.40 (95% CI: 1.28 – 1.54). For the validation cohort, which comprised of patients from the Critical carE Database for Advanced Research, estimates for 28-day mortality for the RW and RI groups were 1.24 (95% CI: 1.05 – 1.46) and 1.34 (95% CI: 1.14 – 1.59), respectively. For secondary outcomes, the RW group had a shorter time to ICU discharge and time to cessation of mechanical ventilation with corticosteroid treatment, where the RI group again demonstrated harm. The findings support matching treatment strategies to empirically observed pathobiology and offer a more nuanced understanding of corticosteroid utility. Our results have implications for the design and interpretation of both observational studies and randomized controlled trials (RCTs), suggesting the need for stratification methods that account for the differential response to standard of care.