标题： 基于多事件生存分析的肌萎缩侧索硬化症功能下降有意义的预测 显示英文标题

标题： A meaningful prediction of functional decline in amyotrophic lateral sclerosis based on multi-event survival analysis

摘要： 肌萎缩侧索硬化症（ALS）是一种运动神经元的退行性疾病，会导致患者进行性瘫痪。目前的治疗选择旨在延长生存期和提高生活质量；然而，由于该疾病的异质性，在确定潜在疗法或医学干预的最佳时间时往往很困难。 在这项研究中，我们提出了一种新的方法，根据五个常见功能（说话、吞咽、书写、行走和呼吸）来预测ALS患者经历显著功能障碍（ALSFRS-R≤2）的时间。 我们将此任务表述为一个多事件生存问题，并通过在PRO-ACT数据集上训练五种基于协变量的生存模型来验证我们的方法，以估计基线访问后500天内事件发生的概率。 然后，我们为每位患者预测五种特定事件的个体生存分布（ISD），每个分布都提供了一个可解释且有意义的估计，即该事件在未来何时可能发生。 结果显示，基于协变量的模型在预测事件发生时间方面优于Kaplan-Meier估计器。此外，我们的方法使从业者能够做出个体反事实预测，即改变某些特征（协变量）以观察它们对预测结果的影响。 在这方面，我们发现利鲁唑对预测的功能下降几乎没有影响。然而，对于延髓发作的ALS患者，与肢体发作的ALS相比，我们的方法预测的任务相关的言语和吞咽的反事实事件发生时间明显更短。 所提出的方法可以应用于当前的临床检查数据，以评估功能下降的风险，从而实现更个性化的治疗计划。 显示英文摘要

摘要： Amyotrophic lateral sclerosis (ALS) is a degenerative disorder of motor neurons that causes progressive paralysis in patients. Current treatment options aim to prolong survival and improve quality of life; however, due to the heterogeneity of the disease, it is often difficult to determine the optimal time for potential therapies or medical interventions. In this study, we propose a novel method to predict the time until a patient with ALS experiences significant functional impairment (ALSFRS-R<=2) with respect to five common functions: speaking, swallowing, handwriting, walking and breathing. We formulate this task as a multi-event survival problem and validate our approach in the PRO-ACT dataset by training five covariate-based survival models to estimate the probability of an event over a 500-day period after a baseline visit. We then predict five event-specific individual survival distributions (ISDs) for each patient, each providing an interpretable and meaningful estimate of when that event will likely take place in the future. The results show that covariate-based models are superior to the Kaplan-Meier estimator at predicting time-to-event outcomes. Additionally, our method enables practitioners to make individual counterfactual predictions, where certain features (covariates) can be changed to see their effect on the predicted outcome. In this regard, we find that Riluzole has little to no impact on predicted functional decline. However, for patients with bulbar-onset ALS, our method predicts considerably shorter counterfactual time-to-event estimates for tasks related to speech and swallowing compared to limb-onset ALS. The proposed method can be applied to current clinical examination data to assess the risk of functional decline and thus allow more personalized treatment planning.