Dynamic prediction of residual life with longitudinal covariates using long short-term memory networks

Grace Rhodes, Marie Davidian, Wenbin Lu
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Abstract

Sepsis, a complex medical condition that involves severe infections with life-threatening organ dysfunction, is a leading cause of death worldwide. Treatment of sepsis is highly challenging. When making treatment decisions, clinicians and patients desire accurate predictions of mean residual life (MRL) that leverage all available patient information, including longitudinal biomarker data. Biomarkers are biological, clinical, and other vari-ables reflecting disease progression that are often measured repeatedly on patients in the clinical setting. Dynamic prediction methods leverage accruing biomarker measurements to improve performance, providing updated predictions as new measurements become available. We introduce two methods for dynamic prediction of MRL using longitudinal biomarkers. In both methods, we begin by using long short-term memory networks (LSTMs) to construct encoded representations of the biomarker trajectories, referred to as “context vectors.” In our first method, the LSTM-GLM, we dynamically predict MRL via a transformed MRL model that includes the context vectors as covariates. In our second method, the LSTM-NN, we dynamically predict MRL from the context vectors using a feed-forward neural network. We demonstrate the improved performance of both proposed methods relative to competing methods in simulation studies. We apply the proposed methods to dynamically predict the restricted mean residual life (RMRL) of septic patients in the intensive care unit using electronic medical record data. We demonstrate that the LSTM-GLM and the LSTM-NN are useful tools for producing individualized, real-time predictions of RMRL that can help inform the treatment decisions of septic patients.
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利用长短期记忆网络纵向协变量动态预测剩余寿命
脓毒症是一种复杂的疾病,包括严重感染和危及生命的器官功能障碍,是世界范围内死亡的主要原因。败血症的治疗极具挑战性。在制定治疗决策时,临床医生和患者希望利用所有可用的患者信息(包括纵向生物标志物数据)准确预测平均剩余寿命(MRL)。生物标志物是反映疾病进展的生物学、临床和其他变量,通常在临床环境中对患者进行反复测量。动态预测方法利用累积的生物标志物测量值来提高性能,并在新的测量值可用时提供更新的预测。我们介绍了两种利用纵向生物标志物动态预测MRL的方法。在这两种方法中,我们首先使用长短期记忆网络(LSTMs)来构建生物标志物轨迹的编码表示,称为“上下文向量”。在我们的第一种方法LSTM-GLM中,我们通过包含上下文向量作为协变量的转换后的MRL模型动态预测MRL。在我们的第二种方法,LSTM-NN中,我们使用前馈神经网络从上下文向量动态预测MRL。我们在仿真研究中证明了两种方法相对于竞争方法的性能改进。我们将提出的方法应用于利用电子病历数据动态预测重症监护病房脓毒症患者的受限平均剩余寿命(RMRL)。我们证明LSTM-GLM和LSTM-NN是产生RMRL的个性化实时预测的有用工具,可以帮助告知脓毒症患者的治疗决策。
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