论文标题

贝叶斯非均匀隐藏的马尔可夫模型,其可变选择用于研究癫痫发作驱动器

Bayesian Non-Homogeneous Hidden Markov Model with Variable Selection for Investigating Drivers of Seizure Risk Cycling

论文作者

Wang, Emily T., Chiang, Sharon, Haneef, Zulfi, Rao, Vikram R., Moss, Robert, Vannucci, Marina

论文摘要

癫痫临床管理的一个主要问题是癫痫发作的不可预测性。然而,传统的癫痫发作预测和风险评估的方法在很大程度上取决于原始癫痫发作频率,这是对癫痫发作风险的随机测量。我们考虑一个贝叶斯非均匀隐藏的马尔可夫模型,用于零充气癫痫发作计数数据的无监督聚类。提出的模型允许对单个级别的癫痫发作风险状态序列进行概率估计。它还通过在鉴定临床协变量的鉴定来推动癫痫发作风险变化并适应高度颗粒状数据的临床协变量的情况下合并可变选择,从而提供了对先前方法的显着改善。为了推断,我们实施了采用随机搜索和数据增强技术的有效采样器。我们在模拟癫痫发作计数数据上评估模型性能。然后,我们通过分析通过癫痫发作跟踪器TM系统收集的133例DRAVET综合征患者的每日癫痫发作计数数据(一种患者报告的电子癫痫发作日记),从而证明了该模型的临床实用性。我们报告癫痫发作风险循环的动态,包括验证几种已知的药物关系。我们还揭示了特征在Dravet综合征中风险状态的存在和波动性的新发现,这可能直接告知咨询以减少癫痫病因的患者癫痫发作的不可预测性。

A major issue in the clinical management of epilepsy is the unpredictability of seizures. Yet, traditional approaches to seizure forecasting and risk assessment in epilepsy rely heavily on raw seizure frequencies, which are a stochastic measurement of seizure risk. We consider a Bayesian non-homogeneous hidden Markov model for unsupervised clustering of zero-inflated seizure count data. The proposed model allows for a probabilistic estimate of the sequence of seizure risk states at the individual level. It also offers significant improvement over prior approaches by incorporating a variable selection prior for the identification of clinical covariates that drive seizure risk changes and accommodating highly granular data. For inference, we implement an efficient sampler that employs stochastic search and data augmentation techniques. We evaluate model performance on simulated seizure count data. We then demonstrate the clinical utility of the proposed model by analyzing daily seizure count data from 133 patients with Dravet syndrome collected through the Seizure Tracker TM system, a patient-reported electronic seizure diary. We report on the dynamics of seizure risk cycling, including validation of several known pharmacologic relationships. We also uncover novel findings characterizing the presence and volatility of risk states in Dravet syndrome, which may directly inform counseling to reduce the unpredictability of seizures for patients with this devastating cause of epilepsy.

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