Managing patients with complex multimorbidity has long been recognized as a difficult problem due to complex disease and medication dependencies and the potential risk of adverse drug interactions. Existing work either uses complicated rule-based protocols which are hard to implement and maintain, or simple statistical models that treat each disease independently, which may lead to sub-optimal or even harmful drug combinations. In this work, we propose the LEAP (LEArn to Prescribe) algorithm to decompose the treatment recommendation into a sequential decision-making process while automatically determining the appropriate number of medications. A recurrent decoder is used to model label dependencies and content-based attention is used to capture label instance mapping. We further leverage reinforcement learning to fine tune the model parameters to ensure accuracy and completeness. We incorporate external clinical knowledge into the design of the reinforcement reward to effectively prevent generating unfavorable drug combinations. Both quantitative experiments and qualitative case studies are conducted on two real world electronic health record datasets to verify the effectiveness of our solution. On both datasets, LEAP significantly outperforms baselines by up to 10-30% in terms of mean Jaccard coefficient and removes 99.8% adverse drug interactions in the recommended treatment sets.

Modeling disease relationships and temporal progression are two key problems in health analytics, which have not been studied together due to data and technical challenges. Thanks to the increasing adoption of Electronic Health Records (EHR), rich patient information is being collected over time. Using EHR data as input, we propose a multivariate context-sensitive Hawkes process or cHawkes, which simultaneously infers the disease relationship network and models temporal progression of patients. Besides learning disease network and temporal progression model, cHawkes is able to predict when a specific patient might have other related diseases in future given the patient history, which in turn can have many potential applications in predictive health analytics, public health policy development and customized patient care. Extensive experiments on real EHR data demonstrate that cHawkes not only can uncover meaningful disease relations and model accurate temporal progression of patients, but also has significantly better predictive performance compared to several baseline models.

We propose a new tensor factorization method, called the Sparse Hierarchical-Tucker (Sparse H-Tucker), for sparse and high-order data tensors. Sparse H-Tucker is inspired by its namesake, the classical Hierarchical Tucker method, which aims to compute a tree-structured factorization of an input data set that may be readily interpreted by a domain expert. However, Sparse H-Tucker uses a nested sampling technique to overcome a key scalability problem in Hierarchical Tucker, which is the creation of an unwieldy intermediate dense core tensor, the result of our approach is a faster, more space-efficient, and more accurate method. We test our method on a real healthcare dataset, which is collected from 30K patients and results in an 18th order sparse data tensor. Unlike competing methods, Sparse H-Tucker can analyze the full data set on a single multi-threaded machine. It can also do so more accurately and in less time than the state-of-the-art: on a 12th order subset of the input data, Sparse H-Tucker is 18x more accurate and 7.5x faster than a previously state-of-the-art method. Moreover, we observe that Sparse H-Tucker scales nearly linearly in the number of non-zero tensor elements. The resulting model also provides an interpretable disease hierarchy, which is confirmed by a clinical expert.

Computational phenotyping is the process of converting heterogeneous electronic health records (EHRs) into meaningful clinical concepts. Unsupervised phenotyping methods have the potential to leverage a vast amount of labeled EHR data for phenotype discovery. However, existing unsupervised phenotyping methods do not incorporate current medical knowledge and cannot directly handle missing, or noisy data. We propose Rubik, a constrained non-negative tensor factorization and completion method for phenotyping. Rubik incorporates 1) guidance constraints to align with existing medical knowledge, and 2) pairwise constraints for obtaining distinct, non-overlapping phenotypes. Rubik also has built-in tensor completion that can significantly alleviate the impact of noisy and missing data. We utilize the Alternating Direction Method of Multipliers (ADMM) framework to tensor factorization and completion, which can be easily scaled through parallel computing. We evaluate Rubik on two EHR datasets, one of which contains 647,118 records for 7,744 patients from an outpatient clinic, the other of which is a public dataset containing 1,018,614 CMS claims records for 472,645 patients. Our results show that Rubik can discover more meaningful and distinct phenotypes than the baselines. In particular, by using knowledge guidance constraints, Rubik can also discover sub-phenotypes for several major diseases. Rubik also runs around seven times faster than current state-of-the-art tensor methods. Finally, Rubik is scalable to large datasets containing millions of EHR records.