Dipole: Diagnosis Prediction in Healthcare via Attention-based Bidirectional Recurrent Neural Networks

Predicting the future health information of patients from the historical Electronic Health Records (EHR) is a core research task in the development of personalized healthcare. Patient EHR data consist of sequences of visits over time, where each visit contains multiple medical codes, including diagnosis, medication, and procedure codes. The most important challenges for this task are to model the temporality and high dimensionality of sequential EHR data and to interpret the prediction results. Existing work solves this problem by employing recurrent neural networks (RNNs) to model EHR data and utilizing simple attention mechanism to interpret the results. However, RNN-based approaches suffer from the problem that the performance of RNNs drops when the length of sequences is large, and the relationships between subsequent visits are ignored by current RNN-based approaches. To address these issues, we propose {\sf Dipole}, an end-to-end, simple and robust model for predicting patients' future health information. Dipole employs bidirectional recurrent neural networks to remember all the information of both the past visits and the future visits, and it introduces three attention mechanisms to measure the relationships of different visits for the prediction. With the attention mechanisms, Dipole can interpret the prediction results effectively. Dipole also allows us to interpret the learned medical code representations which are confirmed positively by medical experts. Experimental results on two real world EHR datasets show that the proposed Dipole can significantly improve the prediction accuracy compared with the state-of-the-art diagnosis prediction approaches and provide clinically meaningful interpretation

Limbic Tract Integrity Contributes to Pattern Separation Performance Across the Lifespan.

Accurate memory for discrete events is thought to rely on pattern separation to orthogonalize the representations of similar events. Previously, we reported that a behavioral index of pattern separation was correlated with activity in the hippocampus (dentate gyrus, CA3) and with integrity of the perforant path, which provides input to the hippocampus. If the hippocampus operates as part of a broader neural network, however, pattern separation would likely also relate to integrity of limbic tracts (fornix, cingulum bundle, and uncinate fasciculus) that connect the hippocampus to distributed brain regions. In this study, healthy adults (20-89 years) underwent diffusion tensor imaging and completed the Behavioral Pattern Separation Task-Object Version (BPS-O) and Rey Auditory Verbal Learning Test (RAVLT). After controlling for global effects of brain aging, exploratory skeleton-wise and targeted tractography analyses revealed that fornix integrity (fractional anisotropy, mean diffusivity, and radial diffusivity; but not mode) was significantly related to pattern separation (measured using BPS-O and RAVLT tasks), but not to recognition memory. These data suggest that hippocampal disconnection, via individual- and age-related differences in limbic tract integrity, contributes to pattern separation performance. Extending our earlier work, these results also support the notion that pattern separation relies on broad neural networks interconnecting the hippocampus

DiaTrend: A dataset from advanced diabetes technology to enable development of novel analytic solutions

Objective digital data is scarce yet needed in many domains to enable research that can transform the standard of healthcare. While data from consumer-grade wearables and smartphones is more accessible, there is critical need for similar data from clinical-grade devices used by patients with a diagnosed condition. The prevalence of wearable medical devices in the diabetes domain sets the stage for unique research and development within this field and beyond. However, the scarcity of open-source datasets presents a major barrier to progress. To facilitate broader research on diabetes-relevant problems and accelerate development of robust computational solutions, we provide the DiaTrend dataset. The DiaTrend dataset is composed of intensive longitudinal data from wearable medical devices, including a total of 27,561 days of continuous glucose monitor data and 8,220 days of insulin pump data from 54 patients with diabetes. This dataset is useful for developing novel analytic solutions that can reduce the disease burden for people living with diabetes and increase knowledge on chronic condition management in outpatient settings.Comment: 11 pages, 5 figures, 2 table

DPVis: Visual Analytics with Hidden Markov Models for Disease Progression Pathways

Clinical researchers use disease progression models to understand patient status and characterize progression patterns from longitudinal health records. One approach for disease progression modeling is to describe patient status using a small number of states that represent distinctive distributions over a set of observed measures. Hidden Markov models (HMMs) and its variants are a class of models that both discover these states and make inferences of health states for patients. Despite the advantages of using the algorithms for discovering interesting patterns, it still remains challenging for medical experts to interpret model outputs, understand complex modeling parameters, and clinically make sense of the patterns. To tackle these problems, we conducted a design study with clinical scientists, statisticians, and visualization experts, with the goal to investigate disease progression pathways of chronic diseases, namely type 1 diabetes (T1D), Huntington's disease, Parkinson's disease, and chronic obstructive pulmonary disease (COPD). As a result, we introduce DPVis which seamlessly integrates model parameters and outcomes of HMMs into interpretable and interactive visualizations. In this study, we demonstrate that DPVis is successful in evaluating disease progression models, visually summarizing disease states, interactively exploring disease progression patterns, and building, analyzing, and comparing clinically relevant patient subgroups.Comment: to appear at IEEE Transactions on Visualization and Computer Graphic

Utilizing Temporal Information in The EHR for Developing a Novel Continuous Prediction Model

Type 2 diabetes mellitus (T2DM) is a nation-wide prevalent chronic condition, which includes direct and indirect healthcare costs. T2DM, however, is a preventable chronic condition based on previous clinical research. Many prediction models were based on the risk factors identified by clinical trials. One of the major tasks of the T2DM prediction models is to estimate the risks for further testing by HbA1c or fasting plasma glucose to determine whether the patient has or does not have T2DM because nation-wide screening is not cost-effective. Those models had substantial limitations on data quality, such as missing values. In this dissertation, I tested the conventional models which were based on the most widely used risk factors to predict the possibility of developing T2DM. The AUC was an average of 0.5, which implies the conventional model cannot be used to screen for T2DM risks. Based on this result, I further implemented three types of temporal representations, including non-temporal representation, interval-temporal representation, and continuous-temporal representation for building the T2DM prediction model. According to the results, continuous-temporal representation had the best performance. Continuous-temporal representation was based on deep learning methods. The result implied that the deep learning method could overcome the data quality issue and could achieve better performance. This dissertation also contributes to a continuous risk output model based on the seq2seq model. This model can generate a monotonic increasing function for a given patient to predict the future probability of developing T2DM. The model is workable but still has many limitations to overcome. Finally, this dissertation demonstrates some risks factors which are underestimated and are worthy for further research to revise the current T2DM screening guideline. The results were still preliminary. I need to collaborate with an epidemiologist and other fields to verify the findings. In the future, the methods for building a T2DM prediction model can also be used for other prediction models of chronic conditions

Bariatric surgery and brain health: A longitudinal observational study investigating the effect of surgery on cognitive function and gray matter volume

Dietary modifications leading to weight loss have been suggested as a means to improve brain health. In morbid obesity, bariatric surgery (BARS)—including different procedures, such as vertical sleeve gastrectomy (VSG), gastric banding (GB), or Roux-en-Y gastric bypass (RYGB) surgery—is performed to induce rapid weight loss. Combining reduced food intake and malabsorption of nutrients, RYGB might be most effective, but requires life-long follow-up treatment. Here, we tested 40 patients before and six months after surgery (BARS group) using a neuropsychological test battery and compared them with a waiting list control group. Subsamples of both groups underwent structural MRI and were examined for differences between surgical procedures. No substantial differences between BARS and control group emerged with regard to cognition. However, larger gray matter volume in fronto-temporal brain areas accompanied by smaller volume in the ventral striatum was seen in the BARS group compared to controls. RYGB patients compared to patients with restrictive treatment alone (VSG/GB) had higher weight loss, but did not benefit more in cognitive outcomes. In sum, the data of our study suggest that BARS might lead to brain structure reorganization at long-term follow-up, while the type of surgical procedure does not differentially modulate cognitive performance

Searching for Imaging Biomarkers of Psychotic Dysconnectivity

Background: Progress in precision psychiatry is predicated on identifying reliable individual-level diagnostic biomarkers. For psychosis, measures of structural and functional connectivity could be promising biomarkers given consistent reports of dysconnectivity across psychotic disorders using magnetic resonance imaging. Methods: We leveraged data from four independent cohorts of patients with psychosis and control subjects with observations from approximately 800 individuals. We used group-level analyses and two supervised machine learning algorithms (support vector machines and ridge regression) to test within-, between-, and across-sample classification performance of white matter and resting-state connectivity metrics. Results: Although we replicated group-level differences in brain connectivity, individual-level classification was suboptimal. Classification performance within samples was variable across folds (highest area under the curve [AUC] range = 0.30) and across datasets (average support vector machine AUC range = 0.50; average ridge regression AUC range = 0.18). Classification performance between samples was similarly variable or resulted in AUC values of approximately 0.65, indicating a lack of model generalizability. Furthermore, collapsing across samples (resting-state functional magnetic resonance imaging, N = 888; diffusion tensor imaging, N = 860) did not improve model performance (maximal AUC = 0.67). Ridge regression models generally outperformed support vector machine models, although classification performance was still suboptimal in terms of clinical relevance. Adjusting for demographic covariates did not greatly affect results. Conclusions: Connectivity measures were not suitable as diagnostic biomarkers for psychosis as assessed in this study. Our results do not negate that other approaches may be more successful, although it is clear that a systematic approach to individual-level classification with large independent validation samples is necessary to properly vet neuroimaging features as diagnostic biomarkers