Profiling risk factors for chronic uveitis in juvenile idiopathic arthritis: a new model for EHR-based research.

BackgroundJuvenile idiopathic arthritis is the most common rheumatic disease in children. Chronic uveitis is a common and serious comorbid condition of juvenile idiopathic arthritis, with insidious presentation and potential to cause blindness. Knowledge of clinical associations will improve risk stratification. Based on clinical observation, we hypothesized that allergic conditions are associated with chronic uveitis in juvenile idiopathic arthritis patients.MethodsThis study is a retrospective cohort study using Stanford's clinical data warehouse containing data from Lucile Packard Children's Hospital from 2000-2011 to analyze patient characteristics associated with chronic uveitis in a large juvenile idiopathic arthritis cohort. Clinical notes in patients under 16 years of age were processed via a validated text analytics pipeline. Bivariate-associated variables were used in a multivariate logistic regression adjusted for age, gender, and race. Previously reported associations were evaluated to validate our methods. The main outcome measure was presence of terms indicating allergy or allergy medications use overrepresented in juvenile idiopathic arthritis patients with chronic uveitis. Residual text features were then used in unsupervised hierarchical clustering to compare clinical text similarity between patients with and without uveitis.ResultsPreviously reported associations with uveitis in juvenile idiopathic arthritis patients (earlier age at arthritis diagnosis, oligoarticular-onset disease, antinuclear antibody status, history of psoriasis) were reproduced in our study. Use of allergy medications and terms describing allergic conditions were independently associated with chronic uveitis. The association with allergy drugs when adjusted for known associations remained significant (OR 2.54, 95% CI 1.22-5.4).ConclusionsThis study shows the potential of using a validated text analytics pipeline on clinical data warehouses to examine practice-based evidence for evaluating hypotheses formed during patient care. Our study reproduces four known associations with uveitis development in juvenile idiopathic arthritis patients, and reports a new association between allergic conditions and chronic uveitis in juvenile idiopathic arthritis patients

Learning signals of adverse drug-drug interactions from the unstructured text of electronic health records.

Drug-drug interactions (DDI) account for 30% of all adverse drug reactions, which are the fourth leading cause of death in the US. Current methods for post marketing surveillance primarily use spontaneous reporting systems for learning DDI signals and validate their signals using the structured portions of Electronic Health Records (EHRs). We demonstrate a fast, annotation-based approach, which uses standard odds ratios for identifying signals of DDIs from the textual portion of EHRs directly and which, to our knowledge, is the first effort of its kind. We developed a gold standard of 1,120 DDIs spanning 14 adverse events and 1,164 drugs. Our evaluations on this gold standard using millions of clinical notes from the Stanford Hospital confirm that identifying DDI signals from clinical text is feasible (AUROC=81.5%). We conclude that the text in EHRs contain valuable information for learning DDI signals and has enormous utility in drug surveillance and clinical decision support

Doctor of Philosophy

dissertationDisease-specific ontologies, designed to structure and represent the medical knowledge about disease etiology, diagnosis, treatment, and prognosis, are essential for many advanced applications, such as predictive modeling, cohort identification, and clinical decision support. However, manually building disease-specific ontologies is very labor-intensive, especially in the process of knowledge acquisition. On the other hand, medical knowledge has been documented in a variety of biomedical knowledge resources, such as textbook, clinical guidelines, research articles, and clinical data repositories, which offers a great opportunity for an automated knowledge acquisition. In this dissertation, we aim to facilitate the large-scale development of disease-specific ontologies through automated extraction of disease-specific vocabularies from existing biomedical knowledge resources. Three separate studies presented in this dissertation explored both manual and automated vocabulary extraction. The first study addresses the question of whether disease-specific reference vocabularies derived from manual concept acquisition can achieve a near-saturated coverage (or near the greatest possible amount of disease-pertinent concepts) by using a small number of literature sources. Using a general-purpose, manual acquisition approach we developed, this study concludes that a small number of expert-curated biomedical literature resources can prove sufficient for acquiring near-saturated disease-specific vocabularies. The second and third studies introduce automated techniques for extracting disease-specific vocabularies from both MEDLINE citations (title and abstract) and a clinical data repository. In the second study, we developed and assessed a pipeline-based system which extracts disease-specific treatments from PubMed citations. The system has achieved a mean precision of 0.8 for the top 100 extracted treatment concepts. In the third study, we applied classification models to reduce irrelevant disease-concepts associations extracted from MEDLINE citations and electronic medical records. This study suggested the combination of measures of relevance from disparate sources to improve the identification of true-relevant concepts through classification and also demonstrated the generalizability of the studied classification model to new diseases. With the studies, we concluded that existing biomedical knowledge resources are valuable sources for extracting disease-concept associations, from which classification based on statistical measures of relevance could assist a semi-automated generation of disease-specific vocabularies