Automated Detection of Systematic Off-label Drug Use in Free Text of Electronic Medical Records.

Off-label use of a drug occurs when it is used in a manner that deviates from its FDA label. Studies estimate that 21% of prescriptions are off-label, with only 27% of those uses supported by evidence of safety and efficacy. We have developed methods to detect population level off-label usage using computationally efficient annotation of free text from clinical notes to generate features encoding empirical information about drug-disease mentions. By including additional features encoding prior knowledge about drugs, diseases, and known usage, we trained a highly accurate predictive model that was used to detect novel candidate off-label usages in a very large clinical corpus. We show that the candidate uses are plausible and can be prioritized for further analysis in terms of safety and efficacy

Development of Neural Electromagnetic Ontologies (NEMO): Ontology-based Tools for Representation and Integration of Event-related Brain Potentials

We describe a first-generation ontology for
representation and integration of event-related brain potentials (ERPs). The ontology is designed following OBO “best practices” and is augmented with tools to perform ontology-based labeling and annotation of ERP data, and a database that enables semantically based reasoning over these data. Because certain high-level concepts in the ERP domain are illdefined, we have developed methods to support coordinated updates to each of these three components. This approach consists of “top-down” (knowledge-driven) design and implementation, followed by “bottom-up” (data-driven) validation and refinement. Our goal is to build an ERP ontology that is logically valid, empirically sound, robust in application, and transparent to users. This ontology will be used to support sharing and meta-analysis of EEG and MEG data collected within our Neural Electromagnetic Ontologies (NEMO) project

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

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

Network analysis of unstructured EHR data for clinical research.

In biomedical research, network analysis provides a conceptual framework for interpreting data from high-throughput experiments. For example, protein-protein interaction networks have been successfully used to identify candidate disease genes. Recently, advances in clinical text processing and the increasing availability of clinical data have enabled analogous analyses on data from electronic medical records. We constructed networks of diseases, drugs, medical devices and procedures using concepts recognized in clinical notes from the Stanford clinical data warehouse. We demonstrate the use of the resulting networks for clinical research informatics in two ways-cohort construction and outcomes analysis-by examining the safety of cilostazol in peripheral artery disease patients as a use case. We show that the network-based approaches can be used for constructing patient cohorts as well as for analyzing differences in outcomes by comparing with standard methods, and discuss the advantages offered by network-based approaches