Association Between Genetically Predicted Expression of TPMT and Azathioprine Adverse Events.

Polymorphisms thiopurine-S-methyltransferase (TPMT) and nudix hydrolase 15 (NUDT15) can increase the risk of azathioprine myelotoxicity, but little is known about other genetic factors that increase risk for azathioprine-associated side effects. PrediXcan is a gene-based association method that estimates the expression of individuals' genes and examines their correlation to specified phenotypes. As proof of concept for using PrediXcan as a tool to define the association between genetic factors and azathioprine side effects, we aimed to determine whether the genetically predicted expression of TPMT or NUDT15 was associated with leukopenia or other known side effects. In a retrospective cohort of 1364 new users of azathioprine with EHR-reported White race, we used PrediXcan to impute expression in liver tissue, tested its association with pre-specified phecodes representing known side effects (e.g., skin cancer), and completed chart review to confirm cases. Among confirmed cases, patients in the lowest tertile (i.e., lowest predicted) of TPMT expression had significantly higher odds of developing leukopenia (OR=3.30, 95%CI: 1.07-10.20, p=0.04) versus those in the highest tertile; no other side effects were significant. The results suggest that this methodology could be deployed on a larger scale to uncover associations between genetic factors and drug side effects for more personalized care.

Classification and analysis of asynchronous communication content between care team members involved in breast cancer treatment.

OBJECTIVE: A growing research literature has highlighted the work of managing and triaging clinical messages as a major contributor to professional exhaustion and burnout. The goal of this study was to discover and quantify the distribution of message content sent among care team members treating patients with breast cancer. MATERIALS AND METHODS: We analyzed nearly two years of communication data from the electronic health record (EHR) between care team members at Vanderbilt University Medical Center. We applied natural language processing to perform sentence-level annotation into one of five information types: clinical, medical logistics, nonmedical logistics, social, and other. We combined sentence-level annotations for each respective message. We evaluated message content by team member role and clinic activity. RESULTS: Our dataset included 81 857 messages containing 613 877 sentences. Across all roles, 63.4% and 21.8% of messages contained logistical information and clinical information, respectively. Individuals in administrative or clinical staff roles sent 81% of all messages containing logistical information. There were 33.2% of messages sent by physicians containing clinical information-the most of any role. DISCUSSION AND CONCLUSION: Our results demonstrate that EHR-based asynchronous communication is integral to coordinate care for patients with breast cancer. By understanding the content of messages sent by care team members, we can devise informatics initiatives to improve physicians' clerical burden and reduce unnecessary interruptions.