Publications

Variation in the expression level and activity of genes involved in drug disposition and action ('pharmacogenes') can affect drug response and toxicity, especially when in tissues of pharmacological importance. Previous studies have relied primarily on microarrays to understand gene expression differences, or have focused on a single tissue or small number of samples. The goal of this study was to use RNA-sequencing (RNA-seq) to determine the expression levels and alternative splicing of 389 Pharmacogenomics Research Network pharmacogenes across four tissues (liver, kidney, heart and adipose) and lymphoblastoid cell lines, which are used widely in pharmacogenomics studies. Analysis of RNA-seq data from 139 different individuals across the 5 tissues (20-45 individuals per tissue type) revealed substantial variation in both expression levels and splicing across samples and tissue types. Comparison with GTEx data yielded a consistent picture. This in-depth exploration also revealed 183 splicing events in pharmacogenes that were previously not annotated. Overall, this study serves as a rich resource for the research community to inform biomarker and drug discovery and use.

Exonic enhancers (eExons) are coding exons that also function as enhancers of the gene in which they reside or (a) nearby gene(s). Mutations that affect the enhancer activity of these eExons have been associated with human disease. Therefore, eExon mutations should be taken into account in exome and genome sequencing projects, not only because of the ability of these mutations to modify the encoded proteins but also because of their effects on enhancer activity.

BACKGROUND

Text messaging is an affordable, ubiquitous, and expanding mobile communication technology. However, safety net health systems in the United States that provide more care to uninsured and low-income patients may face additional financial and infrastructural challenges in utilizing this technology. Formative evaluations of texting implementation experiences are limited. We interviewed safety net health systems piloting texting initiatives to study facilitators and barriers to real-world implementation.

METHODS

We conducted telephone interviews with various stakeholders who volunteered from each of the eight California-based safety net systems that received external funding to pilot a texting-based program of their choosing to serve a primary care need. We developed a semi-structured interview guide based partly on the Consolidated Framework for Implementation Research (CFIR), which encompasses several domains: the intervention, individuals involved, contextual factors, and implementation process. We inductively and deductively (using CFIR) coded transcripts, and categorized themes into facilitators and barriers.

RESULTS

We performed eight interviews (one interview per pilot site). Five sites had no prior texting experience. Sites applied texting for programs related to medication adherence and monitoring, appointment reminders, care coordination, and health education and promotion. No site texted patient-identifying health information, and most sites manually obtained informed consent from each participating patient. Facilitators of implementation included perceived enthusiasm from patients, staff and management belief that texting is patient-centered, and the early identification of potential barriers through peer collaboration among grantees. Navigating government regulations that protect patient privacy and guide the handling of protected health information emerged as a crucial barrier. A related technical challenge in five sites was the labor-intensive tracking and documenting of texting communications due to an inability to integrate texting platforms with electronic health records.

CONCLUSIONS

Despite enthusiasm for the texting programs from the involved individuals and organizations, inadequate data management capabilities and unclear privacy and security regulations for mobile health technology slowed the initial implementation and limited the clinical use of texting in the safety net and scope of pilots. Future implementation work and research should investigate how different texting platform and intervention designs affect efficacy, as well as explore issues that may affect sustainability and the scalability.