There is growing interest in utilizing pharmacogenetic (PGx) testing to guide antidepressant use, but there is lack of clarity on how to implement testing into clinical practice. We administered two surveys at 17 sites that had implemented or were in the process of implementing PGx testing for antidepressants. Survey 1 collected data on the process and logistics of testing. Survey 2 asked sites to rank the importance of Consolidated Framework for Implementation Research (CFIR) constructs using best‐worst scaling choice experiments. Of the 17 sites, 13 had implemented testing and four were in the planning stage. Thirteen offered testing in the outpatient setting, and nine in both outpatient/inpatient settings. PGx tests were mainly ordered by psychiatry (92%) and primary care (69%) providers. CYP2C19 and CYP2D6 were the most commonly tested genes. The justification for antidepressants selected for PGx guidance was based on Clinical Pharmacogenetics Implementation Consortium guidelines (94%) and US Food and Drug Administration (FDA; 75.6%) guidance. Both institutional (53%) and commercial laboratories (53%) were used for testing. Sites varied on the methods for returning results to providers and patients. Sites were consistent in ranking CFIR constructs and identified patient needs/resources, leadership engagement, intervention knowledge/beliefs, evidence strength and quality, and the identification of champions as most important for implementation. Sites deployed similar implementation strategies and measured similar outcomes. The process of implementing PGx testing to guide antidepressant therapy varied across sites, but key drivers for successful implementation were similar and may help guide other institutions interested in providing PGx‐guided pharmacotherapy for antidepressant management.

Achieving systemic tumor control across metastases is vital for long-term patient survival but remains intractable in many patients. High lesion-level response heterogeneity persists, conferring many dissociated responses across metastatic lesions. Most studies of metastatic disease focus on tumor molecular and cellular features, which are crucial to elucidating the mechanisms underlying lesion-level variability. However, our understanding of lesion-specific heterogeneity on the macroscopic level, such as lesion dynamics in growth, response, and progression during treatment, remains rudimentary. This study investigates lesion-specific response heterogeneity through analyzing 116,542 observations of 40,612 lesions in 4,308 metastatic colorectal cancer (mCRC) patients. Despite significant differences in their response and progression dynamics, metastatic lesions converge on four phenotypes that vary with anatomical site. Importantly, we find that organ-level progression sequence is closely associated with patient long-term survival, and that patients with the first lesion progression in the liver often have worse survival. In conclusion, our study provides insights into lesion-specific response and progression heterogeneity in mCRC and creates impetus for metastasis-specific therapeutics.

Objective:To describe the proposed mechanisms of chemotherapy-associated cardiomyopathy (CAC) and potential cardioprotective therapies for CAC including a comprehensive review of existing systematic analyses, guideline recommendations, and ongoing clinical trials.Data Sources: A literature search of MEDLINE was performed (from 1990 to June 2020) using the following search terms: anthracycline, trastuzumab, cardiomyopathy, cardiotoxicity, primary prevention, angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), beta blocker, dexrazoxane (DEX) as well as using individual names from select therapeutic categories. Study Selection and Data Extraction:Existing English language systematic analyses and guidelines were considered. Data Synthesis:The mechanisms of CAC are multifaceted, but various cardioprotective therapies target many of these pathways. To date, anthracyclines and HER-2 targeted therapies have been the focus of cardioprotective trials to date as they are the most commonly implicated therapies in CAC. While traditional neurohormonal antagonists (ACEIs, ARBs, and beta blockers) and DEX performed favorably in many small clinical trials, the quality of available evidence remains limited. Hence, major guidelines lack consensus on an approach to primary prevention of CAC. Given the uncertain role of preventive therapy, monitoring for a symptomatic or asymptomatic decline in LV function is imperative with prompt evaluation should this occur.Numerous ongoing randomized controlled trials seek to either confirm the findings of these previous studies or identify new therapeutic agents to prevent CAC. Clinical implications are derived from the available literature as well as current guideline recommendations for CAC cardioprotection. Conclusion:At this time, no single therapy has a clear cardioprotective benefit in preventing CAC nor is any therapy strongly recommended by current guidelines.

Background Despite the increased demand for pharmacogenetic (PGx) testing to guide antidepressant use, little is known about how to implement testing in clinical practice. Best–worst scaling (BWS) is a stated preferences technique for determining the relative importance of alternative scenarios and is increasingly being used as a healthcare assessment tool, with potential applications in implementation research. We conducted a BWS experiment to evaluate the relative importance of implementation factors for PGx testing to guide antidepressant use. Methods We surveyed 17 healthcare organizations that either had implemented or were in the process of implementing PGx testing for antidepressants. The survey included a BWS experiment to evaluate the relative importance of Consolidated Framework for Implementation Research (CFIR) constructs from the perspective of implementing sites. Results Participating sites varied on their PGx testing platform and methods for returning recommendations to providers and patients, but they were consistent in ranking several CFIR constructs as most important for implementation: patient needs/resources, leadership engagement, intervention knowledge/beliefs, evidence strength and quality, and identification of champions. Conclusions This study demonstrates the feasibility of using choice experiments to systematically evaluate the relative importance of implementation determinants from the perspective of implementing organizations. BWS findings can inform other organizations interested in implementing PGx testing for mental health. Further, this study demonstrates the application of BWS to PGx, the findings of which may be used by other organizations to inform implementation of PGx testing for mental health disorders.

The North Carolina Precision Health Collaborative is an interdisciplinary, public-private consortium of precision health experts who strategically align statewide resources and strengths to elevate precision health in the state and beyond. Pharmacogenomics (PGx) is a key area of focus for the North Carolina Precision Health Collaborative. Experts from Atrium Health’s Levine Cancer Institute, Duke University/Duke Health System, Mission Health and the University of North Carolina (UNC) at Chapel Hill/UNC Health System have collaborated since 2017 to implement strategic PGx initiatives, including basic sciences research, translational research and clinical implementation of germline testing into practice and policy. This institutional profile highlights major PGx programs and initiatives across these organizations and how the collaborative is working together to advance PGx science and implementation.