Light Transmission Aggregometry Does Not Correlate With the Severity of δ-Granule Platelet Storage Pool Deficiency.

Delta-granule platelet storage pool deficiency (δ-PSPD) is a poorly studied bleeding diathesis resulting from either decreased granule content or decreased average number of platelet δ-granules. Light transmission aggregometry (LTA) is commonly used to evaluate for δ-PSPD and platelet electron microscopy (EM) is used to confirm the diagnosis. Currently, little data exist examining the relationship between the likelihood of abnormal platelet aggregation findings, severity of δ-granule deficiency on platelet EM, and severity of bleeding symptoms in patients with δ-PSPD. Patients diagnosed with δ-PSPD by platelet EM who also underwent LTA testing were identified at a single institution for correlation between severity of bleeding, average number of platelet δ-granules, and number of agonist abnormalities on LTA. No statistically significant association was identified between the average number of δ-granules per platelet and likelihood of an abnormal LTA. LTA abnormalities were quite varied and only 50% diagnosed with δ-PSPD on EM had abnormal aggregation testing. Also, no correlation was seen between the number of clinical bleeding symptoms, number of average δ-granules per platelet, and the number of LTA agonist abnormalities. Our findings highlight the difficulties inherent in the laboratory evaluation of platelet function.

Considerations for Clinician-Educators Developing Online Educational Content: A Narrative Review.

In modern medical education, clinician-educators are increasingly called upon to develop online education to complement or replace in-person instruction. Despite a growing need for online curricula, many medical professionals lack training and experience in digital content development, deployment, assessment, and maintenance. Previous studies offer guidance on some aspects of online education development but often overlook key components, such as accessibility, legal considerations, financial implications, and sustainability challenges. This review offers medical professionals a broad overview of these important issues. We discuss various pedagogical considerations, including aligning educational goals and objectives with the digital content, choosing the appropriate online interface, and employing strategies to mitigate cognitive load while maximizing accessibility to create an inclusive online learning environment. We offer practical tips for creating effective, high-quality, and enduring audio-visual content and reflect on initial content deployment, testing, assessment, and revision. We discuss the intricacies of obtaining continuing medical education credits when the target audience includes faculty members. We address several legal issues online educators must consider, such as copyright laws, intellectual property rights, and medical liability. The review concludes with a discussion of sustainability mechanisms and financial considerations to ensure the long-term success of the educational program. Our recommendations aim to equip medical professionals embarking on a digital education journey with practical tools to produce effective, inclusive, and sustainable online content while considering legal implications.

Implementation of clopidogrel pharmacogenetic clinical decision support for a preemptive return of results program.

PURPOSE: To describe our experiences implementing and iterating CYP2C19 genotype-guided clopidogrel pharmacogenetic clinical decision support (CDS) tools over time in the setting of a large health system-wide, preemptive pharmacogenomics program. SUMMARY: Clopidogrel-treated patients who are genetically predicted cytochrome P450 isozyme 2C19 (CYP2C19) intermediate or poor metabolizers have an increased risk of atherothrombotic events, some of which can be life-threatening. The Clinical Pharmacogenetics Implementation Consortium provides guidance for the use of clopidogrel based on CYP2C19 genotype in patients with cardiovascular and cerebrovascular diseases. Our multidisciplinary team implemented an automated, interruptive alert that fires when clopidogrel is ordered or refilled for biobank participants with structured CYP2C19 intermediate or poor metabolizer genomic indicators in the electronic health record. The implementation began with a narrow cardiovascular indication and setting and was then scaled in 4 primary dimensions: (1) clinical indication; (2) availability across health-system locations; (3) care venue (e.g., inpatient vs outpatient); and (4) provider groups (eg, cardiology and neurology). We iterated our approach over time based on evolving clinical evidence and proactive strategies to optimize CDS maintenance and sustainability. A key facilitator of expansion was socialization of the broader pharmacogenomics initiative among our academic medical center community, accompanied by clinician acceptance of pharmacogenetic alerts in practice. CONCLUSION: A multidisciplinary collaboration is recommended to facilitate the use of CYP2C19 genotype-guided antiplatelet therapy in patients with cardiovascular and cerebrovascular diseases. Evolving clopidogrel pharmacogenetic evidence necessitates thoughtful iteration of implementation efforts and strategies to optimize long-term maintenance and sustainability.

Are Graduate Medical Trainees Prepared for the Personalized Genomic Medicine Revolution? Trainee Perspectives at One Institution.

Although the use of genomics to inform clinical care is increasing, clinicians feel underprepared to integrate personalized medicine (PM) into care decisions. The educational needs of physician residents and fellows, also known as graduate medical trainees (GMTs), have been overlooked. We administered an anonymous, web-based survey to all GMTs participating in training programs affiliated with our institution to evaluate their knowledge, skills, and attitudes toward PM. Of the 1190 GMTs contacted, 319 (26.8%) returned surveys. Most (88.4%) respondents reported receiving PM education in the past. Although the respondents agreed that knowledge of disease genetics (80.9%) or pharmacogenetics (87.1%) would likely lead to improved clinical outcomes, only 33.2% of the respondents felt sufficiently informed about PM. The respondents who had received PM education in residency and/or fellowship had significantly higher self-reported knowledge, ability, awareness, and adoption of PM than those who had not received this education (p < 0.0001, p < 0.0001, p < 0.0001, and p < 0.01, respectively). Targeted training is needed to improve GMTs' confidence in interpreting and explaining genetic test results. The ideal timing for this education appears to be in residency and/or fellowship rather than in medical school.

Primary care providers' preferences for the communication and management of actionable genomic findings from a research biobank.

Purpose: Little is known about non-genetics health care specialists' attitudes toward the return and utilization of actionable genomic results from a research biobank. We surveyed primary care providers (PCPs) to explore their perspectives on these results and their preferences for return. Methods: We administered a paper and web-based 27-question survey to PCPs residing locally and caring for adult patients. Recruitment was conducted in person and by email, focusing on PCPs likely to interact with results generated by our institution's biobank. Results: Of the ~482 PCPs contacted, 77 (16%) returned surveys. Although most respondents (90%) prefer that a genetics specialist be involved in communicating biobank-generated genomic results to patients, about 40% of respondents reported that a PCP shares the responsibility to discuss these results along with other specialists. A majority of respondents (74%) felt uncomfortable communicating these results to patients. However, respondents reported significantly greater comfort with this process when offered targeted educational resources (62% with vs 10% without resources; P < 10-5). Conclusion: PCPs recognize the need to engage with their patients' biobank-generated genomic results but feel uncomfortable in doing so. Relevant resources are needed to improve PCPs' confidence in the use of these types of results to affect patient care.

Clinical implementation of pharmacogenomics via a health system-wide research biobank: the University of Colorado experience.

In recent years, the genomics community has witnessed the growth of large research biobanks, which collect DNA samples for research purposes. Depending on how and where the samples are genotyped, biobanks also offer the potential opportunity to return actionable genomic results to the clinical setting. We developed a preemptive clinical pharmacogenomic implementation initiative via a health system-wide research biobank at the University of Colorado. Here, we describe how preemptive return of clinical pharmacogenomic results via a research biobank is feasible, particularly when coupled with strong institutional support to maximize the impact and efficiency of biobank resources, a multidisciplinary implementation team, automated clinical decision support tools, and proactive strategies to engage stakeholders early in the clinical decision support tool development process.