The diagnostic and predictive information produced by genomic sequencing may impact medical management, and it is critical that providers and institutions are able to use this information appropriately for patient care. Guided by the patient-centered care model, we investigated provider perspectives of patient, provider, and system-level factors that could influence the implementation of genomic medicine within the integrated healthcare system of the US Department of Defense (DOD).The purpose of this study was to explore patient-centered care elements related to the application of genomic sequencing in a military healthcare facility to understand the current capability and key gaps for patient-centered genomic medicine. Twenty DOD healthcare providers were interviewed regarding their past experiences and future expectations of genetics and genomics. These semi-structured interviews were recorded, transcribed and analyzed. All providers interviewed had some experience with genetics, but the level of experience varied greatly. Providers reported widely differing degrees of knowledge and confidence regarding genetics and about military-specific policies regarding genetics which varied by specialty. In addition, most providers stated that their department did not currently have the infrastructure to allow for the care of patients with secondary genetic findings, defined as genetic findings which are intentionally examined because of their importance to healthcare management, but are unrelated to the reason the individual underwent sequencing.This study reveals gaps in key elements of patient-centered care related to genomic medicine that may be helpful to address in future implementation efforts.

Background Genomic sequencing has become a widely used tool in clinical and research settings in both civilian and military healthcare systems. Methods In this paper, we consider potential military‐specific implications of returning genomic sequencing secondary findings to ensure the proper protections, policies, and processes are in place for the use of this information. Results We specifically use two examples to highlight potential military implications of the return of secondary findings. Conclusion Clinicians and researchers are strongly encouraged to consider the military implications of the return of results for informed consent of service members or their families undergoing clinical or research genomic sequencing.

Introduction Personalized medicine is the right treatment, to the right patient, at the right dose. Knowledge of genetic predisposition to variable metabolism and distribution of drugs within the body is currently available as pharmacogenomic testing and is one of the pillars of personalized medicine. Pharmacogenomic testing is growing. It has become part of guidelines for dosing on FDA labels and has been used by health care organizations to improve outcomes and reduce adverse events. Additionally, it has been FDA approved for direct-to-consumer purchase and has been cause of concern of patient self-dosing and medication changes. Presumably in the near future, pharmacogenomics will be impressed upon the military health system (MHS) provider from either a top-down, command requested, or from a bottom-up, patient requested, approach. To date, widespread implementation of pharmacogenomic testing does not seem to be established within the MHS. This survey sheds light on the knowledge, exposure, use, comfort, and interest among family medicine providers in the MHS. It compares similar results in other national and international surveys and compares results among a small subset of residents to staff. Materials and Methods The questions were part of a larger survey conducted by the Clinical Investigations Committee of the Uniformed Services Academy of Family Physicians (USAFP) at the USAFP 2019 annual meeting. The study received approval from the Uniformed Services University Institutional Review Board. Submitted questions were written using multiple choice, fill-in, five-point Likert scale, and best answer. Direct results are reported as well as chi-square statistics for categorical data with statistical significance to attain a P-value of < 0.05. Results Among the 532 USAFP-registered conference attendees eligible to complete the survey, 387 attendees responded to the survey, for a response rate of 72.7%. Some results included were a knowledge question in which 37% of respondents answered correctly. Less than half of respondents agreed that they could define pharmacogenomics, and resident respondents were more likely to have received teaching in graduate medical education. Additionally, 12% of providers responded to being exposed to direct-to-consumer results, and 28% of those exposed were influenced to change medications, while 14% were influenced to change medications on multiple occasions. Chi-square comparisons resulted in statistically significant direct relationships to exposure to direct to consumer testing, previous training, and confidence of those that answered the knowledge question correctly. Conclusions This survey establishes a baseline for the possible needs associated with implementation of a pharmacogenomic program, and it argues an actionable level for the use of pharmacogenomics among the patient population within the MHS.

Background Clinical genetic testing for heritable cardiovascular disease has become a widely-used tool to aid in the management of patients and their families. A five-category variant classification system is commonly used for genetic test results, but some laboratories further sub-classify variants of uncertain significance (VUS). How and whether patients perceive differences among the variant categories or sub-classifications of VUS is unknown. Methods and Results We tested whether participants perceived differences in genetic variant sub-classifications on outcomes including: risk comprehension, risk perception, worry, perceived uncertainty, and intentions. Order-randomized hypothetical cardiovascular genetic results were given to 289 participants enrolled in a genome sequencing study. Three categories of variants were presented to participants: VUS, Possibly Pathogenic, and Likely Pathogenic. Responses to the first variant presented were analyzed in a between-groups analysis, and responses to all three variants were analyzed in a within-groups analysis. When presented with all three results, participants distinguished among the sub-classifications on all outcomes (p<0.001). When given only a Possibly Pathogenic result, their risk perceptions were similar to those of a VUS, but they were more worried and intended to behave as if they had received a Likely Pathogenic result. Individuals depended more on their affective responses such as worry when they received only one result (p<0.05). Conclusions Participants are better able to distinguish pathogenicity sub-classifications when presented with multiple categories. Individuals who receive a single uncertain result in a cardiovascular disease gene may benefit from interventions to decrease worry, calibrate risk perceptions, and motivate variant-appropriate behaviors.

Introduction High levels of aerobic exercise in individuals who have a gene mutation associated with arrhythmogenic right ventricular cardiomyopathy (ARVC) are associated with clinical disease progression. Guidelines consequently restrict patients from competitive athletics. However, there is minimal literature to guide the safe dosing of physical activity outside of the setting of competitive athletics. Patients may be physically active pursuant to a variety of careers, including military service. This study aimed to define a therapeutic window for exercise for ARVC gene-positive individuals that are compatible with continuing military service and general health while maintaining a level of exercise below that which risks disease progression. Materials and Methods Using standard metabolic equations, we calculated the minimum VO2 max (amount of oxygen utilized at peak exercise capacity) required to pass the physical fitness tests for each branch. We then developed a sample exercise prescription to maintain this level of fitness. We compared the prescribed exercise load with the physical activity levels associated with non-inferior clinical outcomes in ARVC gene-positive individuals. Additionally, we determined the physical activity exposure sustained by service members based on self-report data and compared these values with the upper limit of safe exercise exposure. Results Based on a review of the currently available literature, aerobic exercise exposure less than 700 to 1,100 MET-hours/year (metabolic equivalent-hours per year) is not associated with inferior clinical outcomes for gene-positive individuals. A military service member needs 600 to 700 MET-hours/year to minimally pass the physical fitness test. However, many military members are exercising in excess of this minimum, with typical exposures between 900 and 2,400 MET-hours/year. Conclusions A therapeutic window of aerobic exercise may exist for ARVC gene-positive individuals which would allow continuation of military service while maintaining levels of exercise restriction associated with non-inferior clinical outcomes.

Pharmacogenomics is a pillar of personalized medicine that has the potential to deliver optimized treatment in many medical settings. Military medicine in the deployed setting is unique and therefore warrants separate assessment pertaining to its potential capabilities and impact. Pharmacogenomics for United States Active Duty Service Members medical care in the deployed setting has not, to our knowledge, been previously reviewed. We present potential applications of pharmacogenomics to forward medical care through two comprehensive references for deployed medical care, the Tactical Combat Casualty Care Guidelines (TCCC) and Emergency War Surgery (EWS) fifth edition. All drugs within the deployment manuals, TCCC guidelines and EWS book, were identified and the list was cross-referenced to the Clinical Pharmacogenetics Implementation Consortium guidelines and genes–drugs interactions list as well as the Food and Drug Administration Table of Pharmacogenomics Biomarkers in Drug Labeling. Ten pharmacologic categories were identified, consisting of 15 drugs, along with the classes, aminogylcosides, beta-blockers, and volatile anesthetics. Drugs and pharmacogenomics liabilities were tabulated. Eight specific drugs or classes are expounded upon given the belief of the authors of their potential for impacting future treatment on the battlefield in the setting of prolonged field care. This review outlines several genes with liabilities in the prolonged field care setting and areas that may produce improved care with further study.

No abstract

No abstract