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DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: This article describes the implementation and evaluation of pharmacogenomic testing within the hematology/oncology ambulatory care clinic at the William S. Middleton Memorial Veterans Hospital in Madison, WI. SUMMARY: The Pharmacogenomic Testing for Veterans (PHASER) program provides preemptive pharmacogenomic testing for veterans nationally. Program implementation at the Madison Veterans Affairs site began in the hematology/oncology clinic with the goal of integrating the offer for pharmacogenomic testing, testing completion, and review of the results by the hematology/oncology clinical pharmacist practitioner (CPP) into current workflows to create a sustainable process for PHASER. The hematology/oncology CPP designed workflows outlining how testing would be offered to patients, how results would be reported and to whom, and how documentation would occur in the electronic medical record. Veterans are offered preemptive PHASER testing, before needing therapy requiring pharmacogenomic results. Exceptions to pharmacogenomic testing were patients with a history of liver or allogeneic hematopoietic stem cell transplantation. CONCLUSION: This article provides a summary of the role of the hematology/oncology CPP in the implementation of a pharmacogenomics service and the impact on medication management in a hematology/oncology clinic.

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BACKGROUND: Escalating doses of insulin required with progression of type 2 diabetes may lead to weight gain. Weight loss associated with semaglutide may be beneficial. However, data on the use of semaglutide in patients requiring high daily doses of insulin are currently lacking. OBJECTIVE: The purpose of this project was to evaluate the impact of semaglutide on total daily dose (TDD) of insulin when initiated in patients with type 2 diabetes mellitus (T2DM) on high daily doses of insulin. Secondary objectives assessed included changes in weight, body mass index (BMI), blood pressure, heart rate, and diabetes and blood pressure medications. METHODS: This IRB exempt retrospective medical record review included patients with T2DM prescribed semaglutide and at least 100 units TDD of insulin between January 1, 2019, and December 31, 2019. RESULTS: Of the 72 patients included, the TDD of insulin decreased from baseline to 6 months (183 ± 98 units and 143 ± 99 units, P < 0.001). Average A1c and body weight also decreased from baseline to 6 months (8.9% ± 1.3% and 7.6% ± 1.5%, P < 0.001 and 123.9 ± 23.5 kg and 118.9 ± 22.9 kg, P < 0.001, respectively). Limitations included a homogenous patient population and inability to control confounding factors. CONCLUSION AND RELEVANCE: Improvement in glycemic control occurred despite reductions in TDD of insulin. Improvements in A1c and body weight were clinically significant. This analysis adds to existing literature supporting the use of GLP-1 RAs in patients on high daily doses of insulin.

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Background: Recent guidelines indicate that aspirin affords less cardiovascular protection and greater bleeding risks in adults aged > 70 years. Deprescribing potentially inappropriate medications is particularly important in older adults, as this population experiences a high risk of adverse effects and polypharmacy. Limited data are available regarding targeted aspirin deprescribing approaches by pharmacists. The objective of this study was to implement and evaluate the success and feasibility of a pharmacist-led aspirin deprescribing protocol for older adults in a primary care setting. Observations: This prospective feasibility study in a US Department of Veterans Affairs ambulatory care pharmacy setting included patients aged ≥ 70 years with documented aspirin use. We reviewed 459 patient records and determined that 110 were eligible for deprescribing. A pharmacistinitiated telephone call was attempted for each eligible patient to discuss the risks and benefits of deprescribing aspirin. The primary outcome was the proportion of patients reached for whom aspirin was discontinued. Secondary outcomes included patient rationale for declining deprescribing and the time to complete the intervention. Of 94 patients reached, 45 (48%) agreed to aspirin deprescribing, 3 (3%) agreed to dose reduction, and 29 (31%) declined the intervention. An additional 17 (18%) had previously stopped aspirin, which led to a medication reconciliation intervention. Pharmacists spent about 2 minutes per record review and 12 minutes on each encounter, including documentation. Conclusions: Implementing a pharmacist-driven aspirin deprescribing protocol in a primary care setting led to the discontinuation of inappropriate aspirin prescribing in nearly half of older adults contacted. The protocol was well accepted by collaborating physicians and feasible for pharmacists to implement, with potential for further dissemination across primary care settings.

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OBJECTIVES: Levetiracetam, a commonly prescribed antiseizure medication (ASM), may cause irritability, depression, and anger. The mechanisms underlying these behavioral effects and individual risk factors remain unknown. Mitigation strategies are limited, including discontinuation, supplementation with vitamin B6, or switching to an alternative ASM. Several retrospective studies and anecdotal reports, primarily in pediatric populations, suggest vitamin B6 supplementation may be helpful in reducing levetiracetam-associated irritability. Although data in adult patients is limited, and no data is available for Veterans. The objective of this project was to describe our preliminarily experience with vitamin B6 supplementation for alleviating levetiracetam-associated irritability in male Veterans with epilepsy. METHODS: Retrospective chart reviews were completed for patients who had an active prescription for levetiracetam from the William S. Middleton Memorial Veterans Hospital from January 1, 2015 to June 1, 2020. A total of 26 charts were screened. Patients were excluded if not using vitamin B6 supplementation or if deceased at end of data collection. Baseline characteristics were compared, including age, sex, comorbidities, and concomitant medications. Charts were then reviewed to identify any clinical description of irritability, including subjective assessment of change in symptoms across multiple visits, and scores from standardized instruments including the patient health questionnaire (PHQ-9), generalized anxiety disorder questionnaire (GAD-7), and/or irritability in adult patients with epilepsy (I-EPI) questionnaire. These symptoms and scores were then compared pre- and post-B6 supplementation. RESULTS: Of 22 patients, data was available for 20 (91%). For patients with data available, 9 (45%) showed improved irritability following supplementation with vitamin B6 and 11 (55%) showed no improvement. CONCLUSIONS: This project suggests that vitamin B6 supplementation may have a role in mitigating levetiracetam-associated irritability in a male Veteran population. These results support future prospective controlled studies to assess further the efficacy of this approach and characteristics associated with successful treatment in veterans.

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PrC-210 is a direct-acting ROS-scavenger. It's active when administered orally, IV, or topically; it has none of the nausea/emesis nor hypotension side effects that have precluded human amifostine use. PrC-210 confers 100% survival to mice and rats that received an otherwise 100% lethal radiation dose and 36% reduction of ischemia-reperfusion-induced mouse myocardial infarct damage, and thus is a viable candidate to prevent human ROS-induced ischemia-reperfusion and ionizing radiation toxicities. We report the first assay for the pharmacologically active PrC-210 thiol in blood. PrC-210 has no double-bonds nor light absorption, so derivatizing the thiol with a UV-absorbing fluorochrome enables quantification. This assay: i) is done on the benchtop; it's read with a fluorescence plate reader, ii) provides linear product formation through 60 min, iii) quantifies µM to low mM rodent blood levels of PrC-210 that confer complete radioprotection, iv) accurately reflects PrC-210 thiol formation of mixed disulfides with other thiols in blood, and v) shows excellent between-day assay outcome with very low standard deviation and coefficient of variation. A fluorescence assay quantifying formation of a PrC-210 thiol-bimane adduct enables measurement of blood PrC-210 thiol. A blood assay will help in the development of PrC-210 for use in the human clinical setting.

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Radiation-induced cancer is an ongoing and significant problem, with sources that include clinics worldwide in which 3.1 billion radiology exams are performed each year, as well as a variety of other scenarios such as space travel and nuclear cleanup. These radiation exposures are typically anticipated, and the exposure is typically well below 1 Gy. When radiation-induced (actually ROS-induced) DNA mutation is prevented, then so too are downstream radiation-induced cancers. Currently, there is no protection available against the effects of such <1 Gy radiation exposures. In this study, we address whether the new PrC-210 ROS-scavenger is effective in protecting p53-deficient (p53-/-) mice against X-ray-induced accelerated tumor mortality; this is the most sensitive radiation tumorigenesis model currently known. Six-day-old p53-/- pups received a single intraperitoneal PrC-210 dose [0.5 maximum tolerated dose (MTD)] or vehicle, and 25 min later, pups received 4.0 Gy X-ray irradiation. At 5 min postirradiation, blood was collected to quantify white blood cell c-H2AX foci. Over the next 250 days, tumor-associated deaths were recorded. Findings revealed that when administered 25 min before 4 Gy X-ray irradiation, PrC-210 reduced DNA damage (c-H2AX foci) by 40%, and in a notable coincidence, caused a 40% shift in tumor latency/incidence, and the 0.5 MTD PrC210 dose had no discernible toxicities in these p53-/- mice. Essentially, the moles of PrC-210 thiol within a single 0.5 MTD PrC-210 dose suppressed the moles of ROS generated by 40% of the 4 Gy X-ray dose administered to p53-/- pups, and in doing so, eliminated the lifetime leukemia/lymphoma risk normally residing "downstream" of that 40% of the 4 Gy dose. In conclusion: 1. PrC-210 is readily tolerated by the 6-day-old p53-/- mice, with no discernible lifetime toxicities; 2. PrC-210 does not cause the nausea, emesis or hypotension that preclude clinical use of earlier aminothiols; and 3. PrC-210 significantly increased survival after 4 Gy irradiation in the p53-/- mouse model.

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While computed tomography (CT) is now commonly used and considered to be clinically valuable, significant DNA double-strand breaks (γ-H2AX foci) in white blood cells from adult and pediatric CT patients have been frequently reported. In this study to determine whether γ-H2AX foci and X-ray-induced naked DNA damage are suppressed by administration of the PrC-210 radioprotector, human blood samples were irradiated in a CT scanner at 50-150 mGy with or without PrC-210, and γ-H2AX foci were scored. X-ray-induced naked DNA damage was also studied, and the DNA protective efficacy of PrC-210 was compared against 12 other common "antioxidants." PrC-210 reduced CT radiation-induced γ-H2AX foci in white blood cells to near background ( P < 0.0001) at radiation doses of 50-150 mGy. PrC-210 was most effective among the 13 "antioxidants" in reducing naked DNA X-ray damage, and its addition at 30 s before an •OH pulse reduced to background the •OH insult that otherwise induced >95% DNA damage. A systemic PrC-210 dose known to confer 100% survival in irradiated mice had no discernible effect on micro-CT image signal-to-noise ratio and CT image integrity. PrC-210 suppressed DNA damage to background or near background in each of these assay systems, thus supporting its development as a radioprotector for humans in multiple radiation exposure settings.

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