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Research exploring the integration of pharmacogenomics (PGx) testing by pharmacists into their primary care practices (including community pharmacies) has focused on the "external" factors that impact practice implementation. In this study, additional "internal" factors, related to the capabilities, opportunities, and motivations of pharmacists that influence their ability to implement PGx testing, were analyzed. Semi-structured interview data from the Pharmacists as Personalized Medicine Experts (PRIME) study, which examined the barriers and facilitators to implementing PGx testing by pharmacists into primary care practice, were analyzed. Through thematic analysis, using the theoretical domains framework (TDF) domains as deductive codes, the authors identified the most relevant TDF domains and applied the behavioural change wheel (BCW) to generate intervention types to aid in the implementation of PGx testing. Pharmacists described how their professional identities, practice environments, self-confidence, and beliefs in the benefits of PGx impacted their ability to provide a PGx-testing service. Potential interventions to improve the implementation of the PGx service included preparing pharmacists for managing an increased patient load, helping pharmacists navigate the software and technology requirements associated with the PGx service, and streamlining workflows and documentation requirements. As interest in the wide-scale implementation of PGx testing through community pharmacies grows, additional strategies need to address the "internal" factors that influence the ability of pharmacists to integrate testing into their practices.

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A continuing professional development (CPD) program for pharmacists practicing in community and team-based primary care settings was developed and evaluated using Moore's framework for the assessment of continuing medical education. The program had three components: online lectures, a two-day training workshop, and patient case studies. Knowledge (pre-post multiple choice test); attitudes, readiness, and comfort with applying pharmacogenomics in their practices (pre-post surveys); and experiences of implementing pharmacogenomics in practice (semi-structured interviews) were assessed. Twenty-one of 26 enrolled pharmacists successfully completed the program, and were satisfied with their experience. Almost all achieved a score of 80% or higher on the post-training multiple choice test, with significantly improved scores compared to the pre-training test. Pre- and post-training surveys demonstrated that participants felt that their knowledge and competence increased upon completion of the training. In the follow-up, 15 pharmacists incorporated pharmacogenomics testing into care for 117 patients. Ten pharmacists participated in semi-structured interviews, reporting strong performance in the program, but some difficulty implementing new knowledge in their practices. This multi-component CPD program successfully increased pharmacists' knowledge, readiness, and comfort in applying pharmacogenomics to patient care in the short-term, yet some pharmacists struggled to integrate this new service into their practices.

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OBJECTIVE: To assess the feasibility of a medication sampling program involving community pharmacists. METHODS: A community pharmacy dispensed samples after receiving a voucher given to patients by prescribers. Surveys explored prescribers' and patients' views about sampling and patients' experiences with the program. KEY FINDINGS: Half of prescribers reported providing samples, yet 15 patients redeemed 18 vouchers over 1 year. Patients expressed favourable views towards sampling and pharmacist involvement, despite more than half (n = 8/15, 53%) feeling that visiting the pharmacy was less convenient. CONCLUSION: A voucher-based medication sampling program based in a community pharmacy is a model integrating pharmacist care.

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PURPOSE: The published literature on medication reconciliation (MR) interventions, outcomes, and facilitators in ambulatory care settings is reviewed. METHODS: A scoping review was conducted to characterize ambulatory care-based MR research in terms of study design, elements of interventions, and outcomes examined. English-language articles on comparative studies of MR programs targeting adults in ambulatory care settings were identified using data sources including MEDLINE, PreMEDLINE, EMBASE, and International Pharmaceutical Abstracts. For each study, steps undertaken in the MR process were extracted. The Cochrane Effective Practice and Organisation of Care (EPOC) taxonomy was used to classify types of interventions; taxonomies for reported outcomes and factors facilitating implementation of MR initiatives were developed by the authors. RESULTS: From among 2062 publications screened, 15 were included in the review. In 13 studies, multiple data sources were used to compile a "best possible medication history" (BPMH); however, the BPMH was shared with external healthcare providers in only 4 studies and with patients in only 5 studies. Most reported MR interventions were classified into two EPOC domains: professional (predominantly educational outreach visits and patient reminders) and organizational (predominantly provider-oriented interventions). Process outcomes were reported in 12 studies, with correct performance of MR being the most commonly evaluated process outcome, and 9 studies identified factors that facilitated MR implementation. CONCLUSION: Few studies have examined clinical outcomes of MR in ambulatory care settings, with the majority of pertinent reports focusing instead on process outcomes. Facilitators of successful MR interventions have been identified at the patient, staff, and clinic setting levels.

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BACKGROUND: Medication reconciliation (MR) is associated with reduced discrepancies and adverse events within institutions. In ambulatory care, MR is often considered more challenging due to periodic, brief patient encounters and the involvement of multiple prescribers who lack shared records. MedsCheck, a community pharmacy program in Ontario for patients with diabetes or those taking 3 or more medications, generates a best possible medication history (BPMH) that can serve as a starting point for MR. Our objectives were to develop and evaluate a program to integrate MedsCheck into the workflow of an ambulatory clinic. METHODS: An initiative was implemented within the Complex Care Clinic (CCC), an academic internal medicine clinic at Women's College Hospital (WCH). During booking of their first appointment, patients were encouraged to receive a MedsCheck. A letter was faxed to the patient's preferred community pharmacy with a request to conduct a MedsCheck and send documentation to the clinic. Evaluation included patient and health care provider questionnaires and chart review. RESULTS: Fifty-five of 86 new patients referred to the CCC were eligible for a MedsCheck. Fifty-four patients consented to having their community pharmacy contacted, and documentation was received for 21 (39%) of these reviews. Chart review was conducted for patients who completed the patient feedback questionnaire (n = 32). Community pharmacists reported at least 1 drug therapy problem for 12 (57%) patients with a mean of 2.6 (SD 1.5) per patient. Medical residents reported an estimated mean appointment time savings of 7.9 minutes (SD 2.4). CONCLUSION: The program was feasibly integrated into clinic workflow and shortened the time spent creating BPMHs. This approach could be adopted by other ambulatory care clinics.

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AIMS: It is thought that clopidogrel bioactivation and antiplatelet response are related to cytochrome P450 2C19 (CYP2C19). However, a recent study challenged this notion by proposing CYP2C19 as wholly irrelevant, while identifying paraoxonase-1 (PON1) and its Q192R polymorphism as the major driver of clopidogrel bioactivation and efficacy. The aim of this study was to systematically elucidate the mechanism and relative contribution of PON1 in comparison to CYP2C19 to clopidogrel bioactivation and antiplatelet response. METHODS AND RESULTS: First, the influence of CYP2C19 and PON1 polymorphisms and plasma paraoxonase activity on clopidogrel active metabolite (H4) levels and antiplatelet response was assessed in a cohort of healthy subjects (n = 21) after administration of a single 75 mg dose of clopidogrel. There was a remarkably good correlation between H4 AUC (0-8 h) and antiplatelet response (r2 = 0.78). Furthermore, CYP2C19 but not PON1 genotype was predictive of H4 levels and antiplatelet response. There was no correlation between plasma paraoxonase activity and H4 levels. Secondly, metabolic profiling of clopidogrel in vitro confirmed the role of CYP2C19 in bioactivating clopidogrel to H4. However, heterologous expression of PON1 in cell-based systems revealed that PON1 cannot generate H4, but mediates the formation of another thiol metabolite, termed Endo. Importantly, Endo plasma levels in humans are nearly 20-fold lower than H4 and was not associated with any antiplatelet response. CONCLUSION: Our results demonstrate that PON1 does not mediate clopidogrel active metabolite formation or antiplatelet action, while CYP2C19 activity and genotype remains a predictor of clopidogrel pharmacokinetics and antiplatelet response.

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Variable warfarin response during treatment initiation poses a significant challenge to providing optimal anticoagulation therapy. We investigated the determinants of initial warfarin response in a cohort of 167 patients. During the first nine days of treatment with pharmacogenetics-guided dosing, S-warfarin plasma levels and international normalized ratio were obtained to serve as inputs to a pharmacokinetic-pharmacodynamic (PK-PD) model. Individual PK (S-warfarin clearance) and PD (I(max)) parameter values were estimated. Regression analysis demonstrated that CYP2C9 genotype, kidney function, and gender were independent determinants of S-warfarin clearance. The values for I(max) were dependent on VKORC1 and CYP4F2 genotypes, vitamin K status (as measured by plasma concentrations of proteins induced by vitamin K absence, PIVKA-II) and weight. Importantly, indication for warfarin was a major independent determinant of I(max) during initiation, where PD sensitivity was greater in atrial fibrillation than venous thromboembolism. To demonstrate the utility of the global PK-PD model, we compared the predicted initial anticoagulation responses with previously established warfarin dosing algorithms. These insights and modeling approaches have application to personalized warfarin therapy.

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Single-nucleotide polymorphisms in genes that affect warfarin metabolism (cytochrome P450 2C9 gene, CYP2C9) and response (vitamin K epoxide reductase complex 1 gene, VKORC1) have an important influence on warfarin therapy, particularly during initiation; however, there is a lack of consensus regarding the optimal pharmacogenetics-based initiation strategy. We conducted a prospective cohort study in which patients requiring warfarin therapy for atrial fibrillation or venous thromboembolism were initiated with a novel pharmacogenetics-initiation protocol (WRAPID, Warfarin Regimen using A Pharmacogenetics-guided Initiation Dosing) that incorporated loading and maintenance doses based on genetics, clinical variables, and response (n = 167, followed up for 90 days), to assess the influence of genetic variations on anticoagulation responses. Application of the WRAPID algorithm resulted in a negligible influence of genetic variation in VKORC1 or CYP2C9 on time to achievement of first therapeutic response (P = .52, P = .28) and risk of overanticoagulation (P = .64, P = .96). After adjustment for covariates, time to stable anticoagulation was not influenced by VKORC1 or CYP2C9 genotype. Importantly, time spent within or above the therapeutic range did not differ among VKORC1 and CYP2C9 genotype groups. Moreover, the overall time course of the anticoagulation response among the genotype groups was similar and predictable. We demonstrate the clinical utility of genetics-guided warfarin initiation with the WRAPID protocol to provide safe and optimal anticoagulation therapy for patients with atrial fibrillation or venous thromboembolism.

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PURPOSE: The safety of fixed-dose combination aspirin-extended-release (ER) dipyridamole for stroke prevention in patients with ischemic heart disease is reviewed. SUMMARY: Randomized controlled trials have established the superiority of aspirinER dipyridamole over aspirin alone for secondary stroke prevention. One limitation of this product is the potential risk of worsening angina in patients with coronary artery disease. The English-language medical literature was searched for articles describing the cardiac safety of oral dipyridamole alone or in combination with aspirin. Meta-analyses, randomized controlled trials, observational studies, and case reports presenting information on the cardiac safety of oral dipyridamole were also reviewed. Four meta-analyses described vascular events with dipyridamole using various dosing strategies. Three trials included the endpoint of myocardial infarction in patients receiving ER dipyridamole. The meta-analyses and randomized controlled trials specifically evaluating aspirin-ER dipyridamole did not provide evidence of increased risk of vascular events. One post hoc analysis of a randomized controlled trial specifically assessed the cardiac safety of fixed-dose aspirin-ER dipyridamole and found that dipyridamole was not associated with a higher number of cardiac events compared with aspirin alone. One randomized controlled trial evaluated the efficacy of ER dipyridamole in patients with preexisting ischemic heart disease and found no evidence of increased risk of cardiac events in this population. No published reports were located describing angina with the combination product. CONCLUSION: A literature review revealed that fixed-dose aspirin-ER dipyridamole was not associated with an increased risk of cardiovascular events in patients with ischemic heart disease. However, individual patient factors merit consideration when choosing an antiplatelet agent for stroke prevention.

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