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Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with development of acute hemolytic anemia in the setting of oxidative stress, which can be caused by medication exposure. Regulatory agencies worldwide warn against the use of certain medications in persons with G6PD deficiency, but in many cases, this information is conflicting, and the clinical evidence is sparse. This guideline provides information on using G6PD genotype as part of the diagnosis of G6PD deficiency and classifies medications that have been previously implicated as unsafe in individuals with G6PD deficiency by one or more sources. We classify these medications as high, medium, or low to no risk based on a systematic review of the published evidence of the gene-drug associations and regulatory warnings. In patients with G6PD deficiency, high-risk medications should be avoided, medium-risk medications should be used with caution, and low-to-no risk medications can be used with standard precautions, without regard to G6PD phenotype. This new document replaces the prior Clinical Pharmacogenetics Implementation Consortium guideline for rasburicase therapy in the context of G6PD genotype (updates at: www.cpicpgx.org)., (© 2023 The Authors. Clinical Pharmacology & Therapeutics © 2023 American Society for Clinical Pharmacology and Therapeutics.)

The clinical use of genomic analysis has expanded rapidly resulting in an increased availability and utility of genomic information in clinical care. We have developed an infrastructure utilizing informatics tools and clinical processes to facilitate the use of whole genome sequencing data for population health management across the healthcare system. Our resulting framework scaled well to multiple clinical domains in both pediatric and adult care, although there were domain specific challenges that arose. Our infrastructure was complementary to existing clinical processes and well-received by care providers and patients. Informatics solutions were critical to the successful deployment and scaling of this program. Implementation of genomics at the scale of population health utilizes complicated technologies and processes that for many health systems are not supported by current information systems or in existing clinical workflows. To scale such a system requires a substantial clinical framework backed by informatics tools to facilitate the flow and management of data. Our work represents an early model that has been successful in scaling to 29 different genes with associated genetic conditions in four clinical domains. Work is ongoing to optimize informatics tools; and to identify best practices for translation to smaller healthcare systems.

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., (© 2022. The Author(s).)

Purpose: The Mayo-Baylor RIGHT 10K Study enabled preemptive, sequence-based pharmacogenomics (PGx)-driven drug prescribing practices in routine clinical care within a large cohort. We also generated the tools and resources necessary for clinical PGx implementation and identified challenges that need to be overcome. Furthermore, we measured the frequency of both common genetic variation for which clinical guidelines already exist and rare variation that could be detected by DNA sequencing, rather than genotyping., Methods: Targeted oligonucleotide-capture sequencing of 77 pharmacogenes was performed using DNA from 10,077 consented Mayo Clinic Biobank volunteers. The resulting predicted drug response-related phenotypes for 13 genes, including CYP2D6 and HLA, affecting 21 drug-gene pairs, were deposited preemptively in the Mayo electronic health record., Results: For the 13 pharmacogenes of interest, the genomes of 79% of participants carried clinically actionable variants in 3 or more genes, and DNA sequencing identified an average of 3.3 additional conservatively predicted deleterious variants that would not have been evident using genotyping., Conclusion: Implementation of preemptive rather than reactive and sequence-based rather than genotype-based PGx prescribing revealed nearly universal patient applicability and required integrated institution-wide resources to fully realize individualized drug therapy and to show more efficient use of health care resources., Competing Interests: Conflict of Interest Liewei Wang, John Logan Black III, and Richard M. Weinshilboum are cofounders of and stockholders in OneOme, LLC, which was used only to return results to the study participants. Additionally, John Logan Black III and Mayo Clinic Ventures have applied for a patent on the CNVAR software cited in this study as well as the methodology upon which the software is based. All other authors declare no conflicts of interest., (Copyright © 2022 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

Ineffective pain control is the most commonly cited reason for misuse of prescription opioids and is influenced by genetics. In particular, the gene encoding the CYP2D6 enzyme, which metabolizes some of the most commonly prescribed opioids (e.g., tramadol, hydrocodone) to their more potent forms, is highly polymorphic and can lead to reduced concentrations of the active metabolites and decreased opioid effectiveness. Consideration of the CYP2D6 genotype may allow for predicting opioid response and identifying patients who are likely to respond well to lower potency opioids as well as those who may derive greater pain relief from non-opioid analgesics versus certain opioids. There is emerging evidence that a CYP2D6 -guided approach to pain management improves pain control and reduces opioid consumption and thus may be a promising means for combating opioid misuse. Clinical practice guidelines are available for select opioids and other analgesics to support medication and dose selection based on pharmacogenetic data. This article describes the evidence supporting genotype-guided pain management as a means of improving pain control and reducing opioid misuse and clinical recommendations for genotype-guided analgesic prescribing. In addition, a "how to" guide using patient case examples is provided to demystify the process for implementing pharmacogenetics-guided pain management in order to optimize analgesia and minimize adverse effects. Optimizing pain management through genotype-guided approaches may ultimately provide safer and more effective therapy for pain control while decreasing the risk for opioid misuse., Competing Interests: Conflict of interest: DM Smith reports grants (to institution) from Kailos Genetics

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., (© 2021 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

The Pharmacogenomics Access & Reimbursement Symposium, a landmark event presented by the Golden Helix Foundation and the Pharmacogenomics Access & Reimbursement Coalition, was a 1-day interactive meeting comprised of plenary keynotes from thought leaders across healthcare that focused on value-based strategies to improve patient access to personalized medicine. Stakeholders including patients, healthcare providers, industry, government agencies, payer organizations, health systems and health policy organizations convened to define opportunities to improve patient access to personalized medicine through best practices, successful reimbursement models, high quality economic evaluations and strategic alignment. Session topics included health technology assessment, health economics, health policy and value-based payment models and innovation.

Proton pump inhibitors (PPIs) are widely used for acid suppression in the treatment and prevention of many conditions, including gastroesophageal reflux disease, gastric and duodenal ulcers, erosive esophagitis, Helicobacter pylori infection, and pathological hypersecretory conditions. Most PPIs are metabolized primarily by cytochrome P450 2C19 (CYP2C19) into inactive metabolites, and CYP2C19 genotype has been linked to PPI exposure, efficacy, and adverse effects. We summarize the evidence from the literature and provide therapeutic recommendations for PPI prescribing based on CYP2C19 genotype (updates at www.cpicpgx.org). The potential benefits of using CYP2C19 genotype data to guide PPI therapy include (i) identifying patients with genotypes predictive of lower plasma exposure and prescribing them a higher dose that will increase the likelihood of efficacy, and (ii) identifying patients on chronic therapy with genotypes predictive of higher plasma exposure and prescribing them a decreased dose to minimize the risk of toxicity that is associated with long-term PPI use, particularly at higher plasma concentrations., (© 2020 The Authors Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics.)

Phenytoin is an antiepileptic drug with a narrow therapeutic index and large interpatient pharmacokinetic variability, partly due to genetic variation in CYP2C9. Furthermore, the variant allele HLA-B*15:02 is associated with an increased risk of Stevens-Johnson syndrome and toxic epidermal necrolysis in response to phenytoin treatment. We summarize evidence from the published literature supporting these associations and provide therapeutic recommendations for the use of phenytoin based on CYP2C9 and/or HLA-B genotypes (updates on cpicpgx.org)., (© 2020 The Authors Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics.)

Many practitioners who have not had pharmacogenomic education are required to apply pharmacogenomics to their practices. Although many aspects of pharmacogenomics are similar to traditional concepts of drug-drug interactions, there are some differences. We searched PubMed with the search terms pharmacogenomics and pharmacogenetics (January 1, 2005, through December 31, 2019) and selected articles that supported the application of pharmacogenomics to practice. For inclusion, we gave preference to national and international consortium guidelines for implementation of pharmacogenomics. We discuss special considerations important in the application of pharmacogenomics to assist clinicians with ordering, interpreting, and applying pharmacogenomics in their practices., (Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Purpose: Guidance on alternate care site planning based on the experience of a health-system pharmacy department in preparing for an expected surge in coronavirus disease 2019 (COVID-19) cases is provided., Summary: In disaster response situations such as the COVID-19 pandemic, healthcare institutions may be compelled to transition to a contingency care model in which staffing and supply levels are no longer consistent with daily practice norms and, while usual patient care practices are maintained, establishment of alternate care sites (eg, a convention center) may be necessitated by high patient volumes. Available resources to assist hospitals and health systems in alternate care site planning include online guidance posted within the COVID-19 resources section of the US Army Corps of Engineers website, which provides recommended medication and supply lists; and the Federal Healthcare Resilience Task Force's alternate care site toolkit, a comprehensive resource for all aspects of alternate care site planning, including pharmacy services. Important pharmacy planning issues include security and storage of drugs, state board of pharmacy and Drug Enforcement Administration licensing considerations, and staff credentialing, education, and training. Key medication management issues to be addressed in alternate site care planning include logistical challenges of supply chain maintenance, optimal workflow for compounded sterile preparations (eg, on-site preparation vs off-site preparation and delivery from a nearby hospital), and infusion pump availability and suitability to patient acuity levels., Conclusion: Planning for and operation of alternate care sites in disaster response situations should include involvement of pharmacists in key decision-making processes at the earliest planning stages., (© American Society of Health-System Pharmacists 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used analgesics due to their lack of addictive potential. However, NSAIDs have the potential to cause serious gastrointestinal, renal, and cardiovascular adverse events. CYP2C9 polymorphisms influence metabolism and clearance of several drugs in this class, thereby affecting drug exposure and potentially safety. We summarize evidence from the published literature supporting these associations and provide therapeutic recommendations for NSAIDs based on CYP2C9 genotype (updates at www.cpicpgx.org)., (© 2020 The Authors Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics.)

In this Perspective, the authors discuss the state of pharmacogenomics testing addressing a number of advances, challenges and barriers, including legal ramifications, changes to the regulatory landscape, coverage of testing and the implications of direct-to-consumer genetic testing on the provision of care to patients. Patient attitudes toward pharmacogenomics testing and associated costs will play an increasingly important role in test acquisition and subsequent utilization in a clinical setting. Additional key steps needed include: further research trials demonstrating clinical utility and cost-effectiveness of pharmacogenetic testing, evidence review to better integrate genomic information into clinical practice guidelines in target therapeutic areas to help providers identify patients that may benefit from pharmacogenetic testing and engagement with payers to create a path to reimbursement for pharmacogenetic tests that currently have sufficient evidence of clinical utility. Increased adoption of testing by payers and improved reimbursement practices will be needed to overcome barriers, especially as the healthcare landscape continues to shift toward a system of value-based care.

Pharmacogenomics test coverage and reimbursement are major obstacles to clinical uptake. Several early adopter programs have been successfully initiated through dedicated investments by federal and institutional research funding. As a result of research endeavors, evidence has grown sufficiently to support development of pharmacogenomics guidelines. However, clinical uptake is still limited. Third-party payer support plays an important role in increasing adoption, which to date has been limited to reactive single-gene testing. Access to and interest in direct-to-consumer genetic testing are driving demand for increasing healthcare providers and third-party awareness of this burgeoning field. Pharmacogenomics implementation models developed by early adopters promise to expand patient access and options, as testing continues to increase due to growing consumer interest and falling test prices.

Purpose: This report examines and evaluates pharmacogenomics as an emerging science as it relates to the Practice Advancement Initiative and its predecessor the Pharmacy Practice Model Initiative's consensus statements for optimal pharmacy practice models., Summary: Pharmacogenomics is one of many emerging sciences to impact medication management and delivery of patient care. Increasingly, biomarkers are included in drug labeling and can assist pharmacists with personalizing medicine to optimize patient therapies and avoid adverse effects. The 2011 ASHP Pharmacy Practice Model Summit generated a list of 147 consensus statements for optimal pharmacy practice. Of these, 1 statement explicitly describes adjustment of drug regimens based on genetic factors as an essential activity of pharmacist-provided drug regimens, and 9 other statements provide additional support for incorporation of this emerging science into all aspects of patient care provided by pharmacists. We describe 4 institutions that have made significant inroads to implementing pharmacogenomics, to provide a framework and serve as resources for other institutions initiating their own pharmacogenomics implementation journeys., Conclusion: Through prioritized efforts of the pharmacy profession and health care institutions, pharmacogenomics will be disseminated and implemented, and the goal of the Pharmacy Practice Model Initiative's consensus statements of improving health care using patients' genetic characteristics will be realized., (© American Society of Health-System Pharmacists 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: The development, implementation, and evaluation of a pharmacogenomics education program for pharmacists in a large, integrated multicampus health system are described., Summary: Pharmacogenomics has been described as tailoring medications to each patient's unique genetic sequence with the goals of minimizing harmful effects and optimizing therapeutic effects. Pharmacists are uniquely trained to lead the implementation of pharmacogenomics in clinical care. After assessment of pharmacists' comfort with pharmacogenomics, different approaches were explored to develop, pilot test, and disseminate pharmacogenomics education across a multicampus academic medical center. Limited success with large-audience, single-lecture didactic education led to development and delivery of targeted, competency-based online modules using the institution's academic virtual learning environment and course management system. Implementation steps included (1) collaboration with the Mayo Clinic Center for Individualized Medicine to create an interprofessional development team and project charter, (2) galvanizing pharmacy leadership support across multiple campuses, (3) development of competency-based interactive modules, and (4) assessment of the quality of and learner satisfaction with the modules. Significant improvements in competency scores were observed with each module and across the multiple campuses. Satisfaction with the education program was assessed at the end of a 4-module series., Conclusion: A pharmacogenomics educational program targeting pharmacists was developed through interprofessional collaboration and provided a novel opportunity to construct an educational infrastructure to support enterprise health-system campuses with limited educational resources., Competing Interests: DisclosuresThe project was supported by grant number UL1 TR000135 from the National Center for Advancing Translational Sciences. The authors have declared no potential conflicts of interest., (Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.)

A number of barriers exist for adoption of pharmacogenomics into practice. Physicians, pharmacists, and nurses report limited knowledge about pharmacogenomics and its use in patient care. Lack of pharmacogenomics education curricula as part of professional schools or postgraduate training programs has been reported as a potential cause. Understanding pharmacogenomics is further complicated by a complex and nonstandard lexicon, limited medication guidelines, rapidly changing evidence, and insufficient awareness of test availability and utility., (© 2018 ASCPT.)

Purpose: Results of a study of prescribers' responses to a pharmacogenomics-based clinical decision support (CDS) alert designed to prompt thiopurine S -methyltransferase (TPMT) status testing are reported., Methods: A single-center, retrospective, chart review-based study was conducted to evaluate prescriber compliance with a pretest CDS alert that warned of potential thiopurine drug toxicity resulting from deficient TPMT activity due to TPMT gene polymorphism. The CDS alert was triggered when prescribers ordered thiopurine drugs for patients whose records did not indicate TPMT status or when historical thiopurine use was documented in the electronic health record. The alert pop-up also provided a link to online educational resources to guide thiopurine dosing calculations., Results: During the 9-month study period, 500 CDS alerts were generated: in 101 cases (20%), TPMT phenotyping or TPMT genotyping was ordered; in 399 cases (80%), testing was not ordered. Multivariable regression analysis indicated that documentation of historical thiopurine use was the only independent predictor of test ordering. Among the 99 patients tested subsequent to CDS alerts, 70 (71%) had normal TPMT activity, 29 (29%) had intermediate activity, and none had deficient activity. The online resources provided thiopurine dosing recommendations applicable to 24 patients, but only 3 were prescribed guideline-supported doses after CDS alerts., Conclusion: The pretest CDS rule resulted in a large proportion of neglected alerts due to poor alerting accuracy and consequent alert fatigue. Prescriber usage of online thiopurine dosing resources was low., (Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.)

Persons from Somalia constitute the largest group of immigrants and refugees from Africa among whom diabetes-related health disparities are well documented. As one of the first steps toward developing a behavioral intervention to address diabetes among Somali immigrants and refugees, we administered a face to face interview-based survey to Somali and Latino adults with diabetes in a single community to assess diabetes knowledge, attitudes and behaviors. Respondents (N = 78) reported several barriers to optimal diabetes management for physical activity and glucose self-monitoring, as well as a high burden of disease and negative perceptions of diabetes. High participant engagement in disease management, self-efficacy, and social support were important assets. Similarities suggest that the shared experiences of immigration and related systemic socioeconomic and linguistic factors play a significant role in the understanding and self-management of diabetes in these populations. Together with previously collected qualitative work, the survey findings will inform development of a behavioral intervention to improve outcomes and reduce diabetes-related health disparities among immigrant and refugee groups to the U.S.

Objective: To describe an exploratory project to develop and pilot a novel patient educational tool that explains the concept of pharmacogenomics and its impact on warfarin dosing that can be utilized by health professionals providing patient counseling., Methods: A pharmacogenomics educational tool prototype was developed by an interdisciplinary team. During the pilot of the tool, focus group methodology was used to elicit input from patients based upon their perspectives and experiences with warfarin. Focus group sessions were audio-recorded and transcribed, and the data was analyzed through consensus coding in NVivo., Results: The focus group participants were generally unfamiliar with the concept of pharmacogenomics but were receptive to the information. They thought the patient education tool was informative and would provide the most benefit to patients newly initiated on warfarin therapy., Conclusions: Preliminary results from this exploratory project suggest that implementation and further feasibility testing of this pharmacogenomics patient education tool should be performed in a population of newly initiated patients taking warfarin.

Personalized medicine offers the promise of better diagnoses, targeted therapies and individualized treatment plans. Pharmacogenomics is an integral component of personalized medicine; it aids in the prediction of an individual's response to medications. Despite growing public acceptance and emerging clinical evidence, this rapidly expanding field of medicine is slow to be adopted and utilized by healthcare providers, although many believe that they should be knowledgeable and able to apply pharmacogenomics in clinical practice. Institutional infrastructure must be built to support pharmacogenomic implementation. Multidisciplinary education for healthcare providers is a critical component for pharmacogenomics to achieve its full potential to optimize patient care. We describe our recent experience at the Mayo Clinic implementing pharmacogenomics education in a large, academic healthcare system facilitated by the Mayo Clinic Center for Individualized Medicine., Competing Interests: Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.

Immigrants and refugees to the United States exhibit relatively low levels of physical activity, but reasons for this disparity are poorly understood. 16 gender and age-stratified focus groups were conducted among 127 participants from heterogenous immigrant and refugee groups (Cambodian, Mexican, Somali, Sudanese) in a small Minnesota urban community. We found many similarities in perceived barriers and facilitators to physical activity between heterogeneous immigrant and refugee groups. While the benefits of physical activity were widely acknowledged, lack of familiarity and comfort with taking the first steps towards being physically active were the most significant barriers to physical activity. Participants described being motivated by social support from family, friends, and communities to be physically active. Our findings suggest that shared experiences of immigration and associated social, economic, and linguistic factors influence how physical activity is understood, conceptualized and practiced.

Background: Immigrants and refugees to the United States exhibit lower dietary quality than the general population, but reasons for this disparity are poorly understood. In this study, we describe the meanings of food, health and wellbeing through the reported dietary preferences, beliefs, and practices of adults and adolescents from four immigrant and refugee communities in the Midwestern United States., Methods: Using a community based participatory research approach, we conducted a qualitative research study with 16 audio-recorded focus groups with adults and adolescents who self-identified as Mexican, Somali, Cambodian, and Sudanese. Focus group topics were eating patterns, perceptions of healthy eating in the country of origin and in the U.S., how food decisions are made and who in the family is involved in food preparation and decisions, barriers and facilitators to healthy eating, and gender and generational differences in eating practices. A team of investigators and community research partners analyzed all transcripts in full before reducing data to codes through consensus. Broader themes were created to encompass multiple codes., Results: Results show that participants have similar perspectives about the barriers (personal, environmental, structural) and benefits of healthy eating (e.g., 'junk food is bad'). We identified four themes consistent across all four communities: Ways of Knowing about Healthy Eating ('Meanings;' 'Motivations;' 'Knowledge Sources'), Eating Practices ('Family Practices;' 'Americanized Eating Practices' 'Eating What's Easy'), Barriers ('Taste and Cravings;' 'Easy Access to Junk Food;' 'Role of Family;' Cultural Foods and Traditions;' 'Time;' 'Finances'), and Preferences for Intervention ('Family Counseling;' Community Education;' and 'Healthier Traditional Meals.'). Some generational (adult vs. adolescents) and gender differences were observed., Conclusions: Our study demonstrates how personal, structural, and societal/cultural factors influence meanings of food and dietary practices across immigrant and refugee populations. We conclude that cultural factors are not fixed variables that occur independently from the contexts in which they are embedded.

Objectives. To evaluate hospital and outpatient pharmacists' pharmacogenomics knowledge before and 2 months after participating in a targeted, case-based pharmacogenomics continuing education program.Design. As part of a continuing education program accredited by the Accreditation Council for Pharmacy Education (ACPE), pharmacists were provided with a fundamental pharmacogenomics education program.Evaluation. An 11-question, multiple-choice, electronic survey instrument was distributed to 272 eligible pharmacists at a single campus of a large, academic healthcare system. Pharmacists improved their pharmacogenomics test scores by 0.7 questions (pretest average 46%; posttest average 53%, p=0.0003).Conclusions. Although pharmacists demonstrated improvement, overall retention of educational goals and objectives was marginal. These results suggest that the complex topic of pharmacogenomics requires a large educational effort in order to increase pharmacists' knowledge and comfort level with this emerging therapeutic opportunity.

Objectives: To evaluate the self-perceived knowledge and confidence of inpatient and outpatient pharmacists in applying pharmacogenomics information to clinical practice., Methods: A 19-question multiple-choice, electronic needs-assessment survey instrument was distributed to 480 inpatient and outpatient pharmacists in a large, academic, multi-campus healthcare system., Results: The survey response rate was 64% (303). Most respondents (85%) agreed that pharmacists should be required to be knowledgeable about pharmacogenomics, and 65% agreed that pharmacists should be capable of providing information on the appropriate use of pharmacogenomics testing. Sixty-three percent felt they could not accurately apply the results of pharmacogenomics tests to drug-therapy selection, dosing, or monitoring., Conclusion: Pharmacists believe pharmacogenomics knowledge is important to the profession, but they lack the knowledge and self-confidence to act on the results of pharmacogenomics testing and may benefit from pharmacogenomics education.

While clinical medicine is often well supported by health system information technology infrastructure, clinical research may need to create strategies to use clinical-medicine informational technology tools. The authors describe a medication-safety initiative that was carried out in a National Institutes of Health Clinical and Translational Science Award (CTSA)-sponsored clinical research environment. A web based, medical informatics application was designed and implemented that allowed research groups to build protocol specific, electronic medication templates that were subsequently used to create participant-specific medication order sets for conductance of clinical research activities in the CTSA-sponsored clinical research environment. The medical informatics initiative eliminated typewritten or handwritten medication orders, created research protocol-specific templates meeting institutional order-writing requirements, and formalized a rigorous review and approval process. Enhancing safety in medication ordering and prescribing practices in a clinical research environment provided the background for multidisciplinary cooperation in medical informatics., (© 2010 Wiley Periodicals, Inc.)

Purpose: A collaborative effort between two pharmacy specialty areas for ensuring compliance with United States Pharmacopeia (USP) chapter 797 for compounded sterile preparations (CSPs) is described., Summary: In September 2005, an investigational drug service (IDS) satellite was opened at a 1157-bed, level 1 trauma, academic hospital in Minnesota. After construction of the IDS satellite, a collaborative consulting service was established between the two pharmacy areas. Protocol-specific investigational medications requiring extemporaneous compounding were reviewed by both an IDS pharmacist and a hospital compounding pharmacist to provide recommendations to investigators. High-risk compounding was performed by the hospital compounding pharmacy, and patient-specific, medium- and low-risk compounding of CSP doses was performed by IDS pharmacy personnel for research participants. A small subset of investigational medications met high-risk criteria and was referred to the hospital compounding pharmacy. After final clearance from quarantine, the high-risk preparations were transferred to the inpatient IDS satellite for dispensing of patient-specific investigational medication doses. The compounding pharmacy followed standardized quality-assurance procedures to ensure sterility, purity, and endotoxin appropriateness for the investigational medications. Quality control of investigational CSPs was maintained by hand delivery of the investigational medication and documentation and disposition via hard-copy receipt on the nursing units. Based on chapter 797 requirements, the department of pharmacy's education and training changed to reflect the new compounding requirements for CSPs, including 20 hours of didactic training for aseptic manipulation skills and practical assessments of aseptic technique using growth media., Conclusion: A collaborative effort between two specialty areas of pharmacy services ensured compliance with USP chapter 797 requirements for compounded sterile preparations.

A 19-year-old woman was admitted to receive a kidney transplant from a nonliving donor. At the time of transplantation, she was taking oral phenytoin 300 mg every morning, 100 mg at noon, and 300 mg every evening (total of 700 mg/day) to treat seizures secondary to hemodialysis. Immediately after the transplantation, phenytoin treatment was resumed, and immunosuppressive therapy consisting of antithymocyte globulin, cyclosporine, mycophenolate mofetil, and corticosteroids was started. Her cyclosporine blood levels varied over the first 10 days after transplantation. Cyclosporine was discontinued, and tacrolimus was begun after acute rejection was discovered. The rejection was treated with antithymocyte globulin, plasmapheresis, and intravenous immunoglobulin, and subsequently resolved; however, the patient's blood concentrations of tacrolimus varied widely. Phenytoin is an antiepileptic drug that induces hepatic enzymes, affecting the cytochrome P450 3A family. These enzymes metabolize approximately 50% of all prescribed drugs, including cyclosporine and tacrolimus. According to the Naranjo adverse drug reaction probability scale, this patient's adverse drug reaction probably occurred from altered metabolism of cyclosporine and tacrolimus due to phenytoin therapy. Clinicians must identify drug interactions between metabolic enzyme inducers or inhibitors and drug substrates with narrow therapeutic ranges, closely monitor drug concentrations, and observe patients for clinical signs and symptoms of therapeutic failure or toxicity. In daily practice, clinicians should explore the metabolic characteristics of drugs and their biotransformation pathways to identify patients who require alternative therapy.

Azathioprine (AZA) is an immunosuppressive prodrug that undergoes metabolism by thiopurine S-methyltransferase (TPMT). Eighty to ninety-five percent of low or deficient TPMT enzyme activity is genetically determined by the presence of three nonfunctional mutant alleles: TPMT*2, TPMT*3A and TPMT*3C. Using TPMT as a pharmacogenetic paradigm, we explored the association between these genetic mutations and development of adverse drug effects in an ethnically diverse renal transplant population receiving azathioprine. Biochemical and clinical data were retrospectively evaluated during the first four weeks after kidney transplantation. TPMT nonfunctional mutant alleles were identified by polymerase chain reaction-based methods. Of 89 patients initially consented, 36 met inclusion criteria for this retrospective study. Five patients possessing a single TPMT nonfunctional mutant allele were identified: TPMT*3A: n = 2 Caucasians; TPMT*3B: n = 1 Caucasian; TPMT*3C: n = 2 African-Americans. TPMT nonfunctional mutant alleles were associated with significant reductions in hematological indices and a significant increase in cyclosporine plasma concentrations in the first month post-transplant. TPMT genotype was an independent predictor for hemoglobin, hematocrit and red blood cell changes while mean azathioprine dose (mg/kg/day), azathioprine dose (mg/kg/day) at day 30 and cyclosporinemia at day 30 were not. Prospective application of pharmacogenetic principles may assist in optimization of immunosuppressive drug therapy and minimize drug toxicities.

Brain injured patients may exhibit altered gastric emptying; thus, some believe post-pyloric feeding to be tolerated better than gastric feeding. Reliable post-pylorus access can be difficult to obtain, so gastric feeding remains the preferred route for administering nutrition. Feeding intolerance may be associated with increased complications and costs. We sought to compare bolus (B) versus continuous (C) gastric feeding in brain injured patients. This retrospective cohort study was carried out at a neurological/neurosurgical intensive care unit at a Level 1 trauma and tertiary referral center. Our subjects were 152 consecutive patients over two years. Use of B or C feedings was based on clinicians' preferences. Abdominal examination and gastric residuals (> 75 mL over four hours) defined feeding intolerance (FI). Putative risks for FI were compared between the groups. Demographic characteristics were similar between groups B (n = 86) and C (n = 66). Feeding intolerance occurred more often in group B than in group C (60.5% vs. 37.9%, p = 0.009). Group C patients achieved 75% of nutritional goals faster than group B patients (median 3.3 vs. 4.6 days; p = 0.03). Prokinetic agent use was similar between the groups and did not reduce the time to achieve nutritional goals. There was a trend towards a reduction in the incidence of infections in group C (p = 0.05). Independent predictors of FI included: sucralfate (OR 2.3), propofol (OR 2.1), pentobarbital (OR 3.9) or paralytic (OR 3) use; older age (OR 5); days receiving mechanical ventilation (OR 1.2); and admission diagnosis of either intracerebral hemorrhage (OR 2.2) or ischemic stroke (OR 1.9). Continuous gastric feeding is better tolerated than B feedings in patients with acute brain injuries. Use of prokinetic agents did not affect time to achievement of nutritional goals. Use of common medications including sucralfate and propofol were associated with FI.