Polypharmacy as Formal Training and a Model of Practice.

Traditional definitions of polypharmacy may largely not account for the market proliferation of herbal and dietary supplements, cannabis products, or incorporate the new science of pharmacogenomics (PGx). Polypharmacy is encountered by most pharmacists providing patient care in many settings. The "polypharmacist" can assist patients and providers with solving medication-related problems (MRPs) in this new and challenging environment of supplements and cannabis products by utilizing traditional pharmacology and pharmacokinetic principles, including PGx, broadly across many medical disciplines. One may encounter polypharmacy more in the geriatric population, though in an age of supplements and cannabis proliferation, polypharmacy is increasingly being encountered at younger ages. Not only is polypharmacy training at best fragmented in pharmacy curricula, but it may also not account for the above-mentioned products that may use the same metabolic pathways to increase drug interactions and adverse drug reactions (ADRs) regarding prescription medications. Polypharmacy being more formally prioritized in pharmacist training may better prepare pharmacists for commonly encountered polypharmacy and can be a viable model of practice.

High-Evidence, Actionable Phenotype Gene Distribution in a Multispecialty, Tertiary Care Clinic: Potentially Actionable Genes and a Referring Department Profile.

Background There has been a trend in recent years toward individualized medicine. Pharmacogenomics (PGx) is the use of patient-specific genetic variations to guide medication selection and treatment. Objective: The primary objective was to characterize the population of referring department patients and identify the number of high-evidence, actionable phenotype (HEAP) genes in this referred population to help guide marketing efforts to the most applicable patient populations and departments. Practice description: Located in a destination, tertiary care clinic. Providers refer patients to a Pharmacogenomics (PGx) specialist for a comprehensive medication review using their pharmacogenomic results. Practice Innovation: The practice is innovative because it has been using PGx in the pharmacy and medical practices since 2016 and has been routinely developing and incorporating PGx best practice alerts (BPAs) into the electronic medical record (EMR) since 2020. Evaluation Methods Genetic results were analyzed from a 27-gene PGx panel test which tests for both pharmacokinetic and pharmacodynamic genes. High-Evidence Actionable Phenotypes (HEAP) are defined as phenotypes with guideline support that may suggest an action by healthcare provider. Low-Evidence Nonactionable Phenotypes (LENP) are defined as phenotypes that do not recommend action. Results There were 1,236 atypical phenotypes identified in the 154 patients referred. Of the atypical genes, 39.97% were HEAP and 60.03% were LENP. Of the HEAP's identified, the majority came from CYP2D6, VKORC1, and UGT1A1. At least 1 HEAP was found in 98.7% of patients (n=152). Conclusion There are a variety of High Evidence Actionable Phenotypes (HEAPs) with a high likelihood of at least one HEAP gene in every patient. These phenotypes can result in serious safety concerns when combined with a medication impacted by one of these HEAP genes. Thus, referral to a pharmacogenomics consultation service may lead to an overall decrease in morbidity and mortality with potential cost avoidance.

New Pneumococcal Vaccines for Prevention of Invasive Pneumococcal Disease in Adult Patients With Inflammatory Bowel Disease.

Patients with inflammatory bowel disease (IBD) are at a high risk of developing invasive pneumococcal infection both before and after they are diagnosed. The Advisory Committee on Immunization Practices now endorses use of 2 new pneumococcal conjugate vaccines, PCV15 (Vaxneuvance) and PCV20 (Prevnar 20), for patients who have never received a pneumococcal conjugate vaccine or those with unknown vaccination history. Previous studies have shown that pneumococcal vaccination can decrease the risk of developing severe pneumococcal disease; therefore, it is important that patients with IBD receive pneumococcal vaccination. This report aims to inform clinicians who care for patients with IBD about the changes in immunization practices, as it pertains to pneumococcal vaccination and provides appropriate direction on administering vaccination series.

Two new pneumococcal vaccines (PCV15 [Vaxneuvance], PCV20 [Prevnar 20]) are now recommended for patients who have not received a pneumococcal conjugate vaccine or those with unknown vaccination history. This report summarizes changes in immunization practices and provides direction on vaccination series for patients with inflammatory bowel disease.

Chronic Serotonin Toxicity in the Older Patient With Polypharmacy.

Clinical pharmacists with experience may identify prescribing patterns resulting in iatrogenic disease, which is commonly encountered in geriatric populations where polypharmacy is common. Serotonin toxicity is one toxidrome clinicians may identify, where specific medications are used in treatment. As a result of their pharmacology training, pharmacists may identify toxidromes caused by medications that other clinicians may overlook. Pharmacogenomic (PGx) testing can provide added insight into a potentially iatrogenic cause for serotonin toxicity, because testing can elucidate how well an individual patient may metabolize serotonergic medications. Using PGx as a resource in addition to clinical experience, pharmacists can better guide therapy in the geriatric, polypharmacy population to avoid serotonin toxicity.

Should Business Training Be a Significant Element of Pharmacy Training?

Because pharmacists cannot be reimbursed for their clinical services and are not listed as providers under the US Social Security Act, they often have difficulty finding ways to financially support their services. Specifically, because pharmacists are not listed as providers, there is not usually sufficient financial support through reimbursement to cover pharmacist labor costs. Further, pharmacists must show that they save more in labor costs through cost avoidance to be accessible to patients in particular health care settings. Business training may provide a foundation for pharmacists to create financially viable models of practice and allow for better communication with administrative decision-makers, thus increasing the accessibility of their clinical services.

Phenytoin Toxicity with High Dose, Concomitant Ascorbic Acid Dosing.

High dose ascorbic acid may increase risk of phenytoin toxicity. This case report demonstrates high phenytoin levels resulting in adverse drug reactions subsequent to dosing concomitantly with high dose vitamin C, or ascorbic acid (AA), as a precaution against acquiring corona virus (COVID) infection. This patient suffered from a major seizure when he ran out of his phenytoin prescription. Subsequent initiation of phenytoin and later addition of high dose AA resulted in truncal ataxia and falls with bilateral wrist and finger extension weakness. Phenytoin and AA were discontinued, and the patient returned to baseline on a new medication regimen of lacosamide and gabapentin without any other major seizures one year later.

Hyponatremic Cognitive Dysfunction Resulting from Drug-Drug-Gene Interaction between Sertraline and Cannabidiol in an Intermediate CYP2C19 Metabolizer Patient.

Background: Pharmacogenomics (PGx) can provide more precision in determining causation of adverse drug reactions (ADRs) from drug-drug-gene interaction clinical application. Case Summary: Patient was an intermediate CYP2C19 metabolizer on stable therapy taking a low but therapeutic dose of sertraline for depression and anxiety over a period of 20 years. The patient then became hyponatremic and cognitively impaired after addition of cannabidiol (CBD) to this sertraline regimen. The proposed mechanism was drug-drug-gene interaction of CBD further inhibiting the CYP2C19 metabolism of sertraline and increasing drug exposure to produce moderate to severe hyponatremia and subsequent cognitive dysfunction. Practice Implications: Pharmacogenomics (PGx) testing may assist in etiology of patient symptoms from adverse drug reactions (ADRs) or drug-drug interactions by combining these with detection and application of drug-gene interactions. This case shows inhibition of CYP2C19 by CBD to further increase sertraline exposure, producing hyponatremia and subsequent cognitive dysfunction through CYP2C19 phenoconversion by CBD.

Implications of Cannabidiol in Pharmacogenomic-Based Drug Interactions with CYP2C19 Substrates.

This is a patient case exploring the importance of evaluating herbal and dietary supplements and how they may impact drug-drug and drug-gene implications based on pharmacogenomics test results. Even though herbal supplements are considered natural by many patients, which is often the reason for starting them, herbal supplements may still be metabolized by the same pathways as other medications, potentially contributing to drug-drug, drug-herb, and drug-gene interactions, and therefore, potentially impacting a patient's response to medications.

Medical Cannabis State and Federal Regulations: Implications for United States Health Care Entities.

Thirty-six states and four territories in the United States have legalized cannabis for medical and/or recreational use. Marijuana, however, continues to be classified as a schedule I substance under the Federal Controlled Substance Act and remains illegal under US federal law. The incongruity between state and federal legislation creates various challenges for stakeholders: patients, medical trainees, providers, and health care institutions. This communication provides an overview of the major policies impacting Cannabis sativa use within the United States, various state and federal regulations, and highlights potential implications for health care institutions moving forward. Existing literature, regulations, and policies on medical marijuana (MMJ) use in health care settings were searched, reviewed, analyzed, and distilled. As a consequence of legislative inconsistencies, there is insufficient clarity and resultant challenges regarding MMJ usage, prescription, possession, education, and research-related policies for health care stakeholders across the United States. Coupled with limited scientific evidence on the clinical efficacy of MMJ, the needs of the patient and the quality of health care delivery may be affected as hospitals balance the competing risks of being legislatively compliant while protecting the rights of patients and health care employees. There is a recognized need to better define acceptable MMJ policies and regulations in health care settings that are evidence-based, legally compliant, and adequately address the needs of both patients and providers. Given the complexity of the legal and policy landscape, there are potential opportunities for improvement, including in medical education and training, research, and usage oversight of MMJ for stakeholders in the United States.

Vaccination of Patients With Inflammatory Bowel Disease During the COVID-19 Pandemic.

Inflammatory bowel disease and the subsequent immunosuppressive regimens used to treat this condition increase the risk for acquiring viral and bacterial infections. Ensuring that patients are up-to-date with their immunizations may help prevent the development of several of these vaccine-preventable diseases. Therefore, it is imperative that gastroenterology providers offer vaccinations to patients or direct vaccination guidance to primary care providers to minimize the risk for vaccine-preventable diseases. To decrease the risk for co-infection in the setting of the coronavirus disease 2019 pandemic and avoid placing any further burden on the health care system, the call to immunize is more important than ever.

Chronic Anticholinergic Toxicity Discovered in a Pharmacogenomics, Polypharmacy Patient.

OBJECTIVE: To report a case of chronic anticholinergic toxicity in a referred, pharmacogenomics (PGx), polypharmacy patient. SUMMARY: The patient is a 67-year-old male who was referred to the polypharmacy service for a PGx consult. This patient has had episodic fever of unknown origin, general cutaneous vasodilation, tremors, jerks, and brain fogginess which have been unexplained. He has seen specialists from infectious disease, rheumatology, endocrinology, and neurology with no contributory condition causing these symptoms, so he was referred for PGx testing and evaluation by the polypharmacy pharmacist. CONCLUSION: This case demonstrates the importance of pharmacist-patient consultations and how a PGx consult may expose polypharmacy medicationrelated problems of greater significance than the PGx indication for the consult. In addition, the case demonstrates positive interprofessional collaboration between pharmacists and physicians to more effectively solve complex medication-related problems that may not be easily diagnosed through objective lab or diagnostic testing.

Tacrolimus-Induced Bradykinesia Secondary to Phenoconversion in an Elderly Post-Bilateral Lung Transplant Patient.

OBJECTIVE: To report pharmacogenomics post-related bradykinesia secondary to phenoconversion in an elderly post-bilateral lung transplant patient.SUMMARY: The patient was a 68-year-old double lung transplant patient taking the immunosuppressant and CYP3A4/5 substrate tacrolimus concomitantly with 2 CYP3A4/5 inhibitor medications, fluconazole and diltiazem. This drug combination post-dosing resulted in debilitating bradykinesia 1-2 hours after dosing, increasing the risk of falls and possible increased mortality and morbidity risk.CONCLUSION: Taking tacrolimus in combination with CYP3A4/5 inhibitors may increase neurologic adverse effects resulting in increased fall and associated increased mortality and morbidity risk.

Use of Pharmacogenomics to Guide Proton Pump Inhibitor Therapy in Clinical Practice.

Prescribing the right medication, at the right dose, to the right patient is the goal of every physician. Pharmacogenomic information is an emerging tool that can be used to deliver precision medicine. In this review, we discuss the pharmacogenomics of available PPIs, racial differences of CYP2C19 and how PPI pharmacogenomics affects the treatment of common gastrointestinal diseases. We also provide practical guidance on when to order pharmacogenomic testing, which test to order, and how to modify treatment based on published guidelines.

Tacrolimus Therapeutic Drug Monitoring in Kidney Transplant Patients Before and After Pharmacist Post-transplant Consults.

Objectives: This quality improvement project sought to determine if clinical pharmacist office visits, or consults, had an impact on therapeutic tacrolimus levels in patients after kidney transplant through analysis of tacrolimus serum concentrations before versus after a pharmacist visit. Methods: A retrospective chart review was conducted for all patients that attended a clinical pharmacist office visit, also known as a consult, after kidney transplantation for a four month period. Pharmacists during the post-transplant consult reviewed adherence but also educated patients in detail about timing and logging of tacrolimus dosing, dosing with regard to labs to assure trough dosing, dosing with or without food in the stomach, what to do with a dose is taken late or if a dose is missed and foods, herbal supplements to avoid that may inhibit CYP3A4 to elevate tacrolimus levels. Results: After the post-transplant visit with a clinical pharmacist there was a 46% increase in the number of tacrolimus trough levels in therapeutic range versus before the pharmacist visit. Sixty-four percent of kidney transplant patients experienced an increase in the number of therapeutic drug levels in range after the pharmacist visit versus before the pharmacist visit. Conclusions: An increase in the quantity of therapeutic tacrolimus trough levels and the number of patients with therapeutic drug levels in range was observed after patients received pharmacist provided medication education post-transplant with emphasis on proper immunosuppressant medication administration, adherence and potential drug and food interactions. This finding demonstrates the importance of pharmacist clinical services in producing improved therapeutic drug levels in post-transplant kidney patients.

Conversion Disorder in a Pharmacogenomics, Polypharmacy Patient: Case Report.

Background: Conversion disorder (CD) is a relatively common psychiatric disorder likely encountered by clinical pharmacists but probably not easily identified by pharmacists. Case Summary: This is a patient case where a patient with a tremor was referred to the pharmacist led, polypharmacy, pharmacogenomics (PGx) service to rule out a PGx cause due to medication metabolism. No pharmacologic or PGx cause was found for the tremor which helped support and confirm a diagnosis of CD. Practice Implications: By working collaboratively with psychiatrists, neurologists, physical medicine colleagues, clinical pharmacists may add value to patient care by assisting with diagnoses and appropriate treatment.

Pharmacogenomics Testing Confirmation of Carbamazepine Induced DRESS Reaction of an HLA-A*31:01 Positive, Polypharmacy Patient.

Pharmacogenomics (PGx) melds well with polypharmacy as another tool to identify medication related problems (MRPs) more specifically so they may be solved most effectively. PGx can pre-emptively assist in medication selection, medication dosing or identify better medications for patients already taking a medication. PGx can also confirm suspect medications of causing MRPs such as adverse drug reactions (ADRs) or drug interactions. In this case, PGx testing confirmed presence of a serious human leukocyte antigen (HLA) drug reaction with eosinophilia and systemic symptoms (DRESS) after a suspect medication had been stopped.

Multivariate time series dataset for space weather data analytics.

We introduce and make openly accessible a comprehensive, multivariate time series (MVTS) dataset extracted from solar photospheric vector magnetograms in Spaceweather HMI Active Region Patch (SHARP) series. Our dataset also includes a cross-checked NOAA solar flare catalog that immediately facilitates solar flare prediction efforts. We discuss methods used for data collection, cleaning and pre-processing of the solar active region and flare data, and we further describe a novel data integration and sampling methodology. Our dataset covers 4,098 MVTS data collections from active regions occurring between May 2010 and December 2018, includes 51 flare-predictive parameters, and integrates over 10,000 flare reports. Potential directions toward expansion of the time series, either "horizontally" - by adding more prediction-specific parameters, or "vertically" - by generalizing flare into integrated solar eruption prediction, are also explained. The immediate tasks enabled by the disseminated dataset include: optimization of solar flare prediction and detailed investigation for elusive flare predictors or precursors, with both operational (research-to-operations), and basic research (operations-to-research) benefits potentially following in the future.

Improving Pain Management with Pharmacogenomics: A General Introduction.

Tailoring an individual patient's pain treatment is paramount to decreasing patient suffering and diminishing morbidity. Performing pharmacogenomic (PGx) testing can help guide prescribing decisions for current and future medication therapy by assisting dosage adjustments to increase therapeutic efficacy, decrease adverse drug reactions and avoid potentially ineffective medications. Pharmacogenomics is the study of inherited genetic information that influences drug response. Therapeutic response to pain medications is influenced by several factors including age, sex, body weight, concomitant diseases, compliance, lifestyle, drug interactions and genes. Genes of interest associated with pain medications include cytochrome P450 (CYP) enzymes, OPRM1, COMT, ABCB1, UGT, COX, OPRK1, OPRD1. To properly use PGx results in clinical application requires the healthcare provider to distinguish the difference between types of PGx tests, interpret test results, be familiar with PGx databases to use for prescribing guidance, and evaluate the level of evidence for specific gene-drug associations. This article introduces these concepts to assist the healthcare provider with incorporating PGx into practice to improve pain management.