Impact of using dosing criteria to refine pharmacogenomic clinical decision support for tricyclic antidepressants.

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.

Optimal Timing of Organs-at-Risk-Sparing Adaptive Radiation Therapy for Head- and-Neck Cancer under Re-planning Resource Constraints.

Background And Purpose: Prior work on adaptive organ-at-risk (OAR)-sparing radiation therapy has typically reported outcomes based on fixed-number or fixed-interval re-planning, which represent one-size-fits-all approaches and do not account for the variable progression of individual patients' toxicities. The purpose of this study was to determine the personalized optimal timing for re-planning in adaptive OAR-sparing radiation therapy, considering limited re-planning resources, for patients with head and neck cancer (HNC).

Materials And Methods: A novel Markov decision process (MDP) model was developed to determine optimal timing of re-planning based on the patient's expected toxicity, characterized by normal tissue complication probability (NTCP), for four toxicities.

Evaluation of pharmacogenetic automated clinical decision support for clopidogrel.

Clopidogrel requires activation to have antiplatelet effects. Pharmacogenetic testing to identify patients with impaired function can be coupled with clinical decision support (CDS) alerts to guide antiplatelet prescribing. We evaluated the impact of alerts on clopidogrel prescribing.

Incidence of statin-associated muscle symptoms in patients taking statins with or variants.

Statins are commonly used medications. Variants in , , and are known predictors of muscle effects when taking statins. More exploratory genes include and , which can also be associated with disease conditions.

A multicentric randomized controlled phase III trial of adaptive and 18F-FDG-PET-guided dose-redistribution in locally advanced head and neck squamous cell carcinoma (ARTFORCE).

Background And Purpose: This multicenter randomized phase III trial evaluated whether locoregional control of patients with LAHNSCC could be improved by fluorodeoxyglucose-positron emission tomography (FDG-PET)-guided dose-escalation while minimizing the risk of increasing toxicity using a dose-redistribution and scheduled adaptation strategy.

Materials And Methods: Patients with T3-4-N0-3-M0 LAHNSCC were randomly assigned (1:1) to either receive a dose distribution ranging from 64-84 Gy/35 fractions with adaptation at the 10thfraction (rRT) or conventional 70 Gy/35 fractions (cRT). Both arms received concurrent three-cycle 100 mg/mcisplatin.

Implementation of CYP2C19 and CYP2D6 genotyping to guide antidepressant use in a large rural health system.

Purpose: We describe the implementation and ongoing maintenance of CYP2C19 and CYP2D6 focused pharmacogenetic (PGx) testing to guide antidepressant and antianxiety medication prescriptions in a large rural, nonprofit health system.

Summary: Depression and anxiety are common psychiatric conditions. Sanford Health implemented PGx testing for metabolism of cytochrome P450 (CYP) isozymes 2C19 and 2D6 in 2014 to inform prescribing for multiple medications, including antidepressant and antianxiety therapies.

Professional development through mentoring: Final evaluation of the pilot mentoring programme of the European society of radiotherapy and oncology.

The European SocieTy for Radiotherapy and Oncology (ESTRO) organized a one-year pilot mentoring programme. At evaluation after one year, both mentors and mentees scored the programme with a median score of 9 on a scale of 10. All of the mentors indicated that they wanted to participate again as mentors.

Clinical impact of preemptive pharmacogenomic testing on antiplatelet therapy in a real-world setting.

CYP2C19 genotyping to guide antiplatelet therapy after patients develop acute coronary syndromes (ACS) or require percutaneous coronary interventions (PCIs) reduces the likelihood of major adverse cardiovascular events (MACE). Evidence about the impact of preemptive testing, where genotyping occurs while patients are healthy, is lacking. In patients initiating antiplatelet therapy for ACS or PCI, we compared medical records data from 67 patients who received CYP2C19 genotyping preemptively (results >7 days before need), against medical records data from 67 propensity score-matched patients who received early genotyping (results within 7 days of need).

Evolution of pharmacogenomic services and implementation of a multi-state pharmacogenomics clinic across a large rural healthcare system.

Pharmacogenomics (PGx) aims to maximize drug benefits while minimizing risk of toxicity. Although PGx has proven beneficial in many settings, clinical uptake lags. Lack of clinician confidence and limited availability of PGx testing can deter patients from completing PGx testing.

Attitudes about pharmacogenomic testing vary by healthcare specialty.

To understand how attitudes toward pharmacogenomic (PGx) testing among healthcare providers varies by specialty. Providers reported comfort ordering PGx testing and its perceived utility on web-based surveys before and after genetics education. Primary quantitative analyses compared primary care providers (PCPs) to specialty providers at both timepoints.

gene-based clinical decision support reduces statin-associated muscle symptoms risk with simvastatin.

variants are known to be a strong predictor of statin-associated muscle symptoms (SAMS) risk with simvastatin. The authors conducted a retrospective chart review on 20,341 patients who had genotyping to quantify the uptake of clinical decision support (CDS) for genetic variants known to impact SAMS risk. A total of 182 patients had 417 CDS alerts generated, and 150 of these patients (82.

Behavioral mechanisms of oxycodone's effects in female and male rats: Reinforcement delay and impulsive choice.

μ-Opioid agonists (e.g., morphine) typically increase which has been interpreted as an opioid-induced increase in sensitivity to reinforcement delay.

Can Artificial Intelligence Enhance Syncope Management?: A Multidisciplinary Collaborative Statement.

Syncope, a form of transient loss of consciousness, remains a complex medical condition for which adverse cardiovascular outcomes, including death, are of major concern but rarely occur. Current risk stratification algorithms have not completely delineated which patients benefit from hospitalization and specific interventions. Patients are often admitted unnecessarily and at high cost.

Patient satisfaction with return of pharmacogenomic results utilizing a patient portal message.

Returning pharmacogenomics (PGx) results to patients is complex and challenging. Patients prefer provider education; however, a gap in provider comfort in PGx results has been documented. This study's purpose was to evaluate satisfaction with the return of PGx test results using a patient portal message.

Metoprolol and : A Retrospective Cohort Study Evaluating Genotype-Based Outcomes.

Metoprolol is a medication commonly utilized in select patients to achieve a reduction in heart rate, systolic blood pressure, or other indications. A majority of metoprolol metabolism occurs via . Decreased expression of the CYP2D6 enzyme increases the concentration of metoprolol.

The effect of medication reconciliation on generating an accurate medication list in a pharmacogenomics practice.

Background: Medication reconciliation is recognized as a critically important medication safety element and a key initiative by multiple organizations. Within our precision medicine program, accurate medication lists are essential to our ability to make specific medication recommendations based on pharmacogenetic results. Our study aimed to identify discrepancies within the patient's medication list to improve medication management via genetic factors through a pharmacy team-based approach.

Escalating schedules of incentives increase physical activity with no differences between deposit and no-deposit groups: A systematic replication.

Physical inactivity has increasingly affected public health in the United States during the COVID-19 pandemic as it is associated with chronic diseases such as arthritis, cancer, and heart disease. Contingency management has been shown to increase physical activity. Therefore, the present study sought to evaluate the effects of an escalating schedule of monetary reinforcement with a reset contingency on physical activity, as compared between 2 counterbalanced groups in which a monetary deposit of $25 was either required (deposit group) or not (no-deposit group).

Leveraging clinical decision support to reduce the risk of discordant pharmacogenomics results.

Pharmacogenomics (PGx) testing is commonly utilized to predict a patient's response to medications based on the presence of genetic variants. However, certain conditions have been associated with potentially inaccurate PGx results. The majority of medications are predominantly metabolized in the liver; therefore, in the case of liver transplantation, PGx results may be misinterpreted in the context of drug-metabolizing enzymes.

Progression of precision statin prescribing for reduction of statin-associated muscle symptoms.

Statins are among the most commonly prescribed medications, and improve patient outcomes by lowering cholesterol levels, but also have side effects. Variations in statin response can be attributed to a handful of factors that include pharmacogenetics. While not a true review article, this work was written using various search engines and terms and previous and newly published Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for statins to provide a historical perspective in addition to the current status of statin-related pharmacogenetics and future perspectives.

Spontaneous epiglottic hematoma secondary to direct oral anticoagulant.

Spontaneous hemorrhage is a known risk for patients on anticoagulation therapy. Most previous spontaneous airway hemorrhage cases reported involve warfarin, and of the few that involved a direct oral anticoagulant, none involved the epiglottis. The following case describes a spontaneous epiglottic hematoma in a patient one week after starting a direct oral anticoagulant.

A method for studying reinforcement factors controlling impulsive choice for use in behavioral neuroscience.

Although procedures originating within the experimental analysis of behavior commonly are used in behavioral neuroscience to produce behavioral endpoints, they are used less often to analyze the behavioral processes involved, particularly at the level of individual organisms (see Soto, 2020). Concurrent-chains procedures have been used extensively to study choice and to quantify relations between various dimensions of reinforcement and preference. Unfortunately, parametric analysis of those relations using traditional steady-state, single-subject experimental designs can be time-consuming, often rendering these procedures impractical for use in behavioral neuroscience.

MR-Guided Adaptive Radiotherapy for OAR Sparing in Head and Neck Cancers.

MR-linac devices offer the potential for advancements in radiotherapy (RT) treatment of head and neck cancer (HNC) by using daily MR imaging performed at the time and setup of treatment delivery. This article aims to present a review of current adaptive RT (ART) methods on MR-Linac devices directed towards the sparing of organs at risk (OAR) and a view of future adaptive techniques seeking to improve the therapeutic ratio. This ratio expresses the relationship between the probability of tumor control and the probability of normal tissue damage and is thus an important conceptual metric of success in the sparing of OARs.

SARS-CoV-2 Seroprevalence and Drug Use in Trauma Patients from Six Sites in the United States.

In comparison to the general patient population, trauma patients show higher level detections of bloodborne infectious diseases, such as Hepatitis and Human Immunodeficiency Virus. In comparison to bloodborne pathogens, the prevalence of respiratory infections such as SARS-CoV-2 and how that relates with other variables, such as drug usage and trauma type, is currently unknown in trauma populations. Here, we evaluated SARS-CoV-2 seropositivity and antibody isotype profile in 2,542 trauma patients from six Level-1 trauma centers between April and October of 2020 during the first wave of the COVID-19 pandemic.

Precision Population Medicine in Primary Care: The Sanford Chip Experience.

Genetic testing has the potential to revolutionize primary care, but few health systems have developed the infrastructure to support precision population medicine applications or attempted to evaluate its impact on patient and provider outcomes. In 2018, Sanford Health, the nation's largest rural nonprofit health care system, began offering genetic testing to its primary care patients. To date, more than 11,000 patients have participated in the Sanford Chip Program, over 90% of whom have been identified with at least one informative pharmacogenomic variant, and about 1.

The role of alexithymia and empathy on radiation therapists' professional quality of life.

Background And Purpose: Physical and mental well-being are crucial for oncology professionals as they affect performance at work. Personality traits, as alexithymia and empathy, may influence professional quality of life. Alexithymia involves diminished skills in emotion processing and awareness.