Publications by authors named "James C Coons"

49 Publications

A pilot study of oral treprostinil pharmacogenomics and treatment persistence in patients with pulmonary arterial hypertension.

Ther Adv Respir Dis 2021 Jan-Dec;15:17534666211013688

Pharmacogenomics Center of Excellence, Institute for Personalized Medicine, Department of Pharmacy and Therapeutics, Center for Clinical Pharmaceutical Sciences and the Clinical and Translational Science Institute, University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA.

Background And Aims: Treprostinil is a prostacyclin analog used to treat pulmonary arterial hypertension. Dosing is empiric and based on tolerability. Adverse effects are common and can affect treatment persistence. Pharmacogenomic variants that may affect treprostinil metabolism and transport have not been well-characterized. We aimed to investigate the pharmacogenomic sources of variability in treatment persistence and dosing.

Methods: Patients were prospectively recruited from an IRB approved biobank registry at a single pulmonary hypertension center. A cohort of patients who received oral treprostinil were screened for participation. Pharmacogenomic analysis was for variants in , , and . A retrospective review was conducted for demographics, clinical status, dosing, and response. Fisher's exact test was used for categorical data and Kruskal-Wallis test or Wilcoxon rank sum were used for continuous data.

Results: A total of 15 patients received oral treprostinil and were consented. Their median age was 53 years, 73% were female, and 93% were White. The median total daily dose was 22.5 mg (13.5, 41) at last clinical observation. 40% of patients discontinued treatment with a majority due to adverse effects. Approximately 27% of patients had a loss-of-function variant in (*1/*3 or *1/*4), whereas 47% of patients had a loss-of-function variant in (*1/*2, *1/*3, or *2/*2). Minor allele frequencies for (rs1751034 and rs3742106) were 0.17 and 0.43, respectively. Survival analysis showed that increased CYP2C9 activity score was associated with decreased risk for treatment discontinuation [hazard ratio (HR): 0.13; 95% confidence interval (CI): 0.02, 0.91;  = 0.04]. Genetic variants were not significantly associated with dosing.

Conclusion: Genetic variants responsible for the metabolism and transport of oral treprostinil were common. Increased CYP2C9 activity score was associated with decreased risk for treatment discontinuation. However, dosing was not associated with genetic variants in metabolizing enzymes for treprostinil. Our findings suggest significant variability in treatment persistence to oral treprostinil, with pharmacogenomics being a potentially important contributor.
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http://dx.doi.org/10.1177/17534666211013688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111525PMC
April 2021

Direct Oral Anticoagulant Use in Special Populations: Elderly, Obesity, and Renal Failure.

Curr Cardiol Rep 2021 03 2;23(4):27. Epub 2021 Mar 2.

Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA.

Purpose Of Review: The purpose of this review is to examine the safety and effectiveness of direct oral anticoagulants and provide recommendations for the treatment of venous thromboembolism and atrial fibrillation in obese patients, elderly patients, and patients with chronic kidney disease.

Recent Findings: Multiple retrospective cohort studies have shown no difference in bleeding, stroke, or venous thromboembolism outcomes between DOACs and warfarin in patients who are obese, elderly, or those with chronic kidney disease or on dialysis. Some studies have shown that DOACs have a lower bleeding risk than warfarin in these populations. DOACs may be a safe and effective alternative to warfarin for the prevention of stroke in atrial fibrillation patients who are obese, elderly, or those with chronic kidney disease or on dialysis. Apixaban may improve clinical outcomes by lowering the risk of bleeding versus warfarin. DOACs may also be an effective and safe alternative to warfarin for the treatment of venous thromboembolism in obese patients; however, additional studies are needed to assess their use in elderly patients and those with CKD.
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http://dx.doi.org/10.1007/s11886-021-01456-9DOI Listing
March 2021

Pharmacologic Prevention of Myocardial Ischemia-Reperfusion Injury in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

J Cardiovasc Pharmacol 2021 04;77(4):430-449

Department of Clinical Pharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Abstract: Establishing efficient perfusion into the myocardium is the main purpose in patients with acute coronary syndrome, but the process of reperfusion is not without risk and can damage the myocardium paradoxically. Unfortunately, there is no effective treatment for reperfusion injury, and efforts to find an efficient preventive approach are still ongoing. In the past 3 decades, there have been many successful animal studies on how to prevent reperfusion injury; nonetheless, translation to the clinical setting has almost always proven disappointing. In this article, we review clinical studies on the prevention of reperfusion injury in patients with acute coronary syndrome undergoing primary percutaneous coronary intervention in a pharmacologic-based approach. We categorize all the agents that are evaluated for the prevention of myocardial reperfusion injury based on their mechanisms of action into 5 groups: drugs that can reduce oxidative stress, drugs that can affect cellular metabolism, rheological agents that target microvascular obstruction, anti-inflammatory agents, and agents with mixed mechanisms of action. Then, review all the clinical studies of these agents in the setting of primary percutaneous coronary intervention. Finally, we will discuss the possible reasons for the failure in translation of studies into practice and propose potential solutions to overcome this problem.
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http://dx.doi.org/10.1097/FJC.0000000000000980DOI Listing
April 2021

Use of Disproportionality Analysis to Identify Previously Unknown Drug-Associated Causes of Cardiac Arrhythmias Using the Food and Drug Administration Adverse Event Reporting System (FAERS) Database.

J Cardiovasc Pharmacol Ther 2021 07 6;26(4):341-348. Epub 2021 Jan 6.

Department of Pharmacy, 6595UPMC Presbyterian Hospital, Pittsburgh, PA, USA.

Introduction: Drug-induced QT-prolongation is a well-known adverse drug reaction (ADR), however there is limited knowledge of other drug-induced arrhythmias.

Purpose: The objective of this study is to determine the drugs reported to be associated with arrhythmias other than QT-prolongation using the FAERS database, possibly identifying potential drug causes that have not been reported previously.

Methods: FAERS reports from 2004 quarter 1 through 2019 quarter 1 were combined to create a dataset of approximately 11.6 million reports. Search terms for arrhythmias of interest were selected from the Standardized MedDRA Queries (SMQ) Version 12.0. Frequency of the cardiac arrhythmias were determined for atrial fibrillation, atrioventricular block, bradyarrhythmia, bundle branch block, supraventricular tachycardia, and ventricular fibrillation and linked to the reported causal medications. Reports were further categorized by prior evidence associations using package inserts and established drug databases. A reporting odds ratio (ROR) and confidence interval (CI) were calculated for the ADRs for each drug and each of the 6 cardiac arrhythmias.

Results: Of the 11.6 million reports in the FAERS database, 68,989 were specific to cardiac arrhythmias of interest. There were 61 identified medication-reported arrhythmia pairs for the 6 arrhythmia groups with 33 found to have an unknown reported association. Rosiglitazone was the most frequently medication reported across all arrhythmias [ROR 6.02 (CI: 5.82-6.22)]. Other medications with significant findings included: rofecoxib, digoxin, alendronate, lenalidomide, dronedarone, zoledronic acid, adalimumab, dabigatran, and interferon beta-1b.

Conclusion: Upon retrospective analysis of the FAERS database, the majority of drug-associated arrhythmias reported were unknown suggesting new potential drug causes. Cardiac arrhythmias other than QTc prolongation are a new area of focus for pharmacovigilance and medication safety. Consideration of future studies should be given to using the FAERS database as a timely pharmacovigilance tool to identify unknown adverse events of medications.
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http://dx.doi.org/10.1177/1074248420984082DOI Listing
July 2021

Impact of the CYP2C19*17 Allele on Outcomes in Patients Receiving Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention.

Clin Pharmacol Ther 2021 03 2;109(3):705-715. Epub 2020 Oct 2.

Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics and Precision Medicine, University of Florida, Gainesville, Florida, USA.

Genotyping for CYP2C19 no function alleles to guide antiplatelet therapy after percutaneous coronary intervention (PCI) improves clinical outcomes. Although results for the increased function CYP2C19*17 allele are also reported, its clinical relevance in this setting remains unclear. A collaboration across nine sites examined antiplatelet therapy prescribing and clinical outcomes in 3,342 patients after implementation of CYP2C19-guided antiplatelet therapy. Risk of major atherothrombotic and bleeding events over 12 months after PCI were compared across cytochrome P450 2C19 isozyme (CYP2C19) metabolizer phenotype and antiplatelet therapy groups by proportional hazards regression. Clopidogrel was prescribed to a similar proportion of CYP2C19 normal (84.5%), rapid (82.9%), and ultrarapid metabolizers (80.6%) (P = 0.360). Clopidogrel-treated normal metabolizers (20.4 events/100 patient-years; adjusted hazard ratio (HR) 1.00, 95% confidence interval (CI), 0.75-1.33, P = 0.993) and clopidogrel-treated rapid or ultrarapid metabolizers (19.1 events/100 patient-years; adjusted HR 0.95, 95% CI, 0.69-1.30, P = 0.734) exhibited no difference in major atherothrombotic events compared with patients treated with prasugrel or ticagrelor (17.6 events/100 patient-years). In contrast, clopidogrel-treated intermediate and poor metabolizers exhibited significantly higher atherothrombotic event risk compared with prasugrel/ticagrelor-treated patients (adjusted HR 1.56, 95% CI, 1.12-2.16, P = 0.008). When comparing clopidogrel-treated rapid or ultrarapid metabolizers to normal metabolizers, no difference in atherothrombotic (adjusted HR 0.97, 95% CI, 0.73-1.29, P = 0.808) or bleeding events (adjusted HR 1.34, 95% CI, 0.83-2.17, P = 0.224) were observed. In a real-world setting of genotype-guided antiplatelet therapy, the CYP2C19*17 allele did not significantly impact post-PCI prescribing decisions or clinical outcomes. These results suggest the CYP2C19 *1/*17 and *17/*17 genotypes have limited clinical utility to guide antiplatelet therapy after PCI.
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http://dx.doi.org/10.1002/cpt.2039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902344PMC
March 2021

A Systemwide Approach for Navigating the Dilemma of Oral Factor Xa Inhibitor Interference With Unfractionated Heparin Anti-Factor Xa Concentrations.

Ann Pharmacother 2021 05 4;55(5):618-623. Epub 2020 Sep 4.

UPMC Presbyterian-Shadyside, Pittsburgh, PA, USA.

Background: Oral factor Xa inhibitors are known to significantly increase heparin anti-Xa concentrations, which leads to inaccuracies when monitoring intravenous unfractionated heparin (IV UFH). Guidance for managing this laboratory interference is lacking, creating substantial uncertainty in clinical practice.

Objective: To describe a strategy used by a large academic institution for managing the controversy of laboratory interference in the setting of oral factor Xa inhibitor use and provide effectiveness and safety data for this approach.

Methods: In December 2016, a new Heparin IV Direct Oral Anticoagulant (DOAC) Interference PowerPlan (a comprehensive order set) was made available in the electronic health record (Cerner, North Kansas City, MO) throughout the health system. We retrospectively examined 169 patients with events reported in the error reporting system, RISKMASTER, and evaluated reports with and without the use of the PowerPlan. Effectiveness was determined through evaluation of thrombosis. The Naranjo criteria for causality were applied to assess thrombotic events.

Results: Of 56 events that were reported with apixaban when the PowerPlan was not ordered, 4 (7%) thrombotic events occurred within 7 days of UFH initiation. One out of the 4 events (25%) that occurred when the PowerPlan was not appropriately initiated was considered probable using the Naranjo Scale. Three additional events (75%) were possible using the Naranjo Scale.

Conclusion And Relevance: The Heparin IV DOAC Interference PowerPlan appears to be conducive to positive patient outcomes when evaluating voluntary reported events and may assist clinicians with managing the therapeutic dilemma of this laboratory interference.
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http://dx.doi.org/10.1177/1060028020956271DOI Listing
May 2021

Effectiveness and Safety of Direct Oral Anticoagulants versus Warfarin in Obese Patients with Acute Venous Thromboembolism.

Pharmacotherapy 2020 03 11;40(3):204-210. Epub 2020 Feb 11.

Department of Pharmacy and Therapeutics, Clinical Pharmacist, Lung Transplantation UPMC Presbyterian Hospital, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania.

Study Objective: Studies on the use of direct oral anticoagulants (DOACs) in obese patients are limited. Current guidelines advise against DOAC use in patients with a body weight more than 120 kg or body mass index higher than 40 kg/m . Therefore, the aim of this study was to evaluate the effectiveness and safety of DOACs versus warfarin for the treatment of acute venous thromboembolism (VTE) in obese patients.

Design: Retrospective matched cohort study.

Setting: Integrated delivery system of 40 academic, community, and specialty hospitals.

Patients: A total of 1840 adults with a primary admission diagnosis of acute VTE who received a DOAC (apixaban, dabigatran, or rivaroxaban [632 patients] or warfarin [1208 patients]) while hospitalized between January 1, 2011, and October 1, 2015, and who had a body weight more than 100 kg and less than 300 kg, were included. Patients in the warfarin group were matched in a 2:1 ratio to patients who received a DOAC based on history of VTE, chronic kidney disease, race, and age.

Measurements And Main Results: The primary outcome was recurrence of VTE within 12 months of the index admission date. Secondary outcomes included occurrence of pulmonary embolism (PE) and deep vein thrombosis (DVT) events separately within the study time frame, as well as bleeding within 12 months of the index admission date. No significant difference in the recurrence of VTE was observed between patients who received a DOAC compared with those who received warfarin (6.5% vs 6.4%, p=0.93). Likewise, no significant differences in the occurrence of PE and DVT were seen between the DOAC- and warfarin-treated patients (3.7% vs 3.8%, p=0.94, and 3% vs 3.5%, p=0.56, respectively). Bleeding occurred in 1.7% and 1.2% of patients in the DOAC and warfarin groups, respectively (p=0.31).

Conclusion: To our knowledge, this is the largest clinical study to date showing that patients with obesity can be treated effectively and safely with a DOAC compared with warfarin for acute VTE. Thus DOACs should be considered a reasonable alternative to warfarin for treatment of acute VTE in obese patients.
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http://dx.doi.org/10.1002/phar.2369DOI Listing
March 2020

A Pharmacotherapy Scholars Program to Provide Intensive Training to Enhance Pharmacy Students' Postgraduate Readiness.

Am J Pharm Educ 2019 11;83(9):7327

Florida Hospital Orlando, Orlando, Florida.

To design, integrate the curriculum for, and evaluate an innovative program to facilitate placement of students into postgraduate pharmacy residency training programs involving direct patient care. The Pharmacotherapy Scholars Program (PSP) was designed to prepare fourth-professional year students to become highly proficient in a direct patient care role and to successfully match with postgraduate residency training programs. The following elements were included in the year-long curriculum: integrated synchronous advanced pharmacy practice experiences with personal advising, team-based mentoring, peer-to-peer learning, longitudinal research, and professional development. Program goals were modeled after the accreditation standards for postgraduate year one (PGY1) pharmacy residency programs. Program faculty members ensured that the PSP had a broad scope, included rigorous student assessments, had a strong research focus, and provided scholarship opportunities. Sixty-eight students completed the program from fall 2013 through spring 2019. The overall residency match rate was 93%. Students' performance on both knowledge and clinical skills assessments significantly improved after completing the program. There was an approximately 15% increase in knowledge and a 30% improvement in clinical skills based on comprehensive readiness assessments and an intermittent clinical examination that used patient simulation, respectively. The Pharmacotherapy Scholars Program is an innovative training program designed to enhance PharmD students' preparation for advanced clinical training. Students who completed the PSP achieved a high PGY1 residency placement rate while demonstrating significant improvements in pharmacotherapy knowledge and clinical skills in direct patient care activities.
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http://dx.doi.org/10.5688/ajpe7327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920655PMC
November 2019

Survey of Anticoagulation Practices with the Impella Percutaneous Ventricular Assist Device at High-Volume Centers.

J Interv Cardiol 2019 4;2019:3791307. Epub 2019 Mar 4.

New York Presbyterian Columbia University Medical Center, USA.

Objectives: To characterize anticoagulation practices with the Impella percutaneous ventricular assist device (pVAD).

Background: Managing anticoagulation in patients being supported by the Impella pVAD is made challenging by several unique features of the device. These include the release of a dextrose-based purge solution containing unfractionated heparin (UFH), the need to concurrently administer systemic anticoagulation with intravenous UFH, and the lack of an alternative strategy in patients with contraindications to UFH.

Methods: To characterize anticoagulation practices with the Impella pVAD, we conducted a survey of centers in the United States performing a high volume of Impella cases, which we defined as > 1 per month. Centers were contacted via email or phone and individuals who agreed to participate were provided with a link to complete the survey online. The primary measures of interest were variations in practice across centers and variations from the manufacturer's recommendations.

Results: Practices varied considerably among respondents (65 of 182 centers, or 35.7%) and often diverged from manufacturer recommendations. Approximately half of centers (52.4%) reported using a UFH concentration of 50 units/mL in the purge solution, whereas most of the remaining centers (41.3%) reported using lower concentrations. Strategies for the initiation and adjustment of systemic therapy also varied, as did practices for routinely monitoring for hemolysis. Nearly one-fifth of centers (16.7%) had not developed an alternative strategy for the purge solution in patients with contraindications to UFH. Most centers (58.4%) reported using argatroban or bivalirudin in this scenario, a strategy that diverges from the manufacturer's recommendations.

Conclusions: Given these findings, studies to determine a systematic approach to anticoagulation with the Impella device are warranted.
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http://dx.doi.org/10.1155/2019/3791307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739784PMC
March 2020

Pulmonary Arterial Hypertension: a Pharmacotherapeutic Update.

Curr Cardiol Rep 2019 11 22;21(11):141. Epub 2019 Nov 22.

Division of Pulmonary, Critical Care & Sleep Medicine, Department of Medicine, National Jewish Health, Denver, CO, USA.

Purpose Of Review: Pulmonary arterial hypertension (PAH) leads to progressive increases in pulmonary vascular resistance (PVR), right heart failure, and death if left untreated. This review will summarize and discuss recent updates in the classification and management of patients with PAH.

Recent Findings: PAH requires careful hemodynamic assessment and is defined by a mean pulmonary artery pressure > 20 mmHg with normal left-sided filling pressures and a PVR ≥ 3 Wood units. Most patients with PAH require targeted pharmacotherapy based on multiparametric risk stratification. Significant improvements in clinical outcome have been realized through the approval of 14 unique pharmacotherapeutic options. The latest clinical recommendations provide the updated hemodynamic definition and clinical classification as well as evidence-based treatment recommendations. An important change is the focus on initial upfront combination therapy for most patients with PAH. Structured follow-up and escalation of treatment for those not achieving low-risk status is paramount.
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http://dx.doi.org/10.1007/s11886-019-1235-4DOI Listing
November 2019

Efficacy and Safety of the Use of Pulmonary Arterial Hypertension Pharmacotherapy in Patients with Pulmonary Hypertension Secondary to Left Heart Disease: A Systematic Review.

Pharmacotherapy 2019 09 4;39(9):929-945. Epub 2019 Sep 4.

Department of Pharmacy and Therapeutics, School of Pharmacy, University of Pittsburgh, Clinical Pharmacist, Cardiology, UPMC Presbyterian Hospital, Pittsburgh, Pennsylvania.

Pulmonary hypertension (PH) is often caused by left heart disease (LHD) such as heart failure (HF) or valvular heart disease. Historically, few randomized controlled trials have evaluated the off-label use of medications for treating pulmonary arterial hypertension (PAH) in patients with PH-LHD. However, multiple randomized controlled trials have been published over the last decade that investigated their use in patients with PH-LHD. In addition, recent updates in the classification and definitions of PH have led to an improved recognition of PH-LHD phenotypes, notably combined post-capillary and pre-capillary PH and isolated post-capillary PH. In this systematic review, we show that PAH medications should not be recommended in two distinct HF populations: patients with HF without definitive PH diagnosis and patients with isolated post-capillary PH due to HF. In addition, the use of bosentan or macitentan is not recommended in patients with combined post-capillary and pre-capillary PH due to HF, but sildenafil may be considered to improve pulmonary hemodynamics and exercise capacity in patients with combined post-capillary and pre-capillary PH due to HF. Riociguat 2 mg 3 times daily may also be considered to improve pulmonary hemodynamics in patients with combined post-capillary and pre-capillary PH due to heart failure with reduced ejection fraction but not heart failure with preserved ejection fraction. The postoperative use of sildenafil in the setting of PH after valvular heart disease intervention was evaluated. Limited clinical data and safety concern warrants caution with the postoperative use of sildenafil in patients with PH due to valvular heart disease. Despite recent advances in the understanding of PAH medications for patients with PH-LHD, uncertainty remains about their utility in distinct subgroups. Nonetheless, PAH pharmacotherapy should generally be avoided for most patients with PH-LHD.
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http://dx.doi.org/10.1002/phar.2314DOI Listing
September 2019

Clinical outcomes with unfractionated heparin monitored by anti-factor Xa vs. activated partial Thromboplastin time.

Am J Hematol 2019 09 16;94(9):1015-1019. Epub 2019 Jul 16.

Department of Pharmacy and Therapeutics, UPMC Presbyterian-Shadyside Hospital, Pittsburgh, Pennsylvania.

Anti-factor Xa (anti-Xa) monitoring of unfractionated heparin (UFH) is associated with less time to achieve therapeutic anticoagulation compared to the activated partial thromboplastin time (aPTT). However, it is unknown whether clinical outcomes differ between these methods of monitoring. The aim of this research was to compare the rate of venous thrombosis and bleeding events in patients that received UFH monitored by anti-Xa compared to the aPTT. A retrospective review of electronic health records identified adult patients that received UFH given intravenously (IV) for ≥2 days, with either anti-Xa or aPTT monitoring at an academic tertiary care hospital. This was a pre/post study design conducted between January 1 to December 30, 2014 (aPTT), and January 1 to December 30, 2016 (anti-Xa). All UFH adjustments were based on institutional nomograms. The primary outcome was venous thrombosis and the secondary outcome was bleeding, both of which occurred between UFH administration and discharge from the index hospitalization. A total of 2500 patients were in the anti-Xa group and 2847 patients aPTT group. Venous thrombosis occurred in 10.2% vs 10.8% of patients in the anti-Xa and aPTT groups, respectively (P = .49). Bleeding occurred in 33.7% vs 33.6% of patients in the anti-Xa and aPTT groups, respectively (P = .94). Anti-Xa monitoring was not an independent predictor of either outcome in multivariate logistic regression analyses. Our study found no difference in clinical outcomes between anti-Xa and aPTT-based monitoring of UFH IV.
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http://dx.doi.org/10.1002/ajh.25565DOI Listing
September 2019

Engaging and Empowering Stakeholders to Advance Pharmacogenomics.

Clin Pharmacol Ther 2019 08 26;106(2):305-308. Epub 2019 Jun 26.

Department of Pharmacy and Therapeutics, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

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http://dx.doi.org/10.1002/cpt.1470DOI Listing
August 2019

Precision Pharmacotherapy: Integrating Pharmacogenomics into Clinical Pharmacy Practice.

J Am Coll Clin Pharm 2019 Jun 10;2(3):303-313. Epub 2019 Jun 10.

American College of Clinical Pharmacy.

Precision pharmacotherapy encompasses the use of therapeutic drug monitoring; evaluation of liver and renal function, genomics, and environmental and lifestyle exposures; and analysis of other unique patient or disease characteristics to guide drug selection and dosing. This paper articulates real-world clinical applications of precision pharmacotherapy, focusing exclusively on the emerging field of clinical pharmacogenomics. This field is evolving rapidly, and clinical pharmacists now play an invaluable role in the clinical implementation, education, and research applications of pharmacogenomics. This paper provides an overview of the evolution of pharmacogenomics in clinical pharmacy practice, together with recommendations on how the American College of Clinical Pharmacy (ACCP) can support the advancement of clinical pharmacogenomics implementation, education, and research. Commonalities among successful clinical pharmacogenomics implementation and education programs are identified, with recommendations for how ACCP can leverage and advance these common themes. Opportunities are also provided to support the research needed to move the practice and application of pharmacogenomics forward.
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http://dx.doi.org/10.1002/jac5.1118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516785PMC
June 2019

Effect of Selective Serotonin Reuptake Inhibitors on Cardiovascular Outcomes After Percutaneous Coronary Intervention: A Retrospective Cohort Study.

Clin Drug Investig 2019 Jun;39(6):543-551

Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, 335 Sutherland Drive, Room 209 Salk Pavilion, Pittsburgh, PA, 15261, USA.

Background: Depression and coronary artery disease (CAD) are leading causes of death and disability and commonly co-occur. Different antidepressant classes have similar efficacy for depressed patients with CAD, but cardiovascular implications are unclear. Selective serotonin reuptake inhibitors (SSRIs) and mirtazapine are first-line options for depressed patients with CAD. SSRIs, but not mirtazapine, have known antiplatelet effects. Whether this affects risk of bleeding and major adverse cardiac events (MACE) in patients requiring dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) is unknown.

Objective: The aim of this analysis is to examine the impact of SSRI treatment on the co-primary endpoints of composite MACE (death, myocardial infarction, or stroke) and composite bleeding events in patients treated with clopidogrel-based DAPT after PCI.

Methods: We conducted a retrospective study with co-primary endpoints of bleeding and MACE within 1 year of PCI. Three groups were compared: SSRI patients, mirtazapine patients, and patients on neither agent. Mirtazapine acted as a comparator to control for depression, for which diagnosis coding was inadequate. Time-to-event analyses were performed with Kaplan-Meier estimators and adjusted analyses utilized Cox proportional hazards. There were 6874 (820 SSRI, 55 mirtazapine, 5999 neither) patients included.

Results: SSRI patients had lower MACE risk than mirtazapine patients (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.38-0.97, p = 0.036) but higher MACE risk than patients on neither agent (HR 1.21, 95% CI 1.02-1.43, p = 0.030) in adjusted analyses. No significant differences were associated with bleeding risk (SSRI vs. neither adjusted HR 1.07, 95% CI 0.93-1.24, p = 0.36).

Conclusion: SSRI use was associated with a significant decrease in MACE rates compared with patients receiving mirtazapine. Bleeding risk was not affected by either antidepressant treatment. SSRIs may have cardioprotective benefits compared with mirtazapine.
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http://dx.doi.org/10.1007/s40261-019-00776-7DOI Listing
June 2019

Design and testing of Medivate, a mobile app to achieve medication list portability via Fast Healthcare Interoperability Resources.

J Am Pharm Assoc (2003) 2019 Mar - Apr;59(2S):S78-S85.e2. Epub 2019 Feb 5.

Objectives: To describe the architecture, design, and testing of an innovative mobile application (Medivate) that facilities accurate sharing of medication lists with linked education.

Setting: The deployment and testing of this app occurred in both the community and hospital settings in Pittsburgh, PA.

Practice Innovation: Medivate is an iOS smartphone application and cloud architecture for patients and providers to keep medication and vaccine lists accurate by providing a method and tool to easily exchange these data. Medications are added directly to the app from the electronic health record (EHR) or by the patient manually. Quick response (QR) code technology is used to trigger the secure transfer and sharing of medications on demand via HL-7 Fast Healthcare Interoperability Resources-based data transfer. An iterative user-centered design process involving patients and student pharmacists practicing in community settings was used to develop and refine functionality.

Practice Description: Adults with an iPhone were approached for participation in the design and evaluation of Medivate. Its functionality and integration into clinical workflow at hospital discharge or vaccine administration in the community were determined.

Evaluation: In the community setting, interviews of pharmacists were conducted. In the hospital, metrics of study participation and experience with app deployment were determined.

Results: The app was deployed in the community for patients that received vaccinations. Interviews provided insight into barriers and logistics for successful engagement. The app was integrated into hospital workflow and demonstrated interoperability with the inpatient EHR. Thirteen patients were provided the app before discharge. Engagement with the app was evident through medication list shares, education access, and changes to medication lists. Patients noted strong agreement with usefulness of the app to learn more about the purposes and adverse effects of medications prescribed.

Conclusion: A mobile app to achieve medication and vaccine list portability was successfully designed and integrated into the inpatient and community settings.
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http://dx.doi.org/10.1016/j.japh.2019.01.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411446PMC
June 2020

Development of best practice recommendations for the safe use of pulmonary hypertension pharmacotherapies using a modified Delphi method.

Am J Health Syst Pharm 2019 Jan;76(3):153-165

Department of Pharmacy, Henry Ford Hospital, Detroit, Michigan.

Purpose: The Delphi method was used to develop best practice recommendations (BPR) for safe use of pulmonary hypertension (PH) pharmacotherapies and to describe the pharmacist's role in provision of care.

Methods: A core group reviewed PH medication-safety literature and developed initial BPR. Pharmacists practicing at PH-accredited Centers of Comprehensive Care who met defined PH expert criteria were invited to participate on an expert panel. In round 1 of a 4-round Delphi process, expert input was provided on the BPR. Feedback was incorporated into BPR for the next round. Round 2 proceeded in identical fashion to round 1. In round 3, BPR were deliberated in a teleconference and underwent voting at the cessation of the round using a 5-point Likert scale. Median scores of < 2.5, 2.5-3.75, and > 3.75 resulted in a best practice statement being rejected, reviewed in round 4, or accepted in the final BPR, respectively. In round 4, the remaining BPR were discussed and underwent voting. BPR were assigned a level of evidence and strength of recommendation based on voting results.

Results: Eleven PH experts agreed to participate and met expert inclusion criteria, along with 2 pharmacists from the core group, bringing the total number of expert panel members to 13. To guide safe use of PH pharmacotherapies, 26 BPR were developed, categorized into 5 practice domains, comprising the PH Care Center accreditation process, inpatient practice, formulary management, diagnostics, and ambulatory care. BPR included provisions for safe use of parenteral prostacyclin agents and healthcare practitioner education.

Conclusion: The Delphi method was used to develop BPR to guide safe use of PH pharmacotherapies.
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http://dx.doi.org/10.1093/ajhp/zxy020DOI Listing
January 2019

Virtual Electronic Health Record Technology with Simulation-Based Learning in an Acute Care Pharmacotherapy Course.

Pharmacy (Basel) 2018 Nov 28;6(4). Epub 2018 Nov 28.

Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, Pittsburgh, PA 15261, USA.

Electronic health record (EHR) technology use in the educational setting to advance pharmacy practice skills with patient simulation has not been described previously in the literature. Therefore, the purpose of this study was to evaluate the impact of a virtual EHR on learning efficiency, perceptions of clinical skills, communication, and satisfaction. This was a prospective study conducted in a cardiovascular therapeutics course in the Doctor of Pharmacy curriculum. Students were randomized to use of a virtual EHR with patient simulation or to patient simulation alone (control). The efficiency of learning was assessed by the time to optimal recommendation for each scenario. Surveys ( = 12 questions) were administered electronically to evaluate perceptions of clinical skills, communication, and learning satisfaction. Data were analyzed with the Mann⁻Whitney U or Wilcoxon signed-rank test as appropriate. Use of the virtual EHR decreased the amount of time needed to provide the optimal treatment recommendations by 25% compared to control. The virtual EHR also significantly improved students' perceptions of their clinical skills, communication, and satisfaction compared to control. The virtual EHR demonstrated value in learning efficiency while providing students with an engaging means of practicing essential pharmacist functions in a simulated setting.
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http://dx.doi.org/10.3390/pharmacy6040123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6306838PMC
November 2018

Extended-release oral treprostinil in the management of pulmonary arterial hypertension: clinical evidence and experience.

Ther Adv Respir Dis 2018 Jan-Dec;12:1753466618766490

Clinical Pharmacist, Cardiology, UPMC Presbyterian University Hospital, Pittsburgh, PA, USA.

Treprostinil diolamine is the first oral prostacyclin approved for the treatment of pulmonary arterial hypertension (PAH) to improve exercise capacity. Clinical studies have demonstrated modest benefit as monotherapy, whereas no difference in exercise capacity was observed with combination therapy. However, these trials were limited by subtherapeutic dosing owing to intolerable adverse effects. Prostacyclin-related adverse effects, such as nausea, diarrhea, headache, flushing, and jaw pain, are prevalent. More recent pharmacokinetic and clinical studies illustrate the dose-response relationship and the importance of achieving clinically effective doses. Therefore, efforts to improve tolerability are paramount. Oral treprostinil is recommended to be administered three times daily in order to facilitate more rapid titration, higher doses achieved, and improved tolerability. Oral treprostinil has also been studied in carefully selected, stable patients that transitioned from parenteral or inhaled therapy with close monitoring for late deterioration. Ongoing clinical trials will determine the long-term effects of higher doses of oral treprostinil on clinical outcomes. This review describes the clinical evidence and practical experience with the use of oral treprostinil for PAH.
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http://dx.doi.org/10.1177/1753466618766490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5941659PMC
January 2019

Multisite Investigation of Strategies for the Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy.

Clin Pharmacol Ther 2018 10 30;104(4):664-674. Epub 2018 Jan 30.

Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

CYP2C19 genotype-guided antiplatelet therapy following percutaneous coronary intervention is increasingly implemented in clinical practice. However, challenges such as selecting a testing platform, communicating test results, building clinical decision support processes, providing patient and provider education, and integrating methods to support the translation of emerging evidence to clinical practice are barriers to broad adoption. In this report, we compare and contrast implementation strategies of 12 early adopters, describing solutions to common problems and initial performance metrics for each program. Key differences between programs included the test result turnaround time and timing of therapy changes, which are both related to the CYP2C19 testing model and platform used. Sites reported the need for new informatics infrastructure, expert clinicians such as pharmacists to interpret results, physician champions, and ongoing education. Consensus lessons learned are presented to provide a path forward for those seeking to implement similar clinical pharmacogenomics programs within their institutions.
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http://dx.doi.org/10.1002/cpt.1006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019555PMC
October 2018

Performance of Anti-Factor Xa Versus Activated Partial Thromboplastin Time for Heparin Monitoring Using Multiple Nomograms.

Clin Appl Thromb Hemost 2018 Mar 6;24(2):310-316. Epub 2017 Dec 6.

1 Presbyterian-Shadyside Hospital, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, USA.

The purpose of this study was to compare the performance of anti-factor Xa concentration versus activated partial thromboplastin time (aPTT) monitoring with multiple indication-specific heparin nomograms. This was a prospective, nonrandomized study with historical control at a large academic medical center. A total of 201 patients who received intravenous heparin in the cardiology units were included. The prospective cohort included patients (n = 101) with anti-factor Xa (anti-Xa) monitoring, and the historical control group included patients (n = 100) who had aPTT monitoring. Patients in the prospective group had both anti-Xa and aPTT samples drawn, but anti-Xa was used for dosing adjustment. The anti-Xa cohort achieved a significantly faster time to therapeutic range ( P < .01) and required fewer dose adjustments per 24-hour period compared to the aPTT control ( P = .01). Results were consistent across heparin nomograms. The overall discordance rate between the 2 tests was 49%. No significant differences in clinical outcomes were observed. In summary, anti-Xa monitoring improved the time to therapeutic anticoagulation and led to fewer dose adjustments compared to the aPTT with multiple indication-based heparin nomograms.
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http://dx.doi.org/10.1177/1076029617741363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714688PMC
March 2018

Impact of four times daily dosing of oral treprostinil on tolerability and daily dose achieved in pulmonary hypertension.

Pulm Circ 2018 Jan-Mar;8(1):2045893217744512

9 Department of Medicine/Division of Cardiology, Vascular Medicine Institute, University of Pittsburgh, Heart and Vascular Institute, Pittsburgh, PA, USA.

Oral treprostinil (TRE) is a prostacylin that is approved for the treatment of patients with pulmonary arterial hypertension (PAH). Dosing is approved for two or three times daily (t.i.d.); however, adverse effects, including gastrointestinal-related symptoms, may limit the ability to reach optimal doses. We report our experience with a four times daily (q.i.d.) regimen of oral TRE for goal-directed therapy of PAH. We describe three patients that were transitioned from infusion or inhaled TRE to oral TRE with initial t.i.d. dosing over a four-day hospital stay. All patients were subsequently further dose-adjusted in the outpatient setting; however, adverse effects limited additional up-titration despite persistent dyspnea. In a carefully monitored outpatient setting, patients were switched from t.i.d. to q.i.d. dosing of oral TRE. All three patients were successfully dosed q.i.d., having achieved a higher total daily dose compared with a t.i.d. dose regimen. Furthermore, patients were able to maintain functional class II symptoms with mitigation of adverse effects using the q.i.d. dose regimen.
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http://dx.doi.org/10.1177/2045893217744512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731722PMC
December 2017

Multisite Investigation of Outcomes With Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention.

JACC Cardiovasc Interv 2018 01 1;11(2):181-191. Epub 2017 Nov 1.

Department of Medicine, University of Maryland, Baltimore, Maryland.

Objectives: This multicenter pragmatic investigation assessed outcomes following clinical implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention (PCI).

Background: CYP2C19 loss-of-function alleles impair clopidogrel effectiveness after PCI.

Methods: After clinical genotyping, each institution recommended alternative antiplatelet therapy (prasugrel, ticagrelor) in PCI patients with a loss-of-function allele. Major adverse cardiovascular events (defined as myocardial infarction, stroke, or death) within 12 months of PCI were compared between patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy. Risk was also compared between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy. Cox regression was performed, adjusting for group differences with inverse probability of treatment weights.

Results: Among 1,815 patients, 572 (31.5%) had a loss-of-function allele. The risk for major adverse cardiovascular events was significantly higher in patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy (23.4 vs. 8.7 per 100 patient-years; adjusted hazard ratio: 2.26; 95% confidence interval: 1.18 to 4.32; p = 0.013). Similar results were observed among 1,210 patients with acute coronary syndromes at the time of PCI (adjusted hazard ratio: 2.87; 95% confidence interval: 1.35 to 6.09; p = 0.013). There was no difference in major adverse cardiovascular events between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy (adjusted hazard ratio: 1.14; 95% confidence interval: 0.69 to 1.88; p = 0.60).

Conclusions: These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value.
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http://dx.doi.org/10.1016/j.jcin.2017.07.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5775044PMC
January 2018

Pharmacologic Considerations in the Management of Patients Receiving Left Ventricular Percutaneous Mechanical Circulatory Support.

Pharmacotherapy 2017 Oct 19;37(10):1272-1283. Epub 2017 Sep 19.

Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy and UPMC Presbyterian Hospital, Pittsburgh, Pennsylvania.

Percutaneous mechanical circulatory support (MCS) devices, including the intraaortic balloon pump, Impella, and TandemHeart, are often used for hemodynamic support in the setting of refractory cardiogenic shock. The thrombotic and bleeding complications associated with these devices is well recognized, and the Impella and TandemHeart devices have unique anticoagulation considerations that may influence patient outcomes. Both devices typically require use of a heparinized purge solution in combination with intravenous unfractionated heparin, thereby providing multiple sources of heparin exposure. Each device also has specific monitoring requirements and goal ranges. This review provides an overview of percutaneous MCS devices commonly used in the acute management of left ventricular failure, with an emphasis on pharmacologic considerations. We review recent evidence and guidelines and provide recommendations for appropriate use of anticoagulation during device support. Approaches to managing heparinized purge solutions, monitoring, and the utility of nonheparin anticoagulants are also provided because high-quality evidence in the literature is limited.
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http://dx.doi.org/10.1002/phar.1995DOI Listing
October 2017

Comparative Effectiveness and Safety Analysis of Dual Antiplatelet Therapies Within an Integrated Delivery System.

Ann Pharmacother 2017 Aug 24;51(8):649-655. Epub 2017 Apr 24.

1 University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA.

Background: Dual antiplatelet therapy is a mainstay of care for percutaneous coronary intervention (PCI) patients; however, uncertainty exists in real-world practice about comparative effectiveness and safety outcomes.

Objective: To evaluate outcomes of different oral P2Y12 inhibitors in PCI patients.

Methods: We retrospectively studied patients treated between July 1, 2010, and December 31, 2013. Patients received clopidogrel, prasugrel, ticagrelor, or more than 1 antiplatelet (switch) during PCI. Outcomes were evaluated for major adverse cardiovascular events (MACE) and bleeding at 1 year. Propensity score matching with Cox proportional hazards analysis was used to determine predictors of MACE and bleeding.

Results: A total of 8127 patients were included: clopidogrel (n = 6872), prasugrel (n = 605), ticagrelor (n = 181), and switch (n = 469). Treatment with prasugrel was associated with the lowest risk of MACE using multivariate regression (odds ratio [OR] = 0.57; 95% CI = 0.36-0.92; P = 0.02). In the propensity score-matched analysis, only the prasugrel group was associated with a lower risk of MACE compared with the clopidogrel group. Clopidogrel was associated with the lowest risk of major bleeding using multivariate regression (OR = 0.64; 95% CI = 0.42-0.98; P = 0.042). Both ticagrelor (hazard ratio [HR] = 2.00; 95% CI = 1.11-3.59) and the switch groups (HR = 1.65; 95% CI = 1.09-2.50) were associated with a greater risk of major bleeding compared with clopidogrel. However, no differences were found in the propensity score-matched analysis.

Conclusions: Dual antiplatelet therapies differed in both MACE and bleeds in a real-world setting of PCI. Prasugrel was associated with fewer MACE, whereas clopidogrel had fewer major bleeding events.
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http://dx.doi.org/10.1177/1060028017706977DOI Listing
August 2017

Triple Antithrombotic Therapy With Aspirin, P2Y12 Inhibitor, and Warfarin After Percutaneous Coronary Intervention: An Evaluation of Prasugrel or Ticagrelor Versus Clopidogrel.

J Cardiovasc Pharmacol Ther 2017 Nov 9;22(6):546-551. Epub 2017 Mar 9.

3 Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA.

Background: Triple antithrombotic therapy is used in patients who require systemic anticoagulation and undergo percutaneous coronary intervention (PCI) requiring dual antiplatelet therapy. Bleeding with this combination is significant; however, few studies have described outcomes with the use of newer oral P2Y inhibitors in this setting.

Objectives: We aimed to compare outcomes among patients prescribed triple therapy with prasugrel or ticagrelor compared to triple therapy with clopidogrel in patients who underwent PCI and required warfarin.

Methods: We retrospectively evaluated 168 patients who received either prasugrel (n = 32) or ticagrelor (n = 10) and were matched (1:3) to those who received clopidogrel (n = 126) at the time of discharge from the index PCI visit. Matching was performed based on age ±10 years, sex, and indication for PCI. The primary outcome was the incidence of any bleeding during the 12-month follow-up. We also evaluated major adverse cardiovascular and cerebrovascular events (MACCEs).

Results: Patient baseline characteristics were similar between groups. There was a significant excess of bleeding in patients who received prasugrel or ticagrelor compared to clopidogrel as part of triple therapy (28.6% vs 12.7%; odds ratio, 3.3; 95% confidence interval, 1.38-8.34). No differences were seen between groups in MACCEs.

Conclusions: The use of prasugrel or ticagrelor as part of triple antithrombotic therapy among patients who underwent PCI and received warfarin was associated with significantly more bleeding compared to patients who received clopidogrel. Therefore, higher potency P2Y inhibitors should be used cautiously in these patients.
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http://dx.doi.org/10.1177/1074248417698042DOI Listing
November 2017

Oral treprostinil for the treatment of pulmonary arterial hypertension in patients transitioned from parenteral or inhaled prostacyclins: case series and treatment protocol.

Pulm Circ 2016 Mar;6(1):132-5

Heart and Vascular Institute, UPMC, Pittsburgh, Pennsylvania, USA; University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

Oral treprostinil (TRE) is a prostacylin approved for the management of pulmonary arterial hypertension (PAH). Few data exist to guide the use of oral TRE as a replacement for parenteral or inhaled prostacyclins. Therefore, the purpose of this report was to describe our experience with oral TRE to transition patients from parenteral or inhaled TRE. We describe a case series of patients admitted for a 4-day hospital stay to transition from parenteral or inhaled TRE. Appropriate criteria for transition included stable patients with improved symptoms/functional capacity, patients who could not tolerate intravenous prostacyclin due to infection or subcutaneous prostacyclin due to pain, and patient preference for transition. The dosing protocol for transition is described. A total of 9 patients generally representative of a typical PAH demographic and background medical therapy were included. Patients were initiated at either 0.5 or 1 mg 3 times daily and discharged on a median dose of 8 mg 3 times daily. Our protocol resulted in 6 of 9 patients who successfully transitioned at a median follow-up of 47 weeks. Two patients had to return to their previous prostacyclin therapy based on the presence of clinical worsening and adverse events (n = 1) and adverse events alone (n = 1). Another patient discontinued therapy due to plans for hospice care. Oral TRE may serve an important role in prostacyclin transitions in carefully selected, stable patients who receive background oral therapy for PAH.
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http://dx.doi.org/10.1086/685111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4860543PMC
March 2016

Advancing Pharmacogenomics Education in the Core PharmD Curriculum through Student Personal Genomic Testing.

Am J Pharm Educ 2016 Feb;80(1)

Department of Pharmacy and Therapeutics, School of Pharmacy.

Objective: To develop, implement, and evaluate "Test2Learn" a program to enhance pharmacogenomics education through the use of personal genomic testing (PGT) and real genetic data.

Design: One hundred twenty-two second-year doctor of pharmacy (PharmD) students in a required course were offered PGT as part of a larger program approach to teach pharmacogenomics within a robust ethical framework. The program added novel learning objectives, lecture materials, analysis tools, and exercises using individual-level and population-level genetic data. Outcomes were assessed with objective measures and pre/post survey instruments.

Assessment: One hundred students (82%) underwent PGT. Knowledge significantly improved on multiple assessments. Genotyped students reported a greater increase in confidence in understanding test results by the end of the course. Similarly, undergoing PGT improved student's self-perceived ability to empathize with patients compared to those not genotyped. Most students (71%) reported feeling PGT was an important part of the course, and 60% reported they had a better understanding of pharmacogenomics specifically because of the opportunity.

Conclusion: Implementation of PGT in the core pharmacy curriculum was feasible, well-received, and enhanced student learning of pharmacogenomics.
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http://dx.doi.org/10.5688/ajpe8013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4776296PMC
February 2016

Clinical effectiveness and safety outcomes associated with prothrombin complex concentrates.

J Thromb Thrombolysis 2016 Jul;42(1):6-10

Hematology/Oncology Division, UPMC Presbyterian-Shadyside Hospital, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA.

Prothrombin complex concentrates (PCCs) are indicated for urgent reversal of warfarin and used for reversal of novel oral anticoagulants, in patients with acute major bleeding or need for an urgent procedure. The research goal was to evaluate effectiveness and safety outcomes with PCC usage at our institution. A retrospective review of electronic medical records identified patients that received a PCC commercially available in the United States (KCentra(®) or Profilnine(®)) at twelve hospitals in a tertiary care health system from July 1, 2013 to April 30, 2014. A total of 193 patients received PCC, of which 184 patients received four-factor PCC. The patient population was 48 % male and 75 % Caucasian, with a mean age of 73 years old. Clinical outcomes of interest included time to achieve a target INR ≤1.3, time to Hgb >7 g/dL, and incidence of thromboembolism. A total of 143 patients were on warfarin (74.1 %) at baseline, whereas 18 patients (9.3 %) were taking a novel anticoagulant. Target INR of ≤1.3 was achieved in 125 patients (65.8 %), within a median time of 8.03 h (IQR 3.38-34.07). Among patients with a baseline Hgb <7 g/L (n = 13), the median time to Hgb >7 g/dL was 8.48 h (IQR 6.95-13.00). Eight patients (4.1 %) developed an acute venous thromboembolism following PCC administration. INR reversal was achieved in approximately two-thirds of patients, with a low incidence of venous thromboembolism. Four-factor PCC is a viable alternative to plasma.
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http://dx.doi.org/10.1007/s11239-015-1321-4DOI Listing
July 2016

Disopyramide for Hypertrophic Cardiomyopathy: A Pragmatic Reappraisal of an Old Drug.

Pharmacotherapy 2015 Dec;35(12):1164-72

Department of Pharmacy, UPMC Presbyterian University Hospital, Pittsburgh, Pennsylvania.

Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disorder characterized by unexplained left ventricular hypertrophy in the absence of other cardiac or systemic etiologies. Approximately two-thirds of patients with HCM develop left ventricular outflow tract (LVOT) obstruction with or without provocation, whereas nearly half develop heart failure with preserved ejection fraction. Medical management of heart failure with preserved ejection fraction is based on the presence of symptoms and LVOT obstruction and frequently includes β-blockers or verapamil. Disopyramide is a class Ia antiarrhythmic that historically was used for the treatment of arrhythmias; however, its contemporary use is often reserved for patients with HCM who are persistently symptomatic despite β-blockers or verapamil and have evidence of LVOT obstruction. The pharmacologic rationale for use of disopyramide is largely based on its strong negative inotropic property. Three clinical studies have showed significant improvements in heart failure symptoms and a reduction in the need for invasive therapy in patients treated with disopyramide. Appropriate dosing and monitoring of disopyramide are important to mitigate the potential for anticholinergic adverse events and proarrhythmias. Disopyramide is a safe and effective medication that reduces heart failure symptoms and LVOT gradient and delays the need for invasive therapy in patients with obstructive HCM.
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http://dx.doi.org/10.1002/phar.1664DOI Listing
December 2015
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