Publications by authors named "Dyson T Wake"

8 Publications

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Synthesis of major pharmacogenomics pretest counseling themes: a multisite comparison.

Pharmacogenomics 2021 Feb 19;22(3):165-176. Epub 2021 Jan 19.

Neaman Center for Personalized Medicine, NorthShore University HealthSystem, Evanston, IL 60201, USA.

The accessibility of pharmacogenomic (PGx) testing has grown substantially over the last decade and with it has arisen a demand for patients to be counseled on the use of these tests. While guidelines exist for the use of PGx results; objective determinants for who should receive PGx testing remain incomplete. PGx clinical services have been created to meet these screening and education needs and significant variability exists between these programs. This article describes the practices of four PGx clinics during pretest counseling sessions. A description of the major tenets of the benefits, limitations and risks of testing are compiled. Additional tools are provided to serve as a foundation for those wishing to begin or expand their own counseling service.
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http://dx.doi.org/10.2217/pgs-2020-0168DOI Listing
February 2021

Flype: Software for enabling personalized medicine.

Am J Med Genet C Semin Med Genet 2021 03 3;187(1):37-47. Epub 2020 Dec 3.

Mark R. Neaman Center for Personalized Medicine, NorthShore University HealthSystem, Evanston, Illinois, USA.

The advent of next generation DNA sequencing (NGS) has revolutionized clinical medicine by enabling wide-spread testing for genomic anomalies and polymorphisms. With that explosion in testing, however, come several informatics challenges including managing large amounts of data, interpreting the results and providing clinical decision support. We present Flype, a web-based bioinformatics platform built by a small group of bioinformaticians working in a community hospital setting, to address these challenges by allowing us to: (a) securely accept data from a variety of sources, (b) send orders to a variety of destinations, (c) perform secondary analysis and annotation of NGS data, (d) provide a central repository for all genomic variants, (e) assist with tertiary analysis and clinical interpretation, (f) send signed out data to our EHR as both PDF and discrete data elements, (g) allow population frequency analysis and (h) update variant annotation when literature knowledge evolves. We discuss the multiple use cases Flype supports such as (a) in-house NGS tests, (b) in-house pharmacogenomics (PGX) tests, (c) dramatic scale-up of genomic testing using an external lab, (d) consumer genomics using two external partners, and (e) a variety of reporting tools. The source code for Flype is available upon request to the authors.
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http://dx.doi.org/10.1002/ajmg.c.31867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984435PMC
March 2021

Pharmacogenomics: Prescribing Precisely.

Med Clin North Am 2019 Nov 24;103(6):977-990. Epub 2019 Aug 24.

Center for Medical Genetics, Mark R. Neaman Center for Personalized Medicine, NorthShore University HealthSystem, University of Chicago, Pritzker School of Medicine, 1000 Central Street Suite 610, Evanston, IL 60201, USA. Electronic address:

Pharmacogenomics (PGx) is a powerful tool that can predict increased risks of adverse effects and sub-therapeutic response to medications. This article establishes the core principles necessary for a primary care provider to meaningfully and prudently use PGx testing. Key topics include in which patients PGx testing should be considered, how PGx tests are ordered, how the results are translated into clinical recommendations, and what further advancements are likely in the near future. This will provide clinicians with a foundational knowledge of PGx that can allow incorporation of this tool into their practice or support further personal investigation.
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http://dx.doi.org/10.1016/j.mcna.2019.07.002DOI Listing
November 2019

CYP2D6-guided opioid therapy improves pain control in CYP2D6 intermediate and poor metabolizers: a pragmatic clinical trial.

Genet Med 2019 08 23;21(8):1842-1850. Epub 2019 Jan 23.

Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA.

Purpose: CYP2D6 bioactivates codeine and tramadol, with intermediate and poor metabolizers (IMs and PMs) expected to have impaired analgesia. This pragmatic proof-of-concept trial tested the effects of CYP2D6-guided opioid prescribing on pain control.

Methods: Participants with chronic pain (94% on an opioid) from seven clinics were enrolled into CYP2D6-guided (n = 235) or usual care (n = 135) arms using a cluster design. CYP2D6 phenotypes were assigned based on genotype and CYP2D6 inhibitor use, with recommendations for opioid prescribing made in the CYP2D6-guided arm. Pain was assessed at baseline and 3 months using PROMIS measures.

Results: On stepwise multiple linear regression, the primary outcome of composite pain intensity (composite of current pain and worst and average pain in the past week) among IM/PMs initially prescribed tramadol/codeine (n = 45) had greater improvement in the CYP2D6-guided versus usual care arm (-1.01 ± 1.59 vs. -0.40 ± 1.20; adj P = 0.016); 24% of CYP2D6-guided versus 0% of usual care participants reported ≥30% (clinically meaningful) reduction in the composite outcome. In contrast, among normal metabolizers prescribed tramadol or codeine at baseline, there was no difference in the change in composite pain intensity at 3 months between CYP2D6-guided (-0.61 ± 1.39) and usual care (-0.54 ± 1.69) groups (adj P = 0.540).

Conclusion: These data support the potential benefits of CYP2D6-guided pain management.
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http://dx.doi.org/10.1038/s41436-018-0431-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6650382PMC
August 2019

Primary care physician experiences with integrated pharmacogenomic testing in a community health system.

Per Med 2017 09 2;14(5):389-400. Epub 2017 Aug 2.

Center for Personalized Medicine, NorthShore University HealthSystem, 1001 University Place, Suite 160, Evanston, IL 60201, USA.

Aim: To explore primary care physicians' views of the utility and delivery of direct access to pharmacogenomics (PGx) testing in a community health system.

Methods: This descriptive study assessed the perspectives of 15 healthcare providers utilizing qualitative individual interviews.

Results: Three main themes emerged: perceived value and utility of PGx testing; challenges to implementation in practice; and provider as well as patient needs.

Conclusion: While providers in this study viewed benefits of PGx testing as avoiding side effects, titrating doses more quickly, improving shared decision-making and providing psychological reassurance, challenges will need to be addressed such as privacy concerns, cost, insurance coverage and understanding the complexity of PGx test results.
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http://dx.doi.org/10.2217/pme-2017-0036DOI Listing
September 2017

Patient perspectives following pharmacogenomics results disclosure in an integrated health system.

Pharmacogenomics 2018 03 22;19(4):321-331. Epub 2018 Feb 22.

Center for Personalized Medicine, NorthShore University HealthSystem, 1001 University Place, Suite 160, Evanston, IL 60201, USA.

Aim: To assess patient perceptions and utilization of pharmacogenomics (PGx) testing in an integrated community health system.

Methods: Fifty-seven patients completed an online survey assessing their experiences with PGx testing offered through two methods: a designated PGx clinic or direct access in-home testing.

Results: The majority of participants perceived PGx testing as helpful in their healthcare and reported understanding their results. Some had concerns about privacy and discrimination; most lacked familiarity with the Genetic Information Nondiscrimination Act. There were no significant differences in views between participants tested through either model.

Conclusion: Participants reported value in both methods of PGx testing. Patient experiences, understanding and result utilization will play an important role in informing future development and implementation of PGx programs.
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http://dx.doi.org/10.2217/pgs-2017-0191DOI Listing
March 2018

Implementation of Standardized Clinical Processes for TPMT Testing in a Diverse Multidisciplinary Population: Challenges and Lessons Learned.

Clin Transl Sci 2018 03 19;11(2):175-181. Epub 2018 Jan 19.

University of Florida Health Personalized Medicine Program, Gainesville, Florida, USA.

Although thiopurine S-methyltransferase (TPMT) genotyping to guide thiopurine dosing is common in the pediatric cancer population, limited data exist on TPMT testing implementation in diverse, multidisciplinary settings. We established TPMT testing (genotype and enzyme) with clinical decision support, provider/patient education, and pharmacist consultations in a tertiary medical center and collected data over 3 years. During this time, 834 patients underwent 873 TPMT tests (147 (17%) genotype, 726 (83%) enzyme). TPMT tests were most commonly ordered for gastroenterology, rheumatology, dermatology, and hematology/oncology patients (661 of 834 patients (79.2%); 580 outpatient vs. 293 inpatient; P < 0.0001). Thirty-nine patients had both genotype and enzyme tests (n = 2 discordant results). We observed significant differences between TPMT test use and characteristics in a diverse, multispecialty environment vs. a pediatric cancer setting, which led to unique implementation needs. As pharmacogenetic implementations expand, disseminating lessons learned in diverse, real-world environments will be important to support routine adoption.
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http://dx.doi.org/10.1111/cts.12533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5867028PMC
March 2018

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