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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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Medicina de Precisão , Software , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , FarmacogenéticaRESUMO
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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Analgésicos Opioides/administração & dosagem , Citocromo P-450 CYP2D6/genética , Manejo da Dor/métodos , Dor/tratamento farmacológico , Adulto , Analgésicos Opioides/efeitos adversos , Codeína/administração & dosagem , Codeína/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/genética , Dor/patologia , Farmacogenética , Polimorfismo Genético , Medicina de PrecisãoRESUMO
Clinical decision support (CDS) is often cited as an essential part of pharmacogenomics (PGx) implementations. A multitude of strategies are available; however, it is unclear which strategies are effective and which metrics are used to quantify clinical utility. The objective of this scoping review was to aggregate previous studies into a cohesive depiction of the current state of PGx CDS implementations and identify areas for future research on PGx CDS. Articles were included if they (i) described electronic CDS tools for PGx and (ii) reported metrics related to PGx CDS. Twenty of 3,449 articles were included and provided data on PGx CDS metrics from 15 institutions, with 93% of programs located at academic medical centers. The most common tools in CDS implementations were interruptive post-test alerts. Metrics for clinical response and alert response ranged from 12-73% and 21-98%, respectively. Few data were found on changes in metrics over time and measures that drove the evolution of CDS systems. Relatively few data were available regarding support of optimal approaches for PGx CDS. Post-test alerts were the most widely studied approach, and their effectiveness varied greatly. Further research on the usability, effectiveness, and optimization of CDS tools is needed.
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Sistemas de Apoio a Decisões Clínicas , Sistemas de Registro de Ordens Médicas , Humanos , Farmacogenética , Registros Eletrônicos de Saúde , SoftwareRESUMO
Genomic and personalized medicine implementation efforts have largely centered on specialty care in tertiary health systems. There are few examples of fully integrated care systems that span the healthcare continuum. In 2014, NorthShore University HealthSystem launched the Center for Personalized Medicine to catalyze the delivery of personalized medicine. Successful implementation required the development of a scalable family history collection tool, the Genetic and Wellness Assessment (GWA) and Breast Health Assessment (BHA) tools; integrated pharmacogenomics programming; educational programming; electronic medical record integration; and robust clinical decision support tools. To date, more than 225,000 patients have been screened for increased hereditary conditions, such as cancer risk, through these tools in primary care. More than 35,000 patients completed clinical genetic testing following GWA or BHA completion. An innovative program trained more than 100 primary care providers in genomic medicine, activated with clinical decision support and access to patient genetic counseling services and digital healthcare tools. The development of a novel bioinformatics platform (FLYPE) enabled the incorporation of genomics data into electronic medical records. To date, over 4,000 patients have been identified to have a pathogenic or likely pathogenic variant in a gene with medical management implications. Over 33,000 patients have clinical pharmacogenomics data incorporated into the electronic health record supported by clinical decision support tools. This manuscript describes the evolution, strategy, and successful multispecialty partnerships aligned with health system leadership that enabled the implementation of a comprehensive personalized medicine program with measurable patient outcomes through a genomics-enabled learning health system model that utilizes implementation science frameworks.
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Clinical decision support (CDS) is an essential part of any pharmacogenomics (PGx) implementation. Increasingly, institutions have implemented CDS tools in the clinical setting to bring PGx data into patient care, and several have published their experiences with these implementations. However, barriers remain that limit the ability of some programs to create CDS tools to fit their PGx needs. Therefore, the purpose of this review is to summarize the types, functions, and limitations of PGx CDS currently in practice. Then, we provide an approachable step-by-step how-to guide with a case example to help implementers bring PGx to the front lines of care regardless of their setting. Particular focus is paid to the five "rights" of CDS as a core around designing PGx CDS tools. Finally, we conclude with a discussion of opportunities and areas of growth for PGx CDS.
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Sistemas de Apoio a Decisões Clínicas , Farmacogenética , Registros Eletrônicos de Saúde , Humanos , Assistência ao Paciente , SoftwareRESUMO
Pharmacogenomics (PGx) implementation has become increasingly widespread. One of the most important aspects of this implementation process is the development of appropriate clinical decision support (CDS). Major PGx resources, such as the Clinical Pharmacogenetics Implementation Consortium, provide valuable recommendations for the development of CDS for specific gene-drug pairs but do not specify whether the administration route of a drug is clinically relevant. It is also unknown if PGx alerts for nonorally and non-intravenously administered PGx-relevant medications should be suppressed to reduce alert fatigue. The purpose of this scoping review was to identify studies and their clinical, pharmacokinetic and pharmacodynamic outcomes to better determine if CDS alerts are relevant for nonorally and non-intravenously administered PGx-relevant medications. Although this scoping review identified multiple PGx studies, the results of these studies were inconsistent, and more evidence is needed regarding different routes of medication administration and PGx.
Pharmacogenomics (PGx) is the study of how a person's genes and DNA may impact their response to certain medications. There are many hospitals and large academic medical centers that have begun using pharmacogenomic testing to better help guide treatment decisions for patients. Currently, there are few standards in place to guide these institutions on how to put a patient's pharmacogenomic information into their personal medical chart. To help create these standards, a consensus is needed on what types of medication orders will alert physicians to patients who may have pharmacogenomic-related concerns. One area that must be addressed to help with these standardizations involves the route of administration of a medication. Do pharmacogenomic considerations depend on how a medication is given to the patient (e.g., by mouth or through a vein or muscle)? The purpose of this scoping review was to assess the evidence surrounding this question in the hopes of clarifying what types of medication orders should trigger alerts to physicians. If the administration route results in no concerns regarding a patient's pharmacogenomic data, then the physician should not be shown an alert for that medication order. Too many of these alerts may cause 'alert fatigue' and lead to more errors in medication ordering, which may result in patient harm. It is important to address this area of pharmacogenomics to ensure this information is being used appropriately for patient care.
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Sistemas de Apoio a Decisões Clínicas , Farmacogenética , Humanos , Farmacogenética/métodos , Registros Eletrônicos de SaúdeRESUMO
PURPOSE: This article explores approaches to pharmacogenomic counseling for patients who have undergone multigene panel testing by describing the collective experience of 5 institutions. SUMMARY: Multigene panel pharmacogenomic testing has the potential to unlock a myriad of information about a patient's past, present, and future drug response. The multifaceted nature of drug response coupled with the complexity of genetic results necessitates some form of patient education through pharmacogenomic counseling. Published literature regarding disclosure of pharmacogenomic test results is limited. This article compares the counseling practices of pharmacists from 5 different institutions with pharmacogenomics clinics whose experience represents perspectives ranging from academia to community clinical environments. Overarching counseling themes discussed during result disclosure center around (1) pharmacogenomic results, (2) gene-drug interactions, (3) gene-drug-drug interactions, (4) drug changes (5) future, familial, or disease-risk implications, (6) updates in the interpretation and application of pharmacogenomic results, (7) gauging patient comprehension, and (8) sharing results and supplemental information. CONCLUSION: Dedicating time to counseling patients on the results of a multigene pharmacogenomic panel is important given the lifelong applications of a test that is generally performed only once. The content and methods of disclosing test results shared by the experiences of pharmacists at 5 different institutions serve as guide to be further refined as research addresses effective communication strategies that enhance patient comprehension of pharmacogenomic results.
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Farmacogenética , Testes Farmacogenômicos , Interações Medicamentosas , Humanos , FarmacêuticosRESUMO
The present study builds on our prior work that demonstrated an association between pharmacogenetic interactions and 90-day readmission. In a substantially larger, more diverse study population of 19,999 adults tracked from 2010 through 2020 who underwent testing with a 13-gene pharmacogenetic panel, we included additional covariates to evaluate aggregate contribution of social determinants and medical comorbidity with the presence of identified gene-x-drug interactions to moderate 90-day hospital readmission (primary outcome). Univariate logistic regression analyses demonstrated that strongest associations with 90 day hospital readmissions were the number of medications prescribed within 30 days of a first hospital admission that had Clinical Pharmacogenomics Implementation Consortium (CPIC) guidance (CPIC medications) (5+ CPIC medications, odds ratio (OR) = 7.66, 95% confidence interval 5.45−10.77) (p < 0.0001), major comorbidities (5+ comorbidities, OR 3.36, 2.61−4.32) (p < 0.0001), age (65 + years, OR = 2.35, 1.77−3.12) (p < 0.0001), unemployment (OR = 2.19, 1.88−2.64) (p < 0.0001), Black/African-American race (OR 2.12, 1.47−3.07) (p < 0.0001), median household income (OR = 1.63, 1.03−2.58) (p = 0.035), male gender (OR = 1.47, 1.21−1.80) (p = 0.0001), and one or more gene-x-drug interaction (defined as a prescribed CPIC medication for a patient with a corresponding actionable pharmacogenetic variant) (OR = 1.41, 1.18−1.70). Health insurance was not associated with risk of 90-day readmission. Race, income, employment status, and gene-x-drug interactions were robust in a multivariable logistic regression model. The odds of 90-day readmission for patients with one or more identified gene-x-drug interactions after adjustment for these covariates was attenuated by 10% (OR = 1.31, 1.08−1.59) (p = 0.006). Although the interaction between race and gene-x-drug interactions was not statistically significant, White patients were more likely to have a gene-x-drug interaction (35.2%) than Black/African-American patients (25.9%) who were not readmitted (p < 0.0001). These results highlight the major contribution of social determinants and medical complexity to risk for hospital readmission, and that these determinants may modify the effect of gene-x-drug interactions on rehospitalization risk.
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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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Tomada de Decisão Clínica/métodos , Aconselhamento Genético/métodos , Educação de Pacientes como Assunto/métodos , Testes Farmacogenômicos/métodos , Medicina de Precisão/métodos , Aconselhamento Genético/normas , Humanos , Educação de Pacientes como Assunto/normas , Testes Farmacogenômicos/normas , Medicina de Precisão/normasRESUMO
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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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Farmacogenética/métodos , Medicina de Precisão , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/genética , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Humanos , Atenção Primária à Saúde/métodosRESUMO
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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Atenção à Saúde/estatística & dados numéricos , Farmacogenética/estatística & dados numéricos , Testes Farmacogenômicos/estatística & dados numéricos , Medicina de Precisão/psicologia , Adolescente , Adulto , Planejamento em Saúde Comunitária/estatística & dados numéricos , Revelação , Feminino , Testes Genéticos/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto JovemRESUMO
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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Antimetabólitos Antineoplásicos/farmacologia , Metiltransferases/genética , Neoplasias/tratamento farmacológico , Farmacogenética/métodos , Adulto , Fatores Etários , Antimetabólitos Antineoplásicos/normas , Antimetabólitos Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Sistemas de Apoio a Decisões Clínicas , Ensaios Enzimáticos/métodos , Feminino , Testes Genéticos/métodos , Genótipo , Humanos , Comunicação Interdisciplinar , Masculino , Metiltransferases/metabolismo , Pessoa de Meia-Idade , Neoplasias/genética , Educação de Pacientes como Assunto , Farmacêuticos , Fenótipo , Polimorfismo Genético , Guias de Prática Clínica como Assunto , Medicina de Precisão/métodos , Centros de Atenção TerciáriaRESUMO
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.