Pediatric pharmacogenomics: challenges and opportunities: on behalf of the Sanford Children’s Genomic Medicine Consortium

Gregornik, David; Salyakina, Daria; Brown, Marilyn; Roiko, Samuel A.; Ramos, Kenneth S.

doi:10.1038/s41397-020-00181-w

Cited by 29 publications

(38 citation statements)

References 47 publications

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“… 34 However, data on the implementation outcomes of such a program among a pediatric population are scarce. 34 , 35 , 36 The current results focused on deviation from standard regimens, but PGx results warranting the use of a standard regimen are equally important in clinical pharmacotherapeutic decision-making. The term actionable phenotypes is misleading if used only to describe phenotype results warranting deviation from standard regimens because results supporting both modified and standard regimens are actionable.…”

Section: Discussionmentioning

confidence: 99%

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Assessment of the Implementation of Pharmacogenomic Testing in a Pediatric Tertiary Care Setting

et al. 2021

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Key Points Question What is the clinical utility of a pharmacogenomic testing program that uses both point-of-care and preemptive approaches to assess potential responses to drugs in a pediatric tertiary care setting? Findings In this cohort study of 172 pediatric patients, pharmacogenomic testing of 6 pharmacogenes ( CYP2D6 , CYP2C9 , CYP2C19 , CYP3A5 , TPMT , and VKORC1 ) provided results that warranted deviation from standard treatment regimens in approximately 40% of patients in the point-of-care evaluation of targeted drugs and 80% of patients in the preemptive evaluation of a broader range of drugs for potential therapy. Meaning The study’s findings suggest that a pharmacogenomic program using both point-of-care targeted drug–guided testing and preemptive whole-genome sequencing–guided testing enhances the knowledge necessary for patient care decision-making, providing informed rationales for drug selection and dosing options.

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Section: Discussionmentioning

confidence: 99%

“…Overall, the study’s results suggest that a PGx testing program in a tertiary care setting provides important information to guide patient care decisions for children with complex medical problems, and these findings are comparable with those of previous studies. 33 , 34 , 35 , 36 , 37 , 38 , 39 …”

Section: Discussionmentioning

confidence: 99%

Assessment of the Implementation of Pharmacogenomic Testing in a Pediatric Tertiary Care Setting

et al. 2021

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“…The level of integration includes real-time at the point of care PGx treatment guidelines and dosing recommendations, ranging from interruptive alerts suggesting treatment recommendations to providing guidance to the presence of a specific PGx variant for a specific medication [ 11 , 36 , 37 ]. Some institutions leverage the use of machine learning and natural language processing to extract triggers for CDSS [ 38 ], and others have incorporated the patient consent process into the CDS workflow [ 36 ]. More importantly, institutions have established CDSS governance structures to help guide the implementation of PGx CDSS [ 11 , 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

Implementing Pharmacogenomics Testing: Single Center Experience at Arkansas Children’s Hospital

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Porter-Gill

et al. 2021

JPM

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Pharmacogenomics (PGx) is a growing field within precision medicine. Testing can help predict adverse events and sub-therapeutic response risks of certain medications. To date, the US FDA lists over 280 drugs which provide biomarker-based dosing guidance for adults and children. At Arkansas Children’s Hospital (ACH), a clinical PGx laboratory-based test was developed and implemented to provide guidance on 66 pediatric medications for genotype-guided dosing. This PGx test consists of 174 single nucleotide polymorphisms (SNPs) targeting 23 clinically actionable PGx genes or gene variants. Individual genotypes are processed to provide per-gene discrete results in star-allele and phenotype format. These results are then integrated into EPIC- EHR. Genomic indicators built into EPIC-EHR provide the source for clinical decision support (CDS) for clinicians, providing genotype-guided dosing.

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“…Several studies describe the relationship between age and drug metabolism (O'Mahony and Woodhouse, 1994;Benedetti et al, 2007). Pediatric age (Gregornik et al, 2021) and, even more so, geriatric age are at higher risk for ADRs (Seripa et al, 2015). Geriatric patients at higher risk for ADRs as they take several drugs, with possible mutual metabolic interferences.…”

Section: Environmental Age and Gender Factors In Adverse Drug Reactionsmentioning

confidence: 99%

Role of Pharmacogenetics in Adverse Drug Reactions: An Update towards Personalized Medicine

et al. 2021

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Adverse drug reactions (ADRs) are an important and frequent cause of morbidity and mortality. ADR can be related to a variety of drugs, including anticonvulsants, anaesthetics, antibiotics, antiretroviral, anticancer, and antiarrhythmics, and can involve every organ or apparatus. The causes of ADRs are still poorly understood due to their clinical heterogeneity and complexity. In this scenario, genetic predisposition toward ADRs is an emerging issue, not only in anticancer chemotherapy, but also in many other fields of medicine, including hemolytic anemia due to glucose-6-phosphate dehydrogenase (G6PD) deficiency, aplastic anemia, porphyria, malignant hyperthermia, epidermal tissue necrosis (Lyell’s Syndrome and Stevens-Johnson Syndrome), epilepsy, thyroid diseases, diabetes, Long QT and Brugada Syndromes. The role of genetic mutations in the ADRs pathogenesis has been shown either for dose-dependent or for dose-independent reactions. In this review, we present an update of the genetic background of ADRs, with phenotypic manifestations involving blood, muscles, heart, thyroid, liver, and skin disorders. This review aims to illustrate the growing usefulness of genetics both to prevent ADRs and to optimize the safe therapeutic use of many common drugs. In this prospective, ADRs could become an untoward “stress test,” leading to new diagnosis of genetic-determined diseases. Thus, the wider use of pharmacogenetic testing in the work-up of ADRs will lead to new clinical diagnosis of previously unsuspected diseases and to improved safety and efficacy of therapies. Improving the genotype-phenotype correlation through new lab techniques and implementation of artificial intelligence in the future may lead to personalized medicine, able to predict ADR and consequently to choose the appropriate compound and dosage for each patient.

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Pediatric pharmacogenomics: challenges and opportunities: on behalf of the Sanford Children’s Genomic Medicine Consortium

Cited by 29 publications

References 47 publications

Assessment of the Implementation of Pharmacogenomic Testing in a Pediatric Tertiary Care Setting

Assessment of the Implementation of Pharmacogenomic Testing in a Pediatric Tertiary Care Setting

Implementing Pharmacogenomics Testing: Single Center Experience at Arkansas Children’s Hospital

Role of Pharmacogenetics in Adverse Drug Reactions: An Update towards Personalized Medicine

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