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Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
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August 2021 List
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
Citation List Month
August 2021 List
URL Address
<a href="http://doi.org/10.1001/jamanetworkopen.2021.10446" target="_blank" rel="noreferrer noopener">http://doi.org/10.1001/jamanetworkopen.2021.10446</a>
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
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Assessment of the Implementation of Pharmacogenomic Testing in a Pediatric Tertiary Care Setting
Publisher
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JAMA Network Open
Date
A point or period of time associated with an event in the lifecycle of the resource
2021
Subject
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pediatric; children with medical complexity; pharmacogenomic testing; pharmacogenes
Creator
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Cohn I; Manshaei R; Liston E; Okello JBA; Khan R; Curtis MR; Krupski AJ; Jobling RK; Kalbfleisch K; Paton TA; Reuter MS; Hayeems RZ; Verstegen RHJ; Goldman A; Kim RH; Ito S
Description
An account of the resource
Pharmacogenomic (PGx) testing provides preemptive pharmacotherapeutic guidance regarding the lack of therapeutic benefit or adverse drug reactions of PGx targeted drugs. Pharmacogenomic information is of particular value among children with complex medical conditions who receive multiple medications and are at higher risk of developing adverse drug reactions.To assess the implementation outcomes of a PGx testing program comprising both a point-of-care model that examined targeted drugs and a preemptive model informed by whole-genome sequencing that evaluated a broad range of drugs for potential therapy among children in a pediatric tertiary care setting.This cohort study was conducted at The Hospital for Sick Children in Toronto, Ontario, from January 2017 to September 2020. Pharmacogenomic analyses were performed among 172 children who were categorized into 2 groups: a point-of-care cohort and a preemptive cohort. The point-of-care cohort comprised 57 patients referred to the consultation clinic for planned therapy with PGx targeted drugs and/or for adverse drug reactions, including lack of therapeutic benefit, after the receipt of current or past medications. The preemptive cohort comprised 115 patients who received exploratory whole-genome sequencing–guided PGx testing for their heart conditions from the cardiac genome clinic at the Ted Rogers Centre for Heart Research.Patients received PGx analysis of whole-genome sequencing data and/or multiplex genotyping of 6 pharmacogenes (CYP2C19, CYP2C9, CYP2D6, CYP3A5, VKORC1, and TPMT) that have established PGx clinical guidelines.The number of patients for whom PGx test results warranted deviation from standard dosing regimens.A total of 172 children (mean [SD] age, 8.5 [5.6] years; 108 boys [62.8%]) were enrolled in the study. In the point-of-care cohort, a median of 2 target genes (range, 1-5 genes) were investigated per individual, with CYP2C19 being the most frequently examined; genotypes in 21 of 57 children (36.8%) were incompatible with standard treatment regimens. As expected from population allelic frequencies, among the 115 children in the whole-genome sequencing–guided preemptive cohort, 92 children (80.0%) were recommended to receive nonstandard treatment regimens for potential drug therapies based on their 6-gene pharmacogenetic profile.In this cohort study, among both the point-of-care and preemptive cohorts, the multiplex PGx testing program provided dosing recommendations that deviated from standard regimens at an overall rate that was similar to the population frequencies of relevant variants.
Identifier
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<a href="http://doi.org/10.1001/jamanetworkopen.2021.10446" target="_blank" rel="noreferrer noopener">10.1001/jamanetworkopen.2021.10446</a>
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
2021
August 2021 List
Children With Medical Complexity
Cohn I
Curtis MR
Goldman A
Hayeems RZ
Ito S
JAMA Network Open
Jobling RK
Kalbfleisch K
Khan R
Kim RH
Krupski AJ
Liston E
Manshaei R
Okello JBA
Paton TA
Pediatric
pharmacogenes
pharmacogenomic testing
Reuter MS
Verstegen RHJ
-
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
March 2021 List
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
Citation List Month
March 2021 List
URL Address
<a href="http://doi.org/10.1001/jamanetworkopen.2020.18109" target="_blank" rel="noreferrer noopener">http://doi.org/10.1001/jamanetworkopen.2020.18109</a>
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
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Genome Sequencing as a Diagnostic Test in Children With Unexplained Medical Complexity
Publisher
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JAMA Network Open
Date
A point or period of time associated with an event in the lifecycle of the resource
2020
Subject
The topic of the resource
Child; Female; Humans; Male; Reproducibility of Results; Child Preschool; Canada; Prospective Studies; Predictive Value of Tests; Genetic Testing/statistics & numerical data; Somatoform Disorders/diagnosis; Whole Genome Sequencing/statistics & numerical data
Creator
An entity primarily responsible for making the resource
Costain G; Walker S; Marano M; Veenma D; Snell M; Curtis M; Luca S; Buera J; Arje D; Reuter MS; Thiruvahindrapuram B; Trost B; Sung WWL; Yuen RKC; Chitayat D; Mendoza-Londono R; Stavropoulos DJ; Scherer SW; Marshall CR; Cohn RD; Cohen E; Orkin J; Meyn MS; Hayeems RZ
Description
An account of the resource
IMPORTANCE: Children with medical complexity (CMC) represent a growing population in the pediatric health care system, with high resource use and associated health care costs. A genetic diagnosis can inform prognosis, anticipatory care, management, and reproductive planning. Conventional genetic testing strategies for CMC are often costly, time consuming, and ultimately unsuccessful. OBJECTIVE: To evaluate the analytical and clinical validity of genome sequencing as a comprehensive diagnostic genetic test for CMC. DESIGN, SETTING, AND PARTICIPANTS: In this cohort study of the prospective use of genome sequencing and comparison with standard-of-care genetic testing, CMC were recruited from May 1, 2017, to November 30, 2018, from a structured complex care program based at a tertiary care pediatric hospital in Toronto, Canada. Recruited CMC had at least 1 chronic condition, technology dependence (child is dependent at least part of each day on mechanical ventilators, and/or child requires prolonged intravenous administration of nutritional substances or drugs, and/or child is expected to have prolonged dependence on other device-based support), multiple subspecialist involvement, and substantial health care use. Review of the care plans for 545 CMC identified 143 suspected of having an undiagnosed genetic condition. Fifty-four families met inclusion criteria and were interested in participating, and 49 completed the study. Probands, similarly affected siblings, and biological parents were eligible for genome sequencing. EXPOSURES: Genome sequencing was performed using blood-derived DNA from probands and family members using established methods and a bioinformatics pipeline for clinical genome annotation. MAIN OUTCOMES AND MEASURES: The primary study outcome was the diagnostic yield of genome sequencing (proportion of CMC for whom the test result yielded a new diagnosis). RESULTS: Genome sequencing was performed for 138 individuals from 49 families of CMC (29 male and 20 female probands; mean [SD] age, 7.0 [4.5] years). Genome sequencing detected all genomic variation previously identified by conventional genetic testing. A total of 15 probands (30.6%; 95% CI 19.5%-44.6%) received a new primary molecular genetic diagnosis after genome sequencing. Three individuals had novel diseases and an additional 9 had either ultrarare genetic conditions or rare genetic conditions with atypical features. At least 11 families received diagnostic information that had clinical management implications beyond genetic and reproductive counseling. CONCLUSIONS AND RELEVANCE: This study suggests that genome sequencing has high analytical and clinical validity and can result in new diagnoses in CMC even in the setting of extensive prior investigations. This clinical population may be enriched for ultrarare and novel genetic disorders. Genome sequencing is a potentially first-tier genetic test for CMC.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1001/jamanetworkopen.2020.18109" target="_blank" rel="noreferrer noopener">10.1001/jamanetworkopen.2020.18109</a>
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
2020
Arje D
Buera J
Canada
Child
Child Preschool
Chitayat D
Cohen E
Cohn RD
Costain G
Curtis M
Female
Genetic Testing/statistics & numerical data
Hayeems RZ
Humans
JAMA Network Open
Luca S
Male
Marano M
March 2021 List
Marshall CR
Mendoza-Londono R
Meyn MS
Orkin J
Predictive Value of Tests
Prospective Studies
Reproducibility of Results
Reuter MS
Scherer SW
Snell M
Somatoform Disorders/diagnosis
Stavropoulos DJ
Sung WWL
Thiruvahindrapuram B
Trost B
Veenma D
Walker S
Whole Genome Sequencing/statistics & numerical data
Yuen RKC