Pediatric Outcomes in Transplant: Personalising Immunosuppression To Improve Efficacy (POSITIVE Study): The Collaboration and Design of a National Transplant Precision Medicine Program

Despite age-related differences in biology, physiology, and behavior, transplant immunosuppression is not tailored by age. This likely contributes to high graft failure and posttransplant complications. We present the aims, design, and methods of the Pediatric Outcomes in Transplant: PersOnaliSing Immunosuppression To ImproVe Efficacy Study aimed at personalizing posttransplant immunosuppression in children and young adults.; In this prospective observational cohort study, we recruited pediatric and young adult solid organ transplant, pediatric allogeneic hematopoietic stem cell transplant recipients, and matched living and deceased organ donors from 14 transplant centers across Canada. Clinical data, questionnaires, biospecimens, and pharmacy records were collected at serial time points: (1) to identify genetic and host immune factors that influence immunosuppression dose requirements across different ages and transplant types, (2) to identify viral-host interactions that increase susceptibility to Epstein-Barr virus infection, and (3) to define care processes and structures associated with medication adherence in adolescents and young adults.; From 2015 to 2018, 1662 new and prevalent transplant recipients were screened, 1166 were recruited for the various aims, including 370 liver, 445 kidney, 277 heart, 19 lung, 19 multiple, and 36 hematopoietic stem cell transplant transplants. Twelve percent were younger than 2 years, 30% were 2 to 10 years, 42% were 10 to 18 years, and 16% were 18 to 24 years at enrollment. Nine hundred thirty-one consented to participation in aims 1 and 2 (90% consent rate), 287 to aim 3 (82% consent rate). Biospecimens collected included 898 for DNA, 276 for immunoassays, and 717 for biomarker studies. Seventy percent participants have completed follow-up; 30% are pending study completion.; The design of this national multicenter cross-organ network helped maximize recruitment of a large patient cohort for studying age and organ-related differences in immunosuppression needs that would not otherwise be feasible. Leveraging the unique clinical, biological, environmental, and behavioral characteristics of this cohort will help develop precision medicine strategies for individualizing posttransplant immunosuppression

Pediatric Outcomes in Transplant: PersOnaliSing Immunosuppression To ImproVe Efficacy (POSITIVE Study): The Collaboration and Design of a National Transplant Precision Medicine Program (vol 4, e410, 2018)

© The Authors. Transplantation Direct. Published by Wolters Kluwer Health, Inc. In the article by Papaz et al, Pediatric Outcomes in Transplant: PersOnaliSing Immunosuppression To ImproVe Efficacy (POSITIVE Study): The Collaboration and Design of a National Transplant Precision Medicine Program, published November 27, 2018 in Transplantation Direct, Sabina De Geest, PhD should have been listed as an author.status: publishe

Return of genetic and genomic research findings: Experience of a pediatric biorepository

Background: Assess process, uptake, validity and resource needs for return of actionable research findings to biobank participants. Methods: Participants were prospectively enrolled in a multicenter biorepository of childhood onset heart disease. Clinically actionable research findings were reviewed by a Return of Research Results Committee (RRR) and returned to the physician or disclosed directly to the participant through a research genetic counselor. Action taken following receipt of this information was reviewed. Results: Genetic data was generated in 1963 of 7408 participants. Fifty-nine new findings were presented to the RRR committee; 20 (34%) were deemed reportable. Twelve were returned to the physician, of which 7 were disclosed to participants (median time to disclosure, 192 days). Seven findings were returned to the research genetic counselor; all have been disclosed (median time to disclosure, 19 days). Twelve families (86%) opted for referral to clinical genetics after disclosure of findings; 7 results have been validated, 5 results are pending. Average cost of return and disclosure per reportable finding incurred by the research program was $750 when utilizing a research genetic counselor; clinical costs associated with return were not included. Conclusions: Return of actionable research findings was faster if disclosed directly to the participant by a research genetic counselor. There was a high acceptability amongst participants for receiving the findings, for referral to clinical genetics, and for clinical validation of research findings, with all referred cases being clinically confirmed

Return of genetic and genomic research findings: experience of a pediatric biorepository

Abstract Background Assess process, uptake, validity and resource needs for return of actionable research findings to biobank participants. Methods Participants were prospectively enrolled in a multicenter biorepository of childhood onset heart disease. Clinically actionable research findings were reviewed by a Return of Research Results Committee (RRR) and returned to the physician or disclosed directly to the participant through a research genetic counselor. Action taken following receipt of this information was reviewed. Results Genetic data was generated in 1963 of 7408 participants. Fifty-nine new findings were presented to the RRR committee; 20 (34%) were deemed reportable. Twelve were returned to the physician, of which 7 were disclosed to participants (median time to disclosure, 192 days). Seven findings were returned to the research genetic counselor; all have been disclosed (median time to disclosure, 19 days). Twelve families (86%) opted for referral to clinical genetics after disclosure of findings; 7 results have been validated, 5 results are pending. Average cost of return and disclosure per reportable finding incurred by the research program was $750 when utilizing a research genetic counselor; clinical costs associated with return were not included. Conclusions Return of actionable research findings was faster if disclosed directly to the participant by a research genetic counselor. There was a high acceptability amongst participants for receiving the findings, for referral to clinical genetics, and for clinical validation of research findings, with all referred cases being clinically confirmed

Return of genetic and genomic research findings: experience of a pediatric biorepository

BACKGROUND: Assess process, uptake, validity and resource needs for return of actionable research findings to biobank participants. METHODS: Participants were prospectively enrolled in a multicenter biorepository of childhood onset heart disease. Clinically actionable research findings were reviewed by a Return of Research Results Committee (RRR) and returned to the physician or disclosed directly to the participant through a research genetic counselor. Action taken following receipt of this information was reviewed. RESULTS: Genetic data was generated in 1963 of 7408 participants. Fifty-nine new findings were presented to the RRR committee; 20 (34%) were deemed reportable. Twelve were returned to the physician, of which 7 were disclosed to participants (median time to disclosure, 192 days). Seven findings were returned to the research genetic counselor; all have been disclosed (median time to disclosure, 19 days). Twelve families (86%) opted for referral to clinical genetics after disclosure of findings; 7 results have been validated, 5 results are pending. Average cost of return and disclosure per reportable finding incurred by the research program was $750 when utilizing a research genetic counselor; clinical costs associated with return were not included. CONCLUSIONS: Return of actionable research findings was faster if disclosed directly to the participant by a research genetic counselor. There was a high acceptability amongst participants for receiving the findings, for referral to clinical genetics, and for clinical validation of research findings, with all referred cases being clinically confirmed.status: publishe

A Validated Model for Sudden Cardiac Death Risk Prediction in Pediatric Hypertrophic Cardiomyopathy

Background: Hypertrophic cardiomyopathy is the leading cause of sudden cardiac death (SCD) in children and young adults. Our objective was to develop and validate a SCD risk prediction model in pediatric hypertrophic cardiomyopathy to guide SCD prevention strategies. Methods: In an international multicenter observational cohort study, phenotype-positive patients with isolated hypertrophic cardiomyopathy 70% prediction accuracy and incorporates risk factors that are unique to pediatric hypertrophic cardiomyopathy. An individualized risk prediction model has the potential to improve the application of clinical practice guidelines and shared decision making for implantable cardioverter defibrillator insertion. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT0403679