Improving reporting standards for polygenic scores in risk prediction studies.

Polygenic risk scores (PRSs), which often aggregate results from genome-wide association studies, can bridge the gap between initial discovery efforts and clinical applications for the estimation of disease risk using genetics. However, there is notable heterogeneity in the application and reporting of these risk scores, which hinders the translation of PRSs into clinical care. Here, in a collaboration between the Clinical Genome Resource (ClinGen) Complex Disease Working Group and the Polygenic Score (PGS) Catalog, we present the Polygenic Risk Score Reporting Standards (PRS-RS), in which we update the Genetic Risk Prediction Studies (GRIPS) Statement to reflect the present state of the field. Drawing on the input of experts in epidemiology, statistics, disease-specific applications, implementation and policy, this comprehensive reporting framework defines the minimal information that is needed to interpret and evaluate PRSs, especially with respect to downstream clinical applications. Items span detailed descriptions of study populations, statistical methods for the development and validation of PRSs and considerations for the potential limitations of these scores. In addition, we emphasize the need for data availability and transparency, and we encourage researchers to deposit and share PRSs through the PGS Catalog to facilitate reproducibility and comparative benchmarking. By providing these criteria in a structured format that builds on existing standards and ontologies, the use of this framework in publishing PRSs will facilitate translation into clinical care and progress towards defining best practice.

Integration of stakeholder engagement from development to dissemination in genomic medicine research: Approaches and outcomes from the CSER Consortium.

PURPOSE: There is a critical need for genomic medicine research that reflects and benefits socioeconomically and ancestrally diverse populations. However, disparities in research populations persist, highlighting that traditional study designs and materials may be insufficient or inaccessible to all groups. New approaches can be gained through collaborations with patient/community stakeholders. Although some benefits of stakeholder engagement are recognized, routine incorporation into the design and implementation of genomics research has yet to be realized. METHODS: The National Institutes of Health-funded Clinical Sequencing Evidence-Generating Research (CSER) consortium required stakeholder engagement as a dedicated project component. Each CSER project planned and carried out stakeholder engagement activities with differing goals and expected outcomes. Examples were curated from each project to highlight engagement strategies and outcomes throughout the research lifecycle from development through dissemination. RESULTS: Projects tailored strategies to individual study needs, logistical constraints, and other challenges. Lessons learned include starting early with engagement efforts across project stakeholder groups and planned flexibility to enable adaptations throughout the project lifecycle. CONCLUSION: Each CSER project used more than 1 approach to engage with relevant stakeholders, resulting in numerous adaptations and tremendous value added throughout the full research lifecycle. Incorporation of community stakeholder insight improves the outcomes and relevance of genomic medicine research.

Genetic counselor roles in the undiagnosed diseases network research study: Clinical care, collaboration, and curation.

Genetic counselors (GCs) are increasingly filling important positions on research study teams, but there is limited literature describing the roles of GCs in these settings. GCs on the Undiagnosed Diseases Network (UDN) study team serve in a variety of roles across the research network and provide an opportunity to better understand genetic counselor roles in research. To quantitatively characterize the tasks regularly performed and professional fulfillment derived from these tasks, two surveys were administered to UDN GCs in a stepwise fashion. Responses from the first, free-response survey elicited the scope of tasks which informed development of a second structured, multiple-select survey. In survey 2, respondents were asked to select which roles they performed. Across 19 respondents, roles in survey 2 received a total of 947 selections averaging approximately 10 selections per role. When asked to indicate what roles they performed, respondent selected a mean of 50 roles (range 22-70). Survey 2 data were analyzed via thematic coding of responses and hierarchical cluster analysis to identify patterns in responses. From the thematic analysis, 20 non-overlapping codes emerged in seven categories: clinical interaction and care, communication, curation, leadership, participant management, research, and team management. Three themes emerged from the categories that represented the roles of GCs in the UDN: clinical care, collaboration, and curation. Cluster analyses showed that responses were more similar among individuals at the same institution than between institutions. This study highlights the ways GCs apply their unique skill set in the context of a clinical translational research network. Additionally, findings from this study reinforce the wide applicability of core skills that are part of genetic counseling training. Clinical literacy, genomics expertise and analysis, interpersonal, psychosocial and counseling skills, education, professional practice skills, and an understanding of research processes make genetic counselors well suited for such roles and poised to positively impact research experiences and outcomes for participants.

High Area Deprivation Index is Associated With Discharge to Foster Care in Pediatric Patients With Non-accidental Trauma.

BACKGROUND: Outcomes after non-accidental trauma (NAT) have been shown to be impacted by social determinants of health. Our study aims to investigate the association between NAT, patient demographics, neighborhood disadvantage as measured by the Area Deprivation Index (ADI), and patient disposition. METHODS: An 8-year retrospective chart review was conducted in pediatric patients presenting to our level I trauma center with suspected NAT. Patient demographics, ADI, injury severity score (ISS), Glasgow coma scale (GCS), length of stay, and discharge disposition were analyzed using univariate and multivariate techniques to evaluate associations between patient demographics, injury severity, and patient outcomes. RESULTS: A total of 84 patients were admitted with suspected NAT. Of our study population, 45% of patients were White and 26% were Black. Black children were overrepresented in this cohort compared to general population means, while White children were underrepresented (p < 0.05). Median ADI was 6.5 (IQR 4.0-8.0). Of our cohort, 65 patients were discharged home, and 18 patients to foster care. One patient in our cohort died. An ADI >6 was the only factor significantly associated with discharge to foster care. This association held on both univariate (OR 1.4; 95% CI 1.07-1.84, p = 0.02) and multivariate (OR 1.4; 95% CI 1.05-1.86, p = 0.02) analyses. CONCLUSION: Our study found that neighborhood disadvantage, as measured by ADI, is an independent predictor of discharge to foster care. Additionally, Black children remain over-represented in the NAT population referred to our institution, including those discharged to foster care. Efforts to address healthcare disparities and community-based NAT prevention and reunification programs are necessary. TYPE OF STUDY: Prognosis Study (Retrospective Case-Control Study). LEVEL OF EVIDENCE: Level III.

Treatment trends and clinical outcomes of endovascular embolization for unruptured intracranial aneurysms in the pediatric population.

BACKGROUND: Owing to the relative rarity of unruptured intracranial aneurysms (UIAs) in the pediatric population, evidence regarding treatment modalities and clinical outcomes remains limited. OBJECTIVE: To characterize the use and clinical outcomes of endovascular therapy (EVT) and microsurgical clipping (MSC) for pediatric UIAs over a two-decade interval using a large national registry. METHODS: Pediatric (<18 years of age) UIA hospitalizations were identified in the National Inpatient Sample from 2002 to 2019. Temporal use and clinical outcomes were compared for treatment with EVT and MSC. RESULTS: Among 734 UIAs identified, 64.9% (n=476) were treated with EVT. Use of EVT significantly increased during the study period from 54.3% (2002-2004) to 78.6% (2017-2019) (P=0.002 by Cochrane-Armitage test). In comparison with those treated with MSC, pediatric patients treated with EVT demonstrated higher rates of favorable outcomes (discharge to home without services) (96.0% vs 91.1%, P=0.006), shorter durations of hospital stay (4.6 vs 10.0 days, P<0.001), and lower rates of ischemic or hemorrhagic procedural-related complications (1% vs 4%, P=0.010). Conservative management also increased significantly over the study period (P<0.001 by Cochrane-Armitage test). CONCLUSION: A retrospective evaluation of nearly 20 years of population-level data from the United States demonstrates increasing use of EVT for the treatment of pediatric UIAs, with high rates of favorable outcomes and shorter hospital stays in comparison with those treated with microsurgery.