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Aims: To describe unit leadership and climates for evidence-based practice implementation and test for differences in unit leader and staff nurses' perceptions within maternal-infant units., Design: A cross-sectional descriptive study., Methods: A convenience sample of maternal-infant unit leaders and nurses (labour, postpartum, neonatal intensive care, paediatrics) from four Midwestern United States hospitals completed a survey including the Implementation Leadership Scale (ILS) and Implementation Climate Scale (ICS). Descriptive statistics described items, subscales and total scores. Independent t-tests with Bonferroni correction tested for differences in perceptions., Results: A total of 470 nurses and 21 unit leaders responded, representing 17 units. Ratings of unit leadership and climates for implementation were modest at best [ICS: M = 2.17 (nurses), 2.41 (leaders); ILS: M = 2.4 (nurses), 2.98 (leaders)]. Unit leader ratings were statistically significant and higher than nurse ratings., Conclusion: This study is one of the first to describe unit leadership and climates for implementation in maternal-infant health. To improve outcomes and equity in maternal-infant health, attention on leadership behaviours and unit climates for evidence-based practice implementation is needed., Implications for the Profession: Nurse leaders are encouraged to evaluate their leadership behaviours and the unit climates they facilitate, and work to improve areas of concern or where staff perceptions differ. Staff nurses should work with their leaders to identify resources and rewards/recognition which support and facilitate EBP implementation., Impact: This study addressed a gap in research examining the social dynamic factors of unit leadership and climate for evidence-based practice implementation in maternal-infant units. Leadership behaviours for implementation and unit climate were rated moderately by both staff and leaders. Unit leaders rated their implementation leadership and climates higher in almost all items. This study is relevant to unit leaders and nurses in maternal-infant units in the United States., Reporting Method: This study adhered to STROBE guidelines., Patient or Public Contribution: No patient or public contribution., (© 2024 The Author(s). Journal of Advanced Nursing published by John Wiley & Sons Ltd.)

Introduction: Genetic testing is used across medical disciplines leading to unprecedented demand for genetic services. This has resulted in excessive waitlists and unsustainable pressure on the standard model of genetic healthcare. Alternative models are needed; e-health tools represent scalable and evidence-based solution. We aim to evaluate the effectiveness of the Genetics Navigator, an interactive patient-centred digital platform that supports the collection of medical and family history, provision of pregenetic and postgenetic counselling and return of genetic testing results across paediatric and adult settings., Methods and Analysis: We will evaluate the effectiveness of the Genetics Navigator combined with usual care by a genetics clinician (physician or counsellor) to usual care alone in a randomised controlled trial. One hundred and thirty participants (adults patients or parents of paediatric patients) eligible for genetic testing through standard of care will be recruited across Ontario genetics clinics. Participants randomised into the intervention arm will use the Genetics Navigator for pretest and post-test genetic counselling and results disclosure in conjunction with their clinician. Participants randomised into the control arm will receive usual care, that is, clinician-delivered pretest and post-test genetic counselling, and results disclosure. The primary outcome is participant distress 2 weeks after test results disclosure. Secondary outcomes include knowledge, decisional conflict, anxiety, empowerment, quality of life, satisfaction, acceptability, digital health literacy and health resource use. Quantitative data will be analysed using statistical hypothesis tests and regression models. A subset of participants will be interviewed to explore user experience; data will be analysed using interpretive description. A cost-effectiveness analysis will examine the incremental cost of the Navigator compared with usual care per unit reduction in distress or unit improvement in quality of life from public payer and societal perspectives., Ethics and Dissemination: This study was approved by Clinical Trials Ontario. Results will be shared through stakeholder workshops, national and international conferences and peer-reviewed journals., Trial Registration Number: NCT06455384., Competing Interests: Competing interests: YB and MC are cofounders of Genetics Adviser., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

45,X/46,XY chromosomal mosaicism presents a range of clinical manifestations, including phenotypes from Turner syndrome through genital abnormalities to apparently unaffected phenotypic males; however, the full clinical spectrum has not yet been fully delineated since prior studies on the clinical phenotype and associated risk of gonadal tumors included small cohorts and limited follow-up. To better describe the clinical manifestations and long-term outcome of patients with 45,X/46,XY mosaicism. We conducted a retrospective chart review of patients with 45,X/46,XY from three health centers (Hospital for Sick Children and Mount Sinai Hospital in Canada, and University of Pittsburgh Medical Center in United States). Of 100 patients with 45,X/46,XY karyotype, 47 were raised as females and 53 as males. Females were significantly shorter than males (p = 0.04) and height Z-score was significantly decreased with age for both genders (p = 0.02). Growth hormone (GH) treatment did not result in a significant height increase compared to the untreated group (p = 0.5). All females required puberty induction in contrast to majority of males. Five females were diagnosed with gonadal tumors, while no males were affected. Around 58% of patients exhibited at least one Turner syndrome stigmata. This study expands the clinical spectrum, long-term outcomes, and associated tumor risk in a large cohort of patients with 45,X/46,XY mosaicism. Additionally, it highlights our experience with GH therapy and prophylactic gonadectomy., (© 2023 Wiley Periodicals LLC.)

Objective: Increasing numbers of Canadians living with complex, life-limiting conditions demand high-quality palliative care. Timely access to palliative care can help to reduce stress, improve quality of life, and provide relief for patients and their families. The purpose of this study is to explore the experiences of family physicians (FPs) regarding the decision and process of introducing palliative care to patients with chronic diseases., Methods: Interpretive description methodology was used to guide the investigation of the research question. Thirteen Calgary Zone FPs participated in individual interviews. Data was collected iteratively and analyzed using constant comparative analysis., Results: Analysis of interviews identified the overarching themes of dignity and empowerment, which describe the experience of FPs introducing palliative care to chronically ill patients. Four subthemes were woven throughout, including the art of conversation, therapeutic relationships, timing, and preparation of the patient and family., Discussion: While the benefits of palliative conversations are widely accepted, a deeper understanding of how FPs can be supported in developing this aspect of their practice is needed. Understanding their experience provides knowledge that can serve as a framework for future education, mentorship, and competency development., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Keys to Embracing Aging (KTEA) is a community-based educational program that introduces and reinforces health behaviors that promote healthy aging. Data from 12 distinct KTEA lessons delivered by 42 Cooperative Extension educators to 764 unique participants across one year were examined to determine the program's impact on attitude, diet, physical activity, brain health, belonging, staying up-to-date, safety, health, stress, finances, sleep, and self-care. The most frequent immediate behavior changes occurred in practicing self-care, developing a positive attitude, and making safe choices. And longer-term behavior change was reported in the areas of maintaining a positive attitude, brain health, and healthy eating. Participants discussed challenges related to time, commitment, and maintaining a habitual routine of healthy behaviors. KTEA outcomes indicated a promising community-based educational program and supported continued investigation and development in health promotion within Cooperative Extension. Future research is needed to examine the versatility and long-term effects of the KTEA intervention.

Chatbots, web-based artificial intelligence tools that simulate human conversation, are increasingly in use to support many areas of genomic medicine. However, patient preferences towards using chatbots across the range of clinical settings are unknown. We conducted a qualitative study with individuals who underwent genetic testing for themselves or their child. Participants were asked about their preferences for using a chatbot within the genetic testing journey. Thematic analysis employing interpretive description was used. We interviewed 30 participants (67% female, 50% 50 + years). Participants considered chatbots to be inefficient for very simple tasks (e.g., answering FAQs) or very complex tasks (e.g., explaining results). Chatbots were acceptable for moderately complex tasks where participants perceived a favorable return on their investment of time and energy. In addition to achieving this "sweet spot," participants anticipated that their comfort with chatbots would increase if the chatbot was used as a complement to but not a replacement for usual care. Participants wanted a "safety net" (i.e., access to a clinician) for needs not addressed by the chatbot. This study provides timely insights into patients' comfort with and perceived limitations of chatbots for genomic medicine and can inform their implementation in practice., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To develop and evaluate a storytelling communication facilitation tool designed to help parents overcome barriers to discussing a complex multisystem genetic diagnosis with their affected children, using 22q11.2 deletion syndrome (22q11DS) as an exemplar condition., Methods: A story telling communication facilitation tool (SCFT), entitled 22q and Me , was developed for a target audience of children with 22q11DS aged 9 to 12. The SCFT was evaluated by 14 parents to assess usability and utility by comparing responses to survey questions before and after viewing the SCFT, using a Likert scale., Results: After viewing 22q and Me , parents reported that barriers to discussion were mitigated. Participants indicated they felt more comfortable and better prepared to talk to their children about 22q11DS and worried less that the diagnosis would affect their children's self-esteem. Parents described 22q and Me as engaging and able to address parental concerns., Conclusion: 22q and Me was found to be an effective tool for increasing parental comfort and ability to talk to their children about their diagnosis of 22q11DS., Innovation: This novel storytelling communication facilitation tool can serve as a model for the development of other educational tools geared at facilitating disclosure and discussion of other genetic conditions., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Authors.)

Aims/purpose: To investigate Leber congenital amaurosis (LCA) patients' expectations, decision-making processes and gene therapy-related concerns., Methods: Using a qualitative approach, we explored perceptions of gene therapy and clinical trials among individuals with LCA. Young adults with a clinical diagnosis of LCA were recruited through the Ocular Genetics Programme at the Hospital for Sick Children. Semi-structured interviews were conducted with ten patients and analysed following the principles of qualitative description., Results: Study participants were aware of ongoing gene therapy research trials and actively sought information regarding advances in ophthalmology and vision restoration. The majority of participants would enrol or were enrolled in a gene-replacement therapy trial, while a minority was ambivalent or would not enrol if provided an opportunity. Participants attributed different values to clinical trials, which influenced their willingness to participate. Intrinsic factors related to coping, adaptation to vision loss and resilience also influenced decision-making., Discussion: This study highlights the complex factors involved in gene-therapy-related decision-making and acts as a proponent for adopting patient-centred care strategies when counselling individuals considering gene therapy or clinical trial participation., (© 2021. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Objective: We aimed to characterize male and female adolescents' use of e-cigarettes, cigarettes and dual use, and seven symptoms of nicotine/tobacco dependence using four waves of national data from the Population Assessment of Tobacco and Health (PATH) Study., Methods: The analytic sample included 2902 adolescents 12-17 years who indicated past 30-day e-cigarette or cigarette use at least once between 2013-2018. Items from the Wisconsin Inventory of Smoking Dependence Motives (WISDM-68) were used to report dependence symptoms., Results: Compared to cigarette users, exclusive e-cigarette users reported fewer symptoms of nicotine dependency. There were no differences between males and females and the odds of any reported dependency symptom. Among cigarette only users, the odds of indicating that their tobacco use helps them think better (adjusted odds ratio (AOR) = 2.38, 95% confidence interval (CI) = 1.08, 5.23) and wanting tobacco after waking up (AOR = 5.50, 95% CI = 1.10, 27.5) was higher among females when compared to males., Conclusions: The current study extends earlier findings regarding subgroup differences in nicotine/tobacco dependency symptoms participating in the PATH Study and highlights the importance of identifying nicotine/tobacco dependency symptoms when counseling adolescent males and females., Competing Interests: Conflict of Interest Disclosure Statement The authors have no conflicts of interest to report.

Introduction: The high demand for genetic tests and limited supply of genetics professionals has created a need for alternative service delivery models. Digital tools are increasingly being used to support multiple points in the genetic testing journey; however, none are transferable across multiple clinical specialties and settings nor do they encompass the entire trajectory of the journey. We aim to evaluate the effectiveness of the Genetics Adviser, an interactive, patient-facing, online digital health tool that delivers pre-test counselling, provides support during the waiting period for results, and returns results with post-test counselling, encompassing the entire patient genetic testing journey., Methods and Analysis: We will compare the Genetics Adviser paired with a brief genetic counselling session to genetic counselling alone in a randomised controlled trial. One hundred and forty patients who previously received uninformative genetic test results for their personal and family history of cancer will be recruited from familial cancer clinics in Toronto and offered all clinically significant results from genomic sequencing. Participants randomised into the intervention arm will use the Genetics Adviser to learn about genomic sequencing, receive pre-test counselling, support during the waiting period and results, supplemented with brief counselling from a genetic counsellor. Participants in the control arm will receive standard pre-test and post-test counselling for genomic sequencing from a genetic counsellor. Our primary outcome is decisional conflict following pre-test counselling from the Genetics Adviser+genetic counsellor or counsellor alone. Secondary outcomes include: knowledge, satisfaction with decision-making, anxiety, quality of life, psychological impact of results, empowerment, acceptability and economic impact for patients and the health system. A subset of patients will be interviewed to assess user experience., Ethics and Dissemination: This study has been approved by Clinical Trials Ontario Streamlined Research Ethics Review System (REB#20-035). Results will be shared through stakeholder workshops, national and international conferences and peer-reviewed journals., Trial Registration Number: NCT04725565., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Demonstrating the clinical utility of genetic testing is fundamental to clinical adoption and reimbursement, but standardized definitions and measurement strategies for this construct do not exist. The Clinician-reported Genetic testing Utility InDEx (C-GUIDE) offers a novel measure to fill this gap. This study assessed its validity and inter-rater reliability., Methods: Genetics professionals completed C-GUIDE after disclosure of test results to patients. Construct validity was assessed using regression analysis to measure associations between C-GUIDE and global item scores as well as potentially explanatory variables. Inter-rater reliability was assessed by administering a vignette-based survey to genetics professionals and calculating Krippendorff's α., Results: On average, a 1-point increase in the global item score was associated with an increase of 3.0 in the C-GUIDE score (P < .001). Compared with diagnostic results, partially/potentially diagnostic and nondiagnostic results were associated with a reduction in C-GUIDE score of 9.5 (P < .001) and 10.2 (P < .001), respectively. Across 19 vignettes, Krippendorff's α was 0.68 (95% CI: 0.63-0.72)., Conclusion: C-GUIDE showed acceptable validity and inter-rater reliability. Although further evaluation is required, C-GUIDE version 1.2 can be useful as a standardized approach to assess the clinical utility of genetic testing., Competing Interests: Conflict of Interest This work was funded by the Canadian Institutes of Health Research. The authors declare no conflict of interest., (Copyright © 2021 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

Objective: Describe the prevalence, perinatal and long-term outcomes of Beckwith-Wiedemann syndrome (BWS) among prenatally detected omphaloceles., Methods: All prenatally diagnosed omphaloceles from 2010 to 2015 within a single tertiary care centre were identified. An echocardiogram and detailed fetal ultrasound were performed, and amniocentesis was offered with karyotype/microarray analysis and BWS molecular testing. Perinatal, neonatal, and long-term outcomes were retrieved for BWS cases., Results: Among 92 omphaloceles, 62 had additional anomalies. Abnormal karyotypes were identified in 23/62 (37%) non-isolated and 2/30 (7%) isolated cases. One BWS case (5%) was identified among non-isolated omphaloceles and six BWS cases (37.5%) were identified among isolated omphaloceles after exclusion of aneuploidy. Among 19 BWS cases, 21% were conceived by ART. All omphaloceles underwent primary closure. Prenatally, macrosomia and polyhydramnios were seen in 42%. Macroglossia and nephromegaly were more commonly detected postnatally. Preterm birth occurred in 10/19 (53%) cases and cesarean deliveries were performed in 7/19 (40%) cases. Overall mortality was 20% (4/19). Embryonal tumors were diagnosed in 2/16 (12.5%) children, and neurodevelopmental outcomes were normal in 9/12 (75%) survivors., Conclusions: After excluding aneuploidy, BWS was identified in 37.5% and 5% of isolated and non-isolated omphaloceles, respectively. Omphaloceles were small-moderate size with good long-term surgical and neurodevelopmental outcomes when isolated., (© 2021 John Wiley & Sons Ltd.)

Purpose: Alternative models of genetic counseling are needed to meet the rising demand for genomic sequencing. Digital tools have been proposed as a method to augment traditional counseling and reduce burden on professionals; however, their role in delivery of genetic counseling is not established. This study explored the role of the Genomics ADvISER, a digital decision aid, in delivery of genomic counseling., Methods: We performed secondary analysis of 52 pretest genetic counseling sessions that were conducted over the course of a randomized controlled trial evaluating the effectiveness of the Genomics ADvISER. As part of the trial, participants were randomized to receive standard counseling or use the tool and then speak with a counselor. A qualitative interpretive description approach using thematic analysis and constant comparison was used for analysis., Results: In the delivery of genomic counseling, the Genomics ADvISER contributed to enhancing counseling by (1) promoting informed dialogue, (2) facilitating preference-sensitive deliberation, and (3) deepening personalization of decisions, all of which represent fundamental principles of patient-centered care: providing clear high-quality information, respecting patients' values, preferences, and expressed needs, and providing emotional support., Conclusion: This study demonstrates that our digital tool contributed to enhancing patient-centered care in the delivery of genomic counseling.

Background: High-quality PhD nursing student mentorship facilitates student and program success. Extant literature recommends evaluating and improving mentorship to foster optimal PhD student development. However, a comprehensive measure capturing all aspects of mentorship salient to PhD nursing student wellbeing and success is not available., Objectives: The purpose of this pilot study was to develop a new instrument - the Collaboration for Leadership and Innovation in Mentoring (CLIM) - for quantifying important components of PhD student mentorship in nursing, and to preliminarily test its psychometric properties (content validity, sensitivity, test-retest reliability)., Design: The study employed a cross-sectional design., Setting: The CLIM instrument was administered to nursing PhD students at a public state university in the United States., Participants: Sixteen nursing PhD students at various stages in their degree progression completed the instrument., Methods: PhD nursing students developed unique items based on qualitative data collected by the University using an Appreciative Inquiry framework. Seven nursing and non-nursing experts with experience in PhD mentorship evaluated content validity. After revisions, the final 44-item instrument was administered at two time points (one month apart) to allow assessment of test-retest reliability. Test-retest reliability was evaluated using Spearman-rank correlations and data from students with ≥1 year of experience with their mentor., Results: Response rates were 94% for both administrations (n = 16). The instrument's overall Content Validity Index (CVI) was 0.91 (p = 0.05). Test-retest analyses resulted in high correlations (r = 0.91, p < 0.001), further supporting reliability of the CLIM instrument., Conclusions: Preliminary evidence suggests that the CLIM instrument is a reliable instrument of PhD mentorship in nursing. However, additional testing in larger and more diverse graduate student populations is needed to evaluate internal consistency reliability, among other psychometric properties., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Although cure rates for Wilms tumours (WT) are high, many patients receive therapy with attendant long-term complications. Our goal was to stratify WT using genome-wide analyses to identify candidate molecular features for patients who would benefit from a reduction in therapy., Methods: We generated DNA methylation and exome sequencing data on WT-kidney pairs (n = 57) and unpaired tumours (n = 27) collected either at our centre or by the Children's Oncology Group. Samples were divided into a discovery set (n = 32) and validation set (n = 52)., Results: Analysis of DNA methylation revealed two subgroups of WT with distinct features. Subgroup A has a similar DNA methylation profile to mature kidney, while Subgroup B has genome-wide dysregulation of DNA methylation. The rate of non-synonymous missense mutations and segmental chromosomal aberrations was higher in Subgroup B tumours, suggesting that this group has genome instability related to its epigenetic state. Subgroup A had a higher proportion of cases of bilateral disease. Tumours with high-risk histology or from patients who relapsed were only found in Subgroup B., Conclusion: We have identified subgroup-specific molecular events that could inform future work supporting more targeted therapeutic approaches and patient stratification. We propose a novel developmental tumour model based on these findings.

Pine Island Glacier and Thwaites Glacier in the Amundsen Sea Embayment are among the fastest changing outlet glaciers in West Antarctica with large consequences for global sea level. Yet, assessing how much and how fast both glaciers will weaken if these changes continue remains a major uncertainty as many of the processes that control their ice shelf weakening and grounding line retreat are not well understood. Here, we combine multisource satellite imagery with modeling to uncover the rapid development of damage areas in the shear zones of Pine Island and Thwaites ice shelves. These damage areas consist of highly crevassed areas and open fractures and are first signs that the shear zones of both ice shelves have structurally weakened over the past decade. Idealized model results reveal moreover that the damage initiates a feedback process where initial ice shelf weakening triggers the development of damage in their shear zones, which results in further speedup, shearing, and weakening, hence promoting additional damage development. This damage feedback potentially preconditions these ice shelves for disintegration and enhances grounding line retreat. The results of this study suggest that damage feedback processes are key to future ice shelf stability, grounding line retreat, and sea level contributions from Antarctica. Moreover, they underline the need for incorporating these feedback processes, which are currently not accounted for in most ice sheet models, to improve sea level rise projections., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

Purpose: To assess participants' acceptability of the FOCUS program, a psychoeducational intervention, delivered to multiple patient-caregiver dyads in a small-group format., Participants & Setting: A total of 72 adults diagnosed with cancer and their caregivers (36 dyads) who participated in 1 of 11 FOCUS programs delivered at two Cancer Support Community affiliates., Methodologic Approach: A pre-/postintervention design was used to implement the FOCUS program. The FOCUS Satisfaction Instrument measured participants' satisfaction with the program, usefulness of the materials, helpfulness in coping with cancer, duplication of services, willingness to recommend the program to others, and the most and least beneficial aspects. Descriptive statistics, t tests, and content analysis were used., Findings: Most participants reported that the program did not duplicate services, that it helped them cope with cancer, and that they would recommend the program to others. The most beneficial aspects of the program were the group format and the dyadic approach., Implications for Nursing: A group format and dyadic approach to address the psychosocial impact of cancer is highly valued by individuals with cancer and their caregivers. Nurses are well positioned to lead implementation of programs like the FOCUS program that complement other cancer support services.

Consanguinity, the union between two individuals who are related as second cousins or closer, is a long-standing and respected tradition in many communities. Although there are social and economic benefits of consanguineous unions, offspring are at increased risk of having an inherited genetic condition or congenital anomaly. Genetic counseling services for consanguinity are available to couples at many centers. However, little is known about patient expectations of and experiences with genetic counseling for this indication, or their perspectives on genetic screening relevant to family planning, such as expanded carrier screening (ECS). This exploratory qualitative study involved interviews with 13 individuals who had recently received preconception or prenatal genetic counseling for consanguinity at a single center. We sought to gain insight into their expectations for the genetic counseling session, experiences discussing family history and reproductive risks with the genetic counselor, and views on ECS. Interview transcripts were analyzed using an interpretive descriptive approach. Data analysis revealed three main themes: (a) anticipation balances apprehension before the appointment; (b) genetic counseling reduces anxiety and empowers; and (c) the need for wider information dissemination about consanguinity-related risks and genetic services. Our findings support the personal utility of genetic counseling for consanguinity and demonstrate the need for increased visibility and access to genetics information, counseling, and testing relevant to this patient population., (© 2019 National Society of Genetic Counselors.)

Pharmacogenomic (PGx) tests represent significant advances in precision medicine. Our aim was to explore perceptions following the return of PGx results, medication management, and disclosure to providers. We surveyed clients who had PGx testing and conducted a chart review of PGx results. Respectively, 84% and 94% of participants found pre- and post-test genetic counseling helpful. There was a significant difference in disclosure, while 6% disclosed results to a pharmacist, 50% disclosed to a physician. Qualitative analysis identified three themes: 1) psychological response; 2) perceived utility; 3) experiences with disclosure. Our study supports the provision of genetic counseling for a non-disease related genetic test. Benefits of PGx testing can be optimized by the collaboration of physicians, pharmacists, genetic counselors and patients.

Background: Hereditary tumor predisposition syndromes (HTPSs) are being recognized more frequently in the etiology of pediatric cancer. Previous research indicates that disclosure of tumor susceptibility is a significant event in adolescents' lives. Insight into adolescents' adjustment to knowledge of their syndromes can guide healthcare delivery, particularly genetic counseling. This study explored the experiences of adolescents with hereditary tumor predisposition and their perceptions of living at risk., Methods: Seven adolescents, ages 14 to 17, representing six different childhood-onset HTPSs, were purposively sampled and interviewed using a study-specific semistructured interview guide. We explored the disclosure process, support systems, and the perceived benefits and harms of knowledge of hereditary tumor susceptibility. Interview transcripts were analyzed via interpretive description., Results: Three major themes emerged from the data: (1) The benefits of knowledge outweigh the harms; (2) context surrounding genetic testing must be recognized; and (3) self-concept is influenced but not defined by tumor risk., Conclusions: We conclude that adolescents recognize the challenges associated with awareness of tumor predisposition but may also identify positive aspects in their experiences, reflecting a changed life perspective. Results of this exploratory study suggest strategies that can guide pretest and posttest genetic counseling of adolescents for HTPSs, facilitating the adaptive incorporation of genetic information into an adolescent's self-concept., (© 2018 Wiley Periodicals, Inc.)

The introduction of chromosomal microarray (CMA) into the prenatal setting has involved considerable deliberation due to the wide range of possible outcomes (e.g., copy number variants of uncertain clinical significance). Such issues are typically discussed in pre-test counseling for pregnant women to support informed decision-making regarding prenatal testing options. This research study aimed to assess the level of informed decision-making with respect to prenatal CMA and the factor(s) influencing decision-making to accept CMA for the selected prenatal testing procedure (i.e., chorionic villus sampling or amniocentesis). We employed a questionnaire that was adapted from a three-dimensional measure previously used to assess informed decision-making with respect to prenatal screening for Down syndrome and neural tube defects. This measure classifies an informed decision as one that is knowledgeable, value-consistent, and deliberated. Our questionnaire also included an optional open-ended question, soliciting factors that may have influenced the participants' decision to accept prenatal CMA; these responses were analyzed qualitatively. Data analysis on 106 participants indicated that 49% made an informed decision (i.e., meeting all three criteria of knowledgeable, deliberated, and value-consistent). Analysis of 59 responses to the open-ended question showed that "the more information the better" emerged as the dominant factor influencing both informed and uninformed participants' decisions to accept prenatal CMA. Despite learning about the key issues in pre-test genetic counseling, our study classified a significant portion of women as making uninformed decisions due to insufficient knowledge, lack of deliberation, value-inconsistency, or a combination of these three measures. Future efforts should focus on developing educational approaches and counseling strategies to effectively increase the rate of informed decision-making among women offered prenatal CMA.

Whole-genome sequencing (WGS) as a first-tier diagnostic test could transform medical genetic assessments, but there are limited data regarding its clinical use. We previously showed that WGS could feasibly be deployed as a single molecular test capable of a higher diagnostic rate than current practices, in a prospectively recruited cohort of 100 children meeting criteria for chromosomal microarray analysis. In this study, we report on the added diagnostic yield with re-annotation and reanalysis of these WGS data ~2 years later. Explanatory variants have been discovered in seven (10.9%) of 64 previously undiagnosed cases, in emerging disease genes like HMGA2. No new genetic diagnoses were made by any other method in the interval period as part of ongoing clinical care. The results increase the cumulative diagnostic yield of WGS in the study cohort to 41%. This represents a greater than 5-fold increase over the chromosomal microarrays, and a greater than 3-fold increase over all the clinical genetic testing ordered in practice. These findings highlight periodic reanalysis as yet another advantage of genomic sequencing in heterogeneous disorders. We recommend reanalysis of an individual's genome-wide sequencing data every 1-2 years until diagnosis, or sooner if their phenotype evolves.

PurposeGenetic testing is an integral diagnostic component of pediatric medicine. Standard of care is often a time-consuming stepwise approach involving chromosomal microarray analysis and targeted gene sequencing panels, which can be costly and inconclusive. Whole-genome sequencing (WGS) provides a comprehensive testing platform that has the potential to streamline genetic assessments, but there are limited comparative data to guide its clinical use.MethodsWe prospectively recruited 103 patients from pediatric non-genetic subspecialty clinics, each with a clinical phenotype suggestive of an underlying genetic disorder, and compared the diagnostic yield and coverage of WGS with those of conventional genetic testing.ResultsWGS identified diagnostic variants in 41% of individuals, representing a significant increase over conventional testing results (24%; P = 0.01). Genes clinically sequenced in the cohort (n = 1,226) were well covered by WGS, with a median exonic coverage of 40 × ±8 × (mean ±SD). All the molecular diagnoses made by conventional methods were captured by WGS. The 18 new diagnoses made with WGS included structural and non-exonic sequence variants not detectable with whole-exome sequencing, and confirmed recent disease associations with the genes PIGG, RNU4ATAC, TRIO, and UNC13A.ConclusionWGS as a primary clinical test provided a higher diagnostic yield than conventional genetic testing in a clinically heterogeneous cohort.