Trisomy 21 and Congenital Heart Disease: Impact on Health and Functional Outcomes From Birth Through Adolescence: A Scientific Statement From the American Heart Association.

Due to improvements in recognition and management of their multisystem disease, the long-term survival of infants, children, and adolescents with trisomy 21 and congenital heart disease now matches children with congenital heart disease and no genetic condition in many scenarios. Although this improved survival is a triumph, individuals with trisomy 21 and congenital heart disease have unique and complex care needs in the domains of physical, developmental, and psychosocial health, which affect functional status and quality of life. Pulmonary hypertension and single ventricle heart disease are 2 known cardiovascular conditions that reduce life expectancy in individuals with trisomy 21. Multisystem involvement with respiratory, endocrine, gastrointestinal, hematological, neurological, and sensory systems can interact with cardiovascular health concerns to amplify adverse effects. Neurodevelopmental, psychological, and functional challenges can also affect quality of life. A highly coordinated interdisciplinary care team model, or medical home, can help address these complex and interactive conditions from infancy through the transition to adult care settings. The purpose of this Scientific Statement is to identify ongoing cardiovascular and multisystem, developmental, and psychosocial health concerns for children with trisomy 21 and congenital heart disease from birth through adolescence and to provide a framework for monitoring and management to optimize quality of life and functional status.

Everyday Clinical Ethics: Essential Skills and Educational Case Scenarios.

Bioethics conjures images of dramatic healthcare challenges, yet everyday clinical ethics issues unfold regularly. Without sufficient ethical awareness and a relevant working skillset, clinicians can feel ill-equipped to respond to the ethical dimensions of everyday care. Bioethicists were interviewed to identify the essential skills associated with everyday clinical ethics and to identify educational case scenarios to illustrate everyday clinical ethics. Individual, semi-structured interviews were conducted with a convenience sample of bioethicists. Bioethicists were asked: (1) What are the essential skills required for everyday clinical ethics? And (2) What are potential educational case scenarios to illustrate and teach everyday clinical ethics? Participant interviews were analyzed using qualitative content analysis. Twenty-five (25) bioethicists completed interviews (64% female; mean 14.76 years bioethics experience; 80% white). Five categories of general skills and three categories of ethics-specific skills essential for everyday clinical ethics were identified. General skills included: (1) Awareness of Core Values and Self-Reflective Capacity; (2) Perspective-Taking and Empathic Presence; (3) Communication and Relational Skills; (4) Cultural Humility and Respect; and (5) Organizational Understanding and Know-How. Ethics-specific skills included: (1) Ethical Awareness; (2) Ethical Knowledge and Literacy; and (3) Ethical Analysis and Interaction. Collectively, these skills comprise a Toolbox of Everyday Clinical Ethics Skills. Educational case scenarios were identified to promote everyday ethics. Bioethicists identified skills essential to everyday clinical ethics. Educational case scenarios were identified for the purpose of promoting proficiency in this domain. Future research could explore the impact of integrating educational case scenarios on clinicians' ethical competencies.

It is Time to Screen for Homozygous Familial Hypercholesterolemia in the United States.

Homozygous familial hypercholesterolemia (HoFH) is an ultra-rare inherited condition that affects approximately one in 300,000 people. The disorder is characterized by extremely high, life-threatening levels of low-density lipoprotein (LDL) cholesterol from birth, leading to significant premature cardiovascular morbidity and mortality, if left untreated. Homozygous familial hypercholesterolemia is severely underdiagnosed and undertreated in the United States (US), despite guidelines recommendations for universal pediatric lipid screening in children aged 9-11. Early diagnosis and adequate treatment are critical in averting premature cardiovascular disease in individuals affected by HoFH. Yet, an unacceptably high number of people living with HoFH remain undiagnosed, misdiagnosed, and/or receive a late diagnosis, often after a major cardiovascular event. The emergence of novel lipid-lowering therapies, along with the realization that diagnosis is too often delayed, have highlighted an urgency to implement policies that ensure timely detection of HoFH in the US. Evidence from around the world suggests that a combination of universal pediatric screening and cascade screening strategies constitutes an effective approach to identifying heterozygous familial hypercholesterolemia (HeFH). Nevertheless, HoFH and its complications manifest much earlier in life compared to HeFH. To date, little focus has been placed on the detection of HoFH in very young children and/or infants. The 2023 Updated European Atherosclerosis Society Consensus Statement on HoFH has recommended, for the first time, broadening pediatric guidelines to include lipid screening of newborn infants. Some unique aspects of HoFH need to be considered before implementing newborn screening. As such, insights from pilot studies conducted in Europe may provide some preliminary guidance. Our paper proposes a set of actionable measures that states can implement to reduce the burden of HoFH. It also outlines key research and policy gaps that need to be addressed in order to pave the way for universal newborn screening of HoFH in the US.

Being a "Good Parent" to a NICU Infant With a Major Congenital Anomaly.

BACKGROUND: In the United States, up to one-third of infants with a congenital anomaly require neonatal intensive care unit (NICU) hospitalization. Parents of these infants may have different decision-making priorities, which may be influenced by the timing of the infant's diagnosis. PURPOSE: (1) To compare the ranked importance of decision-making beliefs for parents of infants who received a prenatal versus postnatal congenital diagnosis and (2) explore how parents describe their decision-making beliefs. METHODS: A cross-sectional, sequential mixed-methods pilot design was applied to collect quantitative data using the Good Parent Ranking Exercise and further explore parents' decision-making beliefs through qualitative interviews. Maximum difference scaling/hierarchical Bayes estimation and content analysis were used to analyze the quantitative and qualitative data, respectively. RESULTS: Forty mothers completed the Good Parent Ranking Exercise and 20 mothers completed qualitative interviews. Four of the top 5 ranked parenting beliefs were shared by mothers in the prenatal and postnatal groups. Mothers in the postnatal group ranked "focusing on my child's quality of life" higher. Qualitative interviews revealed that previously identified decision-making beliefs were consistent in this NICU parent population, with 1 additional belief identified. Mixed-methods analysis revealed high concordance between the prenatal and postnatal groups. IMPLICATIONS FOR PRACTICE: NICU nurses need to know that decision-making beliefs for parents who receive a prenatal versus postnatal congenital diagnosis, while largely similar, may have differences. IMPLICATIONS FOR RESEARCH: Future research should explore decision-making beliefs in demographically diverse parent groups (ie, fathers, partnered vs nonpartnered couples) and effective strategies for promoting NICU parents' decision-making beliefs.

Actionability of unanticipated monogenic disease risks in newborn genomic screening: Findings from the BabySeq Project.

Newborn genomic sequencing (NBSeq) to screen for medically important genetic information is of considerable interest but data characterizing the actionability of such findings, and the downstream medical efforts in response to discovery of unanticipated genetic risk variants, are lacking. From a clinical trial of comprehensive exome sequencing in 127 apparently healthy infants and 32 infants in intensive care, we previously identified 17 infants (10.7%) with unanticipated monogenic disease risks (uMDRs). In this analysis, we assessed actionability for each of these uMDRs with a modified ClinGen actionability semiquantitative metric (CASQM) and created radar plots representing degrees of penetrance of the condition, severity of the condition, effectiveness of intervention, and tolerability of intervention. In addition, we followed each of these infants for 3-5 years after disclosure and tracked the medical actions prompted by these findings. All 17 uMDR findings were scored as moderately or highly actionable on the CASQM (mean 9, range: 7-11 on a 0-12 scale) and several distinctive visual patterns emerged on the radar plots. In three infants, uMDRs revealed unsuspected genetic etiologies for existing phenotypes, and in the remaining 14 infants, uMDRs provided risk stratification for future medical surveillance. In 13 infants, uMDRs prompted screening for at-risk family members, three of whom underwent cancer-risk-reducing surgeries. Although assessments of clinical utility and cost-effectiveness will require larger datasets, these findings suggest that large-scale comprehensive sequencing of newborns will reveal numerous actionable uMDRs and precipitate substantial, and in some cases lifesaving, downstream medical care in newborns and their family members.

Parents' decision-making regarding whether to receive adult-onset only genetic findings for their children: Findings from the BabySeq Project.

PURPOSE: Most professional guidelines recommend against genetic screening for adult-onset only (AO) conditions until adulthood, yet others argue that there may be benefit to disclosing such results. We explored parents' decision-making on this issue in the BabySeq Project, a clinical trial of newborn genomic sequencing. METHODS: We conducted interviews with parents (N = 24) who were given the option to receive actionable AO results for their children. Interviews explored parents' motivations to receive and reasons to decline AO genetic disease risk information, their decision-making process, and their suggestions for supporting parents in making this decision. RESULTS: Parents noted several motivations to receive and reasons to decline AO results. Most commonly, parents cited early intervention/surveillance (n = 11), implications for family health (n = 7), and the ability to prepare (n = 6) as motivations to receive these results. The most common reasons to decline were protection of the child's future autonomy (n = 4), negative effect on parenting (n = 3), and anxiety about future disease (n = 3). Parents identified a number of ways to support parents in making this decision. CONCLUSION: Results show considerations to better support parental decision-making that aligns with their values when offering AO genetic information because it is more commonly integrated into pediatric clinical care.

ACCESS: an empirically-based framework developed by the International Nursing CASCADE Consortium to address genomic disparities through the nursing workforce.

Introduction: Efforts are needed across disciplines to close disparities in genomic healthcare. Nurses are the most numerous trained healthcare professionals worldwide and can play a key role in addressing disparities across the continuum of care. ACCESS is an empirically-based theoretical framework to guide clinical practice in order to ameliorate genomic disparities. Methods: The framework was developed by the International Nursing CASCADE Consortium based on evidence collected between 2005 and 2023 from individuals and families of various ethnic backgrounds, with diverse hereditary conditions, and in different healthcare systems, i.e., Israel, Korea, Switzerland, and several U.S. States. The components of the framework were validated against published scientific literature. Results: ACCESS stands for Advocating, Coping, Communication, cascadE Screening, and Surveillance. Each component is demonstrated in concrete examples of clinical practice within the scope of the nursing profession related to genomic healthcare. Key outcomes include advocacy, active coping, intrafamilial communication, cascade screening, and lifelong surveillance. Advocacy entails timely identification of at-risk individuals, facilitating referrals to specialized services, and informed decision-making for testing. Active coping enhances lifelong adaptation and management of disease risk. Effective intrafamilial communication of predisposition to hereditary disease supports cascade testing of unaffected at-risk relatives. Lifelong surveillance is essential for identifying recurrence, changes in health status, and disease trajectory for life-threatening and for life-altering conditions. Discussion: ACCESS provides a standardized, systematic, situational, and unifying guide to practice and is applicable for nursing and for other healthcare professions. When appropriately enacted it will contribute towards equitable access to genomic resources and services.

Advancing qualitative rare disease research methodology: a comparison of virtual and in-person focus group formats.

BACKGROUND: Rare disease research is hampered in part by the fact that patients are geographically dispersed. Rare disease patient communities are recognized for their use of the internet to learn about their condition and find peer-to-peer support. As such, web-based technologies offer promise for overcoming geographic barriers in rare disease research for many. Qualitative focus groups (FGs) are a widely used methodology used to understand patients and parents/families 'lived experience' and unmet needs is important to improve care for rare diseases. It is unclear if web-enabled (virtual) FGs are comparable to traditional in-person approaches. We conducted in-person (n = 3) and virtual (n = 3) FGs with rare disease patients to determine if virtual FGs produce similar results in-person FGs. RESULTS: Three in-person (n = 33 participants) and three virtual (n = 25 participants) FGs were conducted examining attitudes and beliefs regarding genetic testing and family communication of risk. Participants included 30 males, 18 females, and 10 parents/guardians. Two independent investigators identified excerpts (meaningful sections of text) and coded themes/sub-themes using a codebook. Inter-coder agreement across identified excerpts (n = 530) in both FG formats was 844/875 (96.5%). Two additional investigators reviewed coded excerpts and did not identify additional themes/sub-themes-supporting data saturation across FG formats. Virtual FGs accounted for 303/530 (57.2%) of total excerpts and 957/1721 (55.7%) of all identified themes/sub-themes. Formats were similar in terms of overall number of excerpts (101 ± 7.8 vs. 75.7 ± 18.8, p = 0.26) and themes/sub-themes (319 ± 6.1 vs. 254.7 ± 103.6, p = 0.34) between virtual and in-person FGs. However, virtual FGs had significantly more coded excerpts specifically relating to sensitive/intimate topics including 'attitudes and beliefs' (n = 320 vs. n = 235, p < 0.001), 'information and support' (n = 184 vs. n = 99, p < 0.001), and 'family communication' (n = 208 vs. n = 114, p < 0.001). CONCLUSIONS: Virtual FGs yielded similar numbers of coded excerpts compared to traditional in-person FGs. Virtual FGs appear to support the relative anonymity of participants, resulting in richer discussion of highly sensitive, intimate topics. Findings support the validity and methodologic rigor of using web-enabled technologies for conducting FGs in rare diseases.

Exploring Rare Disease Patient Attitudes and Beliefs regarding Genetic Testing: Implications for Person-Centered Care.

Most rare diseases are genetic in etiology and characterized by a 'diagnostic odyssey'. Genomic advances have helped speed up the diagnosis for many rare disorders, opening new avenues for precision therapies. Little is known about patient attitudes, experiences, and beliefs about genetic testing for the rare disease congenital hypogonadotropic hypogonadism (CHH). METHODS: We conducted six focus groups with patients with CHH (n = 58). Transcripts were coded by independent investigators and validated by external reviewers. RESULTS: Major themes relating to pre-test experiences were 'attitudes & beliefs' (most frequently cited theme), which revealed altruism as a strong motivator for pursuing research testing and 'information and support,' which revealed a striking lack of pre-testing decisional support/genetic counseling. Major post-test themes included 'return of results,' revealing frustration with the lack of return of results and limited emotional support, and 'family communication,' describing challenging intrafamilial communication. Themes describing ethical concerns (i.e., privacy, use of samples) were least frequently noted and related to pre- and post-test experiences. CONCLUSIONS: Patients with CHH are highly motivated by altruism when pursuing testing but have significant unmet needs for pre-test decisional support and post-test counseling. It is regarded that patient values, beliefs and experiences can inform more person-centered approaches to genetic testing for rare diseases.

Strategies for success in a nursing PhD program and beyond.

PURPOSE: The purpose of this article is to inform newly enrolled PhD students of program expectations, strategies for success, and next steps in the career of a nurse scientist. METHODS: We used empirical evidence and insights from the authors to describe strategies for success during a nursing PhD program and continued career development following graduation. FINDINGS: Measures of success included maintaining health, focus, integrity, and a supportive network, identifying mentors, pursuing new knowledge and advancing research to transform health outcomes. CONCLUSION: Nursing PhD programs help to shape future researchers and leaders. Choosing to obtain a PhD in nursing is an investment in oneself, the discipline, and the science. CLINICAL RELEVANCE: Nursing PhD programs offer opportunities to advance science, impact healthcare and health outcomes, and prepare for a variety of career opportunities. Informing newly enrolled PhD students may better prepare them for what lies ahead and facilitate student retention.

Effects of participation in a U.S. trial of newborn genomic sequencing on parents at risk for depression.

Much emphasis has been placed on participant's psychological safety within genomic research studies; however, few studies have addressed parental psychological health effects associated with their child's participation in genomic studies, particularly when parents meet the threshold for clinical concern for depression. We aimed to determine if parents' depressive symptoms were associated with their child's participation in a randomized-controlled trial of newborn exome sequencing. Parents completed the Edinburgh Postnatal Depression Scale (EPDS) at baseline, immediately post-disclosure, and 3 months post-disclosure. Mothers and fathers scoring at or above thresholds for clinical concern on the EPDS, 12 and 10, respectively, indicating possible Major Depressive Disorder with Peripartum Onset, were contacted by study staff for mental health screening. Parental concerns identified in follow-up conversations were coded for themes. Forty-five parents had EPDS scores above the clinical threshold at baseline, which decreased by an average of 2.9 points immediately post-disclosure and another 1.1 points 3 months post-disclosure (both p ≤ .014). For 28 parents, EPDS scores were below the threshold for clinical concern at baseline, increased by an average of 4.7 points into the elevated range immediately post-disclosure, and decreased by 3.8 points at 3 months post-disclosure (both p < .001). Nine parents scored above thresholds only at 3 months post-disclosure after increasing an average of 5.7 points from immediately post-disclosure (p < .001). Of the 82 parents who scored above the threshold at any time point, 43 (52.4%) were reached and 30 (69.7%) of these 43 parents attributed their elevated scores to parenting stress, balancing work and family responsibilities, and/or child health concerns. Only three parents (7.0%) raised concerns about their participation in the trial, particularly their randomization to the control arm. Elevated scores on the EPDS were typically transient and parents attributed their symptomatology to life stressors in the postpartum period rather than participation in a trial of newborn exome sequencing.

Returning actionable genomic results in a research biobank: Analytic validity, clinical implementation, and resource utilization.

Over 100 million research participants around the world have had research array-based genotyping (GT) or genome sequencing (GS), but only a small fraction of these have been offered return of actionable genomic findings (gRoR). Between 2017 and 2021, we analyzed genomic results from 36,417 participants in the Mass General Brigham Biobank and offered to confirm and return pathogenic and likely pathogenic variants (PLPVs) in 59 genes. Variant verification prior to participant recontact revealed that GT falsely identified PLPVs in 44.9% of samples, and GT failed to identify 72.0% of PLPVs detected in a subset of samples that were also sequenced. GT and GS detected verified PLPVs in 1% and 2.5% of the cohort, respectively. Of 256 participants who were alerted that they carried actionable PLPVs, 37.5% actively or passively declined further disclosure. 76.3% of those carrying PLPVs were unaware that they were carrying the variant, and over half of those met published professional criteria for genetic testing but had never been tested. This gRoR protocol cost approximately $129,000 USD per year in laboratory testing and research staff support, representing $14 per participant whose DNA was analyzed or $3,224 per participant in whom a PLPV was confirmed and disclosed. These data provide logistical details around gRoR that could help other investigators planning to return genomic results.

Employing a mobile health decision aid to improve decision-making for patients with advanced prostate cancer and their decision partners/proxies: the CHAMPION randomized controlled trial study design.

BACKGROUND: Metastatic prostate cancer remains a lethal malignancy that warrants novel supportive interventions for patients and their decision partners and proxies. Decision aids have been applied primarily to patients with localized disease, with minimal inclusion of patients with advanced prostate cancer and their decision partners. The use of a community patient navigator (CPN) has been shown to have a positive supportive role in health care, particularly with individuals from minority populations. Research is needed to evaluate decision support interventions tailored to the needs of advanced prostate cancer patients and their decision partners in diverse populations. METHODS: Guided by Janis and Mann's Conflict Model of Decision Making, the Cancer Health Aid to Manage Preferences and Improve Outcomes through Navigation (CHAMPION) is a randomized controlled trial to assess the feasibility and acceptability of a mobile health (mHealth), CPN-administered decision support intervention designed to facilitate communication between patients, their decision partners, and the healthcare team. Adult prostate cancer patients and their decision partners at three mid-Atlantic hospitals in the USA were randomized to receive enhanced usual care or the decision intervention. The CHAMPION intervention includes a theory-based decision-making process tutorial, immediate and health-related quality of life graphical summaries over time (using mHealth), values clarification via a balance sheet procedure with the CPN support during difficult decisions, and facilitated discussions with providers to enhance informed, shared decision-making. DISCUSSION: The CHAMPION intervention is designed to leverage dynamic resources, such as CPN teams, mHealth technology, and theory-based information, to support decision-making for advanced prostate cancer patients and their decision partners. This intervention is intended to engage decision partners in addition to patients and represents a novel, sustainable, and scalable way to build on individual and community strengths. Patients from minority populations, in particular, may face unique challenges during clinical communication. CHAMPION emphasizes the inclusion of decision partners and CPNs as facilitators to help address these barriers to care. Thus, the CHAMPION intervention has the potential to positively impact patient and decision partner well-being by reducing decisional conflict and decision regret related to complex, treatment-based decisions, and to reduce cancer health disparities. Trial registration ClinicalTrials.gov NCT03327103 . Registered on 31 October 2017-retrospectively registered. World Health Organization Trial Registration Data Set included in Supplementary Materials.

Current Trends in Genetics and Neonatal Care.

BACKGROUND: Genetic and genomic health applications are rapidly changing. A clear and updated description of these applications for the neonatal population is needed to guide current nursing practice. PURPOSE: To provide scientific evidence and guidance on the current genetic and genomic applications pertinent to neonatal care. METHODS: A search of CINAHL and PubMed was conducted using the search terms "newborn/neonatal" and "genetics," "genomics," "newborn screening," "pharmacogenomics," "ethical," and "legal." Google searches were also conducted to synthesize professional guidelines, position statements, and current genetic practices. FINDINGS/RESULTS: Components of the newborn genetic assessment, including details on the newborn physical examination, family history, and laboratory tests pertinent to the newborn, are reported. The history and process of newborn screening are described, in addition to the impact of advancements, such as whole exome and genome sequencing, on newborn screening. Pharmacogenomics, a genomic application that is currently utilized primarily in the research context for neonates, is described and future implications stated. Finally, the specific ethical and legal implications for these genetic and genomic applications are detailed, along with genetic/genomic resources for nurses. IMPLICATIONS FOR PRACTICE: Providing nurses with the most up-to-date evidence on genetic and genomic applications ensures their involvement and contributions to quality neonatal care. IMPLICATIONS FOR RESEARCH: Ongoing genetic/genomic research is needed to understand the implications of genetic/genomic applications on the neonatal population and how these new applications will change neonatal care.