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.

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.

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.

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.

Mentoring in research-focused doctoral nursing programs and student perceptions of career readiness in the United States.

BACKGROUND: Research-focused doctorate nursing programs are expanding and seek to double the number of doctoral-prepared nurses by 2020. There is little empirical evidence of the contributions of mentoring to doctoral nursing students' readiness for their desired careers. PURPOSE: This study assessed characteristics and practices of nursing PhD students, the mentoring practices of their advisors, and the likelihood of self-reported career readiness. DESIGN: A nationwide descriptive, cross-sectional study of PhD students in the United States was conducted using an electronic survey platform. A sample of 380 PhD students representing 64 schools was surveyed from January to July 2016. METHODS: Descriptive statistics and ordered logistic regression were used to describe the sample and determine likelihood of career readiness by three readiness levels. FINDINGS: Results revealed greater likelihood of career readiness for students that: (1) perceived their proficiency in key scholarly skills as high, (2) were older, (3) worked a larger number of hours per week, (4) had more responsibilities outside of school, (5) had both advising and mentoring support, (6) had a co-advisor, and (7) attended a private university. CONCLUSION: Enrollment targets should be based on a faculty-to-doctoral student ratio that optimizes advising and mentoring and schools should provide mentoring guidelines and training for faculty.

Does Parent Training Format Affect Treatment Engagement? A Randomized Study of Families at Social Risk?

We examined whether parent engagement in parent training (PT) differed based on PT format (parent group-based with video versus mastery-based individual coaching with child) in an economically disadvantaged sample of families seeking behavioral treatment for their preschool children in an urban mental health clinic. Parents (N=159; 76.1% mothers, 69.8% African American, 73% low-income) were randomized to one of two interventions, Chicago Parent Program (parent group + video; CPP) or Parent Child Interaction Therapy (individualized mastery-based coaching; PCIT). Parent engagement indicators compared were PT attendance and completion rates, participation quality, and parent satisfaction. Risk factors predictive of PT attrition (parent depression, psychosocial adversity, child behavior problem severity, length of wait time to start PT) were also compared to determine whether they were more likely to affect engagement in one PT format versus the other. No significant differences were found in PT attendance or completion rates by format. Clinicians rated parents' engagement higher in PCIT than in CPP while satisfaction with PT was rated higher by parents in CPP compared to PCIT. Never attending PT was associated with more psychosocial adversity and externalizing behavior problems for CPP and with higher baseline depression for PCIT. Parents with more psychosocial adversities and higher baseline depression were less likely to complete PCIT. None of the risk factors differentiated CPP completers from non-completers. Delay to treatment start was longer for PCIT than CPP. Strengths and limitations of each PT format are discussed as they relate to the needs and realities of families living in urban poverty.