The value of genetic testing for family health history of adopted persons.

Lack of family health history experienced by most adopted persons can represent a marked disadvantage. This Comment discusses the role of genetic testing in filling this informational gap and the challenges that need to be overcome.

Are Public Repository Requirements Exacerbating Lack of Diversity?

Although public repository requirements are aimed at researchers and designed to ensure that the utility of the limited data we have is optimized, these policies also have ramifications for research participants. In this opinion article, I discuss how the nature of such repositories can subject participants whose data are 'banked' to unwitting participation in scientific projects they might find objectionable. In addition, concerns about the privacy of banked genomic data are exacerbated by recent projects that demonstrate the ability to re-identify genomic data, raising the specter of discriminatory or oppressive use of this information. These concerns are most likely to discourage participation in research that requires data sharing among those who have experienced these phenomena and are less likely to discount their likelihood.

Clinically Indicated Genomic Sequencing of Children in Foster Care: Legal and Ethical Issues.

There are approximately 400 000 children in foster care in the US, approximately one-half of whom have chronic health problems and approximately 10% of whom have complex healthcare needs. Given the increasing relevance of genomic sequencing to guide clinical care for children with rare, chronic, and undiagnosed conditions, it may be an important component of diagnostic evaluation for children in foster care. Clinically indicated genomic sequencing may provide information that has health implications for children in foster care, as well as for their biological parents and other relatives. Whether and how genomic sequencing results impact legal decision making and family court outcomes is not yet well-understood. We describe scenarios that highlight legal, ethical, and policy issues surrounding genomic sequencing for children in foster care using 3 cases adapted from real-world events. Together, these cases highlight important yet underexplored issues that arise when genomic information has legal relevance in family court and ethical implications for child and family well-being. As genomic sequencing becomes more routine for the general pediatric population, additional research is needed to better understand its impacts on children and other stakeholders within the foster care system.

Does genetic testing offer utility as a supplement to traditional family health history intake for inherited disease risk?

CONTENT: This study examines the potential utility of genetic testing as a supplement to family health history to screen for increased risk of inherited disease. Medical conditions are often misreported or misunderstood, especially those related to different forms of cardiac disease (arrhythmias vs. structural heart disease vs. coronary artery disease), female organ cancers (uterine vs. ovarian vs. cervical), and type of cancer (differentiating primary cancer from metastases to other organs). While these nuances appear subtle, they can dramatically alter medical management. For example, different types of cardiac failure (structural, arrhythmia, and coronary artery disease) have inherited forms that are managed with vastly different approaches. METHODS: Using a dataset of over 6,200 individuals who underwent genetic screening, we compared the ability of genetic testing and traditional family health history to identify increased risk of inherited disease. A further, in-depth qualitative study of individuals for whom risk identified through each method was discordant, explored whether this discordance could be addressed through changes in family health history intake. FINDINGS: Of 90 individuals for whom genetic testing indicated significant increased risk for inherited disease, two-thirds (66%) had no corroborating family health history. Specifically, we identify cardiomyopathy, arrhythmia, and malignant hyperthermia as conditions for which discordance between genetic testing and traditional family health history was greatest, and familial hypercholesterolaemia, Lynch syndrome, and hereditary breast and ovarian cancer as conditions for which greater concordance existed. CONCLUSION: We conclude that genetic testing offers utility as a supplement to traditional family health history intake over certain conditions.

Anesthetic Considerations in the Electrophysiology Laboratory: A Comprehensive Review.

Catheter ablation procedures for arrhythmias or implantation and/or extraction of cardiac pacemakers can present many clinical challenges. It is imperative that there is clear communication and understanding between the anesthesiologist and electrophysiologist during the perioperative period regarding the mode of ventilation, hemodynamic considerations, and various procedural complications. This article provides a comprehensive narrative review of the anesthetic techniques and considerations for catheter ablation procedures, ventilatory modes using techniques such as high-frequency jet ventilation, and strategies such as esophageal deviation and luminal temperature monitoring to decrease the risk of esophageal injury during catheter ablation. Various hemodynamic considerations, such as the intraprocedural triaging of cardiac tamponade and fluid administration during catheter ablation, also are discussed. Finally, this review briefly highlights the early research findings on pulse-field ablation, a new and evolving ablation modality.

A state-based approach to genomics for rare disease and population screening.

PURPOSE: The Alabama Genomic Health Initiative (AGHI) is a state-funded effort to provide genomic testing. AGHI engages two distinct cohorts across the state of Alabama. One cohort includes children and adults with undiagnosed rare disease; a second includes an unselected adult population. Here we describe findings from the first 176 rare disease and 5369 population cohort AGHI participants. METHODS: AGHI participants enroll in one of two arms of a research protocol that provides access to genomic testing results and biobank participation. Rare disease cohort participants receive genome sequencing to identify primary and secondary findings. Population cohort participants receive genotyping to identify pathogenic and likely pathogenic variants for actionable conditions. RESULTS: Within the rare disease cohort, genome sequencing identified likely pathogenic or pathogenic variation in 20% of affected individuals. Within the population cohort, 1.5% of individuals received a positive genotyping result. The rate of genotyping results corroborated by reported personal or family history varied by gene. CONCLUSIONS: AGHI demonstrates the ability to provide useful health information in two contexts: rare undiagnosed disease and population screening. This utility should motivate continued exploration of ways in which emerging genomic technologies might benefit broad populations.

Recruiting diversity where it exists: The Alabama Genomic Health Initiative.

Lack of diversity among genomic research participants results in disparities in benefits from genetic testing. To address this, the Alabama Genomic Health Initiative employed community engagement strategies to recruit diverse populations where they lived. In this paper, we describe our engagement techniques and recruitment strategies, which resulted in significant improvement in representation of African American participants. While African American participation has not reached the representation of this community as a percentage of Alabama's overall population (26%-27%), we have achieved an overall representation exceeding 20% for African Americans. We believe this demonstrates the value of engagement and recruitment where diverse populations reside.

Anti-Vaxxers, Politicization of Science, and the Need for Trust in Pandemic Response.

The effectiveness of the next stages of pandemic response will require widespread compliance with vaccination recommendations once effective vaccines become available. Challenges to routine childhood immunization from anti-vaccination activists illustrate the importance of trust for achieving compliance. Unfortunately, we live in a time of political polarization that results in competing distortion of scientific study results. Science should take care to maintain objectivity, or we will lose the common ground of shared facts upon which progress depends.

How the Atacama Skeleton Might Advance Discussion of Responsible Conduct of Research Responsibilities.

Controversies resulting from genetic testing on skeletal remains of disputed stewardship raise important questions about obligations inherent on genetic researchers to assure ethical chain of custody. In this article, we analyze and evaluate several proposed positions on whether such research should be published. Following jurisprudential standards for legitimate regulatory systems, we argue that responsible conduct of research requires reasonable attention to chain of custody but cannot require guarantees, particularly in cases of ancient remains.

Clarifying a Clinical Ethics Service's Value, the Visible and the Hidden.

Our aim in this article is to define the difficulties that clinical ethics services encounter when they are asked to demonstrate the value a clinical ethics service (CES) could and should have for an institution and those it serves. The topic emerged out of numerous related presentations at the Un-Conference hosted by the Cleveland Clinic in August 2018 that identified challenges of articulating the value of clinical ethics work for hospital administrators. After a review these talks, it was apparent that the field of clinical ethics may be at a crisis of sorts due to increased pressure to provide explicit measures to healthcare institutions to concretely demonstrate that CESs make a valuable difference in healthcare delivery. In this article we grapple with how to satisfy the need for demonstrable value in a field in which metrics alone may not capture the scope of clinical ethics practice. We suggest that capturing the value of a CES has been difficult because the benefits of ethics consultation may be overt or attributable to the CES, but are often hidden due to the systems-level and process-oriented nature of clinical ethics work. Part of the difficulty in demonstrating the value of CESs is capturing and conveying all of the ways the integration of a CES throughout an institution positively affects patients, families, visitors, healthcare professionals, administrators, and the institution itself. Our aim is to (1) elucidate the multifaceted value added by a CES, including value that tends to be hidden and (2) suggest how to demonstrate value to others in a way that is not simplistic or reductionistic.

Genome sequencing in the clinic: the past, present, and future of genomic medicine.

Genomic sequencing has undergone massive expansion in the past 10 yr, from a rarely used research tool into an approach that has broad applications in a clinical setting. From rare disease to cancer, genomics is transforming our knowledge of biology. The transition from targeted gene sequencing, to whole exome sequencing, to whole genome sequencing has only been made possible due to rapid advancements in technologies and informatics that have plummeted the cost per base of DNA sequencing and analysis. The tools of genomics have resolved the etiology of disease for previously undiagnosable conditions, identified cancer driver gene variants, and have impacted the understanding of pathophysiology for many diseases. However, this expansion of use has also highlighted research's current voids in knowledge. The lack of precise animal models for gene-to-function association, lack of tools for analysis of genomic structural changes, skew in populations used for genetic studies, publication biases, and the "Unknown Proteome" all contribute to voids needing filled for genomics to work in a fast-paced clinical setting. The future will hold the tools to fill in these voids, with new data sets and the continual development of new technologies allowing for expansion of genomic medicine, ushering in the days to come for precision medicine. In this review we highlight these and other points in hopes of advancing and guiding precision medicine into the future for optimal success.

Predictors of the Biomechanical Effects of Customized Foot Orthoses in Adults With Flat-Arched Feet.

OBJECTIVE: To determine the potential presence and characteristics of biomechanical responders to customized foot orthoses during walking in adults with flat-arched feet. DESIGN: Experimental, repeated-measures. SETTING: University clinic and laboratory. PARTICIPANTS: Eighteen symptom-free adults with flat-arched feet. INTERVENTIONS: Customized foot orthoses. MAIN OUTCOME MEASURES: In-shoe foot biomechanics were measured during walking with and without customized foot orthoses using 3D analysis. Selected kinematic and kinetic variables during baseline walking were compared between subgroups who displayed reductions in calcaneal eversion with foot orthoses to those with no change or increases. RESULTS: Biomechanical responders displayed significantly greater peak calcaneal eversion (+2.2 degrees, P = 0.009). Time to peak calcaneal eversion (-11%, P = 0.006), peak dorsiflexion of the hallux (-6 degrees, P = 0.001), and medial-lateral excursion of the center of pressure during loading response were all reduced in the responder subgroup (-2 mm, P ≤ 0.001). Variables significantly different between subgroups were moderately associated with the response to foot orthoses (canonical correlation = 0.687, effect size = 0.47, P = 0.063). CONCLUSIONS: Individuals with increased dynamic foot pronation were more likely to show a favorable biomechanical response to customized foot orthoses, providing preliminary evidence to support the stratified use of foot orthoses to optimize their effectiveness.

Autonomy, Well-Being, and the Value of Genetic Testing for Adopted Persons.

This paper argues that the value of genetic-relative family health history (GRFHx) information and the notion that lack of this information is a disadvantage can be established through its role as a nested goal in comprehensive life projects independent of documentation of particular health outcomes. Health information often plays a significant role in a person's formulation of life goals and projects, as well as in identification of plausible effective means to realize these goals. If health outcomes are valuable in part because of the nested role these play in the successful realization of a person's life projects and goals, then other, similarly nested contributors to such success must also be valued on a similar scale. Some of these other contributors to a successful life may themselves be nested with health considerations, as illustrated in the relationship that will be the focus of this paper. Health information --independent of outcomes per se - influences relationships, reproduction, and the formulation of plausible comprehensive life goals in intricate and very influential ways. Although such information may be valued in part because it is predictive of health outcomes, this relationship does not reduce such information, nor the comprehensive life goals and projects such information promotes, to health outcomes. That is, while health status can both enhance and detract from the autonomous (successful) pursuit of life projects formulated in the context of health information, the value and weight of these projects is independent of particular health status or outcomes, even while in part shaped by them.

Does Lack of "Genetic-Relative Family Health History" Represent a Potentially Avoidable Health Disparity for Adoptees?

Many adoptees face a number of challenges relating to separation from biological parents during the adoption process, including issues concerning identity, intimacy, attachment, and trust, as well as (for older adopted children) language and other cultural challenges. One common health challenge faced by adoptees involves lack of access to genetic-relative family health history (GRFHx). Lack of GRFHx represents a disadvantage due to a reduced capacity to identify diseases and recommend appropriate screening for conditions for which the adopted person may be at increased risk. In this article, we draw out common features of traditionally understood "health disparities" in order to identify analogous features in the context of adoptees' lack of GRFHx.

Using self-determination theory to promote adolescent girls' physical activity: Exploring the theoretical fidelity of the Bristol Girls Dance Project.

OBJECTIVES: To report the theory-based process evaluation of the Bristol Girls' Dance Project, a cluster-randomised controlled trial to increase adolescent girls' physical activity. DESIGN: A mixed-method process evaluation of the intervention's self-determination theory components comprising lesson observations, post-intervention interviews and focus groups. METHOD: Four intervention dance lessons per dance instructor were observed, audio recorded and rated to estimate the use of need-supportive teaching strategies. Intervention participants (n = 281) reported their dance instructors' provision of autonomy-support. Semi-structured interviews with the dance instructors (n = 10) explored fidelity to the theory and focus groups were conducted with participants (n = 59) in each school to explore their receipt of the intervention and views on the dance instructors' motivating style. RESULTS: Although instructors accepted the theory-based approach, intervention fidelity was variable. Relatedness support was the most commonly observed need-supportive teaching behaviour, provision of structure was moderate and autonomy-support was comparatively low. The qualitative findings identified how instructors supported competence and developed trusting relationships with participants. Fidelity was challenged where autonomy provision was limited to option choices rather than input into the pace or direction of lessons and where controlling teaching styles were adopted, often to manage disruptive behaviour. CONCLUSION: The successes and challenges to achieving theoretical fidelity in the Bristol Girls' Dance Project may help explain the intervention effects and can more broadly inform the design of theory-based complex interventions aimed at increasing young people's physical activity in after-school settings.

Effect and cost of an after-school dance programme on the physical activity of 11-12 year old girls: The Bristol Girls Dance Project, a school-based cluster randomised controlled trial.

BACKGROUND: The aim of this study was to examine the effectiveness and cost of an after-school dance intervention at increasing the physical activity levels of Year 7 girls (age 11-12). METHODS: A cluster randomised controlled trial was conducted in 18 secondary schools. Participants were Year 7 girls attending a study school. The Bristol Girls Dance Project (BGDP) intervention consisted of up to forty, 75-minute dance sessions delivered in the period immediately after school by experienced dance instructors over 20-weeks. The pre-specified primary outcome was accelerometer assessed mean minutes of weekday moderate to vigorous physical activity (MVPA) at time 2 (52 weeks are T0 baseline assessments). Secondary outcomes included accelerometer assessed mean minutes of weekday MVPA at time 1 (while the intervention was still running) and psychosocial outcomes. Intervention costs were assessed. RESULTS: 571 girls participated. Valid accelerometer data were collected from 549 girls at baseline with 508 girls providing valid accelerometer data at baseline and time 2. There were no differences between the intervention and control group for accelerometer assessed physical activity at either time 1 or time 2. Only one third of the girls in the intervention arm met the pre-set adherence criteria of attending two thirds of the dance sessions that were available to them. Instrumental variable regression analyses using complier average causal effects provided no evidence of a difference between girls who attended the sessions and the control group. The average cost of the intervention was £73 per girl, which was reduced to £63 when dance instructor travel expenses were excluded. CONCLUSION: This trial showed no evidence that an after-school dance programme can increase the physical activity of Year 7 girls. The trial highlighted the difficulty encountered in maintaining attendance in physical activity programmes delivered in secondary schools. There is a need to find new ways to help adolescent girls to be physically active via identifying ways to support and encourage sustained engagement in physical activity over the life course. TRIAL REGISTRATION: ISRCTN52882523.