Using visual storytelling to share aggregate findings with families participating in clinical genomics research.

Purpose: Sharing aggregate results with research participants is a widely agreed-upon ethical obligation; yet, there is little research on communicating study results to diverse populations enrolled in genomics research. This article describes the cocreation of a visual narrative to explain research findings to families enrolled in a clinical genomics research study.

Methods: The design process involved researchers, clinicians, study participants, a physician illustrator, and a health communications expert.

Experts' Views on Children's Access to Community-Based Therapeutic and Education Services After Genomic Sequencing Results.

Objective: To evaluate how community-based experts respond to families seeking therapeutic and educational support services after pediatric genomic sequencing for rare conditions.

Methods: We interviewed 15 experts in the provision of community-based services for children with intellectual differences, developmental differences, or both, as part of a large study examining the utility of exome sequencing.

Results: Interviewees highlighted the complexity of the overall referral and assessment system for therapeutic or educational needs, that genetic diagnoses are secondary to behavioral observations in respect to eligibility for the provision of services, and that social capital drives service acquisition.

Trust in prenatal exome sequencing for expectant families facing unexplained fetal anomalies.

Objective: Despite exome sequencing (ES) becoming increasingly incorporated into the prenatal setting, few studies have elucidated motivations for and trust in ES and genomic research among a diverse cohort of patients and their partners.

Methods: This is a qualitative study that involved semi-structured interviews with pregnant or recently pregnant individuals and their partners, interviewed separately, in the setting of ES performed through research for a fetal structural anomaly. All interview transcripts were coded thematically and developed by a multidisciplinary team.

"I Have Fought for so Many Things": Disadvantaged families' Efforts to Obtain Community-Based Services for Their Child after Genomic Sequencing.

Background: Families whose child has unexplained intellectual or developmental differences often hope that a genetic diagnosis will lower barriers to community-based therapeutic and support services. However, there is little known about efforts to mobilize genetic information outside the clinic or how socioeconomic disadvantage shapes and constrains outcomes.

Methods: We conducted an ethnographic study with predominantly socioeconomically disadvantaged families enrolled in a multi-year genomics research study, including clinic observations and in-depth interviews in English and Spanish at multiple time points.

Privacy, bias and the clinical use of facial recognition technology: A survey of genetics professionals.

Facial recognition technology (FRT) has been adopted as a precision medicine tool. The medical genetics field highlights both the clinical potential and privacy risks of this technology, putting the discipline at the forefront of a new digital privacy debate. Investigating how geneticists perceive the privacy concerns surrounding FRT can help shape the evolution and regulation of the field, and provide lessons for medicine and research more broadly.

Functional genomics of OCTN2 variants informs protein-specific variant effect predictor for Carnitine Transporter Deficiency.

Genetic variants in , encoding the membrane carnitine transporter OCTN2, cause the rare metabolic disorder Carnitine Transporter Deficiency (CTD). CTD is potentially lethal but actionable if detected early, with confirmatory diagnosis involving sequencing of . Interpretation of missense variants of uncertain significance (VUSs) is a major challenge.

Parental Hopes and Understandings of the Value of Prenatal Diagnostic Genomic Sequencing: A Qualitative Analysis.

To provide qualitative empirical data on parental expectations of diagnostic prenatal genomic sequencing and the value of the results to families. We interviewed 15 families-mothers and/or fathers-who had had prenatal genomic sequencing about their expectations and their respective evaluations of the benefits of genomic sequencing. Families' hopes for genetic sequencing clustered around three themes: hoping to identify the cause of the fetal anomaly in a terminated pregnancy; hopes for guidance as to the likely outcome of current pregnancy; and hopes for information to support future family planning.

"Let's Just Wait Until She's Born": Temporal Factors That Shape Decision-Making for Prenatal Genomic Sequencing Amongst Families Underrepresented in Genomic Research.

Genomic sequencing has been increasingly utilized for prenatal diagnosis in recent years and this trend is likely to continue. However, decision-making for parents in the prenatal period is particularly fraught, and prenatal sequencing would significantly expand the complexity of managing health risk information, reproductive options, and healthcare access. This qualitative study investigates decision-making processes amongst parents who enrolled or declined to enroll in the prenatal arm of the California-based Program in Prenatal and Pediatric Genome Sequencing (P3EGS), a study in the Clinical Sequencing Evidence-Generating Research (CSER) consortium that offered whole exome sequencing for fetal anomalies with a focus on underrepresented groups in genomic research.

Fetal therapies and trials for lysosomal storage diseases: a survey of attitudes of parents and patients.

Background: Lysosomal storage diseases (LSDs) are inherited metabolic disorders that may lead to severe multi-organ disease. Current ERTs are limited by anti-drug antibodies, the blood-brain barrier, and early disease onset and progression before ERT is started. We have opened a phase I clinical trial of enzyme replacement therapy (ERT) for fetuses with LSDs (NCT04532047).

The difficulties of broad data sharing in genomic medicine: Empirical evidence from diverse participants in prenatal and pediatric clinical genomics research.

Purpose: This study aimed to understand broad data sharing decisions among predominantly underserved families participating in genomic research.

Methods: Drawing on clinic observations, semistructured interviews, and survey data from prenatal and pediatric families enrolled in a genomic medicine study focused on historically underserved and underrepresented populations, this paper expands empirical evidence regarding genomic data sharing communication and decision-making.

Results: One-third of parents declined to share family data, and pediatric participants were significantly more likely to decline than prenatal participants.

Ethical, Legal, and Social Implications of Fetal Gene Therapy.

As fetal gene therapies move from experimental animal models to human in utero phase I clinical trials, there is a need to consider the ethical, legal, and social implications. While fetal gene therapies are attracting more regulatory oversight than previous fetal interventions such as fetal surgery, old sociological questions should be applied to this new context. As health care pathways around fetal therapy are shaped by the ways in which a pregnant person and the fetus are constituted, and as risks and benefits are evaluated, we cannot afford to lose sight of long-term consequences, especially those pertaining to social inclusion.

Opportunities and challenges for the computational interpretation of rare variation in clinically important genes.

Genome sequencing is enabling precision medicine-tailoring treatment to the unique constellation of variants in an individual's genome. The impact of recurrent pathogenic variants is often understood, however there is a long tail of rare genetic variants that are uncharacterized. The problem of uncharacterized rare variation is especially acute when it occurs in genes of known clinical importance with functionally consequential variants and associated mechanisms.

The impact of public health palliative care interventions on health system outcomes: A systematic review.

Background: Public health palliative care interventions are increasingly implemented, with growing recognition of the importance of building evidence to support their utility in end-of-life care. Previous efforts have focused on community outcomes.

Aim: To examine the impact of public health palliative care on patterns of health service use at the end of life (primary) and explore which outcomes are being measured within this field of research (secondary).

Relegating Psychosis: Blood Work and "Routine Connection" in the Clozapine Clinic.

This paper attends to the sociality available in the clozapine clinic regimen and suggests that the social dimensions of clozapine treatment may be as important as the biochemical efficacy of clozapine. The clozapine clinic is where people diagnosed with chronic schizophrenia who take the antipsychotic clozapine go for routine monitoring of clozapine side effects, particularly haematological effects. Psychopharmaceutical treatments are often criticized for being reductionistic and dehumanizing, but clozapine clinics offer increased clinical contact in the age of deinstitutionalization.

Actively Negotiating the Mind-Body Divide: How Clozapine-Treated Schizophrenia Patients Make Health for Themselves.

It is well recognised that antipsychotic treatments impact the whole body, not just the target area of the brain. For people with refractory schizophrenia on clozapine, the gold standard antipsychotic treatment in England and Australia, the separation of mental and physical regimes of health is particularly pronounced, resulting in multiple, compartmentalised treatment registers. Clinicians often focus on the mental health aspects of clozapine use, using physical indicators to determine whether treatment can continue.

Well-being in clozapine-treated schizophrenia patients: The significance of positive symptoms.

Objectives: Well-being perception is seldom explored in schizophrenia patients. Recurrent limitations, such as the questionable applicability of gold standard definitions of health and well-being, and fewer tools available to assess well-being, are pronounced in this subpopulation. This cross-sectional study sought to explore potential clinical factors that may predict subjective well-being scores in chronic schizophrenia patients (N=142) receiving clozapine treatment.