Perceptions and experiences of individuals at-risk of rheumatoid arthritis (RA) knowing about their risk of developing RA and being offered preventive treatment: systematic review and thematic synthesis of qualitative studies

ObjectivesThere is increasing interest in identifying individuals at-risk of rheumatoid arthritis (RA) and initiating early treatment to prevent or delay the onset of arthritis. We aimed to describe the perceptions and experiences of at-risk individuals and to inform the conduct of clinical trials and studies, and clinical practice.MethodsA systematic review and thematic synthesis of qualitative studies was conducted. Two review authors independently screened studies for inclusion, appraised their methodological quality using the Critical Appraisal Skills Programme checklist and assessed confidence in the findings using the Grading of Recommendations Assessment, Development and Evaluation–Confidence in Evidence from Reviews of Qualitative Research approach.ResultsSeven studies involving 115 individuals at-risk of developing RA were included. Three major themes (seven subthemes) were identified: understanding the risk of developing RA (knowledge of RA and identification of potential risk factors); preventive interventions to reduce the risk of developing RA (understanding the value and role of preventive interventions, and engagement with preventive interventions); and perceptions of predictive testing for RA (benefits of predictive testing, decision to undertake predictive testing and concerns about predictive testing). Moderate confidence in most review findings was evident.ConclusionWhile there are clear benefits in informing individuals at-risk of RA about their risk following predictive testing and offering preventive treatment, there are potential barriers to engagement, intensified by the burden of uncertainty. Identification of the optimum approaches for presenting risk information, including the risks and benefits of engaging with preventive interventions, is urgently needed to support individuals at-risk of RA in their decision making.PROSPERO registration numberCRD42021236034.

Epigenetics and DOHaD: how translation to predictive testing will require a better public understanding

Epigenetics is likely to play a role in the mediation of the effects of genes and environment in risk for many non-communicable diseases (NCDs). The Developmental Origins of Health and Disease (DOHaD) theory presents unique opportunities regarding the possibility of early life interventions to alter the epigenetic makeup of an individual, thereby modifying their risk for a variety of NCDs. While it is important to determine how we can lower the risk of these NCDs, it is equally important to understand how the public’s knowledge and opinion of DOHaD and epigenetic concepts may influence their willingness to undertake such interventions for themselves and their children. In this review, we provide an overview of epigenetics, DOHaD, NCDs, and the links between them. We explore the issues surrounding using epigenetics to identify those at increased risk of NCDs, including the concept of predictive testing of children. We also outline what is currently understood about the public’s understanding and opinion of epigenetics, DOHaD, and their relation to NCDs. In doing so, we demonstrate that it is essential that future research explores the public’s awareness and understanding of epigenetics and epigenetic concepts. This will provide much-needed information which will prepare health professionals for the introduction of epigenetic testing into future healthcare.

Data sharing in the age of predictive psychiatry: An adolescent perspective

ABSTRACTBackgroundAdvances in genetics and digital phenotyping in psychiatry have given rise to testing services targeting young people, which claim to predict psychiatric outcomes before difficulties emerge. These services raise several ethical challenges surrounding data sharing and information privacy.ObjectivesThis study aimed to investigate young people’s interest in predictive testing for mental health challenges, and their attitudes towards sharing biological, psychosocial and digital data for such purpose.MethodsEighty UK adolescents aged 16-18 participated in the study. Participants took part in a digital role-play where they played the role of clients of a fictional predictive psychiatry company and chose what sources of personal data they wished to provide for a risk assessment. After the role-play, participants reflected upon their choices during a peer-led interview.FindingsParticipants saw multiple benefits in predictive testing services, but were highly selective with regards to type the data they were willing to share. Largely due to privacy concerns, digital data sources such as social media or Google search history were less likely to be shared than psychosocial and biological data, including school grades and one’s DNA. Participants were particularly reluctant to share digital data with schools (but less so with health systems).ConclusionsEmerging predictive psychiatric services are valued by young people; however, these services must consider privacy vs. utility trade-offs from the perspective of different stakeholders, including adolescents.Clinical implicationsRespecting adolescents’ need for transparency, privacy and choice in the age of digital phenotyping is critical to the responsible implementation of predictive psychiatric services.

Impact of Genetic Testing for Cardiomyopathy on Emotional Well-Being and Family Dynamics: A Study of Parents and Adolescents

Background: Genetic testing is indicated for children with a personal or family history of hereditary cardiomyopathy to determine appropriate management and inform risk stratification for family members. The implications of a positive genetic result for children can potentially impact emotional well-being. Given the nuances of cardiomyopathy genetic testing for minors, this study aimed to understand how parents involve their children in the testing process and investigate the impact of genetic results on family dynamics. Methods: A survey was distributed to participants recruited from the Children’s Cardiomyopathy Foundation and 7 North American sites in the Pediatric Cardiomyopathy Registry. The survey explored adolescent and parent participants’ emotions upon receiving their/their child’s genetic results, parent-child result communication and its impact on family functionality, using the McMaster Family Assessment Device. Results: One hundred sixty-two parents of minors and 48 adolescents who were offered genetic testing for a personal or family history of cardiomyopathy completed the survey. Parents whose child had cardiomyopathy were more likely to disclose positive diagnostic genetic results to their child ( P =0.014). Parents with unaffected children and positive predictive testing results were more likely to experience negative emotions about the result ( P ≤0.001) but also had better family functioning scores than those with negative predictive results ( P =0.019). Most adolescents preferred results communicated directly to the child, but parents were divided about whether their child’s result should first be released to them or their child. Conclusions: These findings have important considerations for how providers structure genetic services for adolescents and facilitate discussion between parents and their children about results.

Moral motivation regarding dementia risk testing among affected persons in Germany and Israel

Recent advances in biomarkers may soon make it possible to identify persons at high risk for late-onset Alzheimer’s disease at a presymptomatic (preclinical) stage. Popular demand for testing is increasing despite the lack of cure and effective prevention options and despite uncertainties regarding the predictive value of biomarker tests. This underscores the relevance of the ethical, cultural and social implications of predictive testing and the need to advance the bioethical debate beyond considerations of clinical consequences. Our qualitative study included three groups of affected persons: People with mild neurocognitive disorder, their relatives and family caregivers of people with dementia. We explored their moral motivations regarding predictive, biomarker-based testing and preclinical diagnostics. We interviewed affected individuals in Germany and Israel (N=88; 44 participants in each country). Transcripts of 12 focus groups and 12 semistructured interviews were content analysed with a focus on the moral motivations of affected persons in their justification of why they accept or reject predictive testing and early diagnosis. We grouped the underlying aspects of moral motivation into four ethical categories: beneficence as a form of personal utility focusing on well-being, the ties of responsibility linking families and their individual members, the importance of self-determination by later life planning and notions of a good life. In general, cultural parallels among these motives were very obvious. Cultural variation occurred mainly in openness to suicide, scepticism about test validity and emphasis on personal autonomy. The study underscores the importance of counselling for life-planning issues and of informing test candidates about problems with test validity and about the ambiguity of test results.

A distinct APC pathogenic germline variant identified in a southern Thai family with familial adenomatous polyposis

Background Familial adenomatous polyposis (FAP) is caused by pathogenic germline variants in the APC gene. To date, multiple pathogenic variants in coding regions, splice sites, and deep intronic regions have been revealed. However, there are still pathogenic variants that remain unidentified. Methods Twenty-nine primer pairs flanking exons 2–16 (i.e., coding exons 1–15) of APC and their exon–intron junctions were used for germline pathogenic variant screening in Southern Thai patients with familial adenomatous polyposis (FAP). Transcription analysis was performed to confirm the pathogenicity of a splice site deletion of intron 10. Family members were interviewed for clinical histories. Blood samples were collected from 18 family members for a segregation study. Subsequently, clinical data of affected members were collected from the hospital databases. Results We found a distinct heterozygous 16-bp deletion at the splice donor site of intron 10 leading to a skipping of exon 10 which was confirmed by transcript analysis (APC: c 1312 + 4_1312 + 19del, r.934_1312del). Predictive testing for the pathogenic APC variant in 18 of the proband’s family members (ten healthy and eight affected) from three generations showed the same heterozygous germline pathogenic variant in eight affected adult members (15–62 years old) and two children (7 and 10 years old). Seven of the ten carriers of the disease-causing variant had undergone colonoscopy, and colonic polyps were found in all cases, which confirmed the segregation of the inherited pathogenic variant. The phenotypic spectrum was found to vary within the family; and some affected family members exhibited extracolonic manifestations. Conclusions To our knowledge, the pathogenic APC variant, c.1312 + 4_1312 + 19del, r.934_1312del, has not previously been reported. This study is one of the few reports describing the phenotypic consequences of a pathogenic APC variant in a high number of affected family members.