A “rotating menu” of medical uncertainty for families affected by telomere biology disorders: A qualitative interview study

Background Medical uncertainty may cause distress and challenge medical decision-making for patients with rare diseases and their caregivers. Few studies have examined the experience and management of medical uncertainty in rare disease and the dynamics of multiple medical uncertainty sources, issues, and management strategies. Objective We explored the experience and management of uncertainty in individuals with telomere biology disorders (TBDs), a set of rare cancer-prone bone marrow failure syndromes, and their caregivers. Design Participants (N=32) in this qualitative-descriptive study were individuals with a TBD (n=17) and/or their caregivers (n=15). We thematically analyzed transcripts to describe the presence and dynamics of medical uncertainty in TBDs using categories from a previously published taxonomy. Results Individuals with TBDs and caregivers described medical uncertainty as a chronic burden embodied amidst a range of interrelated sources and issues. Scientific uncertainty included diagnostic and prognostic ambiguity. Practical uncertainty focused on logistical challenges of building and maintaining medical care teams. Personal uncertainty included difficulty realigning self-identity, goals, and relationship expectations post-diagnosis. Scientific, practical, and personal uncertainty issues were entangled. The rarity of TBDs resulted in limited scientific knowledge, which gave rise to practical and personal uncertainties affecting medical decision-making and relationship formation (e.g., creating trusted care teams where patient knowledge of TBDs may exceed that of clinicians). Participants used multiple strategies for uncertainty management, particularly information-seeking and community-building. However, these management strategies could intensify, rather than resolve, participants’ medical uncertainty. Conclusion In TBDs, medical uncertainty manifests as a network of multiple, interrelated, sources and issues, which require evolving management strategies. Researchers must be mindful that complex, synergistic uncertainty networks contribute to psychosocial challenges in TBDs. Additional research is warranted to address scientific uncertainty in TBDs, including clinical manifestations and underlying biology, and to develop psychosocial interventions that recognize and anticipate evolving uncertainty

Coming of age with Li-Fraumeni syndrome: perspectives of young people and health professionals

© 2020 Rowan Forbes ShepherdThis thesis is situated in the discourse of risk that defines our technology-driven modern society, wherein one’s health is constructed as a personal and moral responsibility. A key contributor to the individualisation of risk in modern medicine is genomic technology. As genomics becomes progressively normalised in mainstream society, individuals of younger and younger ages are seeking to learn of their genetic risk of disease, including cancer. Young people occupy a formative and transitional life stage with complex processes of human development, making them a unique population for which genetic services are currently ill-equipped to serve appropriately. This research contributes to a new field of genetic counselling research that aims to explore and meet the distinctive developmental needs of young people with genetic disease. This thesis comprises of three inter-related studies that explore the psychosocial implications of living with a devastating, early onset inherited cancer condition, Li- Fraumeni syndrome (LFS), from the perspectives of young people and health professionals in Australasia. Informed by a pragmatic-critical realist stance, this thesis uses a mixed-method approach divided into a qualitative and quantitative phase. The qualitative phase consists of two studies, the first is a systematic review and thematic synthesis of 39 studies investigating how young people experience inherited disease with similar implications to LFS. The second and principal study of this research is an interpretive description of how young people experience LFS in their daily lives. To develop findings, I conducted interviews with 30 adolescents and young adults (aged 15- 39 years) with, or at 50% risk of, a pathogenic germline mutation in TP53 from across Australia, and used reflexive thematic analysis. The quantitative phase consists of a survey of 43 Australasian health professionals who care for young people with LFS to document their current practices and how they meet the developmental needs of this population. The first key finding is that experiences of cancer, either familial or personal, strongly influence how young people make sense and meaning of LFS, how they consider genetic testing, and their perceptions of cancer risk and mortality. The nature of LFS in terms of its high penetrance, early onset, and varied phenotype meant young people’s experiences were unique in oncology and genetic settings and require in-depth exploration during genetic counselling. The second key finding was that young people’s growing autonomy from family complicated the process of genetic testing, which was recognised by health professionals who worked to foster their autonomous decision- making. Genetic testing and whole-body cancer risk management represented instrumental actions of control for young people to mitigate their cancer risk from LFS, a perspective shared and promoted by health professionals. Intensive risk management and risk-reducing surgery, however, was emotionally and logistically burdensome for some young people, constructing the body as a material object be scrutinised in great detail by health professionals and blurring boundaries between self and body. The third key finding was that young people felt strongly about preventing the passage of their LFS- causing genetic variant to the next generation, reporting that pre - implantation genetic diagnosis was their preferred method for having a ‘healthy’ biological family. Few had reached a life stage, however, where they appreciated the ethical, financial and logistical burdens of this technology, and many deferred reproductive decision-making until they were ‘ready’. This research argues that young people with inherited disease have unique psychosocial and clinical needs that are directly tied to the formative developmental tasks of their life stage. They require specialist youth-friendly counselling that considers and appreciates their developmental needs both during genetic testing and beyond. Youth-friendly genetic counselling must therefore be longitudinal, incorporating psychosocial check-ups as a key clinical interaction. Further, youth-friendly models of care promote the distinct value of genetic counsellors in managing rare and complex inherited conditions. As the mainstreaming of genetic services begins to outsource tasks of genetic education and pre-test counselling, the genetic counselling profession must make better use of their psychosocial counselling skills to serve high-needs populations. In this context, young people stand out as a key focus. Finally, this research argues that attending genetic counselling exposes young people to a discourse of risk bounded by an ethos of responsibility. Undergoing genetic testing, subjecting their bodies to intensive surveillance and risk-reducing surgery, and having a family with reproductive technology all stand out as the ‘right thing’ to do when living with genetic risk of disease. Yet, each presented complex psychosocial implications for young people that were intrinsically linked to the broader effects of our modern risk society defined by Beck (1992) and Giddens (1991). Young people’s decision-making and preferences during this developmentally labile life stage therefore need to be interpreted in relation to normative societal pressures that dictate expected behaviour around risk

A relational approach to genetic counseling for hereditary breast and ovarian cancer

Ethical issues arise for genetic counselors when aclient fails to disclose a genetic diagnosis of hereditary diseaseto family: they must consider the rights of the individual clientto privacy and confidentiality as well as the rights of thefamily to know their genetic risk. Although considerable workhas addressed issues of non-disclosure from the client’sperspective, there is a lack of qualitative research into howgenetic counselors address this issue in practice. In this study,a qualitative approach was taken to investigate whethergenetic counselors in Australia use a relational approach toencourage the disclosure of genetic information from hereditarybreast and ovarian cancer (HBOC) clients among familymembers; and if so, how they use it. Semi-structured qualitativeinterviews were conducted with 16 genetic counselorsfrom selected states across Australia. Data collection andanalysis were guided by a basic iterative approach incorporatinga hybrid methodology to thematic analysis. The findingsprovide indicative evidence of genetic counselors employing arelational approach in three escalating stages—covert, overtand authoritative—to encourage the disclosure of geneticinformation. The findings lend credence to the notion thatgenetic counselors envision a form of relational autonomyfor their clients in the context of sharing genetic information,and they depart from individualistic conceptions of care/solely client-centered counseling when addressing the needsof other family members to know their genetic status

A Relational Approach to Genetic Counseling for Hereditary Breast and Ovarian Cancer

Ethical issues arise for genetic counselors when a client fails to disclose a genetic diagnosis of hereditary disease to family: they must consider the rights of the individual client to privacy and confidentiality as well as the rights of the family to know their genetic risk. Although considerable work has addressed issues of non-disclosure from the client's perspective, there is a lack of qualitative research into how genetic counselors address this issue in practice. In this study, a qualitative approach was taken to investigate whether genetic counselors in Australia use a relational approach to encourage the disclosure of genetic information from hereditary breast and ovarian cancer (HBOC) clients among family members; and if so, how they use it. Semi-structured qualitative interviews were conducted with 16 genetic counselors from selected states across Australia. Data collection and analysis were guided by a basic iterative approach incorporating a hybrid methodology to thematic analysis. The findings provide indicative evidence of genetic counselors employing a relational approach in three escalating stages--covert, overt and authoritative--to encourage the disclosure of genetic information. The findings lend credence to the notion that genetic counselors envision a form of relational autonomy for their clients in the context of sharing genetic information, and they depart from individualistic conceptions of care/solely client-centered counseling when addressing the needs of other family members to know their genetic status

The Clinical and Psychosocial Outcomes for Women Who Received Unexpected Clinically Actionable Germline Information Identified through Research: An Exploratory Sequential Mixed-Methods Comparative Study

Background Research identifying and returning clinically actionable germline variants offer a new avenue of access to genetic information. The psychosocial and clinical outcomes for women who have received this ‘genome-first care’ delivering hereditary breast and ovarian cancer risk information outside of clinical genetics services are unknown. Methods: An exploratory sequential mixed-methods case-control study compared outcomes between women who did (cases; group 1) and did not (controls; group 2) receive clinically actionable genetic information from a research cohort in Victoria, Australia. Participants completed an online survey examining cancer risk perception and worry, and group 1 also completed distress and adaptation measures. Group 1 participants subsequently completed a semi structured interview. Results: Forty-five participants (group 1) and 96 (group 2) completed the online survey, and 31 group 1 participants were interviewed. There were no demographic differences between groups 1 and 2, although more of group 1 participants had children (p = 0.03). Group 1 reported significantly higher breast cancer risk perception (p < 0.001) compared to group 2, and higher cancer worry than group 2 (p < 0.001). Some group 1 participants described how receiving their genetic information heightened their cancer risk perception and exacerbated their cancer worry while waiting for risk-reducing surgery. Group 1 participants reported a MICRA mean score of 27.4 (SD 11.8, range 9–56; possible range 0–95), and an adaptation score of 2.9 (SD = 1.1). Conclusion: There were no adverse psychological outcomes amongst women who received clinically actionable germline information through a model of ‘genome-first’ care compared to those who did not. These findings support the return of clinically actionable research results to research participants

Measuring the Flow of Energy and Matter in Marine Benthic Animal Populations

Traditionally, the rationale for energy flow studies was found in the elucidation of energy transfers within ecosystems or within the practical context of the rational management of resources, but it is now widely recognised that its scope embodies almost all biology, including the field of population dynamics and evolutionary studies. Here, we first describe conceptual models of energy and mass budgets at the level of the individual, the population and the community. However, the emphasis is on the next part in which the practicalities of measuring the various components of these budgets in the marine zoobenthic community are described in detail. The measurement of, among other things, ingestion, absorption, defaecation, excretion, growth, reproduction and respiration is discussed. Finally, attention is paid to the estimation of secondary production of benthic populations and to community-level modelling methods