[Righteous fertility care for transgender persons]. / Rechtvaardige fertiliteitszorg voor transgender personen.

Medically assisted reproduction for transgender individuals has been a subject of discussion and debate. While the primary focus used to be whether transgender individuals should have access to assisted reproduction at all, the question has now shifted to what constitutes just access to assisted reproduction for transgender people. It is instructive to compare their access to this care with that of cisgender heterosexual individuals and to critically reflect on the cis- and heteronormative context in which this care takes place. To establish just fertility care for transgender individuals, it is essential to dismantle the barriers imposed by these norms.

Exploring uncertainties regarding unsolicited findings in genetic testing.

OBJECTIVES: Non-normative uncertainty (uncertainty about empirical facts) and normative uncertainty (uncertainty about moral values or beliefs) regarding unsolicited findings (UFs) might play an important role in clinical genetics. Identifying normative uncertainty is of special interest since it might guide towards novel directions for counseling practice. This study aims to gain insight into the role of non-normative and normative uncertainty regarding UFs, as expressed by counselees and counselors. METHODS: We performed a secondary qualitative analysis of interviews with counselees (n = 20) and counselors (n = 20) who had been confronted with UFs. Following a deductive approach, we used Han et al.'s existing theoretical framework of uncertainty, in which we additionally incorporated normative uncertainty. RESULTS: Major issues of non-normative uncertainty were practical and personal for counselees, whilst counselors' uncertainty pertained mainly to scientific issues. Normative uncertainty was a major theme throughout the interviews. We encountered the moral conflicts of autonomy vs. beneficence and non-maleficence and of autonomy vs. truthfulness. CONCLUSION: Non-normative uncertainty regarding UFs highlights the need to gain more insight in their penetrance and clinical utility. This study suggests moral conflicts are a major source of feelings of uncertainty in clinical genetics. PRACTICE IMPLICATIONS: Exploring counselees' non-normative uncertainties and normative conflicts seems a prerequisite to optimize genetic counseling.

TurnerFertility trial: fertility preservation in young girls with Turner syndrome by freezing ovarian cortex tissue-a prospective intervention study.

OBJECTIVE: To evaluate which girls with Turner syndrome (TS) could benefit from fertility preservation by ovarian tissue cryopreservation on the basis of karyotype, puberty status, and hormonal data. DESIGN: Prospective intervention study; participants were included between 2018 and 2020. SETTING: Tertiary hospital in the Netherlands. PATIENTS: In total, 106 girls with TS aged between 2 and 18 years were included. Girls with minor X chromosome deletions, Y chromosomal content, active infections, or contraindications for surgery were excluded. INTERVENTION: A laparoscopic unilateral ovariectomy was performed to obtain ovarian cortical tissue for cryopreservation. One tissue fragment per participant was used to determine the number of follicles per ovary by serial sectioning and staining. Chromosome analysis was performed on lymphocytes and buccal cells. A blood sample was taken before the ovariectomy for hormonal analysis. MAIN OUTCOME MEASURES: The presence of follicles in ovarian cortex tissue from girls with TS in relation to karyotype, puberty status, and hormonal data. RESULTS: A unilateral ovariectomy was performed on 93 girls with TS. Complications after surgery occurred in 5 girls, including luxation of psychological symptoms in 2 girls. In 13 (14%) girls, a 46,XX cell line was found in buccal cells that was absent in lymphocytes. Follicles were observed in 30 (32%) of the 93 girls and were found mainly in girls with a 46,XX cell line in lymphocytes or buccal cells (Phi coefficient = 0.55). Spontaneous onset of puberty (Phi coefficient = 0.59), antimüllerian hormone (AMH; point-biserial correlation [r] = 0.82), inhibin B (r = 0.67), and follicle-stimulating hormone (r = -0.46) levels were also correlated strongly with the presence of follicles. Furthermore, AMH levels had a significant correlation with the number of follicles per ovary (r = 0.66). CONCLUSION: Favorable predictive markers for the presence of follicles included either a 46,XX cell line, spontaneous onset of puberty, or a combination of measurable AMH and normal follicle-stimulating hormone levels. Karyotyping of two peripheral cell lines in girls with TS is recommended to reveal hidden mosaicisms. Ovarian tissue cryopreservation should be offered with caution in a research setting to those with a sufficient ovarian reserve, considering the significant loss of follicles after ovarian tissue cryopreservation and autotransplantation. Physicians should pay attention to the mental health of the girls during the whole process. CLINICAL TRIAL REGISTRATION NUMBER: Trial registration number: NCT03381300- Preservation of Ovarian Cortex Tissue in Girls With Turner Syndrome - Full Text View - ClinicalTrials.gov. Registered on: December 21, 2017. First patient recruited on January 1, 2018.

Exploring professionals' views regarding prenatal counselling in congenital diaphragmatic hernia.

OBJECTIVES: Congenital diaphragmatic hernia (CDH) is a congenital malformation in which the diaphragm and lungs are underdeveloped, leading to cardiorespiratory and other problems. This study aimed to explore professionals' views regarding prenatal counselling in CDH. METHODS: A qualitative study was performed among healthcare professionals involved in the care of CDH patients in Radboud university medical center Amalia Children's Hospital. Semi-structured interviews were conducted until saturation was achieved. Transcripts were qualitatively analysed to gain insight into professionals' views regarding counselling. RESULTS: Eighteen professionals with various backgrounds were included. The professionals agreed that the first counselling session should be soon after diagnosis and additional sessions should be offered. Concerning counselling content, participants considered explanation of the diagnosis, prognosis, short- and long-term consequences, treatment options and practical aspects important. As for decision-making about possible termination of pregnancy, all professionals emphasised the importance of the parental role, but the preferred parental involvement varied. Regarding practical aspects, preferred counsellors were a neonatologist, obstetrician, paediatric surgeon and/or medical social worker. Participants emphasised that the counselling should be adjusted to parents' needs. CONCLUSIONS: This study gained insight into professionals' views regarding the timeline, content, decision-making process, and practical aspects of prenatal counselling in CDH.

Putting ICU triage guidelines into practice: A simulation study using observations and interviews.

BACKGROUND: The COVID-19 pandemic has prompted many countries to formulate guidelines on how to deal with a worst-case scenario in which the number of patients needing intensive care unit (ICU) care exceeds the number of available beds. This study aims to explore the experiences of triage teams when triaging fictitious patients with the Dutch triage guidelines. It provides an overview of the factors that influence decision-making when performing ICU triage with triage guidelines. METHODS: Eight triage teams from four hospitals were given files of fictitious patients needing intensive care and instructed to triage these patients. Sessions were observed and audio-recorded. Four focus group interviews with triage team members were held to reflect on the sessions and the Dutch guidelines. The results were analyzed by inductive content analysis. RESULTS: The Dutch triage guidelines were the main basis for making triage decisions. However, some teams also allowed their own considerations (outside of the guidelines) to play a role when making triage decisions, for example to help avoid using non-medical criteria such as prioritization based on age group. Group processes also played a role in decision-making: triage choices can be influenced by the triagists' opinion on the guidelines and the carefulness with which they are applied. Intensivists, being most experienced in prognostication of critical illness, often had the most decisive role during triage sessions. CONCLUSIONS: Using the Dutch triage guidelines is feasible, but there were some inconsistencies in prioritization between teams that may be undesirable. ICU triage guideline writers should consider which aspects of their criteria might, when applied in practice, lead to inconsistencies or ethically questionable prioritization of patients. Practical training of triage team members in applying the guidelines, including explanation of the rationale underlying the triage criteria, might improve the willingness and ability of triage teams to follow the guidelines closely.

Decision-making regarding antibiotic therapy duration: An observational study of multidisciplinary meetings in the intensive care unit.

PURPOSE: Antibiotic therapy is commonly prescribed longer than recommended in intensive care patients (ICU). We aimed to provide insight into the decision-making process on antibiotic therapy duration in the ICU. METHODS: A qualitative study was conducted, involving direct observations of antibiotic decision-making during multidisciplinary meetings in four Dutch ICUs. The study used an observation guide, audio recordings, and detailed field notes to gather information about the discussions on antibiotic therapy duration. We described the participants' roles in the decision-making process and focused on arguments contributing to decision-making. RESULTS: We observed 121 discussions on antibiotic therapy duration in sixty multidisciplinary meetings. 24.8% of discussions led to a decision to stop antibiotics immediately. In 37.2%, a prospective stop date was determined. Arguments for decisions were most often brought forward by intensivists (35.5%) and clinical microbiologists (22.3%). In 28.9% of discussions, multiple healthcare professionals participated equally in the decision. We identified 13 main argument categories. While intensivists mostly used arguments based on clinical status, clinical microbiologists used diagnostic results in the discussion. CONCLUSIONS: Multidisciplinary decision-making regarding the duration of antibiotic therapy is a complex but valuable process, involving different healthcare professionals, using a variety of argument-types to determine the duration of antibiotic therapy. To optimize the decision-making process, structured discussions, involvement of relevant specialties, and clear communication and documentation of the antibiotic plan are recommended.

Patients' lived body experiences in the intensive care unit and beyond - a meta-ethnographic synthesis.

INTRODUCTION: Physical therapists supporting patients in intensive care unit (ICU) rehabilitation can improve their clinical practice with insight in patients' lived body experiences. OBJECTIVE: To gain insight in patients' lived body experiences during ICU stay and in recovery from critical illness. METHODS: Through a comprehensive systematic literature search, 45 empirical phenomenological studies were identified. Patients' lived body experiences were extracted from these studies and synthesized following the seven-phase interpretative approach as described by Noblit and Hare. RESULTS: Three lines of argument were illuminated: 1) "recovery from critical illness starts from a situation in which patients experience the lived body as unable;" 2) "patients experience progress in recovery from critical illness when the lived body is empowered;" and 3) "recovery from critical illness results in a lived body changed for life." Eleven third-order constructs were formulated as different kinds of bodies: 1) "an intolerable body;" 2) "an alienated body;" 3) "a powerless body;" 4) "a dependent body;" 5) "a restricted body;" 6) "a muted body;" 7) "a touched body;" 8) "a transforming body;" 9) "a re-discovering body;" 10) "an unhomelike body;" and 11) "a remembering body." CONCLUSION: Patients' lived body experiences during ICU stay and in recovery from critical illness have richly been described in phenomenological studies and were synthesized in this meta-ethnography.

Deciding on future fertility: considerations of girls with Turner syndrome and their parents to opt for or against ovarian tissue cryopreservation.

RESEARCH QUESTION: What are the considerations of girls with Turner syndrome and their parents to opt for or against ovarian tissue cryopreservation (OTC)? DESIGN: Semi-structured in-depth interviews were conducted with girls with Turner syndrome and their parents until data saturation was reached. Participants were recruited through purposive sampling. Data were analysed using a thematic analysis approach. RESULTS: Thirteen parents and five girls who opted for OTC, and seven parents and three girls who declined OTC, were interviewed. Parents and girls mentioned that OTC offered hope, an opportunity to have genetic offspring and clarity about their current fertility status. Most participants were not afraid of the risks of surgery and trusted healthcare providers with this procedure. In contrast, families had to deal with uncertainties, owing to the lack of information on the success rate and long-term consequences of OTC in this group. Families indicated that they had to go through an important decision-making process in a short period of time, because of the limited number of participants in the OTC study. CONCLUSION: A new opportunity and hope for future fertility were considerations for opting for OTC. However, OTC also came with uncertainties owing to the experimental nature of this procedure in girls with Turner syndrome. Healthcare providers could share these experiences with girls with Turner syndrome and their parents to improve fertility-preservation counselling in this group.

Uncertainty in complex healthcare settings - The need for a comprehensive approach.

Uncertainty is increasingly recognized as a crucial phenomenon throughout medical practice. Research on uncertainty so far has been scattered across disciplines, leading to a lack of consensus about what uncertainty represents and minimal integration of knowledge obtained within isolated disciplines. Currently, a comprehensive view of uncertainty which does justice to normatively or interactionally challenging healthcare settings is lacking. This impedes research teasing apart when and how uncertainty manifests, how all stakeholders experience and value it, and how it affects medical communication and decision-making. In this paper, we argue that we need a more integrated understanding of uncertainty. We illustrate our argument using the context of adolescent transgender care, in which uncertainty occurs in myriad ways. We first sketch how theories of uncertainty have emerged from isolated disciplines, leading to a lack of conceptual integration. Subsequently, we emphasize why it is problematic that no comprehensive approach to uncertainty has yet been developed, using examples from adolescent transgender care. Finally, we advocate an integrated approach of uncertainty to further advance empirical research and to ultimately benefit clinical practice.

Clinical geneticists' views on and experiences with unsolicited findings in next-generation sequencing: "A great technology creating new dilemmas".

Unsolicited findings (UFs) from diagnostic genetic testing are a subject of debate. The emerging consensus is that some UFs from genetic testing should be disclosed, but recommendations on UF disclosure generally leave room for variation in practice. This study aimed to explore clinical geneticists' views on and experiences with UFs during pretest counseling and UF disclosure. We interviewed 20 certified clinical genetics medical specialists and clinical genetics residents, working in 7 Dutch genetic centers. Participants indicated that discussing the probability of detecting UFs is an integral part of pretest counseling and informed consent. However, they expressed doubts about the degree to which this discussion should occur and about what information they should share with patients. They argued that the contents of their counseling should depend on the individual patient's capacity to understand information. These results endorse the importance of tailored pretest counseling alongside informed consent for optimal genetic consultations. While "medical actionability" is broadly accepted as an important criterion for the disclosure of UFs, participants experienced substantial uncertainty regarding this concept. This study underscores the need for further demarcation of what exactly constitutes medical actionability. Installation of an expert panel to help healthcare professionals decide what variants to disclose will support them when facing the dilemmas presented by UFs.

Posterior Tibial Nerve Stimulation in Children with Lower Urinary Tract Dysfunction: A Mixed-Methods Analysis of Experiences, Quality of Life and Treatment Effect.

BACKGROUND: Posterior tibial nerve stimulation (PTNS) is one of the treatment modalities for children with therapy-refractory lower urinary tract dysfunction (LUTD). This study used a mixed-methods analysis to gain insight into the experiences of children treated with PTNS and their parents, the effect of treatment on quality of life (QOL) and the effect of PTNS on urinary symptoms. METHODS: Quantitative outcomes were assessed through a single-centre retrospective chart analysis of all children treated with PTNS in a group setting between 2016-2021. Voiding parameters and QOL scores before and after treatment were compared. Qualitative outcomes were assessed by an explorative study involving semi-structured interviews transcribed verbatim and inductively analysed using the constant-comparative method. RESULTS: The data of 101 children treated with PTNS were analysed. Overall improvement of LUTD was seen in 42% and complete resolution in 10%. Average and maximum voided volumes significantly increased. QOL improved in both parents and children independent of the actual effect on urinary symptoms. Interviews revealed PTNS to be well-tolerated. Facilitating PTNS in a group setting led to feelings of recognition in both children and parents. CONCLUSIONS: PTNS is a good treatment in children with therapy-refractory LUTD and provides valuable opportunities for peer support if given in a group setting.

The Decision-Making Process regarding Ovarian Tissue Cryopreservation in Girls with Turner Syndrome by Patients, Parents, and Healthcare Providers: A Mixed-Methods Study.

INTRODUCTION: Ovarian tissue cryopreservation (OTC) has proven to be effective in other patient groups, but the effectiveness in girls with Turner syndrome (TS) is still unclear. Guidelines for counselling about OTC in TS are lacking. The aim of this study was to gain insight into the experiences of patients, parents, and healthcare providers with the decision-making process regarding OTC in girls with TS. METHODS: Within a year after counselling, a survey was sent to 132 girls with TS and their parents. Furthermore, focus groups were conducted with (1) gynaecologists with subspeciality reproductive medicine, (2) paediatric endocrinologists, (3) parents of girls aged 2-12, and (4) parents of girls aged 13-18. Transcripts were analysed using a thematic analysis approach. RESULTS: The response rate of the survey was 45%. Of the survey respondents, 90% appreciated counselling regarding their future parenting options and considered it an addition to existing healthcare. Girls with TS and their parents indicated that the option of OTC raised hope for future genetic offspring and instantly made them feel that their only option was to seize this opportunity. Gynaecologists and paediatricians found it challenging to truly make families grasp a realistic perspective of OTC in girls with TS. DISCUSSION AND CONCLUSION: Offering young girls with TS the possibility of fertility preservation in an experimental setting raised high hopes and led to challenges for healthcare providers in ensuring a considered decision. The appropriate moment for counselling should be tailored to the individual and discussed with patient, parents, and paediatrician.

Longing for homelikeness: A hermeneutic phenomenological analysis of patients' lived experiences in recovery from COVID-19-associated intensive care unit acquired weakness.

AIMS: To explore lived experiences of patients recovering from COVID-19-associated intensive care unit acquired weakness and to provide phenomenological descriptions of their recovery. DESIGN: A qualitative study following hermeneutic phenomenology. METHODS: Through purposeful sampling, 13 participants with COVID-19-associated intensive care unit acquired weakness were recruited with diversity in age, sex, duration of hospitalization and severity of muscle weakness. Semi-structured in-depth interviews were conducted from 4 to 8 months after hospital discharge, between July 2020 and January 2021. Interviews were transcribed verbatim and analysed using hermeneutic phenomenological analysis. RESULTS: The analysis yielded five themes: 'waking up in alienation', 'valuing human contact in isolation', 'making progress by being challenged', 'coming home but still recovering' and 'finding a new balance'. The phenomenological descriptions reflect a recovery process that does not follow a linear build-up, but comes with moments of success, setbacks, trying new steps and breakthrough moments of achieving mobilizing milestones. CONCLUSION: Recovery from COVID-19-associated intensive care unit acquired weakness starts from a situation of alienation. Patients long for familiarity, for security and for recognition. Patients want to return to the familiar situation, back to the old, balanced, bodily self. It seems possible for patients to feel homelike again, not only by changing their outer circumstances but also by changing the understanding of themselves and finding a new balance in the altered situation. IMPACT: Muscle weakness impacts many different aspects of ICU recovery in critically ill patients with COVID-19-associated intensive care unit acquired weakness. Their narratives can help nurses and other healthcare professionals, both inside and outside of the intensive care unit, to empathize with patient experiences. When healthcare professionals connect to the lifeworld of patients, they will start to act and communicate differently. These insights could lead to optimized care delivery and meeting patients' needs in this pandemic or a possible next.

Why we prescribe antibiotics for too long in the hospital setting: a systematic scoping review.

BACKGROUND: In daily hospital practice, antibiotic therapy is commonly prescribed for longer than recommended in guidelines. Understanding the key drivers of prescribing behaviour is crucial to generate meaningful interventions to bridge this evidence-to-practice gap. OBJECTIVES: To identify behavioural determinants that might prevent or enable improvements in duration of antibiotic therapy in daily practice. METHODS: We systematically searched PubMed, Embase, PsycINFO and Web of Science for relevant studies that were published between January 2000 and August 2021. All qualitative, quantitative and mixed-method studies in adults in a hospital setting that reported determinants of antibiotic therapy duration were included. RESULTS: Twenty-two papers were included in this review. A first set of studies provided 82 behavioural determinants that shape how health professionals make decisions about duration; most of these were related to individual health professionals' knowledge, skills and cognitions, and to professionals' interactions. A second set of studies provided 17 determinants that point to differences in duration regarding various pathogens, diseases, or patient, professional or hospital department characteristics, but do not explain why or how these differences occur. CONCLUSIONS: Limited literature is available describing a wide range of determinants that influence duration of antibiotic therapy in daily practice. This review provides a stepping stone for the development of stewardship interventions to optimize antibiotic therapy duration, but more research is warranted. Stewardship teams must develop complex improvement interventions to address the wide variety of behavioural determinants, adapted to the specific pathogen, disease, patient, professional and/or hospital department involved.

A Sense of Being Needed: A Phenomenological Analysis of Hospital-Based Rehabilitation Professionals' Experiences During the COVID-19 Pandemic.

OBJECTIVE: The purpose of this study was to explore lived experiences of rehabilitation professionals working in hospitals during the COVID-19 pandemic, including the ethical issues and moral distress that these professionals might have encountered. METHODS: An interpretative phenomenological study was performed. First-person experiences of rehabilitation professionals (dieticians, occupational therapists, physical therapists, and speech-language therapists) were collected with semi-structured interviews and analyzed with interpretative phenomenological analysis. RESULTS: The data of 39 hospital-based rehabilitation professionals revealed 4 themes: a disease with great impact, personal health and safety, staying human in chaotic times, and solidarity and changing roles. Participant experiences show that the virus and COVID-19 measures had a significant impact on the in-hospital working environment due to the massive downscaling of regular care, due to infection prevention measures, and due to unknown risks to rehabilitation professionals' personal health. At the same time, participants experienced a certain freedom, which made room for authentic motives, connection, and solidarity. Participants felt welcomed and appreciated at the COVID-19 wards and intensive care units and were proud that they were able to fulfill their roles. The findings reflect a wide range of situations that were morally complex and led to moral distress. CONCLUSION: To diminish the long-lasting negative impact of the COVID-19 pandemic and moral distress, employers should empathize with the experiences of hospital-based rehabilitation professionals and create conditions for ethical reflection. Our data show that hospital-based rehabilitation professionals value professional autonomy. Creating room for professional autonomy helps them feel needed, connected, and energized. However, the needs of hospital-based rehabilitation professionals may conflict with organizational rules and structures. IMPACT: Hospital-based rehabilitation professionals were involved in situations they considered morally undesirable, and they inevitably faced moral distress during the COVID-19 crisis. This study offers rationale and guidance to employers regarding how to reduce the long-term negative impact of the COVID-19 pandemic on rehabilitation professionals.

Implementation of Nationwide Evidence- and Consensus-Based Guidelines to Harmonize Neonatal Care in The Netherlands.

BACKGROUND: A Dutch committee for National Guidelines in Neonatology developed nineteen evidence- and consensus-based guidelines to be used in all Dutch neonatal intensive care units (NICUs). The primary goal was to make clinical practices more uniform and consistent. OBJECTIVE: This study investigated to what extent the guidelines were implemented and which factors played a role in implementation. STUDY DESIGN: A mixed method study design was used to investigate both the level and the process of implementation. A nationwide, multicenter, cross-sectional survey was performed using a validated instrument for measuring the level of implementation (Normalization MeAsure Development questionnaire, NoMAD). The number of implemented guidelines per NICU and the frequency and content of the amendments that NICUs made to the original consensus guidelines were analyzed. Through semi-structured interviews, perceived barriers and facilitators for implementation were explored. PARTICIPANTS: Fellows and neonatologists working at all ten Dutch level 3-4 NICUs were eligible. RESULTS: On an average, NICUs implemented 12.6 (of 19) guidelines (range 6-17). The Normalization Process Scale was 54 (of 65). Main influencing factors impeding implementation were guideline-related (e.g., unpractical, lengthy guidelines) and personal (e.g., an active representative responsible for local implementation). CONCLUSION: The implementation of our guidelines appears to be successful. Ways for improvement can be distinguished in personal, guideline-related and external factors. Empowerment of local representatives was considered most essential.

What is it like to organize a large-scale educational event for fellow students? A qualitative exploration of student participation in curriculum design.

BACKGROUND: Although students are increasingly involved in curriculum design, empirical research on practices of actual student participation is sparse. The purpose of this study is to explore the experiences of students who collaborated in the organizing committee of a large-scale educational event, the Radboud Student Conference (RSC), for fellow students. METHODS: We conducted three focus group interviews, in which 17 (bio) medical students of three different organizing teams shared their experiences regarding the organization of the large-scale teaching event. The analysis was conducted using thematic content analysis, in which the codes and codebook were constructed on the basis of the data. RESULTS: The following four themes were derived from the data. 1) Collaboration, which concentrated on fellow students, teachers who were involved as supervisors, and persons outside the organizing team such as caterers, educational support office members, lecturers, physicians and researchers. 2) Planning and division of labor, with students experiencing a mutual dependence and noticing a gradual improvement of their skills. 3) Freedom implies responsibility, which indicted that students experienced a significant freedom to develop the RSC week, but at the same time felt the responsibility to deliver a successful final week of the academic year. 4) Personal development, where students mentioned the opportunity to practice skills that differed from standard (bio) medical electives. CONCLUSIONS: We conclude that (bio) medical students are capable of bearing the responsibility to organize a large-scale educational event. Organizing the RSC was an educational experience in the form of cooperative and experiential learning which contributed to students' personal development. Organizing the event gave students both a sense of freedom and the responsibility to succeed. Supervision of faculty members seemed a prerequisite, and tended to be supportive rather than guiding.

Impact of incidental findings on young adult participants in brain imaging research: an interview study.

OBJECTIVES: The current study aims to investigate young adult research participants' experiences with and preferences regarding the disclosure of MRI incidental findings (IFs) in brain imaging research, and to elucidate the impact and long-term effects of IF disclosure on these participants. METHODS: We conducted 11 semi-structured interviews with 10 research participants to whom an IF was disclosed after they participated in brain MRI research at the Donders Institute, Centre for Cognitive Neuroimaging (DCCN) in the Netherlands. Interview transcripts were analyzed using the constant comparative method. RESULTS: The analysis yielded five themes regarding the impact of IF disclosure: the initial shock of disclosure, a period of uncertainty, results of the follow-up examination, long-term impact, and participants' biomedical background. Participants were primarily impacted by the uncertainty in the period immediately following IF disclosure. For our participants, disclosure has had no health benefits and some, albeit mostly temporary and limited, negative impact. CONCLUSIONS: Our study suggests that it is important to carefully consider IF disclosure in a population of young healthy participants and emphasizes the relevance of systematic, large-scale follow-up studies to monitor risks and benefits of IF disclosure in this population. The insights from this study can be of added value to improve current research procedures or frameworks for the management and disclosure of IFs in imaging studies. KEY POINTS: • Participants were primarily impacted by the uncertainty in the period immediately following IF disclosure. • Our study suggests that it is important to carefully consider IF disclosure in a population of healthy young adult participants. • Our study emphasizes the relevance of systematic, large-scale follow-up studies to monitor the risks and benefits of IF disclosure in this population.

Lessons learned from unsolicited findings in clinical exome sequencing of 16,482 individuals.

Unsolicited findings (UFs) are uncovered unintentionally and predispose to a disease unrelated to the clinical question. The frequency and nature of UFs uncovered in clinical practice remain largely unexplored. We here evaluated UFs identified during a 5-year period in which 16,482 index patients received clinical whole-exome sequencing (WES). UFs were identified in 0.58% (95/16,482) of index patients, indicating that the overall frequency of UFs in clinical WES is low. Fewer UFs were identified using restricted disease-gene panels (0.03%) than when using whole-exome/Mendeliome analysis (1.03%). The UF was disclosed to 86 of 95 individuals, for reasons of medical actionability. Only 61% of these UFs reside in a gene that is listed on the "ACMG59"-list, representing a list of 59 genes for which the American College of Medical Genetics recommends UF disclosure. The remaining 39% were grouped into four categories: disorders similar to "ACMG59"-listed disorders (25%); disorders for which disease manifestation could be influenced (7%); UFs providing reproductive options (2%); and UFs with pharmacogenetic implications (5%). Hence, our experience shows that UFs predisposing to medically actionable disorders affect a broader range of genes than listed on the "ACMG59", advocating that a pre-defined gene list is too restrictive, and that UFs may require ad hoc evaluation of medical actionability. While both the identification and disclosure of UFs depend on local policy, our lessons learned provide general essential insight into the nature and odds of UFs in clinical exome sequencing.