Genome-wide screening can be offered at various stages of life and serve multiple purposes, including early detection of treatable conditions, achieving health benefits, or enhancing reproductive choices. Although genome-wide screening offers many new possibilities, determining which genomic data to analyse, how to interpret results, and how to communicate findings, presents significant challenges. In our research, we explored considerations for responsible genome-wide screening by combining a normative analysis of three different settings (population screening, opportunistic screening, and direct-to-consumer genetic testing) with an exploration of stakeholder views (among 25 professionals and 15 potential users of screening). In doing so, we focused on the proportionality criterion and four key screening issues: (1) dealing with unsolicited, secondary and uncertain findings; (2) information and consent; (3) privacy, storage, and (re)use of data; and (4) non-participation in screening. Our findings show broad consensus on the need for a cautious approach towards genome-wide screening. The proportionality criterion requires that benefits outweigh harm on both individual and societal level. Although genome-wide testing offers a range of possible expansions of screening, evidence for the proportionality of an expansion is not always available. The expansion of direct-to-consumer genetic testing raises the most concerns in terms of proportionality. In all screening settings, the position of and advocacy for newborns and children deserve special attention. Given the already scarce resources and personnel in healthcare, responsible implementation of genome-wide screening must be grounded in well-defined normative frameworks, supported by pilot studies that critically evaluate harms and benefits on both individual and societal level.

Introduction The integration of artificial intelligence into healthcare, particularly in surgery, aims to enhance patient outcomes and quality of care. Despite the anticipated benefits of artificial intelligence (AI), little research has examined patient perceptions towards this development. Considering the critical role patients play in the adoption of AI, alongside the profound influence these innovations might have on their health outcomes, integrating patient involvement is essential. This review examines patient involvement and perspectives on the use of artificial intelligence in surgery. Methods A qualitative literature review adhering to the PRISMA and ENTREQ statement was conducted using Medline, Embase, Web of Science, and Cochrane databases up to February 16th, 2025. Eligible studies focused on the application of AI in surgery with patient involvement. A thematic synthesis was conducted of the data from the included studies. The quality of the studies was assessed using the COREQ checklist. Results After deduplication, 1276 unique records were identified and screened by title and abstract. Three relevant studies were included, conducted in Australia, the United States, and the United Kingdom between 2020 and 2023, involving a total of 437 patients. Key themes related to patients’ perceptions included patient acceptance, concerns, dynamics of autonomy and responsibility. Patients valued AI for personalised prognostic information and risk assessments but had concerns about AI control, familiarity, and data privacy. Conclusion Patient involvement in research and research on patient perspectives regarding artificial intelligence in surgery is limited. While participants seem open to AI for personalised information regarding surgical treatment options, they emphasise the importance of shared responsibility, autonomy, transparency, and education to build trust.

Background The use of next generation sequencing (NGS) to expand current newborn screening (NBS) is being explored. NGS would enable early detection of more early onset diseases. However, to interpret a large amount of data within a short turn-around time, it is necessary to use artificial intelligence (AI). Use of AI in NGS-based NBS raises ethical and societal issues that require investigation of how healthcare professionals view the use of AI in this context and which requirements need to be met to realize responsible development and deployment of AI in NGS-based NBS. Objective To explore professionals’ perspectives on the requirements that are important for responsible development and deployment of AI in NGS-based NBS. Methods Q methodology was used to examine the perspectives of professionals, involving two steps: 1) an online focus group discussion to provide input for the development of 40 statements regarding requirements for responsible use of AI in NGS-based NBS and 2) an online sorting by the participants (N=30) of the list of statements, according to their importance. Results The Q methodology approach identified two participant perspectives. The first emphasized the importance for professionals that they retain control over the task for which the AI is used. The second prioritized the importance of parental acceptance and of high uptake of the screening offer. Conclusions The findings indicate an overall optimistic attitude and suggest that for responsible development and implementation of AI in an NGS-based NBS, it is important to consider requirements covering ethical, legal and societal aspects.

Rare disease clinical trials are notorious for complexities that frequently result in study-start delays. However, there is limited knowledge about how participants and researchers perceive these delays and what factors shape their experiences. A clinical trial in the rare, progressive disorder Pantothenate Kinase-Associated Neurodegeneration—the PKAN trial—encountered an unexpected delay. As this delay caused noticeable challenges for both PKAN participants and researchers, we sought to unravel their experiences in order to mitigate the impact of a study-start delay in future trials. Fourteen semi-structured qualitative interviews were performed with PKAN participants (n = 9), represented by their caregivers or patient organisations, and researchers (n = 5) involved in the PKAN trial. During the delay, worries arose among some participants, which were directed towards the researchers. These participants expressed desperation to be included in the study in the early stages of the disease and held overly optimistic expectations for the PKAN trial. However, most participants did not experience a significant impact of the delay on their lives. On their side, the researchers mentioned the challenge of managing expectations while preserving hope. Most participants were satisfied with the communication; however, some participants highlighted concerns regarding the lack of transparency. Different interests between participants and researchers came to light during the delay. Some researchers advised providing background information on clinical trials, whereas all participants indicated that they did not need this information. Our study indicates that the delay in the start of the clinical trial had a significant effect on all the researchers and on some PKAN participants, especially those who urgently wanted the research to start, due to the pressure of the severe and progressive nature of the disorder. For these participants, there was a sense of discontent with how the researchers communicated, which made them feel that the researchers had different interests. This study also revealed that researchers had different perceptions of what information was needed than what participants wanted. To lessen the impact of such delays on participants and researchers, we recommend both honest and transparent communication and adjusting communication to meet participants’ needs. Close collaboration between participants, patient organisations and researchers can help achieve this goal.

With the introduction of Next Generation Sequencing (NGS) techniques increasing numbers of disease-associated variants are being identified. This ongoing progress might lead to diagnoses in formerly undiagnosed patients and novel insights in already solved cases. Therefore, many studies suggest introducing systematic reanalysis of NGS data in routine diagnostics. Introduction will, however, also have ethical, economic, legal and (psycho)social (ELSI) implications that Genetic Health Professionals (GHPs) from laboratories should consider before possible implementation of systematic reanalysis. To get a first impression we performed a scoping literature review. Our findings show that for the vast majority of included articles ELSI aspects were not mentioned as such. However, often these issues were raised implicitly. In total, we identified nine ELSI aspects, such as (perceived) professional responsibilities, implications for consent and cost-effectiveness. The identified ELSI aspects brought forward necessary trade-offs for GHPs to consciously take into account when considering responsible implementation of systematic reanalysis of NGS data in routine diagnostics, balancing the various strains on their laboratories and personnel while creating optimal results for new and former patients. Some important aspects are not well explored yet. For example, our study shows GHPs see the values of systematic reanalysis but also experience barriers, often mentioned as being practical or financial only, but in fact also being ethical or psychosocial. Engagement of these GHPs in further research on ELSI aspects is important for sustainable implementation.

Background Population-based expanded carrier screening (ECS) involves screening for multiple recessive diseases offered to all couples considering a pregnancy or during pregnancy. Previous research indicates that in some countries primary care professionals are perceived as suitable providers for ECS. However, little is known about their perspectives. We therefore aimed to explore primary care professionals' views on population-based ECS. Methods Four online focus groups with 14 general practitioners (GPs) and 16 community midwives were conducted in the Netherlands. Results Our findings highlight various perspectives on the desirability of population-based ECS. Participants agreed that ECS could enhance reproductive autonomy and thereby prevent suffering of the child and/or parents. However, they also raised several ethical, societal, and psychological concerns, including a tendency towards a perfect society, stigmatization, unequal access to screening and negative psychosocial consequences. Participants believed that provision of population-based ECS would be feasible if prerequisites regarding training and reimbursement for providers would be fulfilled. most GPs considered themselves less suitable or capable of providing ECS, in contrast to midwives who did consider themselves suitable. Nevertheless, participants believed that, if implemented, ECS should be offered in primary care or by public health services rather than as hospital-based specialized care, because they believed a primary care ECS offer increases access in terms of time and location. Conclusions While participants believed that an ECS offer would be feasible, they questioned its desirability and priority. Studies on the desirability and feasibility of population-based ECS offered in primary care or public health settings are needed.

This paper motivates institutional epistemic trust as an important ethical consideration informing the responsible development and implementation of artificial intelligence (AI) technologies (or AI-inclusivity) in healthcare. Drawing on recent literature on epistemic trust and public trust in science, we start by examining the conditions under which we can have institutional epistemic trust in AI-inclusive healthcare systems and their members as providers of medical information and advice. In particular, we discuss that institutional epistemic trust in AI-inclusive healthcare depends, in part, on the reliability of AI-inclusive medical practices and programs, its knowledge and understanding among different stakeholders involved, its effect on epistemic and communicative duties and burdens on medical professionals and, finally, its interaction and alignment with the public's ethical values and interests as well as background sociopolitical conditions against which AI-inclusive healthcare systems are embedded. To assess the applicability of these conditions, we explore a recent proposal for AI-inclusivity within the Dutch Newborn Screening Program. In doing so, we illustrate the importance, scope, and potential challenges of fostering and maintaining institutional epistemic trust in a context where generating, assessing, and providing reliable and timely screening results for genetic risk is of high priority. Finally, to motivate the general relevance of our discussion and case study, we end with suggestions for strategies, interventions, and measures for AI-inclusivity in healthcare more widely.

Background Even with the introduction of new genetic techniques that enable accurate genomic characterization, knowledge about the phenotypic spectrum of rare chromosomal disorders is still limited, both in literature and existing databases. Yet this clinical information is of utmost importance for health professionals and the parents of children with rare diseases. Since existing databases are often hampered by the limited time and willingness of health professionals to input new data, we collected phenotype data directly from parents of children with a chromosome 6 disorder. These parents were reached via social media, and the information was collected via the online Chromosome 6 Questionnaire, which includes 115 main questions on congenital abnormalities, medical problems, behaviour, growth and development. Methods Here, we assess data consistency by comparing parent-reported phenotypes to phenotypes based on copies of medical files for the same individual (n = 20) and data availability by comparing the data available on specific characteristics reported by parents (n = 34) to data available in existing literature (n = 39). Results The reported answers to the main questions on phenotype characteristics were 85–95% consistent, and the consistency of answers to subsequent more detailed questions was 77–96%. For all but two main questions, significantly more data was collected from parents via the Chromosome 6 Questionnaire than was currently available in literature. For the topics developmental delay and brain abnormalities, no significant difference in the amount of available data was found. The only feature for which significantly more data was available in literature was a sub-question on the type of brain abnormality present. Conclusion This is the first study to compare phenotype data collected directly from parents to data extracted from medical files on the same individuals. We found that the data was highly consistent, and phenotype data collected via the online Chromosome 6 Questionnaire resulted in more available information on most clinical characteristics when compared to phenotypes reported in literature reports thus far. We encourage active patient participation in rare disease research and have shown that parent-reported phenotypes are reliable and contribute to our knowledge of the phenotypic spectrum of rare chromosomal disorders.

Carrier screening aims to identify couples at risk of conceiving children with a recessive condition. Until recently, carrier screening was primarily offered ancestry-based. Technological advances now facilitate expanded universal carrier screening (EUCS). This scoping review aimed to map EUCS's potential societal implications based on both theoretical studies and empirical evidence. To this aim, we performed a CoCites search to find relevant articles, including articles describing carrier screening for at-risk populations, based on five selected query articles. Forty articles were included. Three main potential societal implications were identified: (1) unwanted medicalization, (2) stigmatization and discrimination of carriers and people affected with the conditions screened and (3) challenges in achieving equitable access. Within these themes, potential positive implications are reduction of ethnic stigmatization in ancestry-based offers and increased equity. Potential negative implications are reinforcement of disability-based stigmatization, less possibility for developing expertise in healthcare and societal pressure to partake in screening. Empirical evidence on all these implications is however scarce. In conclusion, both positive and negative potential societal implications of implementing EUCS, primarily theoretical, were identified, even in at-risk groups where evidence is mostly lacking. Empirical research in EUCS pilots is needed to identify which societal implications are likely to occur and therefore should be overcome when implementing EUCS.

BACKGROUND:Adding rapid exome sequencing (rES) to conventional genetic tests improves the diagnostic yield of pregnancies showing ultrasound abnormalities but also carries a higher chance of unsolicited findings. We evaluated how rES, including pre- and post-test counseling, was experienced by parents investigating its impact on decision-making and experienced levels of anxiety. METHODS:A mixed-methods approach was adopted. Participating couples (n = 46) were asked to fill in two surveys (pre-test and post-test counseling) and 11 couples were approached for an additional interview. RESULTS:All couples accepted the rES test-offer with the most important reason for testing emphasizing their hope of finding an underlying diagnosis that would aid decision-making. The actual impact on decision-making was low, however, since most parents decided to terminate the pregnancy based on the major and multiple fetal ultrasound anomalies and did not wait for their rES results. Anxiety was elevated for most participants and decreased over time. CONCLUSION:Major congenital anomalies detected on ultrasound seem to have more impact on prenatal parental decision-making and anxiety then the offer and results of rES. However, the impact of rES on reproductive decision-making and experienced anxiety requires further investigation, especially in pregnancies where less (severe) fetal anomalies are detected on ultrasound.

PURPOSE:The aim of expanded preconception carrier screening (ECS) is to inform any couple wishing to conceive about their chances of having children with severe autosomal or X-linked recessive conditions. Responsible implementation of ECS as reproductive genetic screening in routine care requires assessment of benefits and harms. We examined the psychological outcomes of couple-based ECS for 50 autosomal recessive (AR) conditions provided by general practitioners (GPs) to couples from the Dutch general population.METHODS:Dutch GPs invited 4,295 women aged 18-40. We examined anxiety (State-Trait Anxiety Inventory, STAI-6), worry, decisional conflict (DCS) over time in participants declining GP counseling or attending GP counseling with/without testing.RESULTS:One hundred ninety couples participated; 130 attended counseling, of whom 117 proceeded with testing. No carrier couples were identified. Before counseling, worry (median 6.0) and anxiety (mean 30-34) were low and lower than the population reference (36.4), although some individuals reported increased anxiety or worry. At follow-up, test acceptors reported less anxiety than test decliners (mean 29 vs. 35); differences in anxiety after testing compared to before counseling were not meaningful. Most participants (90%) were satisfied with their decision (not) to undergo testing.CONCLUSION:Some individuals reported temporarily clinically relevant distress. Overall, the psychological outcomes are acceptable and no barrier to population-wide implementation.

Pharmacogenomics (PGx) can provide optimized treatment to individual patients while potentially reducing healthcare costs. However, widespread implementation remains absent. We performed a pilot study of PGx screening in Dutch outpatient hospital care to identify the barriers and facilitators to implementation experienced by patients (n = 165), pharmacists (n = 58) and physicians (n = 21). Our results indeed suggest that the current practical experience of healthcare practitioners with PGx is limited, that proper education is necessary, that patients want to know the exact implications of the results, that healthcare practitioners heavily rely on their computer systems, that healthcare practitioners encounter practical problems in the systems used, and a new barrier was identified, namely that there is an unclear allocation of responsibilities between healthcare practitioners about who should discuss PGx with patients and apply PGx results in healthcare. We observed a positive attitude toward PGx among all the stakeholders in our study, and among patients, this was independent of the occurrence of drug-gene interactions during their treatment. Facilitators included the availability of and adherence to Dutch Pharmacogenetics Working Group guidelines. While clinical decision support (CDS) is available and valued in our medical center, the lack of availability of CDS may be an important barrier within Dutch healthcare in general.

We performed a large outcome study at group and individual level in which the goals of genetic counselling were operationalized into cognitive and affective outcomes: empowerment, perceived personal control and anxiety. We then examined which socio-demographic and clinical variables were associated with changes in these outcomes. Data came from 1479 counselees who completed questionnaires (GCOS-18, PPC and STAI) at three time points: before the start of genetic counselling, after the first consultation and after the results of genetic counselling were disclosed. Results showed that at group level empowerment, perceived personal control and anxiety improved significantly after the whole genetic counselling process. Effect-sizes were medium for empowerment and small for the other outcomes. At individual level, 48% of counselees improved in empowerment, 21% in perceived personal control and 17% in anxiety. Around 10% of counselees worsened on all outcomes. Only 'reason for referral' and 'genetic test result' were significantly associated with changes in outcomes. This study demonstrated improvements among counselees in cognitive and affective outcomes after genetic counselling at group level. However, our results also suggest that there are opportunities for improvement at individual level, as many counselees remained stable and some even worsened on all outcomes. Routine outcome monitoring could help to explore the needs of counselees and could help to identify counselees who worsen.

Next generation sequencing has enabled fast and relatively inexpensive expanded carrier screening (ECS) that can inform couples’ reproductive decisions before conception and during pregnancy. We previously showed that a couple-based approach to ECS for autosomal recessive (AR) conditions was acceptable and feasible for both health care professionals and the non-pregnant target population in the Netherlands. This paper describes the acceptance of this free test-offer of preconception ECS for 50 severe conditions, the characteristics of test-offer acceptors and decliners, their views on couplebased ECS and reasons for accepting or declining the test-offer. We used a survey that included self-rated health, intention to accept the test-offer, barriers to test-participation and arguments for and against test-participation. Fifteen percent of the expected target population—couples potentially planning a pregnancy—attended pre-test counselling and 90% of these couples proceeded with testing. Test-offer acceptors and decliners differed in their reproductive characteristics (e.g. how soon they wanted to conceive), educational level and stated barriers to test-participation. Sparing a child a life with a severe genetic condition was the most important reason to accept ECS. The most important reason for declining was that the testresult would not affect participants’ reproductive decisions. Our results demonstrate that previously uninformed couples of reproductive age, albeit a selective part, were interested in and chose to have couple-based ECS. Alleviating practical barriers, which prevented some interested couples from participating, is recommended before nationwide implementation.