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If genome sequencing is performed in health care, in theory the opportunity arises to take a further look at the data: opportunistic genomic screening (OGS). The European Society of Human Genetics (ESHG) in 2013 recommended that genome analysis should be restricted to the original health problem at least for the time being. Other organizations have argued that ‘actionable’ genetic variants should or could be reported (including American College of Medical Genetics and Genomics, French Society of Predictive and Personalized Medicine, Genomics England). They argue that the opportunity should be used to routinely and systematically look for secondary findings—so-called opportunistic screening. From a normative perspective, the distinguishing characteristic of screening is not so much its context (whether public health or health care), but the lack of an indication for having this specific test or investigation in those to whom screening is offered. Screening entails a more precarious benefits-to-risks balance. The ESHG continues to recommend a cautious approach to opportunistic screening. Proportionality and autonomy must be guaranteed, and in collectively funded health-care systems the potential benefits must be balanced against health care expenditures. With regard to genome sequencing in pediatrics, ESHG argues that it is premature to look for later-onset conditions in children. Counseling should be offered and informed consent is and should be a central ethical norm. Depending on developing evidence on penetrance, actionability, and available resources, OGS pilots may be justified to generate data for a future, informed, comparative analysis of OGS and its main alternatives, such as cascade testing.

Background The use of genome-wide (whole genome or exome) sequencing for population-based newborn screening presents an opportunity to detect and treat or prevent many more serious early-onset health conditions than is possible today. Methods The Paediatric Task Team of the Global Alliance for Genomics and Health’s Regulatory and Ethics Working Group reviewed current understanding and concerns regarding the use of genomic technologies for population-based newborn screening and developed, by consensus, eight recommendations for clinicians, clinical laboratory scientists, and policy makers. Results Before genome-wide sequencing can be implemented in newborn screening programs, its clinical utility and cost-effectiveness must be demonstrated, and the ability to distinguish disease-causing and benign variants of all genes screened must be established. In addition, each jurisdiction needs to resolve ethical and policy issues regarding the disclosure of incidental or secondary findings to families and ownership, appropriate storage and sharing of genomic data. Conclusion The best interests of children should be the basis for all decisions regarding the implementation of genomic newborn screening.

Background Incorporating public and patient perspectives is essential to advancing personalised prevention. Personalised prevention focuses on preventing disease onset, progression, and recurrence by tailoring interventions on the basis of an individual’s biological, environmental, behavioural, socioeconomic, and cultural characteristics. This study explored what patients and the public want for better engagement and empowerment in prevention, aiming to develop key considerations across three domains (Research, Care, and Governance), and offering practical points to consider for improving personalised prevention strategies. Methods In cocreation with the European Patients Forum (EPF) and Cittadinanzattiva APS-Active Citizenship Network (ACN), semi-structured individual interviews and focus groups were conducted with 29 participants, comprising of 17 citizen advocates and 12 patients (including advocates) across 16 European countries, with experience in seven distinct disease groups. The participants were recruited through ACN and EPF via newsletters and mailing lists. Thematic analysis was performed via MAXQDA software. This study adhered to the Consolidated Criteria for Reporting Qualitative Research (COREQ). Results Findings were clustered into three key themes for better engagement in personalised prevention: (i) Information and Communication, where patients and the public emphasised the need for clear and accessible health information and user-friendly digital platforms; (ii) Representation and Inclusivity, highlighting calls for inclusive research, community engagement, and mental health integration; and (iii) Ethical and Regulatory Considerations, with concerns over equity and the potential shift from solidarity-based care to individual risk assessment, underscoring the need for robust privacy protection and equitable policies. Conclusions Enhancing patient and public engagement in personalised prevention requires more focus on communication, inclusivity, and secure data use. The findings provide actionable insights, promoting systematic engagement across Research, Care, and Governance. Clear information about prevention strategies and treatment options must be accessible, while diverse voices should be represented in decision-making. Collaboration with communities and better use of patient data can enhance prevention efforts. Policies should ensure ethical implementation, address data protection, and promote equity, transparency, and patient and public empowerment in healthcare, ultimately fostering a more inclusive approach to personalised prevention.

EU legislation prohibits clinical trials that modify germ line 'genetic identity'. 'Genetic identity' however, is left undefined. This study aims to identify the use of the term 'genetic identity' in academic literature, and investigate its relevance for debates on genetic modification. A total of 616 articles that contained the term were identified. Content analysis revealed that the term was used in various and contradicting ways and a clear understanding of the term is lacking. This review demonstrates that the EU legislation is open to interpretation, because of the diversity of meaning with which 'genetic identity' is currently used. Because of the diversity of meaning with which 'genetic identity' is used and understood, further reflection is needed. This requires further medical, legal, ethical and social debate and a coordinated response at both a European and a global level.

Reproductive and genetic medicine are evolving rapidly, and new technologies are already impacting current practices. This includes technologies that can identify a couples’ risk of having a child with a genetic disorder. Responsible implementation of new technologies requires evaluation of safety and ethics. Valuable insights for shaping governance processes are provided by various stakeholders involved, including healthcare professionals. Their willingness to adopt these technologies and guide the necessary systemic changes is required for the successful implementation of these technologies. In this study, twenty-one semi-structured interviews were conducted with professionals from different disciplines in the field of reproductive and genetic healthcare in the Netherlands. Three emerging technologies were discussed: expanded carrier screening (ECS), non-invasive prenatal diagnosis (NIPD) and germline genome editing (GGE). By probing stakeholders’ views, we explored how culture, structure and practice in healthcare is being shaped by innovations and changing dynamics in genetic and reproductive medicine. The general consensus was that the implementation of reproductive genetic technologies nationwide is a slow process in Dutch healthcare. A “typical Dutch approach” emerged that is characterized by restrictive legislation, broad support for people living with disabilities, values of an egalitarian society and limited commercialisation. Different scenarios for embedding ECS in future practice were envisioned, while implementation of NIPD in clinical practice was considered obvious. Views on GGE varied among stakeholders. Previous implementation examples in the Netherlands suggest introduction of new technology involves an organized collective learning process, with pilot studies and stepwise implementation. In addition, introducing and scaling up new technologies is complex due to perceived barriers from the legislative framework and the complex relationship between the government and stakeholders in this area. This paper describes how the international trends and advances of technologies are expected to manifest itself in a national setting.

Background Since the introduction of non-invasive prenatal testing (NIPT) in 2011, mainly by commercial companies, a growing demand for NIPT from the public and healthcare professionals has been putting pressure on the healthcare systems of various countries. This study identifies the challenges of establishing a responsible implementation of NIPT for aneuploidy in prenatal healthcare, by looking at the Netherlands. Methods A mixed methods approach involving 13 stakeholder interviews, document analysis and (participatory) observations of the Dutch NIPT Consortium meetings were used. The Diffusion of Innovation Theory and a Network of Actors model were used to interpret the findings. Results Implementation of NIPT was facilitated by several factors. The set-up of a national NIPT Consortium enabled discussion and collaboration between stakeholders. Moreover, it led to the plan to offer NIPT through a nationwide research setting (TRIDENT studies), which created a learning phase for careful implementation. The Dutch legal context was perceived as a delaying factor, but eventually gave room for the parties involved to organise themselves and their practices. Conclusions This study shows that implementing advanced technologies with profound effects on prenatal care benefit from a learning phase that allows time to carefully evaluate the technical performance and women’s experiences and to enable public debate. Such a coordinated learning phase, involving all stakeholders, will stimulate the process of responsible and sustainable implementation.

Ten years after the Human Genome Project, medicine is still waiting for many of the promised benefits, and experts have tempered their high expectations. Public opinion on genetic testing has generally been favourable but is this still the case? The aim of this study is to compare public experiences, beliefs and expectations concerning genetic testing over the years (2002 vs 2010). A cross-sectional questionnaire survey was conducted using the Dutch Health Care Consumer Panel in 2002 and 2010. Responses to questions in identical wording were compared. In 2002 and 2010, 817 (63%) and 978 (70%) members responded, respectively. Awareness and reported use of genetic tests remained stable over time. In 2010, more respondents expected genetic testing to become more widely applied, believed that knowledge about the genetic background of disease helps people live longer, and that testing should be promoted more intensively. In 2010, they were also more interested in their own genetic make-up. On the one hand, the concern that a dichotomy would emerge between people with 'good genes' and 'bad genes' was higher. On the other hand, respondents thought that insurance companies would be less likely to demand a genetic test in order to calculate health insurance premiums. In conclusion, the results suggest that in 8 years, expectations of benefits and potential use of genetic testing have been raised among the public, resulting in more positive opinions. Worries on inequity remain, although worries about premium differentiation by insurance companies have decreased.

The fluoropyrimidines (FP) (5-Fluorouracil, capecitabine, and tegafur) are commonly used anti-cancer drugs, but lead to moderate to severe toxicity in about 10-40% of patients. DPD testing [either the enzyme activity of dihydropyrimidine dehydrogenase (DPD) or the genotype] identifies patients at higher risk for toxicity who may be treated more safely with a lower drug dose. The Netherland's National guideline for colon carcinoma was updated in 2017 to recommend genotyping before treatment with FP. Pretreatment genotyping identifies approximately 50% of the patients that will develop severe FP toxicity. The aim of the study was to assess the uptake of DPD testing in the Amsterdam University Medical Centers over time and to evaluate stakeholder experiences to indicate barriers and facilitators of implementation in routine clinical care. We used a mixed-method approach involving electronic patient records of 753 unique patients and pharmacy information systems analyses and fifteen semi-structured interviews with oncologists, pharmacists, and patients. The constellation perspective was used to identify barriers and facilitators at the level of practice, culture and structure. The proportion of FP users who were DPD tested pretreatment showed an increase from 1% (1/86) in Q2-2017 up to 87% (73/84) in Q4-2018. Unlike a landmark paper published in 2015, the National guideline for colorectal carcinoma followed by meetings to achieve local consensus led to this steep increase in the proportion of patients tested. Facilitating factors for stakeholders to implement testing included the existence of clear protocols, (anecdotal) evidence of the utility, being aware that peers are adhering to standard practice and clear and simple procedures for ordering and reporting. Main barriers included the lack of clear divisions of responsibilities, the lack of consensus on a test approach, long turn-around times and non-user-friendly IT-infrastructures. More professional education on the utility and limitations of pharmacogenetic testing was desired by most stakeholders. While the evidence for DPD testing was sufficient, only after the update of a National guideline and local consensus meetings the proportion of FP users that were DPD tested pretreatment rose to 87%. The implementation of personalized medicine requires stakeholders involved to attune practice, culture and structure.

Background Advances in understanding the etiology of intellectual disability (ID) has led to insights in potential (targeted) treatments and personalized care. Implications of ID on health are often complex and require a multidisciplinary approach. The aim was to investigate the reporting of genetic diagnoses in multidisciplinary ID care and to identify associated clinical and demographic factors. Methods A retrospective chart review was performed on a randomly selected sample of individuals (n = 380) of a large ID care organization in the Netherlands. Data on genetic etiology, including genetic testing and diagnoses, and clinical and demographic characteristics were collected from files held by multidisciplinary team members. Results Reports on genetic etiology were available in 40% of the study sample (n = 151), with a genetic diagnosis recorded in 34% (n = 51), which is 13% of the total sample. In those with reported genetic diagnoses, this was reported in 90% of medical, 39% of psychodiagnostic, and 75% of professional caregivers’ files. Older age, mild ID, and the legal representative not being a family member were associated with less reported information on genetic etiology. Conclusions This study revealed that genetic diagnoses were often not reported in ID care files. Recommendations were formulated to reduce delay in diagnosis, and enable personalized care for individuals with ID.

This international multidisciplinary document intends to provide clinicians with evidence‐based practical patient‐centered recommendations for evaluating patients and decedents with (aborted) sudden cardiac arrest and their families. The document includes a framework for the investigation of the family allowing steps to be taken, should an inherited condition be found, to minimize further events in affected relatives. Integral to the process is counseling of the patients and families, not only because of the emotionally charged subject, but because finding (or not finding) the cause of the arrest may influence management of family members. The formation of multidisciplinary teams is essential to provide a complete service to the patients and their families, and the varied expertise of the writing committee was formulated to reflect this need. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by Class of Recommendation and Level of Evidence. The recommendations were opened for public comment and reviewed by the relevant scientific and clinical document committees of the Asia Pacific Heart Rhythm Society (APHRS) and the Heart Rhythm Society (HRS); the document underwent external review and endorsement by the partner and collaborating societies. While the recommendations are for optimal care, it is recognized that not all resources will be available to all clinicians. Nevertheless, this document articulates the evaluation that the clinician should aspire to provide for patients with sudden cardiac arrest, decedents with sudden unexplained death, and their families.