Expanded carrier screening for autosomal recessive conditions in health care: Arguments for a couple-based approach and examination of couples' views.

BACKGROUND: Expanded carrier screening (ECS) is aimed at detecting carrier states for autosomal recessive (AR) or X-linked conditions in couples from the general population planning a pregnancy. ECS is currently usually offered on an individual basis despite the fact that, for AR conditions, only carrier couples are at risk of affected offspring. In this paper, we present a couple-based ECS test-offer for AR conditions, where results are offered as couple-results only, and describe how couples view such an offer. METHODS AND RESULTS: An online survey covering attitudes, perceived difficulty, and intention to take up couple-based ECS was used to examine couples' views. Results show that in 76% of the participating couples there is no objection at all towards receiving couple-results only. Most couples display similar views. Observed discrepancies usually involved one of the couple members having a positive view, whilst the other was neutral. Although views stayed strikingly stable after discussion, the partner's opinion was regarded as important in deciding whether or not to have testing. CONCLUSION: This study shows that most couples do not object to receiving couple rather than individual ECS results, have similar views towards the offer, and are able to discuss differences in views and intentions.

Is there a duty to recontact in light of new genetic technologies? A systematic review of the literature.

PURPOSE: With rapid advances in genetic technologies, new genetic information becomes available much faster today than just a few years ago. This has raised questions about whether clinicians have a duty to recontact eligible patients when new genetic information becomes available and, if such duties exist, how they might be implemented in practice. METHODS: We report the results of a systematic literature search on the ethical, legal, social (including psychological), and practical issues involved in recontacting former patients who received genetic services. We identified 1,428 articles, of which 61 are covered in this review. RESULTS: The empirical evidence available indicates that most but not all patients value being recontacted. A minority of (older) articles conclude that recontacting should be a legal duty. Most authors consider recontacting to be ethically desirable but practically unfeasible. Various solutions to overcome these practical barriers have been proposed, involving efforts of laboratories, clinicians, and patients. CONCLUSION: To advance the discussion on implementing recontacting in clinical genetics, we suggest focusing on the question of in what situations recontacting might be regarded as good standard of care. To this end, reaching a professional consensus, obtaining more extensive empirical evidence, and developing professional guidelines are important.

Parental experience at the end-of-life in children with cancer: 'preservation' and 'letting go' in relation to loss.

PURPOSE: For children with incurable cancer death usually is anticipated and preceded by a phase of palliative care. Despite recognition that parents have difficulty adapting to a palliative perspective there is little insight into this process. This study explored, from a parental perspective, the process parents go through when cure is no longer a possibility. PARTICIPANTS AND METHODS: A multicenter study using qualitative research was undertaken during the EoL phase. One-time and repeated open interviews were conducted with 44 parents of 23 children with incurable cancer. RESULTS: Feelings of loss play a prominent role during the EoL phase. Dealing with loss is a process of stepwise relinquishing that becomes manifest in an internal struggle between preservation and letting go. Preservation means that parents try to maintain the child's status quo. Letting go means parents give up their resistance to loss in service of their child's well-being. Although the relative measure of each changes over time, parents have great difficulty making the transition because it implies a change in source of control. A timely completion of this transition positively influences the child's well-being as well as the evaluation of enacted parenthood. CONCLUSION: For parents the essence of the palliative process is not to accept death but to deal with the loss of their child. Although the need to avoid loss and gain control by means of preservation is fully understandable, the study indicated that parents who made the transition to letting go had an increased receptiveness of their child's real situation and needs.

Theoretical resources for a globalised bioethics.

In an age of global capitalism, pandemics, far-flung biobanks, multinational drug trials and telemedicine it is impossible for bioethicists to ignore the global dimensions of their field. However, if they are to do good work on the issues that globalisation requires of them, they need theoretical resources that are up to the task. This paper identifies four distinct understandings of 'globalised' in the bioethics literature: (1) a focus on global issues; (2) an attempt to develop a universal ethical theory that can transcend cultural differences; (3) an awareness of how bioethics itself has expanded, with new centres and journals emerging in nearly every corner of the globe; (4) a concern to avoid cultural imperialism in encounters with other societies. Each of these approaches to globalisation has some merit, as will be shown. The difficulty with them is that the standard theoretical tools on which they rely are not designed for cross-cultural ethical reflection. As a result, they leave important considerations hidden. A set of theoretical resources is proposed to deal with the moral puzzles of globalisation. Abandoning idealised moral theory, a normative framework is developed that is sensitive enough to account for differences without losing the broader context in which ethical issues arise. An empirically nourished, self-reflexive, socially inquisitive, politically critical and inclusive ethics allows bioethicists the flexibility they need to pick up on the morally relevant particulars of this situation here without losing sight of the broader cultural contexts in which it all takes place.

Expanded carrier screening: what determines intended participation and can this be influenced by message framing and narrative information?

Next-generation sequencing enabled us to create a population-based expanded carrier screening (ECS) test that simultaneously tests for 50 serious autosomal recessive diseases. Before offering this test universally, we wanted to know what factors are related to intended participation and how the general public can be informed about the test without being influenced in their intention to participate. We studied this by measuring to what extent 'message framing' and 'narrative information' can influence people's intended participation. Data were collected by means of an online survey of 504 potential users, and the factors examined were based on the Theory of Planned Behaviour and on previous research on intended participation in preconception carrier screening. Message framing was manipulated by explaining the risk of couple carriership in different ways, while narrative information was provided to only half of the respondents. The factors most positively related to intended participation were perceiving benefits of the screening, having a positive attitude towards the screening, having no religion, having an actual child wish and experiencing the choice to participate as easy. Perceived benefits and a positive attitude were most influential factors by far. Message framing and narrative information had no significant effect on intended participation, reinforcing that message framing and narrative information can help to inform the general public about ECS without influencing their intended participation. Future research should study if the importance of perceived benefits and a positive attitude can be replicated when other factors are included and when actual participation is measured instead of intended participation.

Population-based preconception carrier screening: how potential users from the general population view a test for 50 serious diseases.

With the increased international focus on personalized health care and preventive medicine, next-generation sequencing (NGS) has substantially expanded the options for carrier screening of serious, recessively inherited diseases. NGS screening tests not only offer reproductive options not previously available to couples, but they may also ultimately reduce the number of children born with devastating disorders. To date, preconception carrier screening (PCS) has largely targeted single diseases such as cystic fibrosis, but NGS allows the testing of many genes or diseases simultaneously. We have developed an expanded NGS PCS test for couples; simultaneously it covers 50 very serious, early-onset, autosomal recessive diseases that are untreatable. This is the first, noncommercial, population-based, expanded PCS test to be offered prospectively to couples in a health-care setting in Europe. So far, little is known about how potential users view such a PCS test. We therefore performed an online survey in 2014 among 500 people from the target population in the Netherlands. We enquired about their intention to take an expanded PCS test if one was offered, and through which provider they would like to see it offered. One-third of the respondents said they would take such a test were it to be offered. The majority (44%) preferred the test to be offered via their general practitioner (GP) and 58% would be willing to pay for the test, with a median cost of [euro ]75. Our next step is to perform an implementation study in which this PCS test will be provided via selected GPs in the Northern Netherlands.

Maximising the efficiency of clinical screening programmes: balancing predictive genetic testing with a right not to know.

We explored the dilemma between patients' right not to know their genetic status and the efficient use of health-care resources in the form of clinical cancer screening programmes. Currently, in the Netherlands, 50% risk carriers of heritable cancer syndromes who choose not to know their genetic status have access to the same screening programmes as proven mutation carriers. This implies an inefficient use of health-care resources, because half of this group will not carry the familial mutation. At the moment, only a small number of patients are involved; however, the expanding possibilities for genetic risk profiling means this issue must be addressed because of potentially adverse societal and financial impact. The trade-off between patients' right not to know their genetic status and efficient use of health-care resources was discussed in six focus groups with health-care professionals and patients from three Dutch university hospitals. Professionals prefer patients to undergo a predictive DNA test as a prerequisite for entering cancer screening programmes. Professionals prioritise treating sick patients or proven mutation carriers over screening untested individuals. Participation in cancer screening programmes without prior DNA testing is, however, supported by most professionals, as testing is usually delayed and relatively few patients are involved at present. Reducing the number of 50% risk carriers undergoing screening is expected to be achieved by: offering more psychosocial support, explaining the iatrogenic risks of cancer screening, increasing out-of-pocket costs, and offering a less stringent screening programme for 50% risk carriers.

Ethical aspects of soft tissue engineering for congenital birth defects in children--what do experts in the field say?

This article is part of the EuroSTEC project, which aims at developing tissue engineering-based treatments for structural disorders present at birth. EuroSTEC is positioned at the intersection of three areas with their own ethical issues: (1) regenerative medicine, (2) research with pregnant women and fetuses, and (3) research with neonates. Because of the overlap of these three areas in this project, we can expect to be confronted with new ethical challenges. To be able to respond adequately and timely to current and possible future ethical issues, a prospective and anticipatory ethical analysis is essential. To obtain a first survey of ethical issues that might arise during the different phases of the project, the Delphi method was used. The professionals directly involved in the EuroSTEC project were questioned about their views on possible ethical issues. The first round yielded 27 ethical issues, which the respondents were asked to prioritize in the second round. For the fundamental research phase, issues deemed most important were privacy and informed consent of the tissue donor. For the animal experimentation phase, three issues were mentioned (in order of decreasing priority): the suffering of animals, the use of animals as means to an end, and the limited adequacy of the animal models. Issues that were deemed most important during the clinical (trial) phase pertained to the problem of weighing risks and benefits for the fetus/child and the pregnant woman.

Two women with multiple sclerosis and their caregivers: conflicting normative expectations.

It is not uncommon that nurses are unable to meet the normative expectations of chronically ill patients. The purpose of this article is to describe and illustrate Walker's expressive-collaborative view of morality to interpret the normative expectations of two women with multiple sclerosis. Both women present themselves as autonomous persons who make their own choices, but who also have to rely on others for many aspects of their lives, for example, to find a new balance between work and social contacts or to find work. We show that their narratives of identity, relationship and value differ from the narratives that others use to understand and identify them. Since identities, relationships and values give rise to normative expectations, in both cases there is a conflict between what the women expect of their caregivers and vice-versa. The narratives also show that two similar persons with multiple sclerosis may need very different care. This implies that nurses caring for such persons should listen carefully to their stories and reflect on their own perceptions of self.