Supporting patient decision-making in non-invasive prenatal testing: a comparative study of professional values and practices in England and France.

BACKGROUND: Non-invasive prenatal testing (NIPT), which can screen for aneuploidies such as trisomy 21, is being implemented in several public healthcare systems across Europe. Comprehensive communication and information have been highlighted in the literature as important elements in supporting women's reproductive decision-making and addressing relevant ethical concerns such as routinisation. Countries such as England and France are adopting broadly similar implementation models, offering NIPT for pregnancies with high aneuploidy probability. However, we do not have a deeper understanding of how professionals' counselling values and practices may differ between these contexts. METHODS: In this paper, we explore how professionals in England and France support patient decision-making in the provision of NIPT and critically compare professional practices and values. We draw on data from semi-structured interviews with healthcare professionals. RESULTS: Both English and French professionals emphasised values relating to patient choice and consent. However, understandings and application of these values into the practice of NIPT provision differed. English interviewees placed a stronger emphasis on interpreting and describing the process of counselling patients and clinical care through a "principle" lens. Their focus was on non-directiveness, standardisation, and the healthcare professional as "decision-facilitator" for patients. French interviewees described their approach through a "procedural" lens. Their focus was on formal consent, information, and the healthcare professional as "information-giver". Both English and French professionals indicated that insufficient resources were a key barrier in effectively translating their values into practice. CONCLUSION: Our findings illustrate that supporting patient choice in the provision of NIPT may be held as an important value in common on a surface level, but can be understood and translated into practice in different ways. Our findings can guide further research and beneficially inform practice and policy around NIPT provision.

Preserving women's reproductive autonomy while promoting the rights of people with disabilities?: the case of Heidi Crowter and Maire Lea-Wilson in the light of NIPT debates in England, France and Germany.

On July 2021, the UK High Court of Justice heard the Case CO/2066/2020 on the application of Heidi Crowter who lives with Down's syndrome, and Máire Lea-Wilson whose son Aidan has Down's syndrome. Crowter and Lea-Wilson, with the support of the disability rights campaign, 'Don't Screen Us Out', have been taking legal action against the Secretary of State for Health and Social Care (the UK Government) for a review of the 1967 Abortion Act: the removal of section 1(1)(d) making termination of pregnancy lawful for 'severe' fetal indications detected after 24 weeks' gestation. On 23 September 2021, the High Court dismissed the claim. This action came at a time when non-invasive prenatal testing (NIPT) was introduced into the NHS England Fetal Anomaly Screening Programme for the trisomies 21, 13 and 18. The implementation of NIPT has been heavily criticised, in particular by 'Don't Screen Us Out' campaigners, for increasing fetal selection and discrimination of people living with disabilities. The case of Crowter and Lea-Wilson echoes debates in other European countries such as in France and Germany, where the introduction of NIPT in the public healthcare system has provoked equally vehement public reactions and discussions. The comparison between these three countries allows contextualising the public discourses around NIPT and the ground for termination of pregnancy in relation to different socio-cultural and political contexts. We examine how each country, and particularly England, deals with the conflict between the principles of promoting the rights of people living with disabilities and preserving women's reproductive autonomy.

Women's preferences for NIPT as a first-line test in England and France: Challenges for genetic counseling practices.

Non-invasive prenatal testing (NIPT) is provided in the private and public sectors worldwide as a first- or second-tier test. In England and France, NIPT is fully funded and offered as a contingent strategy with different probability cut-offs (1:150 and 1:1000). These different approaches to define the target population for NIPT have implications for how women experience their antenatal care. The paper explores and compares the perceptions and difficulties of women in England and France who took NIPT as a second-tier screening test. It is based on a semi-structured qualitative interview study with 17 women in England and France conducted between September 2021 and May 2022. The interviews were cross-analyzed using thematic analysis. Our findings show that most women express a preference for the offer of NIPT as a first-line screening test. Some issues with the contingent model, related to the access to information and termination of pregnancy (TOP), the disparities of NIPT uptake, and risks of generating anxiety with combined first-trimester screening (cFTS), could be addressed by a universal strategy for T21, T13, and T18. Nevertheless, this strategy could present some challenges for genetic counseling due to: women's understanding and expectations of NIPT; adequate information and counseling about the scope and limits of NIPT; concerns about the routinization of NIPT in the first-line offer; limitations and uncertainties associated with the provision of expanded NIPT in France; the remaining importance of other screening tests; and associated costs.

Solidarity during the COVID-19 pandemic: evidence from a nine-country interview study in Europe.

Calls for solidarity have been an ubiquitous feature in the response to the COVID-19 pandemic. However, we know little about how people have thought of and practised solidarity in their everyday lives since the beginning of the pandemic. What role does solidarity play in people's lives, how does it relate to COVID-19 public health measures and how has it changed in different phases of the pandemic? Situated within the medical humanities at the intersection of philosophy, bioethics, social sciences and policy studies, this article explores how the practice-based understanding of solidarity formulated by Prainsack and Buyx helps shed light on these questions. Drawing on 643 qualitative interviews carried out in two phases (April-May 2020 and October 2020) in nine European countries (Austria, Belgium, France, Germany, Ireland, Italy, The Netherlands, German-speaking Switzerland and the UK), the data show that interpersonal acts of solidarity are important, but that they are not sustainable without consistent support at the institutional level. As the pandemic progressed, respondents expressed a longing for more institutionalised forms of solidarity. We argue that the medical humanities have much to gain from directing their attention to individual health issues, and to collective experiences of health or illness. The analysis of experiences through a collective lens such as solidarity offers unique insights to understandings of the individual and the collective. We propose three essential advances for research in the medical humanities that can help uncover collective experiences of disease and health crises: (1) an empirical and practice-oriented approach alongside more normative approaches; (2) the confidence to make recommendations for practice and policymaking and (3) the pursuit of cross-national and multidisciplinary research collaborations.

Predictive Prenatal Diagnosis for Infantile-onset Inflammatory Bowel Disease Because of Interleukin-10 Signalling Defects.

OBJECTIVES: Advances in genetic technologies provide opportunities for patient care and ethical challenges. Clinical care of patients with rare Mendelian disorders is often at the forefront of those developments. Whereas in classical polygenic inflammatory bowel disease (IBD), the predictive value of genetic variants is very low, predictive prenatal genetic diagnosis can inform families at high risk of severe genetic disorders. Patients with IL-10 signalling defects because of pathogenic variants in IL10RA, Il10RB, and IL10 develop severe infantile onset inflammatory bowel disease that is completely penetrant and has a high morbidity and substantial mortality despite treatment. METHODS: We performed a survey among tertiary specialist paediatric centers of 10 countries on the utilization of predictive prenatal genetic diagnosis in IL-10 signalling defects. We retrospectively report prenatal genetics in a series of 8 families. RESULTS: International variation in legislation, guidelines, expert opinion, as well as cultural and religious background of families and clinicians results in variable utilization of preimplantation and prenatal genetic testing for IL-10 signalling defects. Eleven referrals for prenatal diagnosis for IL-10 signalling defects were identified across 4 countries. We report on 8 families who underwent prenatal preimplantation monogenic testing after in vitro fertilization (n = 2) and/or by amniocentesis/chorion villus sampling (n = 6). A genetic diagnosis was established in 1 foetus and excluded in 7 foetuses (all IL10RA variants). CONCLUSIONS: Prenatal genetic testing for IL10R-defects is feasible, yet the legal and ethical considerations are complex and controversial. In some countries, predictive genetics for IL-10-related signalling defects is entering clinical practice.

The right to a self-determined death as expression of the right to freedom of personal development: The German Constitutional Court takes a clear stand on assisted suicide.

On 26 February 2020, the German Constitutional Court rejected a law from 2015 that prohibited any form of 'business-like' assisted suicide as unconstitutional. The landmark ruling of the highest federal court emphasised the high priority given to the rights of autonomy and free personal development, both of which constitute the principle of human dignity, the first principle of the German constitution. The ruling echoes particularities of post-war Germany's end-of-life debate focusing on patient self-determination while rejecting any discussion of active assistance to die through a lethal injection administered by a doctor. This brief report discusses the ruling in the light of the broader sociopolitical and historical context of the German end-of-life debate.

Can there be wrongful life at the end of life? German courts revisit an old problem in a new context.

This article discusses a recent ruling by the German Federal Court concerning medical professional liability due to potentially unlawful clinically assisted nutrition and hydration (CANH) at the end of life. This case raises important ethical and legal questions regarding a third person's right to judge the value of another person's life and the concept of 'wrongful life'. In our brief report, we discuss the concepts of the 'value of life' and wrongful life, which were evoked by the court, and how these concepts apply to the present case. We examine whether and to what extent value-of-life judgements can be avoided in medical decision-making. The wrongful-life concept is crucial to the understanding of this case. It deals with the question whether life, even when suffering is involved, could ever be worse than death. The effects of this ruling on medical and legal practice in Germany are to be seen. It seems likely that it will discourage claims for compensation following life-sustaining treatment (LST). However, it is unclear to what extent physicians' decisions will be affected, especially those concerning withdrawal of CANH. We conclude that there is a risk that LST may come to be seen as the 'safe' option for the physician, and hence, as always appropriate.

Sharing whilst caring: solidarity and public trust in a data-driven healthcare system.

BACKGROUND: In the UK, the solidaristic character of the NHS makes it one of the most trusted public institutions. In recent years, the introduction of data-driven technologies in healthcare has opened up the space for collaborations with private digital companies seeking access to patient data. However, these collaborations appear to challenge the public's trust in the. MAIN TEXT: In this paper we explore how the opening of the healthcare sector to private digital companies challenges the existing social contract and the NHS's solidaristic character, and impacts on public trust. We start by critically discussing different examples of partnerships between the NHS and private companies that collect and use data. We then analyse the relationship between trust and solidarity, and investigate how this relationship changes in the context of digital companies entering the healthcare system. Finally, we show ways for the NHS to maintain public trust by putting in place a solidarity grounded partnership model with companies seeking to access patient data. Such a model would need to serve collective interests through, for example, securing preferential access to goods and services, providing health benefits, and monitoring data access. CONCLUSION: A solidarity grounded partnership model will help establish a social contract or licence that responds to the public's expectations and to principles of a solidaristic healthcare system.

Opening Pandora's box?: ethical issues in prenatal whole genome and exome sequencing.

OBJECTIVE: The development of genomic approaches to prenatal testing such as whole genome and exome sequencing offers the potential for a better understanding of prenatal structural anomalies in the fetus and ultimately for improved patient care and more informed reproductive decision making. In addition to the scientific and clinical challenges of achieving this, the introduction of new reproductive technologies also presents a number of ethical problems. The successful and appropriate development and introduction of prenatal genomics into clinical practice require these problems to be identified, understood and carefully analysed in the development of models of good ethical practice. METHOD: We conducted a critical review of the existing literature on ethical issues in prenatal genomics. RESULTS: We identified and discussed five areas of particular concern: valid consent, management and feed-back of information, responsibilities of health professionals, priority setting and resources and duties towards the future child. CONCLUSION: There is a need for further discussion of the issues we have outlined here, and we hope that this brief summary of ethical arguments in the literature encourages researchers, clinicians, patients and scientists to engage in further discussion of these and other important issues raised by prenatal genomics. © 2017 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd.

The 'French exception': the right to continuous deep sedation at the end of life.

In 2016, a law came into force in France granting terminally ill patients the right to continuous deep sedation (CDS) until death. This right was proposed as an alternative to euthanasia and presented as the 'French response' to problems at the end of life. The law draws a distinction between CDS and euthanasia and other forms of sympton control at the end of life. France is the first country in the world to legislate on CDS . This short report describes the particular context and underlying social values that led to this piece of legislation, and explores its meaning in the wider French context.

Making space for empathy: supporting doctors in the emotional labour of clinical care.

BACKGROUND: The academic and medical literature highlights the positive effects of empathy for patient care. Yet, very little attention has been given to the impact of the requirement for empathy on the physicians themselves and on their emotional wellbeing. DISCUSSION: The medical profession requires doctors to be both clinically competent and empathetic towards the patients. In practice, accommodating both requirements can be difficult for physicians. The image of the technically skilful, rational, and emotionally detached doctor dominates the profession, and inhibits physicians from engaging emotionally with their patients and their own feelings, which forms the basis for empathy. This inhibition has a negative impact not only on the patients but also on the physicians. The expression of emotions in medical practice is perceived as unprofessional and many doctors learn to supress and ignore their feelings. When facing stressful situations, these physicians are more likely to suffer from depression and burnout than those who engage with and reflect on their feelings. Physicians should be supported in their emotional work, which will help them develop empathy. Methods could include questionnaires that aid self-reflection, and discussion groups with peers and supervisors on emotional experiences. Yet, in order for these methods to work, the negative image associated with the expression of emotions should be questioned. Also, the work conditions of physicians should improve to allow them to make use of these tools. Empathy should not only be expected from doctors but should be actively promoted, assisted and cultivated in the medical profession.

The Concept of Dignity and Its Use in End-of-Life Debates in England and France.

Dignity is one of the most controversial and yet commonly used terms in debates regarding end-of-life issues. The term "dignity" can take various meanings. For example, it can be used to denote the respect owed to an individual person, or to signify the intrinsic value of humankind as a whole. These two different understandings of dignity inevitably lead to different approaches to end-of-life decisionmaking. This article explores the meaning of the term "dignity" in two European countries, England and France. Our analysis compares public debates and legislation on end-of-life-related issues in these two countries. We argue that in England dignity is most commonly understood as respect for individual autonomy, whereas in France dignity usually signifies respect for humanity as a whole. We demonstrate that the difference in the conceptualization of the term leads to different ethical, and hence legal and practical, approaches to end-of-life issues and vulnerable patients. Our particular focus is on (1) withdrawing/withholding life-sustaining treatment, (2) respect for patient preferences, and (3) assistance in dying. Given the difference in the understanding of dignity, and the underlying philosophical approaches, it appears that there is still a long way to go before we can establish common guidelines on end-of-life decisions across Europe and beyond. However, clarifying the use of the term "dignity" in different discussions around Europe could hopefully facilitate this endeavor.

Advance directives in english and French law: different concepts, different values, different societies.

In Western societies advance directives are widely recognised as important means to extend patient self-determination under circumstances of incapacity. Following other countries, England and France have adopted legislation aiming to clarify the legal status of advance directives. In this paper, I will explore similarities and differences in both sets of legislation, the arguments employed in the respective debates and the socio-political structures on which these differences are based. The comparison highlights how different legislations express different concepts emphasising different values accorded to the duty to respect autonomy and to protect life, and how these differences are informed by different socio-political contexts. Furthermore each country associates different ethical concerns with ADs which raise doubts about whether these directives are a theoretical idea which is hardly applicable in practice.

"I don't need my patients' opinion to withdraw treatment": patient preferences at the end-of-life and physician attitudes towards advance directives in England and France.

This paper presents the results of a qualitative interview study exploring English and French physicians' moral perspectives and attitudes towards end-of-life decisions when patients lack capacity to make decisions for themselves. The paper aims to examine the importance physicians from different contexts accord to patient preferences and to explore the (potential) role of advance directives (ADs) in each context. The interviews focus on (1) problems that emerge when deciding to withdraw/-hold life-sustaining treatment from both conscious and unconscious patients; (2) decision-making procedures and the participation of proxies/relatives; (3) previous experience with ADs and views on their usefulness; and (4) perspectives on ways in which the decision-making processes in question might be improved. The analysis reveals differences in the way patient preferences are taken into consideration and shows how these differences influence the reasons physicians in each country invoke to justify their reluctance to adhering to ADs. Identifying cultural differences that complicate efforts to develop the practical implementation of ADs can help to inform national policies governing ADs and to better adapt them to practice.

Ethical considerations in prenatal genomic testing.

This paper discusses ethical issues arising in the context of prenatal genomic testing. While genomic information in the prenatal context might increase reproductive choice, e.g. to better understand a phenotype detected during screening, the availability of ever broader screens, even in the absence of a suspicion of abnormality, will generate increasingly complex and uncertain information. This raises questions of how much and what information should be provided prior to testing and what information should be returned (and to whom) once testing has been performed. As prenatal genomic testing becomes broader and more routine, the information generated will have more often implications not only for the fetus, but also for the parents, siblings and the wider family, raising questions about professionals' responsibilities. Further challenges discussed in this paper include access to genomic testing and justice, as well as ongoing management and post-pregnancy follow-up. The paper highlights the importance of taking into account the particular difficulties that arise in the context of prenatal genomic testing: the uncertainty of the information while choices are binary (to continue with or to terminate pregnancy); the time pressure due to the statutory limits on the availability of termination; and the impact the testing of the fetus has on the woman's body and life.

Negotiating severity behind the scenes: prenatal testing in Germany.

Foetal-related severity is a key concept in policy and legislation relating to access to both reproductive technologies and selective abortions in many countries around the world, but not in Germany. This study sheds light on how 'severity' in the context of prenatal testing is understood and negotiated within the particular socio-cultural and legal context of Germany, where 'severity' relating to foetal clinical findings neither counts as a justification to implement population prenatal screening programs, nor as a legal ground to terminate pregnancy. This study explores the views of women who undergo prenatal testing, as well as of professionals who encounter them, through semi-structured interviews. It showcases how they frame severity and questions whether the existing legal and regulatory framework relating to prenatal testing and termination of pregnancy addresses their concerns and needs regarding reproductive decision-making. The interviews (n = 27) reveal that despite it being legally outside the explicit reasons for testing and termination of pregnancy, both women and professionals negotiate severity behind the scenes. Their interpretation of severity is highly context-dependent and relies on clinical, social and familial facets. Their perceptions of severity guide them in their handling of and decision-making around pregnancy management. Acknowledging the personal nature of severity assessment and providing professional or legal guidance which explicitly mentions foetal anomaly as a legitimate factor in pregnancy management could provide healthcare professionals and patients with the room needed to manage the pregnancy favourably.

Simultaneous treatment with tebuconazole and abscisic acid induces drought and salinity stress tolerance in Arabidopsis thaliana by maintaining key plastid protein levels.

Arabidopsis thaliana plants were treated simultaneously with the fungicide tebuconazole and the phytohormone abscisic acid (ABA). We carried out comparative proteomic and transcriptomic analysis against untreated controls under different stress regimes. The chemicals were applied 24 h before the onset of drought stress (removal of the nutrient medium) or salinity stress (hydroponic culture using 150 mM NaCl), and samples were taken during the stress treatments and after a 24 h recovery period. The combined chemical treatment protected plants against both forms of stress. Difference in-gel electrophoresis revealed 18 and 34 unique protein markers representing induced tolerance to drought and salinity stress, respectively. Most of the markers represented plastid functions (such as CO(2) fixation and photosystem II activity), and their abundance was reduced under stress conditions but maintained at near normal levels in the treated plants. The corresponding transcripts were reduced in abundance primarily under drought stress but not salinity stress, indicating that the signal transduction pathways activated by tebuconazole/ABA treatment depend on the nature of the stress stimulus.

Euthanasia and end-of-life practices in France and Germany. A comparative study.

The objective of this paper is to understand from a sociological perspective how the moral question of euthanasia, framed as the "right to die", emerges and is dealt with in society. It takes France and Germany as case studies, two countries in which euthanasia is prohibited and which have similar legislation on the issue. I presuppose that, and explore how, each society has its own specificities in terms of practical, social and political norms that affect the ways in which they deal with these issues. The paper thus seeks to understand how requests for the "right to die" emerge in each society, through both the debate (analysis of daily newspapers, medical and philosophical literature, legal texts) and the practices (ethnographic work in three French and two German hospitals) that elucidate the phenomenon. It does so, however, without attempting to solve the moral question of euthanasia. In spite of the differences observed between these two countries, the central issue at stake in their respective debates is the question of the individual's autonomy to choose the conditions in which he or she wishes to die; these conditions depend, amongst others, on the doctor-patient relationship, the organisation of end-of-life care in hospital settings, and more generally, on the way autonomy is defined and handled in the public debate.

Non-invasive prenatal testing in Germany: a unique ethical and policy landscape.

Non-invasive prenatal testing (NIPT) has been available commercially in Europe since approximately 2012. Currently, many countries are in the process of integrating NIPT into their publicly funded healthcare systems to screen for chromosomal aneuploidies such as trisomy 21 (Down syndrome), with a variety of implementation models. In 2019, the German Federal Joint Committee (G-BA), which plays a significant role in overseeing healthcare decisions in Germany, recommended that NIPT be reimbursed through public insurance. Following this recommendation, NIPT will be offered on a case-by-case basis, when a pregnant woman, after being counselled, makes an informed decision that the test is necessary in her personal situation. This model differs significantly from many other European countries, where NIPT is being implemented either as a first-tier screening offer available for all pregnancies, or a contingent screen for those with a high probability of foetal aneuploidy (with varying probability cut-offs). In this paper we examine how this unique approach to implementing NIPT in Germany is produced by an ethical and policy landscape resulting from a distinctive cultural and historical context with a significant influence on healthcare decision-making. Due in part to the specific legal and regulatory environment, as well as strong objections from various stakeholders, Germany did not implement NIPT as a first-tier screen. However, as Germany does not currently publicly fund as standard other forms of prenatal aneuploidy screening (such as combined first trimester screening), neither can it be implemented as a screen contingent on specific probability cut-offs. We discuss how German policy reflects the echoes of the past shaping approaches to new biotechnologies, and the implications of this unique model for implementing NIPT in a public healthcare system.

Health professionals and scientists' views on genome-wide NIPT in the French public health system: Critical analysis of the ethical issues raised by prenatal genomics.

In France, since January 2020, laboratories have started to make available genome-wide Non-Invasive Prenatal Testing (GW-NIPT) beyond the three common trisomies (T21, T13 and T18) at the same cost as standard NIPT. With the possible margins for interpretation of the legal framework and in the absence of clear and updated guidelines, health professionals are left with questions about which type of screening offer may be clinically responsible, morally appropriate, and, at the same time, respectful of women's values and ability to make autonomous choices. The aim of this study is to provide an analysis and understanding of the challenging dimensions of clinical practices in the context of evolving scientific knowledge and techniques in prenatal genomics. In this article, we develop a critical analysis of the arguments and concerns that emerge around the offer of expanded NIPT and are discussed by health professionals and scientists. To achieve this, we conducted qualitative semi-structured interviews with 17 health professionals and scientists from September 2021 to February 2022 and a comprehensive literature review (regulatory, scientific, medical, institutional sources). The results of our empirical research highlight the importance of addressing ethical issues related to the differing quality of counselling, the complexity of achieving informed consent, and the avoidance of harm to pregnant women in the feedback of findings beyond T21, T18 and T13. If there is an increase in the provision of GW-NIPT within the French public health system, it will be essential to promote medical practices that respect reproductive choices of women, support their autonomous decision and their understanding of the limitations and uncertainties associated with GW screening. Further research is required to provide an insight into women's perceptions in order to refine our analysis from the patients' perspective.