Genomic-Based Newborn Screening for Inborn Errors of Immunity: Practical and Ethical Considerations.

Inborn errors of immunity (IEI) are a group of over 450 genetically distinct conditions associated with significant morbidity and mortality, for which early diagnosis and treatment improve outcomes. Newborn screening for severe combined immunodeficiency (SCID) is currently underway in several countries, utilising a DNA-based technique to quantify T cell receptor excision circles (TREC) and kappa-deleting recombination excision circles (KREC). This strategy will only identify those infants with an IEI associated with T and/or B cell lymphopenia. Other severe forms of IEI will not be detected. Up-front, first-tier genomic-based newborn screening has been proposed as a potential approach by which to concurrently screen infants for hundreds of monogenic diseases at birth. Given the clinical, phenotypic and genetic heterogeneity of IEI, a next-generation sequencing-based newborn screening approach would be suitable. There are, however, several ethical, legal and social issues which must be evaluated in detail prior to adopting a genomic-based newborn screening approach, and these are discussed herein in the context of IEI.

E-cigarettes: The Long-Term Liberal Perspective.

The debate for and against making e-cigarettes available to smokers is to a large extent empirical. We do not know the long-term health effects of vaping and we do not know how smokers will respond to e-cigarettes over time. In addition to these empirical uncertainties, however, there are difficult moral issues to consider. One such issue is that many smokers in some sense choose to smoke. Though smoking is addictive and though many start young, it does not seem impossible to plan for and implement cessation. Yet many choose not to do so and we arguably have some reason to respect this choice. I propose that liberal opposition to strict tobacco control, based on respect for choice, is mitigated when e-cigarettes are available, since they are such a close substitute. Making e-cigarettes available to smokers might therefore not only enable switching in practice, but may make tougher tobacco control more justified. Another moral issue is that making e-cigarettes widely available might induce many people to vape, who would otherwise have neither vaped nor smoked. If this is so, the price of using e-cigarettes to accelerate smoking cessation may be a long-term vaping epidemic. Since vaping is less harmful than smoking, both individuals and society will have less reason to end this epidemic and so it may endure longer than the smoking epidemic would otherwise have done. This raises further questions around the weighing of reduced harm to current smokers against increased harm to future vapers. Implications: Because they are a close substitute, e-cigarettes makes tougher tobacco control more morally and politically feasible. Because e-cigarettes are less harmful than combustibles, making them available may accelerate smoking cessation but also lead to a long-term vaping epidemic, as we have less reason to combat vaping, once established. Moral evaluation of this possible scenario requires considering at least three things: (1) the cost of addiction to autonomy, in addition to health effects, (2) possible distributional effects due to differences between current smokers and future vapers, and (3) the fact that a possible vaping epidemic affects mainly future people and future society.

Healthcare professionals' responsibility for informing relatives at risk of hereditary disease.

Advances in genetic diagnostics lead to more patients being diagnosed with hereditary conditions. These findings are often relevant to patients' relatives. For example, the success of targeted cancer prevention is dependent on effective disclosure to relatives at risk. Without clear information, individuals cannot take advantage of predictive testing and preventive measures. Against this background, we argue that healthcare professionals have a duty to make actionable genetic information available to their patients' at-risk relatives. We do not try to settle the difficult question of how this duty should be balanced against other duties, such as the duty of confidentiality and a possible duty not to know one's genetic predisposition. Instead, we argue for the importance of recognising a general responsibility towards at-risk relatives, to be discharged as well as possible within the limits set by conflicting duties and practical considerations. According to a traditional and still dominant perspective, it is the patient's duty to inform his or her relatives, while healthcare professionals are only obliged to support their patients in discharging this duty. We argue that this perspective is a mistake and an anomaly. Healthcare professionals do not have a duty to ensure that their patients promote the health of third parties. It is often effective and desirable to engage patients in disseminating information to their relatives. However, healthcare professionals should not thereby deflect their own moral responsibility.

Public support for healthcare-mediated disclosure of hereditary cancer risk information: Results from a population-based survey in Sweden.

BACKGROUND: Targeted surveillance of at-risk individuals in families with increased risk of hereditary cancer is an effective prevention strategy if relatives are identified, informed and enrolled in screening programs. Despite the potential benefits, many eligible at-risk relatives remain uninformed of their cancer risk. This study describes the general public's opinion on disclosure of hereditary colorectal cancer (CRC) risk information, as well as preferences on the source and the mode of information. METHODS: A random sample of the general public was assessed through a Swedish citizen web-panel. Respondents were presented with scenarios of being an at-risk relative in a family that had an estimated increased hereditary risk of CRC; either 10% (moderate) or 70% (high) lifetime risk. A colonoscopy was presented as a preventive measure. Results were analysed to identify significant differences between groups using the Pearson's chi-square (χ2) test. RESULTS: Of 1800 invited participants, 977 completed the survey (54%). In the moderate and high-risk scenarios, 89.2 and 90.6% respectively, would like to receive information about a potential hereditary risk of CRC (χ2, p = .755). The desire to be informed was higher among women (91.5%) than men (87.0%, χ2, p = .044). No significant differences were found when comparing different age groups, educational levels, place of residence and having children or not. The preferred source of risk information was a healthcare professional in both moderate and high-risk scenarios (80.1 and 75.5%). However, 18.1 and 20.1% respectively would prefer to be informed by a family member. Assuming that healthcare professionals disclosed the information, the favoured mode of information was letter and phone (38.4 and 33.2%). CONCLUSIONS: In this study a majority of respondents wanted to be informed about a potential hereditary risk of CRC and preferred healthcare professionals to communicate this information. The two presented levels of CRC lifetime risk did not significantly affect the interest in being informed. Our data offer insights into the needs and preferences of the Swedish population, providing a rationale for developing complementary healthcare-assisted communication pathways to realise the full potential of targeted prevention of hereditary CRC.

Shove and Nudge: A Commentary on Iserson.

In this comment on Kenneth Iserson's article, "Do You Believe in Magic? Shove, Don't Nudge: Advising Patients at the Bedside," I discuss the definition of and the moral evaluation of nudging. I propose that using persuasive descriptions and intentionally building trust in patients by one's demeanor is a form of nudging. I argue that nudging is not necessarily morally problematic, but that it can be controlling and can limit liberty, despite proponents' claims to the contrary. I agree with Iserson that clinicians should give their patients explicit advice, but add that they should ideally also be aware of the more subtle psychological effects of advice giving.

Ethical Frameworks in Public Health Decision-Making: Defending a Value-Based and Pluralist Approach.

A number of ethical frameworks have been proposed to support decision-making in public health and the evaluation of public health policy and practice. This is encouraging, since ethical considerations are of paramount importance in health policy. However, these frameworks have various deficiencies, in part because they incorporate substantial ethical positions. In this article, we discuss and criticise a framework developed by James Childress and Ruth Bernheim, which we consider to be the state of the art in the field. Their framework distinguishes aims, such as the promotion of public health, from constraints on the pursuit of those aims, such as the requirement to avoid limitations to liberty, or the requirement to be impartial. We show how this structure creates both theoretical and practical problems. We then go on to present and defend a more practical framework, one that is neutral in avoiding precommitment to particular values and how they ought to be weighted. We believe ethics is at the very heart of such weightings and our framework is developed to reflect this belief. It is therefore both pluralist and value-based. We compare our new framework to Childress and Bernheim's and outline its advantages. It is justified by its impetus to consider a wide range of alternatives and its tendency to direct decisions towards the best alternatives, as well as by the information provided by the ranking of alternatives and transparent explication of the judgements that motivate this ranking. The new framework presented should be useful to decision-makers in public health, as well as being a means to stimulate further reflection on the role of ethics in public health.

Incentives, equity and the Able Chooser Problem.

Health incentive schemes aim to produce healthier behaviours in target populations. They may do so both by making incentivised options more salient and by making them less costly. Changes in costs only result in healthier behaviour if the individual rationally assesses the cost change and acts accordingly. Not all people do this well. Those who fail to respond rationally to incentives will typically include those who are least able to make prudent choices more generally. This group will typically include the least advantaged more generally, since disadvantage inhibits one's effective ability to choose well and since poor choices tend to cause or aggravate disadvantage. Therefore, within the target population, health benefits to the better off may come at the cost of aggravated inequity. This is one instance of a problem I name the Able Chooser Problem, previously emphasised by Richard Arneson in relation to coercive paternalism. I describe and discuss this problem by distinguishing between policy options and their effects on the choice situation of individuals. Both positive and negative incentives, as well as mandates that are less than perfectly effective, require some sort of rational deliberation and action and so face the Able Chooser Problem. In contrast, effective restriction of what options are physically available, as well as choice context design that makes some options more salient or appealing, does not demand rational agency. These considerations provide an equity-based argument for preferring smart design of our choice and living environment to incentives and mandates.

The case for banning cigarettes.

Lifelong smokers lose on average a decade of life vis-à-vis non-smokers. Globally, tobacco causes about 5-6 million deaths annually. One billion tobacco-related deaths are predicted for the 21st century, with about half occurring before the age of 70. In this paper, we consider a complete ban on the sale of cigarettes and find that such a ban, if effective, would be justified. As with many policy decisions, the argument for such a ban requires a weighing of the pros and cons and how they impact on different individuals, both current and future. The weightiest factor supporting a ban, we argue, is the often substantial well-being losses many individuals suffer because of smoking. These harms, moreover, disproportionally affect the disadvantaged. The potential gains in well-being and equality, we argue, outweigh the limits a ban places on individuals' freedom, its failure to respect some individuals' autonomous choice and the likelihood that it may, in individual cases, reduce well-being.