Beyond coercion: reframing the influencing other in medically assisted death.

This essay considers how we are to understand the decision to end one's life under medical aid-in-dying (MAID) statutes and the role of influencing others. Bioethical concerns about the potential for abuse in MAID have focused predominantly on the risk of coercion and other forms of undue influence. Most bioethical analyses of relational influences in MAID have been made by opponents of MAID, who argue that MAID is unethical, in part, because it cannot cleanly accommodate relational influences. In contrast, proponents of MAID have downplayed the role of relational influences because they may threaten the pillars of autonomy and voluntariness on which the ethics of MAID rest. Drawing on a case study collected as part of an ethnographic study of MAID in Vermont, we show how relations of care are central to MAID decision-making. Such relations may muddle motives for assisted death, exposing the limits of conventional bioethics thinking on MAID and relational influence. Here, we argue that ethical frameworks for MAID should account for the role of relational influences in decision-making, and acknowledge that relational influences may support, as well as undermine, a decision for MAID. We then outline an evaluative framework for determining whether relational influences are undue that identifies six key domains for consideration: mental competence, authenticity, relationship context, having an adequate range options, financial considerations and irremediability. We conclude by suggesting that social relationships may constitute an important source of value in end-of-life decision-making and not only a liability.

How Should We Allocate Divisible Resources? An Overlooked Question.

AbstractThe ethical allocation of scarce medical resources has received significant attention, yet a key question remains unaddressed: how should scarce, divisible resources be allocated? We present a case from the COVID-19 pandemic in which scarce resources were divided among patients rather than allocated to some patients over others. We assess how widely accepted allocation principles could be applied to this case, and we show how these principles provide insufficient guidance. We then propose alternatives that may help guide decision-making in such cases, and we evaluate the possibility of treating patients equally by dividing resources equally. Resource scarcity is not limited to pandemic situations, and many healthcare resources are divisible. This question-how to allocate these divisible resources-deserves greater attention from bioethics.

The Ethics of Conscientious Objection to Teaching Physician-Assisted Death.

The literature on the ethics of conscientious objection focuses on objections to participating in morally contested practices. This literature emphasizes the potential for participation to undermine objecting clinicians' moral integrity. Significantly less attention has been given to conscientious objection to teaching morally contested practices. Thus, it is unclear whether teaching morally contested practices has the potential to undermine objecting educators' moral integrity, and to the extent that it does, what steps can be taken to address this concern. We accordingly examine the ethics of conscientious objection to teaching morally contested practices, with a focus on teaching physician-assisted death (PAD) to trainees in US palliative care programs. We focus on three primary components of teaching PAD: (1) teaching the history and context of PAD; (2) teaching trainees how to understand and respond to requests for PAD; and (3) teaching trainees how to provide PAD. We argue that teaching components one and two has little potential to undermine objecting educators' moral integrity. Moreover, permitting objecting educators to opt out of teaching components one and two might undermine the education of trainees. In contrast, allowing objecting educators to opt out of teaching how to provide PAD may be important to preserving their moral integrity, and is unlikely to undermine trainees' education. We argue that educators should be permitted to opt out of teaching trainees how to provide PAD and describe policies that training programs can adopt to implement this approach.

Risk-Sensitive Assessment of Decision-Making Capacity: A Comprehensive Defense.

Should the assessment of decision-making capacity (DMC) be risk sensitive, that is, should the threshold for DMC vary with risk? The debate over this question is now nearly five decades old. To many, the idea that DMC assessments should be risk sensitive is intuitive and commonsense. To others, the idea is paternalistic or incoherent, or both; they argue that the riskiness of a given decision should increase the epistemic scrutiny in the evaluation of DMC, not increase the threshold for DMC. We respond to the critics' main concerns by providing a comprehensive account of how risk-sensitive DMC is coherent, avoids paternalism, and best fulfills the epistemic goal of DMC evaluations.

Rapid-Response Treatments for Depression and Requests for Physician-Assisted Death: An Ethical Analysis.

Depression is common at the end of life, and there is longstanding concern that it may affect terminally ill patients' decisions to request physician-assisted death (PAD). However, it is difficult for clinicians to determine the role of depression in a patient's PAD request. A recent case series described rapid responses to intranasal ketamine in three patients with terminal illness and comorbid depression who had requested PAD. One patient withdrew her request (which, in retrospect, had been driven by her depression) while the others maintained their requests; in all three, the rapid relief clarified the role of depression in the patients' decision-making. In addition to ketamine, there are other emerging rapid-response treatments for depression, including psilocybin with psychological support and functional connectivity-guided transcranial magnetic stimulation. We examine three key ethical implications of such treatments: their role in clarifying the decision-making capacity of depressed patients requesting PAD; the potential tension between the legal definition of irremediability in some jurisdictions and the ethical obligations of clinicians; and the likely obstacles to treatment access and their implications for equal respect for autonomy of patients.

Should Assessments of Decision-Making Capacity Be Risk-Sensitive? A Systematic Review.

Background: The concept of decision-making capacity (DMC) or competence remains controversial, despite widespread use. Risk-sensitive DMC assessment (RS-DMC)-the idea that the higher the risk involved in a decision, the greater the decisional abilities required for DMC-has been particularly controversial. We conducted a systematic, descriptive review of the arguments for and against RS-DMC to clarify the debate. Methods: We searched PubMed/MEDLINE (National Library of Medicine), PsycInfo (American Psychological Association) and Philpapers, updating our search to February 15th, 2022. We targeted peer-reviewed publications in English that argue for or against RS-DMC. Two reviewers independently screened the publications and extracted data from each eligible manuscript. Results: Of 41 eligible publications, 22 supported a risk-sensitive threshold in DMC assessment. Most arguments for RS-DMC rely on its intuitive appeal and practical merits. The arguments against RS-DMC primarily express concerns about paternalism and the seeming asymmetry between consent and refusal; critics of RS-DMC support epistemic, rather than substantive (i.e., variable threshold), risk-sensitivity; counterarguments responding to criticisms of RS-DMC address charges of paternalism and exhibit a notable variety of responses to the issue of asymmetry. Authors used a variety of frameworks regarding the definition of DMC, its elements, and its relation to decisional authority, and these frameworks were significantly associated with positions on RS-DMC. A limitation of our review is that the coding relies on judgment and interpretation. Conclusion: The review suggests that some of the debate about RS-DMC stems from differences in underlying frameworks. Most defenses of RS-DMC rely on its intuitive appeal, while most criticisms reflect concerns about paternalism or the asymmetry between consent and refusal. Defenses of RS-DMC respond to the asymmetry problem in a variety of ways. Further research is needed on the implications of underlying frameworks, the asymmetry problem, and the distinction between epistemic and substantive models of RS-DMC.

Rescue of behavioral and electrophysiological phenotypes in a Pitt-Hopkins syndrome mouse model by genetic restoration of Tcf4 expression.

Pitt-Hopkins syndrome (PTHS) is a neurodevelopmental disorder caused by monoallelic mutation or deletion in the transcription factor 4 (TCF4) gene. Individuals with PTHS typically present in the first year of life with developmental delay and exhibit intellectual disability, lack of speech, and motor incoordination. There are no effective treatments available for PTHS, but the root cause of the disorder, TCF4 haploinsufficiency, suggests that it could be treated by normalizing TCF4 gene expression. Here, we performed proof-of-concept viral gene therapy experiments using a conditional Tcf4 mouse model of PTHS and found that postnatally reinstating Tcf4 expression in neurons improved anxiety-like behavior, activity levels, innate behaviors, and memory. Postnatal reinstatement also partially corrected EEG abnormalities, which we characterized here for the first time, and the expression of key TCF4-regulated genes. Our results support a genetic normalization approach as a treatment strategy for PTHS, and possibly other TCF4-linked disorders.

Resource Limitation and "Forced Irremediability" in Physician-Assisted Deaths for Nonterminal Mental and Physical Conditions: A Survey of the US Public.

BACKGROUND: Physician-assisted death (PAD) for people with nonterminal illnesses (PAD-NT) is a controversial practice legal in some countries and increasingly debated in others, including the United States. A major concern about legalization of PAD-NT is that a lack of resources may drive some with mental illnesses or physical disabilities to seek PAD. OBJECTIVE: To assess US public opinion on PAD-NT under conditions of resource limitation. METHODS: The authors surveyed 2139 US adults matched to the US population in sex, age, race/ethnicity, education, political affiliation, and income. After giving their opinions regarding terminal PAD and PAD-NT in response to traditional PAD survey questions, respondents were randomly presented one of 4 scenarios of persons with nonterminal conditions requesting PAD-NT who lacked adequate resources to maintain their quality of life. The type of resources lacking (social or health care) and medical condition (mental or physical disability) were varied. Respondents' views regarding PAD-NT for the scenario specifically and legalization generally were then reassessed. RESULTS: At baseline, 55.4% of respondents supported legalizing terminal PAD, and 36.9% supported legalizing PAD-NT. After analyzing the scenarios, 28.2% (range 18.6%-39.7%) agreed/strongly agreed with legalizing PAD-NT generally and 23.7% (15.2%-33.7%) agreed/strongly agreed with PAD-NT for the instance depicted, with mental illness scenarios receiving much lower support; respondents' comments suggest devaluation of life with physical disability versus with mental illness. Being politically liberal, not religious, and assigned physical disability scenarios were associated with greater support for PAD-NT in multivariable analyses. CONCLUSIONS: A minority of the US public supports PAD-NT in the context of inadequate resources, with much lower support for PAD-NT for mental illness than for physical disability, suggesting that PAD-NT policy debates and future research should address the issue of whether sufficient resources must be available to potential requestors of PAD-NT.

Region and Cell Type Distribution of TCF4 in the Postnatal Mouse Brain.

Transcription factor 4 is a class I basic helix-loop-helix transcription factor regulating gene expression. Altered TCF4 gene expression has been linked to non-syndromic intellectual disability, schizophrenia, and a severe neurodevelopmental disorder known as Pitt-Hopkins syndrome. An understanding of the cell types expressing TCF4 protein in the mouse brain is needed to help identify potential pathophysiological mechanisms and targets for therapeutic delivery in TCF4-linked disorders. Here we developed a novel green fluorescent protein reporter mouse to visualize TCF4-expressing cells throughout the brain. Using this TCF4 reporter mouse, we observed prominent expression of TCF4 in the pallial region and cerebellum of the postnatal brain. At the cellular level, both glutamatergic and GABAergic neurons express TCF4 in the cortex and hippocampus, while only a subset of GABAergic interneurons express TCF4 in the striatum. Among glial cell groups, TCF4 is present in astrocytes and immature and mature oligodendrocytes. In the cerebellum, cells in the granule and molecular layer express TCF4. Our findings greatly extend our knowledge of the spatiotemporal and cell type-specific expression patterns of TCF4 in the brain, and hence, lay the groundwork to better understand TCF4-linked neurological disorders. Any effort to restore TCF4 functions through small molecule or genetic therapies should target these brain regions and cell groups to best recapitulate TCF4 expression patterns.