Opportunities and challenges for the computational interpretation of rare variation in clinically important genes.

Genome sequencing is enabling precision medicine-tailoring treatment to the unique constellation of variants in an individual's genome. The impact of recurrent pathogenic variants is often understood, however there is a long tail of rare genetic variants that are uncharacterized. The problem of uncharacterized rare variation is especially acute when it occurs in genes of known clinical importance with functionally consequential variants and associated mechanisms. Variants of uncertain significance (VUSs) in these genes are discovered at a rate that outpaces current ability to classify them with databases of previous cases, experimental evaluation, and computational predictors. Clinicians are thus left without guidance about the significance of variants that may have actionable consequences. Computational prediction of the impact of rare genetic variation is increasingly becoming an important capability. In this paper, we review the technical and ethical challenges of interpreting the function of rare variants in two settings: inborn errors of metabolism in newborns and pharmacogenomics. We propose a framework for a genomic learning healthcare system with an initial focus on early-onset treatable disease in newborns and actionable pharmacogenomics. We argue that (1) a genomic learning healthcare system must allow for continuous collection and assessment of rare variants, (2) emerging machine learning methods will enable algorithms to predict the clinical impact of rare variants on protein function, and (3) ethical considerations must inform the construction and deployment of all rare-variation triage strategies, particularly with respect to health disparities arising from unbalanced ancestry representation.

The intersection of traumatic childbirth and obstetric racism: A qualitative study.

BACKGROUND: Traumatic childbirth experiences are common in the United States - affecting a third to a fourth of mothers - with significant negative impacts on maternal health. Yet most research on traumatic childbirth focuses on white mothers' experiences. Drawing on a racially and ethnically diverse sample of mothers who experienced traumatic childbirth, this exploratory qualitative study examined Black, Latina, and Asian mothers' traumatic birth experiences and the role of obstetric racism in shaping these experiences. METHODS: In-depth, semi-structured interviews were conducted in 2019-2020 with 30 mothers who identified as women of color (37% Black, 40% Latina, and 23% Asian) who gave birth in the US and self-identified as having experienced a traumatic childbirth. Data were analyzed using qualitative content analysis. RESULTS: Mothers reported obstetric racism as core to their traumatic birth experiences. This racism manifested through practitioners' use of gendered and racialized stereotypes, denying and delegitimizing mothers' needs. Mothers shared key consequences of the obstetric racism they experienced, including postpartum anxiety and depression, increased medical mistrust, and decreased desire for future children. CONCLUSIONS: Mothers' reports suggest that obstetric racism played a role in their traumatic birth experiences. Particularly, practitioners' deployment of gendered and racialized stereotypes influenced mothers' treatment during birth. These findings point to opportunities to address obstetric racism during childbirth and improve patients' experiences through enhancing their agency and empowerment. The findings, in addition, highlight the need for increased practitioner training in anti-racist practice and cultural humility.

Focusing on Human Rights: a framework for CRISPR germline genome editing ethics and regulation.

The late 2018 announcement of the claimed births of CRISPR-edited babies has stimulated widespread condemnation and calls by some leading scientists for a moratorium on any further germline genome editing (GGE) for reproductive purposes. Concurrently, national and international bodies are calling for the development of robust guidelines and regulations that will identify permissible conditions under which such GGE efforts might eventually proceed. Crucially, these conditions go beyond rigorous safety standards to address some of the social and ethical concerns that arise with germline interventions. As these bodies convene to navigate this unique terrain, we suggest an important standard for generating ethically robust guidelines. Our approach builds from concerns about social exclusion and social justice with a focus on fundamental human rights. We believe that a deontological or rights-based approach, rather than a utilitarian approach, is needed to ensure that this socially disruptive technology minimizes further marginalization of people with disabilities and does not create a new form of social injustice. In pursuit of a deontological framework, we propose the implementation of an objective assessment tool: the Human Rights Impact Assessment (HRIA). Use of the HRIA establishes necessary constraints on applications of GGE in order to safeguard the most vulnerable members of society.

Expectations and Concerns of Older Adults With Cognitive Impairment About Their Relationship With Medical Providers: A Call for Therapeutic Alliances.

We sought to understand the expectations and concerns of older adults with cognitive impairment with regard to their relationship with medical providers. In particular, we observed whether study participants were involved in therapeutic alliances. Medical providers and patients create therapeutic alliances when they agree on the goals of the treatment and share a personal bond. Whereas such alliances have been studied in cancer research, little is known about therapeutic alliances in dementia research. Data were gathered in a qualitative study of 27 older adults with cognitive impairment and analyzed with narrative analysis. We introduce four case studies that illustrate the effects of having or missing a therapeutic alliance. Whereas the participant in the first case benefited from a therapeutic alliance, the other cases are marked by different experiences of abandonment. Findings suggest that interventions should concentrate on ways to enhance the relationship between medical providers and patients with cognitive impairment.

Seeking a Sense of Belonging.

This article draws on investigations by its authors, and from American and Italian interventions to provide recommendations for decreasing social isolation in older adults for policy makers, researchers, and other professionals committed to supporting the improved social integration of older adults. The article argues that to mitigate social isolation it is critical to foster a sense of belonging (personal involvement in a system or environment so people feel they are an integral part of that system or environment). Suggestions are provided on how to leverage systematic interventions to foster isolated older adults' sense of belonging to their communities.

Capacity to Address Social Needs Affects Primary Care Clinician Burnout.

PURPOSE: Primary care clinicians disproportionately report symptoms of burnout, threatening workforce sustainability and quality of care. Recent surveys report that these symptoms are greater when clinicians perceive fewer clinic resources to address patients' social needs. We undertook this study to better understand the relationship between burnout and clinic capacity to address social needs. METHODS: We completed semistructured, in-person interviews and brief surveys with 29 primary care clinicians serving low-income populations. Interview and survey topics included burnout and clinic capacity to address social needs. We analyzed interviews using a modified grounded theory approach to qualitative research and used survey responses to contextualize our qualitative findings. RESULTS: Four key themes emerged from the interview analyses: (1) burnout can affect how clinicians evaluate their clinic's resources to address social needs, with clinicians reporting high emotional exhaustion perceiving low efficacy even in when such resources are available; (2) unmet social needs affect practice by influencing clinic flow, treatment planning, and clinician emotional wellness; (3) social services embedded in primary care clinics buffer against burnout by increasing efficiency, restoring clinicians' medical roles, and improving morale; and (4) clinicians view clinic-level interventions to address patients' social needs as a necessary but insufficient strategy to address burnout. CONCLUSIONS: Primary care clinicians described multiple pathways whereby increased clinic capacity to address patients' social needs mitigates burnout symptoms. These findings may inform burnout prevention strategies that strengthen the capacity to address patients' social needs in primary care clinical settings.

Informed consent for early-phase clinical trials: therapeutic misestimation, unrealistic optimism and appreciation.

Unrealistic therapeutic beliefs are very common-the majority of patient-subjects (up to 94%) enrol in phase 1 trials seeking and expecting significant medical benefit, even though the likelihood of such benefit has historically proven very low. The high prevalence of therapeutic misestimation and unrealistic optimism in particular has stimulated debate about whether unrealistic therapeutic beliefs in early-phase clinical trials preclude adequate informed consent. We seek here to help resolve this controversy by showing that a crucial determination of when such therapeutic beliefs are ethically problematic turns on whether they are causally linked and instrumental to the motivation to participate in the trial. Thus, in practice, it is ethically incumbent on researchers to determine which understanding and beliefs lead to the participant's primary motivation for enrolling, not to simply assess understanding, beliefs and motivations independently. We further contend that assessing patient-subjects' appreciation as a component of informed consent-it is already an established component of decision-making capacity assessments-can help elucidate the link between understanding-beliefs and motivation; appreciation refers to an individual's understanding of the personal significance of both the medical facts and the experience of trial participation. Therefore, we recommend that: (1) in addition to the usual question, 'Why do you want to participate in this trial?', all potential participants should be asked the question: 'What are you giving up by participating in this trial?' and (2) researchers should consider the settings in which it may be possible and practical to obtain 'two-point consent'.

Factors associated with oncology patients' involvement in shared decision making during chemotherapy.

OBJECTIVE: Oncology patients are increasingly encouraged to play an active role in treatment decision making. While previous studies have evaluated relationships between demographic characteristics and decision-making roles, less is known about the association of symptoms and psychological adjustment characteristics (eg, coping styles and personality traits) and decision-making roles. METHODS: As part of a larger study of symptom clusters, patients (n = 765) receiving chemotherapy for breast, gastrointestinal, gynecological, or lung cancer provided information on demographic, clinical, symptom, and psychological adjustment characteristics. Patient-reported treatment decision-making roles (ie, preferred role and role actually played) were assessed using the Control Preferences Scale. Differences among patients, who were classified as passive, collaborative, or active, were evaluated using χ2 analyses and analyses of variance. RESULTS: Over half (56.3%) of the patients reported that they both preferred and actually played a collaborative role. Among those patients with concordant roles, those who were older, those with less education and lower income, and those who were less resilient were more likely to prefer a passive role. Several psychological adjustment characteristics were associated with decision-making role, including coping style, personality, and fatalism. CONCLUSIONS: Oncology patients' preferences for involvement in treatment decision making are associated with demographic characteristics as well as with symptoms and psychological adjustment characteristics, such as coping style and personality. These results reaffirm the complexities of predicting patients' preferences for involvement in decision making. Further study is needed to determine if role or coping style may be influenced by interventions designed to teach adaptive coping skills.

"Editing" Genes: A Case Study About How Language Matters in Bioethics.

Metaphors used to describe new technologies mediate public understanding of the innovations. Analyzing the linguistic, rhetorical, and affective aspects of these metaphors opens the range of issues available for bioethical scrutiny and increases public accountability. This article shows how such a multidisciplinary approach can be useful by looking at a set of texts about one issue, the use of a newly developed technique for genetic modification, CRISPRcas9.

Professional Distress and Meaning in Health Care: Why Professional Empathy Can Help.

For human service care providers working in hospitals, balancing the motivation for interpersonal engagement with patients alongside self-protective emotional boundaries is a familiar struggle. Empathy is a critical, although not thoroughly understood, aspect of patient care as well as an important ingredient for feeling work satisfaction and meaning. However, empathy can lead to feelings of sympathetic emotional distress and even burnout. This article uses an illustrative case study from a medical social worker in the emergency room to explore these themes of empathy, burnout, and the search for meaning in work. The discussion examines areas for further empirical study and intervention to support care-provider empathy and avoid burnout.

What we owe patients when fear undermines autonomy: Concretized emotions and the incapacity to deliberate.

Fear and anxiety can interfere profoundly with a person's ability to deliberate. Patients sometimes face critical medical decisions while subject to intense emotions which involve catastrophic (or wishful) convictions about the future. Medical teams, and even psychiatrists and bioethicists, lack a model for what to do in such cases. Philosophical accounts of autonomy and the clinical criteria for decision-making capacity derived from them fail to address cases in which emotions do not merely skew judgment but rather block decision-making capacity itself. This paper provides an account of when emotions undermine a person's freedom to deliberate, which is the basis of the capacity for autonomy. People subject to what I call 'concretized emotions' meet the cognitive criteria for decision-making capacity. Yet their emotions dictate their views of reality and prevent them from meeting the basic conditions for deliberation. To deliberate one needs to be able to think through alternatives, and this thinking through alternatives needs to be responsive to evidence. With concretized fear, both the ability to think through alternatives and the ability to respond cognitively to evidence is undermined. The person can engage in apparent deliberation, but her thought processes regarding the feared matter are characterized by the rigid view that things are just as they seem from her emotional view. This paper develops a theoretical and clinical model for a more appropriate and nuanced approach to acting responsibly toward patients subject to intense fear and related emotional states that block their decision-making capacity.

When concretized emotion-belief complexes derail decision-making capacity.

There is an important gap in philosophical, clinical and bioethical conceptions of decision-making capacity. These fields recognize that when traumatic life circumstances occur, people not only feel afraid and demoralized, but may develop catastrophic thinking and other beliefs that can lead to poor judgment. Yet there has been no articulation of the ways in which such beliefs may actually derail decision-making capacity. In particular, certain emotionally grounded beliefs are systematically unresponsive to evidence, and this can block the ability to deliberate about alternatives. People who meet medico-legal criteria for decision-making capacity can react to health and personal crises with such capacity-derailing reactions. One aspect of this is that a person who is otherwise cognitively intact may be unable to appreciate her own future quality of life while in this complex state of mind. This raises troubling ethical challenges. We cannot rely on the current standard assessment of cognition to determine decisional rights in medical and other settings. We need to understand better how emotionally grounded beliefs interfere with decision-making capacity, in order to identify when caregivers have an obligation to intervene.

Attending to clinical wisdom.

In response to the article by Baum-Baicker and Sisti, I will consider the kind of wisdom involved in therapeutic listening; the role of life wisdom; and the challenge of imparting clinical wisdom to young health professionals' education.

In principle obstacles for empathic AI: why we can't replace human empathy in healthcare.

What are the limits of the use of artificial intelligence (AI) in the relational aspects of medical and nursing care? There has been a lot of recent work and applications showing the promise and efficiency of AI in clinical medicine, both at the research and treatment levels. Many of the obstacles discussed in the literature are technical in character, regarding how to improve and optimize current practices in clinical medicine and also how to develop better data bases for optimal parameter adjustments and predictive algorithms. This paper argues that there are also in principle obstacles to the application of AI in clinical medicine and care where empathy is important, and that these problems cannot be solved with any of the technical and theoretical approaches that shape the current application of AI in specific areas of clinical medicine in which care for patients is fundamental. This is important, because it generates specific risks that may be overlooked otherwise, and it justifies the necessity of human monitoring and emotional intervention in clinical medicine. Consequently, difficult issues concerning moral and legal responsibility may ensue if these in principle problems are ignored.

Addressing Suicide Risk in Patients Living With Dementia During the COVID-19 Pandemic and Beyond.

Alzheimer's disease and related dementias (ADRD) are progressive illnesses characterized by decline in cognitive function that impairs performing daily activities. People with ADRD are at an increased risk of suicide, especially those who have comorbid mental health conditions, have specific types of ADRD, or have been recently diagnosed. The coronavirus disease 2019 (COVID-19) pandemic has increased the distress of people with ADRD, a population also at increased risk of contracting the COVID-19 virus. In this article, we draw on a case study and use the Interpersonal Theory of Suicide to help describe the association between ADRD and suicide risk. Secondly, we call for new strategies to mitigate suicide risk in people living with ADRD during and beyond the current pandemic by using lessons learned from cancer care. Our goal is not to dictate solutions but rather to start the conversation by outlining a framework for future research aimed at preventing death by suicide in people with ADRD. Specifically, we draw on the updated Framework for Developing and Evaluating Complex Interventions to reflect on the complexity of the issue and to break it down into achievable parts to reduce the risk of suicidal behavior (ideation, plans, attempts) in those living with ADRD.

Can Clinical Empathy Survive? Distress, Burnout, and Malignant Duty in the Age of Covid-19.

The Covid-19 crisis has accelerated a trend toward burnout in health care workers, making starkly clear that burnout is especially likely when providing health care is not only stressful and sad but emotionally alienating; in such situations, there is no mental space for clinicians to experience authentic clinical empathy. Engaged curiosity toward each patient is a source of meaning and connection for health care providers, and it protects against sympathetic distress and burnout. In a prolonged crisis like Covid-19, clinicians provide care out of a sense of duty, especially the duty of nonabandonment. We argue that when duty alone is relied on too heavily, with fear and frustration continually suppressed, the risk of burnout is dramatically increased. Even before Covid-19, clinicians often worked under dehumanizing and unjust conditions, and rates of burnout were 50 percent for physicians and 33 percent for nurses. The Covid-19 intensification of burnout can serve as a wake-up call that the structure of health care needs to be improved if we are to prevent the loss of a whole generation of empathic clinicians.

How Scientists Perceive CRISPR's Translational Promise and the Implications for Individuals with Genetic Conditions.

CRISPR (clustered regularly interspaced short palindromic repeats) somatic genome editing, an important promissory technology, presents a case study of the movement of basic scientists into translational research. In this paper, we explore how scientists experience the pulls of CRISPR's power and the pushes of economic and societal pressures in adopting new translational roles. Given basic scientists' emerging contact with and influence upon individuals with genetic conditions, we also examine how scientists understand the perspectives of affected populations, both as potential subjects of early experiments and as the patients who could receive future treatments. Finally, we consider the ethical implications of our findings and call for innovative approaches to translational research that help scientists engage with people with genetic conditions in early translational research.

The Effects of the COVID-19 Pandemic on the Lived Experience of Diverse Older Adults Living Alone With Cognitive Impairment.

BACKGROUND AND OBJECTIVES: Even before the COVID-19 pandemic, older adults with cognitive impairment living alone (an estimated 4.3 million individuals in the United States) were at high risk for negative health outcomes. There is an urgent need to learn how this population is managing during the pandemic. RESEARCH DESIGN AND METHODS: This is a qualitative study of 24 adults aged 55 and older living alone with cognitive impairment from diverse racial/ethnic backgrounds. Participants' lived experiences during the pandemic were elicited via 59 ethnographic interviews conducted over the phone either in English, Spanish, or Cantonese. Using a qualitative content analysis approach, interview transcripts were analyzed to identify codes and themes. RESULTS: Qualitative analysis of transcripts revealed 5 themes: (a) fear generated by the pandemic, (b) distress stemming from feeling extremely isolated, (c) belief in misinformation, (d) strategies for coping during the pandemic, and (e) the importance of access to essential services. DISCUSSION AND IMPLICATIONS: This pandemic put a spotlight on the precarity and unmet needs of older adults living alone with cognitive impairment. Findings underscore the need to expand access to home care aides and mental health services for this population.

Nursing education, virtual reality and empathy?

An empathic approach to patient-centred care is a core of nursing practice. One of the methods to develop empathy, which is gaining currency is the use of virtual reality simulations in education. This paper posits some questions, does it simply reinforce a 'type' of patient, neglecting caring for the patient as unique, is empathy what results or is it pity, does it result in a greater distance being created between the patient and the health care provider? Can we ever really know what it is like to walk in a patient's shoes when what we experience through virtual reality provides a small snapshot of the vicissitudes of living with an illness or disability. We suggest that what matters most in simulations using virtual reality is how the student exits the experience and if they leave knowing just what patients 'like that' feel, or whether they leave with humility and curiosity.