Research opportunities and ethical considerations for heart and lung xenotransplantation research: A report from the National Heart, Lung, and Blood Institute workshop.

Xenotransplantation offers the potential to meet the critical need for heart and lung transplantation presently constrained by the current human donor organ supply. Much was learned over the past decades regarding gene editing to prevent the immune activation and inflammation that cause early organ injury, and strategies for maintenance of immunosuppression to promote longer-term xenograft survival. However, many scientific questions remain regarding further requirements for genetic modification of donor organs, appropriate contexts for xenotransplantation research (including nonhuman primates, recently deceased humans, and living human recipients), and risk of xenozoonotic disease transmission. Related ethical questions include the appropriate selection of clinical trial participants, challenges with obtaining informed consent, animal rights and welfare considerations, and cost. Research involving recently deceased humans has also emerged as a potentially novel way to understand how xeno-organs will impact the human body. Clinical xenotransplantation and research involving decedents also raise ethical questions and will require consensus regarding regulatory oversight and protocol review. These considerations and the related opportunities for xenotransplantation research were discussed in a workshop sponsored by the National Heart, Lung, and Blood Institute, and are summarized in this meeting report.

Update on the ethical, legal and technical challenges of translating xenotransplantation.

This manuscript reports on a landmark symposium on the ethical, legal and technical challenges of xenotransplantation in the UK. King's College London, with endorsement from the British Transplantation Society (BTS), and the European Society of Organ Transplantation (ESOT), brought together a group of experts in xenotransplantation science, ethics and law to discuss the ethical, regulatory and technical challenges surrounding translating xenotransplantation into the clinical setting. The symposium was the first of its kind in the UK for 20 years. This paper summarises the content of the expert lectures showcasing the progress which has been made in xenotransplantation including-the history of xenotransplantation, advances in gene edited animals and progress towards clinical xenotransplantation. We then set out the ethical and legal issues still to be resolved. Finally, we report the themes of the roundtable discussion highlighting areas of consensus and controversy. While the detail of the legal discussion was directed towards the UK, the principles and summary reported here are intended to be applicable to any jurisdiction seeking to implement clinical xenotransplantation.

Has the Expansion of Health Insurance Coverage via the Implementation of the Affordable Care Act Influenced Inequities in Coronary Revascularization in New York City?

BACKGROUND/PURPOSE: In 2014, New York City implemented the Affordable Care Act (ACA) leading to insurance coverage gains intended to reduce inequities in healthcare services use. The paper documents inequalities in coronary revascularization procedures (percutaneous coronary intervention and coronary artery bypass grafting) usage by race/ethnicity, gender, insurance type, and income before and after the implementation of the ACA. METHODS: We used data from the Healthcare Cost and Utilization Project to identify NYC patients hospitalized with the diagnosis of coronary artery disease (CAD) and/or congestive heart failure (CHF) in 2011-2013 (pre-ACA) and 2014-2017 (post-ACA). Next, we calculated age-adjusted rates of CAD and/or CHF hospitalization and coronary revascularization. Logistic regression models were used to identify the variables associated with receiving a coronary revascularization in each period. RESULTS: Age-adjusted rates of CAD and/or CHF hospitalization and coronary revascularization in patients 45-64 years of age and 65 years of age and older declined in the post-ACA period. Disparities by gender, race/ethnicity, insurance type, and income in the use of coronary revascularization persist in the post-ACA period. CONCLUSIONS: Although this health care reform law led to the narrowing of inequities in the use of coronary revascularization, disparities persist in NYC in the post-ACA period.

Understanding the Underlying Causes of Tensions That Arise in ICU Care for Older Patients.

AbstractObjective: We hypothesized that the reasons behind this tension are complex and can be understood better by applying social psychology theory.Design: A qualitative methodology was drawn on for data collection and thematic analysis, with focus group discussions adopted for interviews with patient families and ICU physicians. Additionally, we used a social psychology theory, the reasoned action approach (RAA) framework, to understand these tensions.Setting: Two 15-bedded ICUs of an academic university-affiliated teaching hospital in Singapore.Subjects: A total of 72 physicians and family members of older ICU patients (>70 years old).Measurements and Main Results: The primary analysis revealed five areas of tension around prognostication in the ICU. These dealt with issues of divergent views, different role expectations, conflicting emotional responses, and issues of communication and trust. Further analysis helped to identify underlying factors leading to tensions and behaviors. Differences in prognostication and in expectation of outcomes between clinicians and family members were the main cause of tensions. When the RAA framework was applied, these tensions could be predicted early on and understood more clearly.Conclusions: Tensions revolve around losing control of the patient's care, differences between hopeful expectations and clinical prognostication, perceived biases of physicians, and underlying mistrust between families and physicians.

Access to outpatient care in Manhattan and Paris: A tale of real change in two world cities.

France's system of universal health insurance (UHI) offers more equitable access to outpatient care than the patchwork system in the U.S., which does not have a UHI system. We investigate the degree to which the implementation of the Patient Protection and Affordable Care Act (ACA) has narrowed the gap in access to outpatient care between France and the U.S. To do so, we update a previous comparison of access to outpatient care in Manhattan and Paris as measured by age-adjusted rates of hospital discharge for avoidable hospital conditions (AHCs). We compare these rates immediately before and after the implementation of the ACA in 2014. We find that AHC rates in Manhattan declined by about 25% and are now lower than those in Paris. Despite evidence that access to outpatient care in Manhattan has improved, Manhattanites continue to experience greater residence-based neighborhood inequalities in AHC rates than Parisians. In Paris, there was a 3% increase in AHC rates and neighborhood-level inequalities increased significantly. Our analysis highlights the persistence of access barriers to outpatient care in Manhattan, particularly among racial and ethnic minorities, even following the expansion of health insurance coverage.

Neighborhood inequalities and the decline of infant mortality in São Paulo.

This paper documents changes in infant mortality (IM) rates in São Paulo, Brazil, between 2003 and 2013 and examines the association among neighborhood characteristics and IM. We investigate the extent to which increased use of health care services and improvements in economic and social conditions are associated with reductions in IM. Using data from the Brazilian Census and the São Paulo Secretaria Municipal da Saúde/SMS, we conducted a longitudinal analysis of panel data in all 96 districts of São Paulo for every year between 2003 and 2013. Our regression model includes district level measures that reflect economic, health care and social determinants of IM. We find that investments in health care have contributed to lower IM rates in the city, but the direct effect of increased spending is most evident for people living in São Paulo's middle- and high-income neighborhoods. Improvements in social conditions were more strongly associated with IM declines than increases in the use of health care among São Paulo's low-income neighborhoods. To reduce health inequalities, policies should target benefits to lower-income neighborhoods. Subsequent research should document the consequences of recent changes in Brazil's economic capacity and commitment to public health spending for population health.

Xenotransplantation Clinical Trials and the Need for Community Engagement.

There are several ethical concerns facing first-in-human clinical trials involving xenotransplantation. Who should participate in these trials? If we limit trial participation to those who have exhausted other treatment options, how can we avoid therapeutic misconception? How should we balance the desire for long-term monitoring of trial participants against the well-established principle that research participants have the right to withdraw from research? Finally, how should we balance concerns about equitable access to these trials with deep mistrust of the scientific community? In particular, should xenotransplant clinical trials attempt to address well-known inequities in clinical trial participation by race and ethnicity? In this commentary, I argue that clinical investigators and regulators have an obligation to engage with underrepresented communities to develop answers to these questions.

The Role of Formal Policy to Promote Informed Consent of Psychotropic Medications for Youth in Child Welfare Custody: A National Examination.

Active participation of youth and surrogate decision-makers in providing informed consent and assent for mental health treatment is critical. However, the procedural elements of an informed consent process, particularly for youth in child welfare custody, are not well defined. Given calls for psychotropic medication oversight for youth in child welfare custody, this study proposes a taxonomy for the procedural elements of informed consent policies based upon formal and informal child welfare policies and then examines whether enacted state formal policies across the United States endorsed these elements. A sequential multi-method study design included: (1) semi-structured interviews with key informants (n = 58) primarily from state child welfare agencies to identify a taxonomy of procedural elements for informed consent of psychotropic medications and then (2) a legislative review of the 50 states and D.C. to characterize whether formal policies endorsed each procedural element through February 2022. Key informants reported five procedural elements in policy, including how to: (1) gather social and medical history, (2) prescribe the medication, (3) authorize its use through consent and youth assent, (4) notify relevant stakeholders, and (5) routinely review the consenting decision. Twenty-three states endorsed relevant legislation; however, only two states specified all five procedural elements. Additionally, the content of a procedural element, when included, varied substantively across policies. Further research and expert consensus are needed to set best practices and guide policymakers in setting policies to advance transparency and accountability for informed consent of mental health treatment among youth in child welfare custody.

The evolution of infant mortality and neighbourhood inequalities in four world cities: 1988-2016.

OBJECTIVES: To determine the level of neighbourhood inequalities in infant mortality (IM) rates in the urban core of four world cities and to examine the association between neighbourhood-level income and IM. We compare our findings with those published in 2004 to better understand how these city health systems have evolved. METHODS: We compare IM rates among and within the four cities using data from four periods: 1988-1992; 1993-1997; 2003-2008 and 2012-2016. Using a maximum-likelihood negative binomial regression model that controls for births, we predict the relationship between neighbourhood-level income and IM. RESULTS: IM rates have declined in all four cities. Neighbourhood-level income is statistically significant for New York and, for the two most recent periods, in Paris. In contrast, there is no significant relationship between neighbourhood income and IM in London or Tokyo. CONCLUSIONS: Despite programmes to reduce IM inequalities at national and local levels, these persist in New York. Until the early part of this century, none of the other cities experienced a relationship between neighbourhood income and IM, but growing income inequalities within Paris have changed this situation. POLICY IMPLICATIONS: Policy-makers in these cities should focus on better understanding the social and economic factors associated with neighbourhood inequalities in IM.

The Impact of Firearm Legislation on Firearm Deaths, 1991-2017.

Firearm violence is a major public health concern in the USA with firearm suicide and homicide accounting for the majority of gun deaths. The present work seeks to explore the role of firearm legislation in reducing suicide and homicide rates. Using the State Firearm Law Database (www.statefirearmlaws.org), suicide and homicide rates were compared across the 50 US states from 1991 to 2017. A firearm regulations index was computed to represent the total number of state firearm laws. Generalized estimating equations were used to explore population-level increases or decreases in firearm regulations and their association with state suicide and homicide rates after controlling for several state-level covariates. Even after accounting for several key covariates (US region; time; gun ownership; percent of the state population that was White, Black, below the poverty line and 25 years or older with a bachelor's degree; incarceration rate, unemployment rate and divorce rate), we found that firearm laws significantly predicted state firearm suicide and homicide rates. States with greater numbers of laws had reduced suicide and homicide rates compared with those with fewer laws. The present findings point to the role of firearm legislation in curbing rates of gun violence across the USA.

Public Deliberation about Gene Editing in the Wild.

Genetic editing technologies have long been used to modify domesticated nonhuman animals and plants. Recently, attention and funding have also been directed toward projects for modifying nonhuman organisms in the shared environment-that is, in the "wild." Interest in gene editing nonhuman organisms for wild release is motivated by a variety of goals, and such releases hold the possibility of significant, potentially transformative benefit. The technologies also pose risks and are often surrounded by a high uncertainty. Given the stakes, scientists and advisory bodies have called for public engagement in the science, ethics, and governance of gene editing research in nonhuman organisms. Most calls for public engagement lack details about how to design a broad public deliberation, including questions about participation, how to structure the conversations, how to report on the content, and how to link the deliberations to policy. We summarize the key design elements that can improve broad public deliberations about gene editing in the wild.

Envisioning Complex Futures: Collective Narratives and Reasoning in Deliberations over Gene Editing in the Wild.

The development of technologies for gene editing in the wild has the potential to generate tremendous benefit, but also raises important concerns. Using some form of public deliberation to inform decisions about the use of these technologies is appealing, but public deliberation about them will tend to fall back on various forms of heuristics to account for limited personal experience with these technologies. Deliberations are likely to involve narrative reasoning-or reasoning embedded within stories. These are used to help people discuss risks, processes, and fears that are otherwise difficult to convey. In this article, we identify three forms of collective narrative that are particularly relevant to debates about modifying genes in the wild. Our purpose is not to privilege any particular narrative, but to encourage people involved in deliberations to make these narratives transparent. Doing so can help guard against the way some narratives-referred to here as "crafted narratives"-may be manipulated by powerful elites and concentrated economic interests for their own strategic ends.

Regulating Gene Editing in the Wild: Building Regulatory Capacity to Incorporate Deliberative Democracy.

The release of genetically engineered organisms into the shared environment raises scientific, ethical, and societal issues. Using some form of democratic deliberation to provide the public with a voice on the policies that govern these technologies is important, but there has not been enough attention to how we should connect public deliberation to the existing regulatory process. Drawing on lessons from previous public deliberative efforts by U.S. federal agencies, we identify several practical issues that will need to be addressed if relevant federal agencies are to undertake public deliberative activities to inform decision-making about gene editing in the wild. We argue that, while agencies may have institutional capacity to undertake public deliberative activities, there may not be sufficient political support for them to do so. Advocates of public deliberation need to make a stronger case to Congress about why federal agencies should be encouraged and supported to conduct public deliberations.

Variation in end-of-life care and hospital palliative care among hospitals and local authorities: A preliminary contribution of big data.

BACKGROUND: Many studies explore the clinical and ethical dimensions of care at the end-of-life, but fewer use administrative data to examine individual and geographic differences, including the use of palliative care. AIM: Provide a population-based perspective on end-of-life and hospital palliative care among local authorities and hospitals in France. DESIGN: Retrospective cohort study of care received by 17,928 decedents 65 and over (last 6 months of life), using the French national health insurance database. RESULTS: 55.7% of decedents died in acute-care hospitals; 79% were hospitalized in them at least once; 11.7% were admitted at least once for hospital palliative care. Among 31 academic medical centers, intensive care unit admissions ranged from 12% to 67.4%; hospital palliative care admissions, from 2% to 30.6%. Across local authorities, for intensive care unit days and hospital palliative care admissions, the ratios between the values at the third and the first quartile were 2.4 and 1.5. The odds of admission for hospital palliative care or to an intensive care unit for more than 7 days were more than twice as high among people ⩽85 years (aOR = 2.11 (1.84-2.43) and aOR = 2.59 (2.12-3.17), respectively). The odds of admission for hospital palliative care were about 25% lower (p = 0.04) among decedents living in local authorities with the lowest levels of education than those with the highest levels. CONCLUSION: The variation we document in end-of-life and hospital palliative care across different categories of hospitals and 95 local authorities raises important questions as to what constitutes appropriate hospital use and intensity at the end-of-life.

Medicaid Waivers and Tenancy Supports for Individuals Experiencing Homelessness: Implementation Challenges in Four States.

Policy Points Medicaid policymakers have a growing interest in addressing homelessness as a social determinant of health and driver of the potentially avoidable use of expensive medical services. Drawing on extensive document reviews and in-depth interviews in four early-adopter states, we examined the implementation of Medicaid's Section 1115 demonstration waivers to test strategies to finance tenancy support services for persons experiencing or at risk of homelessness. CONTEXT: The Affordable Care Act extended Medicaid eligibility to large numbers of individuals experiencing or at risk of homelessness. This legislative development and the growing recognition of homelessness as a significant social determinant of health have encouraged advocates and policymakers to seek new ways to use Medicaid to provide housing supports. METHODS: We conducted 28 semistructured interviews with 36 stakeholders in four states. The stakeholders were government administrators, health care providers, nonprofit housing staff, and consultants. We supplemented these interviews with extensive reviews of public documents, media accounts, think-tank reports, and published literature. We also conducted a systematic inductive qualitative analysis. FINDINGS: We identified seven challenges to the successful implementation of tenancy support demonstration projects: resolving the housing supply and NIMBY, removing silos between health care and homeless services providers, enrolling and retaining the target populations in Medicaid, contracting with and paying tenancy support providers, recruiting and retaining key workers, ensuring Medicaid's waiver durability, and reducing administrative crowd-out and waiver burden. CONCLUSIONS: Notwithstanding these challenges, three of the four states have made significant progress in launching their initiatives. At this point, the fourth state has delayed its start-up to consider alternatives to a Medicaid demonstration waiver to provide tenancy supports. The experience of the four states suggests lessons for Medicaid officials in other jurisdictions that are interested in pursuing tenancy support initiatives. Nevertheless, the limitations of tenancy support waiver programs suggest that federal policymakers should consider allowing states to more directly subsidize housing costs for those experiencing or at risk of homelessness as an optional Medicaid benefit.

Unsanitized and Unfair: How COVID-19 Bailout Funds Refuel Inequity in the US Health Care System.

CONTEXT: The CARES Act of 2020 allocated provider relief funds to hospitals and other providers. We investigate whether these funds were distributed in a way that responded fairly to COVID-19-related medical and financial need. The US health care system is bifurcated into the "haves" and "have nots." The health care safety net hospitals, which were already financially weak, cared for the bulk of COVID-19 cases. In contrast, the "have" hospitals suffered financially because their most profitable procedures are elective and were postponed during the COVID-19 outbreak. METHODS: To obtain relief fund data for each hospital in the United States, we started with data from the HHS website. We use the RAND Hospital Data tool to analyze how fund distributions are associated with hospital characteristics. FINDINGS: Our analysis reveals that the "have" hospitals with the most days of cash on hand received more funding per bed than hospitals with fewer than 50 days of cash on hand (the "have nots"). CONCLUSIONS: Despite extreme racial inequities, which COVID-19 exposed early in the pandemic, the federal government rewards those hospitals that cater to the most privileged in the United States, leaving hospitals that predominantly serve low-income people of color with less.