Immune to addiction: the ethical dimensions of vaccines against substance abuse.

Promising advances have been made in recent years for a unique class of immunotherapies that use vaccination to combat substance-use disorders. Although such vaccines are potentially useful for addictions, they raise a variety of ethical and social questions.

Consideration and Disclosure of Group Risks in Genomics and Other Data-Centric Research: Does the Common Rule Need Revision?

Harms and risks to groups and third-parties can be significant in the context of research, particularly in data-centric studies involving genomic, artificial intelligence, and/or machine learning technologies. This article explores whether and how United States federal regulations should be adapted to better align with current ethical thinking and protect group interests. Three aspects of the Common Rule deserve attention and reconsideration with respect to group interests: institutional review board (IRB) assessment of the risks/benefits of research; disclosure requirements in the informed consent process; and criteria for waivers of informed consent. In accordance with respect for persons and communities, investigators and IRBs should systematically consider potential group harm when designing and reviewing protocols, respectively. Research participants should be informed about any potential group harm in the consent process. We call for additional public discussion, empirical research, and normative analysis on these issues to determine the right regulatory and policy path forward.

Emerging technologies and ethics-exogenic chimeric humanized organs.

Organ transplantation is limited due to the scarcity of donor organs. In order to expand the supply of organs for transplantation, interspecies chimeras have been examined as a potential future source of humanized organs. Recent studies using gene editing technologies in combination with somatic cell nuclear transfer technology and hiPSCs successfully engineered humanized skeletal muscle in the porcine embryo. As these technologies progress, there are ethical issues that warrant consideration and dialogue.

Priority vaccination for mental illness, developmental or intellectual disability.

Coronavirus vaccines have made their debut. Now, allocation practices have stepped into the spotlight. Following Centers for Disease Control and Prevention guidelines, states and healthcare institutions initially prioritised healthcare personnel and elderly residents of congregant facilities; other groups at elevated risk for severe complications are now becoming eligible through locally administered programmes. The question remains, however: who else should be prioritised for immunisation? Here, we call attention to individuals institutionalised with severe mental illnesses and/or developmental or intellectual disabilities-a group highly susceptible to the damages of COVID-19, recent research shows, and critical to consider for priority vaccination. The language describing both federal-level and state-level intentions for this population remains largely vague, despite the population's diversity across age, diagnosis, functional status and living arrangement. Such absence of specificity, in turn, leaves room for confusion and even neglect of various subgroups. We review data stressing this group's vulnerability, as well as select state plans for priority vaccination, highlighting the importance of clarity when describing intentions to vaccinate, or even generally care for, diverse populations composed of distinct subgroups in need.

Virtual surgical planning and data ownership: Navigating the provider-patient-vendor relationship.

The practice of modern craniomaxillofacial surgery has been defined by emergent technologies allowing for the acquisition, storage, utilization, and transfer of massive amounts of sensitive and identifiable patient data. This alone has thrust providers into an unlikely and unprecedented role as the stewards of vast databases of digital information. This data powers the potent surgical tool of virtual surgical planning, a method by which craniomaxillofacial surgeons plan and simulate procedural outcomes in a digital environment. Further complicating this new terrain is the involvement of third-party contractors-a necessary presence in bringing raw data to bear in the office, virtual space, and operating room. The individual privileges and responsibilities of patients, providers, and vendors towards data are situated within the most recent U.S. court rulings and regulations. This paper offers guidance for overseeing the safe and responsible transfer to third-party contractors, and provides suggestions for negotiating the trinary relationship between physicians, their patients, and the vendors offering this transformative technology.

Combined Analysis of Asthma Safety Trials of Long-Acting ß2-Agonists.

BACKGROUND: Safety concerns regarding long-acting ß2-agonists (LABAs) in asthma management were initially identified in a large postmarketing trial in which the risk of death was increased. In 2010, the Food and Drug Administration (FDA) mandated that the four companies marketing LABAs for asthma perform prospective, randomized, controlled trials comparing the safety of combination therapy with a LABA plus an inhaled glucocorticoid with that of an inhaled glucocorticoid alone in adolescents (12 to 17 years of age) and adults. In conjunction with the FDA, the manufacturers harmonized their trial methods to allow an independent joint oversight committee to provide a final combined analysis of the four trials. METHODS: As members of the joint oversight committee, we performed a combined analysis of the four trials comparing an inhaled glucocorticoid plus a LABA (combination therapy) with an inhaled glucocorticoid alone. The primary outcome was a composite of asthma-related intubation or death. Post hoc secondary outcomes included serious asthma-related events and asthma exacerbations. RESULTS: Among the 36,010 patients in the intention-to-treat study, there were three asthma-related intubations (two in the inhaled-glucocorticoid group and one in the combination-therapy group) and two asthma-related deaths (both in the combination-therapy group) in 4 patients. In the secondary analysis of serious asthma-related events (a composite of hospitalization, intubation, or death), 108 of 18,006 patients (0.60%) in the inhaled-glucocorticoid group and 119 of 18,004 patients (0.66%) in the combination-therapy group had at least one composite event (relative risk in the combination-therapy group, 1.09; 95% confidence interval [CI], 0.83 to 1.43; P=0.55); 2100 patients in the inhaled-glucocorticoid group (11.7%) and 1768 in the combination-therapy group (9.8%) had at least one asthma exacerbation (relative risk, 0.83; 95% CI, 0.78 to 0.89; P<0.001). CONCLUSIONS: Combination therapy with a LABA plus an inhaled glucocorticoid did not result in a significantly higher risk of serious asthma-related events than treatment with an inhaled glucocorticoid alone but resulted in significantly fewer asthma exacerbations.

Science in the fight to uphold the rights of children.

The United States is the only major nation to not yet have ratified the United Nations Convention on the Rights of the Child (UNCRC). Recently, there has been an erosion of the rights of children across America, Europe, and elsewhere, but through science, we may have an opportunity to counter some of this alarming trend. In the area of vaccines, the scientific community can raise its voice on the dangers that nonmedical exemptions and delays pose to children at risk for measles, influenza, and other childhood illnesses. Poverty places infants and children at high risk for illness and homelessness. Gun violence and gun-related accidents are killing on average four American children daily, and climate change is promoting global pediatric malnutrition. Increasing international, federal, and state support to seek innovative solutions to these and related issues is a moral imperative.

Knowledge and Attitudes Toward Covid-19 and Vaccines Among a New York Haredi-Orthodox Jewish Community.

The Covid-19 pandemic has exposed the difficulty of the US public health system to respond effectively to vulnerable subpopulations, causing disproportionate rates of morbidity and mortality. New York Haredi-Orthodox Jewish communities represent a group that have been heavily impacted by Covid-19. Little research has examined their experience or perceptions toward Covid-19 and vaccines. We conducted a cross-sectional, observational study to explore the experience of Covid-19 among Haredim. Paper surveys were self-administered between December 2020 and January 2021 in Haredi neighborhood pediatricians' offices in Brooklyn, New York. Of 102 respondents, 43% reported either a positive SARS-CoV-2 viral or antibody test. Participants trusted their physicians, Orthodox medical organizations, and rabbinic leaders for medical information. Knowledge of Covid-19 transmission and risk was good (69% answered ≥ 4/6 questions correctly). Only 12% of respondents would accept a Covid-19 vaccine, 41% were undecided and 47% were strongly hesitant. Independent predictors of strong vaccine hesitancy included believing natural infection to be better than vaccination for developing immunity (adjusted odds ratio [aOR] 4.28; 95% confidence interval [CI] 1.23-14.86), agreement that prior infection provides a path toward resuming communal life (aOR 4.10; 95% CI 1.22-13.77), and pandemic-related loss of trust in physicians (aOR 5.01; 95% CI 1.05-23.96). The primary disseminators of health information for self-protective religious communities should be stakeholders who understand these groups' unique health needs. In communities with significant Covid-19 experience, vaccination messaging may need to be tailored toward protecting infection-naïve individuals and boosting natural immunity against emerging variants.

Importance of Pediatric Inclusion in COVID-19 Therapeutic Trials.

Pediatric patients are excluded from most coronavirus disease 2019 (COVID-19) therapeutic trials. We outline a rationale for the inclusion of children in COVID-19 therapeutic trials, which enabled us to include children of all ages in a therapeutic COVID-19 trial at our institution.

Genome editing: Bioethics shows the way.

When some scientists hear the word "bioethics," they break out in intellectual hives. They shouldn't. Good bioethics is about enabling science to move forward. Bioethics pushes scientists to acknowledge that they operate not within a vacuum but within a society in which diverse perspectives and values must be engaged. Bioethicists give voice to those divergent perspectives and provide a framework to facilitate informed and inclusive discussions that spur progress, rather than stall it. The field is needed to advance cutting-edge biomedical research in domains in which the benefits to be had are enormous, such as genome editing, but ethical concerns persist.

The ethics of testing and research of manufactured organs on brain-dead/recently deceased subjects.

Over 115 000 people are waiting for life-saving organ transplants, of whom a small fraction will receive transplants and many others will die while waiting. Existing efforts to expand the number of available organs, including increasing the number of registered donors and procuring organs in uncontrolled environments, are crucial but unlikely to address the shortage in the near future and will not improve donor/recipient compatibility or organ quality. If successful, organ bioengineering can solve the shortage and improve functional outcomes. Studying manufactured organs in animal models has produced valuable data, but is not sufficient to understand viability in humans. Before risking manufactured organ experimentation in living humans, study of bioengineered organs in recently deceased humans would facilitate evaluation of the function of engineered tissues and the complex interactions between the host and the transplanted tissue. Although such studies do not pose risk to human subjects, they pose unique ethical challenges concerning the previous wishes of the deceased, rights of surviving family members, effective operation and fair distribution of medical services, and public transparency. This article investigates the ethical, legal and social considerations in performing engineered organ research on the recently deceased.

Managing conflicts of interest in pharmacy and therapeutics committees: A proposal for multicentre formulary development.

WHAT IS KNOWN AND OBJECTIVE: While many countries have central agencies responsible for formulary development, within the United States, each hospital, health care system, or insurance provider has their own pharmacy and therapeutic committee, leading to both inefficiencies and inequalities across formularies. The number and variety of processes within pharmacy and therapeutic committees also increases the likelihood that conflicts of interest will influence the development of formularies. We sought to determine how such influences could be reduced by reviewing international evidence related to the presence and harms of conflicts of interest in formulary development. METHODS: Several approaches have been taken to reduce the influence of conflicts of interest in pharmacy and therapeutics committee processes, including include disclosure, recusal, exclusion, universal consideration and dual committees. The feasibility of each of these approaches is considered in the context of the United States. RESULTS AND DISCUSSION: A proposal is drawn from the discussion of various approaches to conflicts of interest in pharmacy and therapeutics committees: multicenter formulary development. WHAT IS NEW AND CONCLUSION: Multicentre formulary development, where resources are pooled across institutions, may lead to a reduction in the influence of conflicts of interest in pharmacy and therapeutics committee processes in the United States, increasing the chances of including the most safe, efficacious and cost-effective drugs on formularies.

Comparative effectiveness of neuroablation and deep brain stimulation for treatment-resistant obsessive-compulsive disorder: a meta-analytic study.

BACKGROUND: The safety and efficacy of neuroablation (ABL) and deep brain stimulation (DBS) for treatment refractory obsessive-compulsive disorder (OCD) has not been examined. This study sought to generate a definitive comparative effectiveness model of these therapies. METHODS: A EMBASE/PubMed search of English-language, peer-reviewed articles reporting ABL and DBS for OCD was performed in January 2018. Change in quality of life (QOL) was quantified based on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the impact of complications on QOL was assessed. Mean response of Y-BOCS was determined using random-effects, inverse-variance weighted meta-analysis of observational data. FINDINGS: Across 56 studies, totalling 681 cases (367 ABL; 314 DBS), ABL exhibited greater overall utility than DBS. Pooled ability to reduce Y-BOCS scores was 50.4% (±22.7%) for ABL and was 40.9% (±13.7%) for DBS. Meta-regression revealed no significant change in per cent improvement in Y-BOCS scores over the length of follow-up for either ABL or DBS. Adverse events occurred in 43.6% (±4.2%) of ABL cases and 64.6% (±4.1%) of DBS cases (p<0.001). Complications reduced ABL utility by 72.6% (±4.0%) and DBS utility by 71.7% (±4.3%). ABL utility (0.189±0.03) was superior to DBS (0.167±0.04) (p<0.001). INTERPRETATION: Overall, ABL utility was greater than DBS, with ABL showing a greater per cent improvement in Y-BOCS than DBS. These findings help guide success thresholds in future clinical trials for treatment refractory OCD.

The Real Impact of the Alabama Supreme Court Decision in LePage v Center for Reproductive Medicine.

This Viewpoint breaks down the myriad ways the Alabama Supreme Court decision to declare frozen embryos as legal equivalents to children harms the health of mothers and fetuses, limits reproductive decision-making based on genetics and out-of-reach costs, and impedes research.

The Ethics of Psychosocial Assessment in Vascularized Composite Allotransplantation: A Call for Transparency of Process to Support the Equitable Selection of Patients.

As the field of vascularized composite allotransplantation (VCA) continues to evolve and technological approaches improve, VCA programs must focus on promoting greater consistency in psychosocial assessment across programs to support the equitable selection of patients. Based on a summary of published reports of VCA, we address the ethical considerations raised by the present heterogeneity of approaches to psychosocial assessment, including weighing risks and benefits, informed consent and the role of decisional capacity, and potential or perceived bias in the assessment process. We propose transparency of process across the field and encourage VCA programs to work collaboratively to share approaches to psychosocial assessment both pre- and post-transplant to promote health equity.

Self-Inflicted Gunshot Wound as a Consideration in the Patient Selection Process for Facial Transplantation.

Facial transplantation is emerging as a therapeutic option for self-inflicted gunshot wounds. The self-inflicted nature of this injury raises questions about the appropriate role of self-harm in determining patient eligibility. Potential candidates for facial transplantation undergo extensive psychosocial screening. The presence of a self-inflicted gunshot wound warrants special attention to ensure that a patient is prepared to undergo a demanding procedure that poses significant risk, as well as stringent lifelong management. Herein, we explore the ethics of considering mechanism of injury in the patient selection process, referring to the precedent set forth in solid organ transplantation. We also consider the available evidence regarding outcomes of individuals transplanted for self-inflicted mechanisms of injury in both solid organ and facial transplantation. We conclude that while the presence of a self-inflicted gunshot wound is significant in the overall evaluation of the candidate, it does not on its own warrant exclusion from consideration for a facial transplantation.

Chloe's Law: A Powerful Legislative Movement Challenging a Core Ethical Norm of Genetic Testing.

Since the early 1970s, the ethical norm governing counselors involved in testing and screening for genetic conditions related to reproduction has been strict neutrality. Counseling about reproductive genetics was to be patient centered but nondirective. Many advocates for people with Down syndrome believe that high abortion rates following a diagnosis of this condition show an unfounded bias against those with Down syndrome. These advocates have succeeded in enacting federal and state legislation that requires women who receive a prenatal diagnosis of Down syndrome to receive positive information about the condition, thereby ending the nominal goal of value-neutral counseling and setting the stage for further normative shifts in clinical reproductive genetics as counseling expands because of cell-free testing.

Fair, just and compassionate: A pilot for making allocation decisions for patients requesting experimental drugs outside of clinical trials.

Patients have received experimental pharmaceuticals outside of clinical trials for decades. There are no industry-wide best practices, and many companies that have granted compassionate use, or 'preapproval', access to their investigational products have done so without fanfare and without divulging the process or grounds on which decisions were made. The number of compassionate use requests has increased over time. Driving the demand are new treatments for serious unmet medical needs; patient advocacy groups pressing for access to emerging treatments; internet platforms enabling broad awareness of compelling cases or novel drugs and a lack of trust among some that the pharmaceutical industry and/or the FDA have patients' best interests in mind. High-profile cases in the media have highlighted the gap between patient expectations for compassionate use and company utilisation of fair processes to adjudicate requests. With many pharmaceutical manufacturers, patient groups, healthcare providers and policy analysts unhappy with the inequities of the status quo, fairer and more ethical management of compassionate use requests was needed. This paper reports on a novel collaboration between a pharmaceutical company and an academic medical ethics department that led to the formation of the Compassionate Use Advisory Committee (CompAC). Comprising medical experts, bioethicists and patient representatives, CompAC established an ethical framework for the allocation of a scarce investigational oncology agent to single patients requesting non-trial access. This is the first account of how the committee was formed and how it built an ethical framework and put it into practice.