Use of a web-based portal to return normal individual research results in Early Check: Exploring user behaviors and attitudes.

Early Check is a voluntary, large-scale expanded newborn screening study in North Carolina that uses a self-directed web-based portal for return of normal individual research results (IRR). Little is known about participant perspectives in using web-based portals to receive IRR. This study explored user attitudes and behaviors within the Early Check portal using three methods: (1) a feedback survey available to the consenting parent of participating infants (typically mothers), (2) semi-structured interviews conducted with a subset of parents, and (3) Google Analytics. During an approximate 3-year period, 17 936 newborns received normal IRR and there were 27 812 visits to the portal. Most surveyed parents reported viewing their baby's results (86%, 1410/1639). Parents largely found the portal easy to use to get results, and helpful in understanding the results. However, 10% of parents said it was difficult to find enough information to understand their baby's results. In Early Check, providing normal IRR via the portal made a large-scale study practical, and was highly rated by most users. Return of normal IRR may be particularly amenable to web-based portals, as the consequences to participants from not viewing results are modest, and the interpretation of a normal result is relatively straightforward.

Out of This World: re-grounding justice through science fiction.

Good science fiction can be a successful vehicle for portraying justice. Science fiction can stimulate moral imagination in much the same way as the most effective justice theories, connecting the world in which we live with a range of alternative futures deliberately and creatively made plausible. A selective examination of classic and recent science fiction stories and novels provides contextual framing for considering questions of climate justice, virtuous personal action in the face of structural injustice, and the problem of what justice means when some people are regarded as "other." By connecting compelling images of individual responsibility with the complex challenges posed by striving for social justice, science fiction can also help render justice work appealing and achievable-an essential step that is reinforced in closing by a brief set of maxims.

Dobbs, the Intrusive State, and the Future of Solidarity.

The intrusive state has long viewed women as fetal containers. The Dobbs decision goes further, essentially causing women to vanish when fetuses are abstracted from their relationships to pregnant persons. The ways in which women are first controlled and then made invisible are clearly connected with the move from obedience to omission that has historically affected black Americans. When personal decisionmaking and participation in democracy are regarded as threats, those threatened restrict decisional freedom and political power, deepening structural injustices relating to sex, race, and poverty. Fear of Dobbs has health effects on conditions unrelated to pregnancy and connects with erasures of human value that are not health-related. We reaffirm solidarity as a countering influence. Taking account of the richly relational context in which issues like abortion and political representation arise should lead to better, more meaningful policies, making so many people impossible to unsee.

Othering and Health Justice.

Bioethics needs to expand its vision. We must examine and interrogate the social and structural barriers that help traditionally privileged communities maintain minoritized groups as inherently inferior "others." Justice requires the field to look beyond the walls of hospitals, clinics, and medical academia to address and ameliorate the structural injustices that give rise to health disparities long before differential access to health services becomes an issue for underserved patients. Doing so means engaging in challenging multidisciplinary collaborations in order to understand the sociohistorical complexities of health and illness, appreciate the factors that contribute to shaming and blaming those "others" who are not "us," and work to lessen the discomfort with uncertainty that impedes equity. All of this necessary work takes bioethics well beyond the well-trodden pathways of our usual scholarship and practice. But we simply have to reach higher to do health justice.

Optimizing antiemetic therapy for children undergoing chemotherapy.

Chemotherapy-induced nausea and vomiting (CINV) is a common side effect of most chemotherapy agents. Suboptimal management of CINV impacts quality of life, nutrition, gastrointestinal (GI) integrity, and adherence to chemotherapy treatment plans. This article reviews the principles of CINV management, planning and implementation of antiemetic regimens, and pharmacology of the antiemetics currently available in the United States appropriate for pediatric use. With the advent of more targeted therapies, increased use of immunotherapy, and the effects of radiotherapy to the brain, spine, and abdomen, treatment of CINV now has a broader application than just for chemotherapeutics alone.

Tracheostomy decision-making for children with medical complexity: What supports and resources do caregivers need?

OBJECTIVES: Caregivers of children with medical complexity (CMC) face decisions about life-sustaining interventions, such as tracheostomy. Our objective is to describe the support needs of caregivers of CMC and the resources they use surrounding tracheostomy decision-making (TDM) for their children. METHODS: This qualitative study, conducted between 2013 and 2015, consisted of semi-structured interviews with 56 caregivers of 41 CMC who had tracheostomies, and 5 focus groups of 33 clinicians at a tertiary care children's hospital. Participants were asked about their perspectives on the TDM process. Qualitative data were transcribed, coded, and organized into themes. RESULTS: Caregivers used five domains of resources surrounding TDM: (1) social network including extended family members, friends, and clergy; (2) healthcare providers including physicians and nurses; (3) other parents of children with tracheostomy; (4) tangible materials such as print materials, videos, tracheostomy tubes, mannequins, and simulation labs; and (5) internet including websites, social media, and online health communities. Caregivers used these resources for (1) decision-making, (2) becoming knowledgeable and skillful about child's diagnosis, tracheostomy, and home care, and (3) emotional and spiritual well-being. Caregivers agreed that they received enough support, but there were gaps. Clinicians were knowledgeable about these resources, discussed social network and internet less often than the other domains, and identified gaps in supporting caregivers. SIGNIFICANCE OF RESULTS: Caregivers' need for support and use of resources surrounding tracheostomy placement for CMC extended beyond decision-making, and included becoming knowledgeable and getting emotional/spiritual support. Healthcare providers exploring these resources with caregivers could improve the quality of TDM communication.

Diabetes and Humor: A Preliminary Investigation.

Diabetes can take a tremendous toll on physical and psychological health. Given the growing evidence of the benefits of humor, this study examined the association between diabetes and humor. The sample consisted of 249 participants: 72.3% with type 1 diabetes, 70.3% female, 89.5% Caucasian, and 70.9% college educated. Participants completed the Humor Styles Questionnaire (HSQ) and were compared with HSQ norms. On the affiliative humor scale, the diabetes group did not differ from the norm (P >0.05), nor did those with type 1 diabetes (P >0.05). Scores of those with type 2 diabetes were lower than the norm (P <0.05). On the self-enhancing humor scale, the diabetes group did not differ from the norm (P >0.05), nor did the subgroups with type 1 diabetes (P >0.05) or type 2 diabetes (P >0.05). The diabetes group was lower than the norm on aggressive humor (P <0.01), as were the subgroups with type 1 diabetes (P <0.01) and type 2 diabetes (P <0.05). The diabetes group was higher than the norm on self-defeating humor (P <0.01), as were the subgroups with type 1 diabetes (P <0.01) and type 2 diabetes (P <0.01). Results suggest that people with either type of diabetes are more inclined toward self-enhancing humor, are less inclined toward aggressive humor, and score higher on self-defeating humor, and those with type 1 diabetes are also inclined toward affiliative humor. Results are discussed relative to the sample being comprised of individuals with good glycemic control (mean A1C 7.06 ± 1.39%). This study offers a preliminary comparison of humor among people with diabetes versus those in a healthy norm group without diabetes.

Early Check: translational science at the intersection of public health and newborn screening.

BACKGROUND: Newborn screening (NBS) occupies a unique space at the intersection of translational science and public health. As the only truly population-based public health program in the United States, NBS offers the promise of making the successes of translational medicine available to every infant with a rare disorder that is difficult to diagnose clinically, but for which strong evidence indicates that presymptomatic treatment will substantially improve outcomes. Realistic NBS policy requires data, but rare disorders face a special challenge: Screening cannot be done without supportive data, but adequate data cannot be collected in the absence of large-scale screening. The magnitude and scale of research to provide this expanse of data require working with public health programs, but most do not have the resources or mandate to conduct research. METHODS: To address this gap, we have established Early Check, a research program in partnership with a state NBS program. Early Check provides the infrastructure needed to identify conditions for which there have been significant advances in treatment potential, but require a large-scale, population-based study to test benefits and risks, demonstrate feasibility, and inform NBS policy. DISCUSSION: Our goal is to prove the benefits of a program that can, when compared with current models, accelerate understanding of diseases and treatments, reduce the time needed to consider inclusion of appropriate conditions in the standard NBS panel, and accelerate future research on new NBS conditions, including clinical trials for investigational interventions. TRIAL REGISTRATION: Clinicaltrials.gov registration # NCT03655223 . Registered on August 31, 2018.

Caregiver Perceptions about their Decision to Pursue Tracheostomy for Children with Medical Complexity.

OBJECTIVE: To describe the perceptions of caregivers of children with medical complexity (CMC) about their decision to pursue tracheostomy for their children, in particular the satisfaction with their decision. STUDY DESIGN: In this qualitative study conducted in western North Carolina between 2013 and 2014, we interviewed 56 caregivers of 41 CMC who had received tracheostomies in the past 5 years. Three of the CMC were deceased at the time of the interview; 8 were decannulated. In-depth interviews (35 English, 6 Spanish) were conducted, audio-recorded, and transcribed verbatim. We used ATLAS.ti software to manage data and identified themes related to caregiver perceptions about tracheostomy decision. RESULTS: We found that caregivers often chose tracheostomy because extending the lives of their children and being able to care for them at home were important. Caregivers reported the many benefits of tracheostomy including improvement in respiratory symptoms, physical and developmental health, quality of life, and means to provide medical care quickly when needed. There were negative effects of tracheostomy such as mucous plugs, excessive secretions, accidental decannulation necessitating emergency tracheostomy tube change, and the increased infection risk. Providing medical care for CMC with tracheostomy at home was difficult, but improved over time. Caregivers were generally satisfied with their decision to pursue tracheostomy for their CMC. CONCLUSIONS: Decisional satisfaction with tracheostomy for CMC is high. In counseling caregivers about tracheostomy, clinicians should present both the benefits and risks. Future studies should quantify the outcomes described in this study.

Ensuring respect for persons in COMPASS: a cluster randomised pragmatic clinical trial.

Cluster randomised clinical trials present unique challenges in meeting ethical obligations to those who are treated at a randomised site. Obtaining informed consent for research within the context of clinical care is one such challenge. In order to solve this problem it is important that an informed consent process be effective and efficient, and that it does not impede the research or the healthcare. The innovative approach to informed consent employed in the COMPASS study demonstrates the feasibility of upholding ethical standards without imposing undue burden on clinical workflows, staff members or patients who may participate in the research by virtue of their presence in a cluster randomised facility. The COMPASS study included 40 randomised sites and compared the effectiveness of a postacute stroke intervention with standard care. Each site provided either the comprehensive postacute stroke intervention or standard care according to the randomisation assignment. Working together, the study team, institutional review board and members of the community designed an ethically appropriate and operationally reasonable consent process which was carried out successfully at all randomised sites. This achievement is noteworthy because it demonstrates how to effectively conduct appropriate informed consent in cluster randomised trials, and because it provides a model that can easily be adapted for other pragmatic studies. With this innovative approach to informed consent, patients have access to the information they need about research occurring where they are seeking care, and medical researchers can conduct their studies without ethical concerns or unreasonable logistical impediments. TRIAL REGISTRATION NUMBER: NCT02588664, recruiting. This article covers the development of consent process that is currentlty being employed in the study.

Who's Winning the IRB Wars? The Struggle for the Soul of Human Research.

The origins and aspirations of institutional review boards (IRBs), the American oversight system for research with human subjects, are well known, and their failures have been documented and disputed for decades. Contention about IRBs is often ideological and unsatisfying, but their shortcomings are real. A new wave of attention to the promise and problems of this oversight system has coincided with the years-long effort to update the federal "Common Rule." Three very different recent books-Rebecca Dresser's Silent Partners, Robert Klitzman's Ethics Police, and Carl Schneider's The Censor's Hand-draw from a wealth of experiential, empirical, and rhetorical resources to triangulate this long-standing set of concerns and tensions at individual, institutional, and system levels. Schneider's volume exemplifies anti-government critiques of the regulation of science; Klitzman's catalogues IRB members' reflections on the ambiguities inherent in their regulatory role; and, by far the most interestingly, Dresser examines the potential contributions of experienced research subjects to the oversight process. Taken together, these books can help refocus the IRB wars on the ever-challenging relationships among goals, uncertainties, and practicalities, and move us toward understanding and addressing those relationships in their current (and rapidly changing) scientific and societal context. Some real progress might even result.

Ethical considerations in tissue engineering research: Case studies in translation.

Tissue engineering research is a complex process that requires investigators to focus on the relationship between their research and anticipated gains in both knowledge and treatment improvements. The ethical considerations arising from tissue engineering research are similarly complex when addressing the translational progression from bench to bedside, and investigators in the field of tissue engineering act as moral agents at each step of their research along the translational pathway, from early benchwork and preclinical studies to clinical research. This review highlights the ethical considerations and challenges at each stage of research, by comparing issues surrounding two translational tissue engineering technologies: the bioartificial pancreas and a tissue engineered skeletal muscle construct. We present relevant ethical issues and questions to consider at each step along the translational pathway, from the basic science bench to preclinical research to first-in-human clinical trials. Topics at the bench level include maintaining data integrity, appropriate reporting and dissemination of results, and ensuring that studies are designed to yield results suitable for advancing research. Topics in preclinical research include the principle of "modest translational distance" and appropriate animal models. Topics in clinical research include key issues that arise in early-stage clinical trials, including selection of patient-subjects, disclosure of uncertainty, and defining success. The comparison of these two technologies and their ethical issues brings to light many challenges for translational tissue engineering research and provides guidance for investigators engaged in development of any tissue engineering technology.

Structural and thermodynamic basis of amprenavir/darunavir and atazanavir resistance in HIV-1 protease with mutations at residue 50.

Drug resistance occurs through a series of subtle changes that maintain substrate recognition but no longer permit inhibitor binding. In HIV-1 protease, mutations at I50 are associated with such subtle changes that confer differential resistance to specific inhibitors. Residue I50 is located at the protease flap tips, closing the active site upon ligand binding. Under selective drug pressure, I50V/L substitutions emerge in patients, compromising drug susceptibility and leading to treatment failure. The I50V substitution is often associated with amprenavir (APV) and darunavir (DRV) resistance, while the I50L substitution is observed in patients failing atazanavir (ATV) therapy. To explain how APV, DRV, and ATV susceptibility are influenced by mutations at residue 50 in HIV-1 protease, structural and binding thermodynamics studies were carried out on I50V/L-substituted protease variants in the compensatory mutation A71V background. Reduced affinity to both I50V/A71V and I50L/A71V double mutants is largely due to decreased binding entropy, which is compensated for by enhanced enthalpy for ATV binding to I50V variants and APV binding to I50L variants, leading to hypersusceptibility in these two cases. Analysis of the crystal structures showed that the substitutions at residue 50 affect how APV, DRV, and ATV bind the protease with altered van der Waals interactions and that the selection of I50V versus I50L is greatly influenced by the chemical moieties at the P1 position for APV/DRV and the P2 position for ATV. Thus, the varied inhibitor susceptibilities of I50V/L protease variants are largely a direct consequence of the interdependent changes in protease inhibitor interactions.

Exploring sleep-wake experiences of mothers during maintenance therapy for their child's acute lymphoblastic leukemia.

A qualitative study was designed to explore sleep-wake experience of mothers of children in maintenance treatment for Acute Lymphoblastic Leukemia. Interviews were conducted with 20 participants using open-ended, semi-structured questions and were transcribed verbatim. Two main themes emerged: "It's a whole new cancer world" and "I don't remember what it's like to have sleep." Mothers experience difficulty sleeping during their children's treatment, and expressed several serious issues. Although the mothers were able to employ various mechanisms to address sleep deprivation and disruption, interventions such as social support, journaling, spiritual guidance, and/or self-talk may be most beneficial.

Why Climate Literacy Is Health Literacy.

Health problems of global warming are daunting in severity and magnitude and will only get worse. Yet literacy about these problems is poor and plans to alleviate them are too early in development to be responsive to current levels of global threat and individual need. Social and ecological determinants of health and illness are exacerbated by excessive heat and flooding; lack of food, safe water, and secure shelter; and loss of arable land for farming. This article considers the nature and scope of ethicists' roles in awakening clinicians and the public to this crisis and offers 4 recommendations to reduce morbidity and mortality from climate change.

Perceptions regarding genetic testing in populations at risk for nephropathy.

BACKGROUND: Population ancestry-based differences exist in genetic risk for many kidney diseases. Substantial debate remains regarding returning genetic test results to participants. African-Americans (AAs) and European-Americans (EAs) at risk for end-stage kidney disease were queried for views on the value and use of genetic testing in research. METHODS: A standardized survey regarding attitudes toward genetic testing was administered to 130 individuals (64 AA, 66 EA) with first-degree relatives on dialysis. Fisher's exact test was used to assess differences in participant attitudes between population groups. RESULTS: Mean (SD) age of surveyed AAs and EAs was 45.5 (12.8) and 50.5 (14.4) years, respectively (p = 0.04), with similar familial relationships (p = 0.22). AAs and EAs wished to know their test results if risk could be: (1) reduced by diet or exercise (100 and 98%, p = 0.99); (2) reduced by medical treatment (100 and 98%, p = 0.99), or (3) if no treatments were available (90 and 82%, p = 0.21). If informed they lacked a disease susceptibility variant, 87% of AAs and 88% of EAs would be extremely or pretty likely to inform family members (p = 0.84). If informed they had a disease susceptibility variant, 92% of AAs and 89% of EAs would be extremely or pretty likely to inform their family (p = 0.43). CONCLUSIONS: Attitudes toward obtaining and using genetic test results for disease in research contexts were similar in AAs and EAs at risk for end-stage kidney disease. A substantial majority would want information regardless of available treatments and would share the information with the family. These results have important implications for patient care, study design and the informed consent process.

Why we should continue to worry about the therapeutic misconception.

In a recent article in The Journal of Clinical Ethics, David Wendler argues that worries about the therapeutic misconception (TM) are not only misconceived, but detract from the larger agenda of a proper informed consent for subjects involved in clinical research.1 By contrast, we argue that Wendler mischaracterizes those who support TM research, and that his arguments are fragmentary, often illogical, and neglect a critical difference between clinical care and clinical research. A clear explanation about the chief aim of research is, in fact, what gives the other elements in a consent process their meaning. We argue that informed consent must be both trial-specific and context-sensitive, and that concern about the TM is needed now more than ever.

DEI Is Not Enough.

The movement under way to increase diversity, equity, and inclusion (DEI) in every workplace, including academia, medicine, and science, is an essential step toward health justice, but only a first step. Bioethics, health care, and health-related research all need more professionals from minoritized groups, but all of us need to do more to address justice at every level. From inclusive workplace policies and practices to research into structural injustices and health disparities, bioethics can and must lead the way in collaborative efforts. The work belongs to all of us, and DEI is only the beginning.