The Ethical Acceptability of a Recipient's Choice of Donor in Directed and Nondirected Transplantation: Japanese Perspective.

In organ transplantation, there is a lack of ethical discussion about the recipient's right not to receive a transplant. Using the current situation of living organ transplantation and deceased organ transplantation in Japan as an example, we prospectively discussed to what extent the recipient's right not to receive a transplant is ethically acceptable. In directed transplantation from a living donor, a recipient may refuse organ donation from a particular donor. It is preferable that a recipient's request for organ donation from a donor occurs as part of a transparent process. In nondirected transplantation from a deceased donor, refusal of transplantation from a particular type of donor appears potentially justifiable. There are both moral and pragmatic considerations. Certain refusals based solely on belief are morally unacceptable, and refusal to transplant a recipient based on the donor's age jeopardizes the entire transplant system. When religious beliefs affect mental and physical health, individualized measures are required for transplant rejection. We also deductively developed a prospective argument based on the current status of donor-recipient communication in living organ transplantation in Japan and the 2010 amendment of the law allowing relatives to be given priority in organ transplantation from deceased donors.

Solitary death and new lifestyles during and after COVID-19: wearable devices and public health ethics.

BACKGROUND: Solitary death (kodokushi) has recently become recognized as a social issue in Japan. The social isolation of older people leads to death without dignity. With the outbreak of COVID-19, efforts to eliminate solitary death need to be adjusted in line with changes in lifestyle and accompanying changes in social structure. Health monitoring services that utilize wearable devices may contribute to this end. Our goals are to outline how wearable devices might be used to (1) detect emergency situations involving solitary older people and swiftly connect them with medical treatment, to (2) reduce the frequency of deaths that remain undiscovered and (3) to reduce social isolation by promoting social interaction. METHODS: Theoretical and philosophical approaches were adopted to examine ethical issues surrounding the application of wearable devices and cloud-based information processing systems to prevent solitary death in the world with/after COVID-19. MAIN BODY: (1) Technology cannot replace social connections; without social support necessary to foster understanding of the benefits of health management through wearable devices among older adults, such devices may remain unused, or not used properly. (2) Maturity of the technology; systems face the difficult task of detecting and responding to a wide range of health conditions and life-threatening events in time to avert avoidable morbidity and mortality. (3) Autonomy and personhood; promoting the voluntary use of wearable devices that are a part of larger efforts to connect isolated individuals to a community or social services might be effective. Legal force should be avoided if possible. There is some concern that landlords may require an older person to sign a contract agreeing to wear a device. The autonomy of solitary older people should be respected. (4) Governance: policies must be developed to limit access to data from wearables and the purposes for which data can be used. CONCLUSION: If thoughtfully deployed under proper policy constraints, wearable devices offer a way to connect solitary older people to health services and could reduce cases of solitary death while respecting the personhood of the user.

Drug Repurposing for COVID-19: Ethical Considerations and Roadmaps.

While the world rushed to develop treatments for COVID-19, some turned hopefully to drug repurposing (drug repositioning). However, little study has addressed issues of drug repurposing in emergency situations from a broader perspective, taking into account the social and ethical ramifications. When drug repurposing is employed in emergency situations, the fairness of resource distribution becomes an issue that requires careful ethical consideration.This paper examines the drug repurposing in emergency situations focusing on the fairness using Japanese cases. Ethical issues under these circumstances addressed by the authors include: maintaining the evidence level, integrity of clinical research ethics, and voluntary consent by original indication patients. In order to address these issues, they argue that rapid accumulation of ethically and scientifically valid evidence is required, as is obtaining information on resource quantity.

Will you give my kidney back? Organ restitution in living-related kidney transplantation: ethical analyses.

In this article, we perform a thought experiment about living donor kidney transplantation. If a living kidney donor becomes in need of renal replacement treatment due to dysfunction of the remaining kidney after donation, can the donor ask the recipient to give back the kidney that had been donated? We call this problem organ restitution and discussed it from the ethical viewpoint. Living organ transplantation is a kind of 'designated donation' and subsequently has a contract-like character. First, assuming a case in which original donor (A) wishes the return of the organ which had been transplanted into B, and the original recipient (B) agrees, organ restitution will be permissible based on contract-like agreement. However, careful and detailed consideration is necessary to determine whether this leaves no room to question the authenticity of B's consent. Second, if B offers to give back the organ to A, then B's act is a supererogatory act, and is praiseworthy and meritorious. Such an offer is a matter of virtue, not obligation. Third, if A wishes B to return the organ, but B does not wish/allow this to happen, it is likely difficult to justify returning the organ to A by violating B's right to bodily integrity. But B's refusal to return the donated organ cannot be deemed praiseworthy, because B forgets the great kindness once received from A. Rather than calling this an obligation, we encourage B to consider such virtuous conduct.

Sacrificing the Fukushima 50 again?

BACKGROUND: In the aftermath of the 2011 Fukushima nuclear plant accident, many workers helped restore the contaminated site, exposing themselves to a highly radioactive environment. They were referred to as the 'Fukushima 50' and applauded as heroes who saved Japan. A cohort study targeting those emergency workers is, currently, underway. We object to the study on ethical grounds. METHODS: Ethical and content analyses. RESULTS: First, the low participation rate raises ethical questions about why potential participants declined. Content analyses of nuclear power plant workers' narratives from a television broadcast extracted eight recurrent themes: disposable, treated like a sacrificial pawn, taboo, fear of contamination, readiness to risk one's life, distrust and dissatisfaction with the nation's response, regret over participating and uncertainty about the future. Second, the unscientific nature of the cohort design undermines the ethical basis for conducting it. Third, public resources were allocated in a way that compromises justice. CONCLUSIONS: We urge re-considering the current Fukushima 50 research study. We also urge applying the public funds now invested in this research project to activities that would directly benefit the Fukushima 50, such as offering free lifetime healthcare and direct financial compensation.

Characterizing patients issued DNR orders who are ultimately discharged alive: a retrospective observational study in Japan.

BACKGROUND: The present study aimed to characterize factors associated with patients issued DNR orders during hospitalization who are discharged alive without any instruction orders by physicians regarding end-of-life treatment, with a focus on the timing of DNR order issuance. METHODS: In total, 2997 DNR cases from all 61,037 patients aged ≥20 years admitted to a representative general hospital in Tokyo were extracted and divided into two groups by patient hospital release status (discharged alive/deceased). Study items included age, sex, disease type (non-cancer/cancer), hospital department (internal medicine/others), timing of DNR order issuance, implementation (or not) of life-sustaining treatment (LST) or the presence of any restrictions on LST and hospital length of stay. We conducted multiple logistic regression analysis, setting hospital release status as the dependent variable and each above study item as explanatory variables. RESULTS: DNR orders were issued at a rate of 4.9%. The analysis revealed that patients with a DNR who were ultimately discharged alive were statistically more likely to be those for whom DNR orders are issued early after admission (adjusted odds ratio: AOR, 13.7), non-cancer patients (AOR, 3.4), internal medicine department patients (AOR, 1.63), females (AOR, 1.34), and elderly (aged ≥85 years; AOR, 1.02); these patients were also less likely to be receiving LST (AOR, 0.36). CONCLUSIONS: By focusing on those with DNR orders who were ultimately discharged alive, we discovered that these patients were likely to have DNR orders issued early after admission, and that they were more likely to be elderly, female, non-cancer patients, or those in internal medicine departments. Further examination of these data may help to elucidate why these particular DNR-related characteristics (including socio-economic and cultural factors) are evident in patients who end up being discharged alive.

What are considered 'good facts'?

In the January edition of the Journal of Medical Ethics, Fujita and Tabuchi (hereafter, Authors) responded that we misunderstood the 'facts' in our previous article. Our article's method was twofold. First, it appealed to normative analysis and publicly accessible materials, and second, it targeted a policy-making approach to public funding. We specifically did not focus on the Center for iPS Cell Research and Application or induced pluripotent stem stock projects. The Authors raised five criticisms, including transparency of our interpretation of public funding policy. We reply to these criticisms by clarifying facts, and demonstrating new data (facts), and asking the Authors what qualifies as a 'good fact' in medical ethics. We note that in some cases, it might be possible to examine to what extent facts are 'true', while in other cases, 'facts' are laden with 'values', which cannot be confirmed or falsified with observation alone. The level of 'good' implicit in a fact is a challenging issue that goes well beyond science and makes metaethical assumptions about the relationships between facts and values more broadly.

Implementation of Japan's First Clinical Research Regulatory Law: Background, Overview, and Challenges.

In April 2018, Japan's first law regulating clinical research went into effect. The law aimed to strengthen regulations on research integrity and conflicts of interest, which had been limited under existing administrative guidelines; the law also provided stipulations for legal penalties. The scope of the new regulations, however, is limited entirely to studies that evaluate unapproved drugs or the off-label use of approved drugs, and those that receive funding from companies. On the other hand, the law's application brings numerous complications, including the establishment of new review committees, troublesome procedures for transitioning studies that are currently underway, and ambiguities about the scope of what constitutes best efforts. Thus, the change has led to substantial strain and confusion in the field. This paper offers an overview of the law and its background, and discusses its future prospects from the practical standpoint of managing ethics committees and providing research ethics support in the field.

Endangerment of the iPSC stock project in Japan: on the ethics of public funding policies.

We examined the ethical justification for a national policy governing public funding for the induced pluripotent stem cell (iPSC) stock project in Japan and argue that the initiation of the iPSC stock project in 2012, when no clinical trial using iPSC-derived products had yet succeeded, was premature and unethical. Our analysis considers a generally accepted justice criterion and shows it fails to justify public funding of the iPSC stock project. We also raise concerns related to the massive amounts of public funding at stake and the absence of evidence supporting claimed success rates. We conclude that the iPSC stock project should be re-considered and deferred until a substantial number of clinical trials using iPSC-derived products are deemed successful. This analysis should benefit others worldwide as they consider their own public funding policies.

Reuse of cardiac organs in transplantation: an ethical analysis.

BACKGROUND: This paper examines the ethical aspects of organ transplant surgery in which a donor heart is transplanted from a first recipient, following determination of death by neurologic criteria, to a second recipient. Retransplantation in this sense differs from that in which one recipient undergoes repeat heart transplantation of a newly donated organ, and is thus referred to here as "reuse cardiac organ transplantation." METHODS: Medical, legal, and ethical analysis, with a main focus on ethical analysis. RESULTS: From the medical perspective, it is critical to ensure the quality and safety of reused organs, but we lack sufficient empirical data pertaining to medical risk. From the legal perspective, a comparative examination of laws in the United States and Japan affirms no illegality, but legal scholars disagree on the appropriate analysis of the issues, including whether or not property rights apply to transplanted organs. Ethical arguments supporting the reuse of organs include the analogous nature of donation to gifts, the value of donations as inheritance property, and the public property theory as it pertains to organs. Meanwhile, ethical arguments such as those that address organ recycling and identity issues challenge organ reuse. CONCLUSION: We conclude that organ reuse is not only ethically permissible, but even ethically desirable. Furthermore, we suggest changes to be implemented in the informed consent process prior to organ transplantation. The organ transplant community worldwide should engage in wider and deeper discussions, in hopes that such efforts will lead to the timely preparation of guidelines to implement reuse cardiac organ transplantation as well as reuse transplantation of other organs such as kidney and liver.

Regulations on Genome Editing of Human Embryos in Japan: Our Moral Moratorium.

The use of human embryos in genome editing research has recently been approved in China and the United Kingdom. In Japan, the debate on regulations on genome editing research studies using human embryos is underway, but is becoming increasingly entangled, to the point of deadlock. One main reason for this is the misalignment between the Japanese government and the research communities, in their awareness surrounding these regulations. In this article, we report on this ongoing and entangled debate in Japan concerning the regulations on genome editing technology using human embryos. The most critically needed next step is a grassroots level discussion among various experts such as those in the arts and humanities.

Pilot Study for the Development of a Self-Care System for Type 2 Diabetes Patients Using a Personal Digital Assistant (PDA).

PURPOSE: The primary objective of the present pilot study was to investigate the feasibility and acceptability of the newly developed self-care system using personal digital assistance in patients with type 2 diabetes. The secondary objective was to investigate changes in daily calorie intake, body weight, and hemoglobin A1c after using the system for 6 months. METHOD: The participants were nine outpatients with type 2 diabetes, aged 34-72 and living in Tokyo or surrounding prefectures. They were instructed to use the electronic food diary and to review the graphs of the total energy intake to control food intake under their own target value for 6 months. After they completed the study, the feasibility indicated by adherence rate for food recording and acceptability of the system rated with 6-point Likert scale from 1 (worst) to 6 (best) by the participants were investigated. RESULTS: Seven participants out of nine completed the study protocol. The median adherence rate for food recording was 80.6 %. Regarding the acceptability, six patients rated 6 for desire to use the system while one rated 5. In addition, regarding improvement in self-care for diabetes, the median score was 5. Daily calorie intake, body weight, and HbA1c, however, did not change significantly over the 6-month period. CONCLUSION: The newly developed self-care system might be feasible and acceptable in diabetes patients, which could be applied as an ecological momentary intervention tool, although there was some room to refine it to raise adherence.

The Social Framework Surrounding the Development of Regenerative Medicine in Japan.

In 2014, the Japanese government amended the laws concerning regenerative medicine. This reform aimed to contribute to the appropriate promotion of regenerative medicine and new drug discovery for intractable diseases using stem cells. It also helped restrict stem cell tourism, that is, provision of stem cell therapy of unclear efficacy and safety to tourists from abroad, and its relaxed regulations may even lead to the resolution of the drug lag problem. Stem cell medicine is positioned as a part of a national growth strategy that requires cooperation among the industry, government, healthcare field, and academia. It can be characterized as a "mesoscopic strategy," in that it aims to achieve high-level technological developments that would allow results from human-induced pluripotent stem cell and traditional stem cell research to contribute to regenerative medicine and drug development for intractable diseases, while attempting to strike a balance with commercialization and improved access of citizens to cutting-edge medical care.

Diamine oxidase activity levels in anorexia nervosa.

OBJECTIVE: Anorexia nervosa (AN) patients often experience gastrointestinal complications caused by their malnutrition. We hypothesized that intestinal integrity is disturbed in AN. Therefore, the objective of the present study was to investigate serum diamine oxidase (DAO) activity, which is considered to be a clinical indicator of the integrity of the intestinal mucosa, in AN patients. METHOD: Thirty-six AN female patients including 21 AN restricting type (AN-R) and 15 AN binge-eating/purging type (AN-BP) were compared with twenty healthy women on serum DAO activity using immunoassay. RESULTS: DAO levels in AN-R patients were significantly lower than in AN-BP patients and healthy controls. DISCUSSION: DAO levels were decreased in AN-R patients. This finding suggests the presence of intestinal structural disturbance as one of the physical complications of malnutrition in AN-R patients.

Autonomic dysfunction responses to head-up tilt in anorexia nervosa.

PURPOSE: Autonomic dysfunction of the cardiovascular system in anorexia nervosa (AN) was reported not only in the rest position, but also in the standing position in some previous studies, which might contribute to cardiac complications such as lethal arrhythmia. However, there has not been sufficient literature in this issue. Therefore, we performed a head-up tilt test, and compared the changes after tilting in indices of autonomic function between AN patients and healthy subjects by heart rate variability (HRV) and blood pressure variability (BPV). METHODS: The subjects were 21 females with AN and 30 age-matched healthy women. A head-up tilt test was performed following the protocol recommended by the American Heart Association. Blood pressure and heart rate data were collected for 10 min before and after tilting. In the frequency analysis, the powers of low-frequency (LF) and high-frequency (HF) components were calculated by a fast Fourier transformation. RESULTS: Regarding interactions between groups and head-up tilting, the head-up tilting-induced reduction of the HF component of HRV was significantly greater in the AN group. In addition, increases in the LF/HF of HRV and the LF component of BPV after head-up tilting were significantly smaller in the AN group. CONCLUSIONS: Regardless of the posture, changes in HF and LF/HF of HRV and LF of BPV in AN patients suggested the presence of autonomic insufficiency.