The return of individual genomic results to research participants: design and pilot study of Tohoku Medical Megabank Project.

Certain large genome cohort studies attempt to return the individual genomic results to the participants; however, the implementation process and psychosocial impacts remain largely unknown. The Tohoku Medical Megabank Project has conducted large genome cohort studies of general residents. To implement the disclosure of individual genomic results, we extracted the potential challenges and obstacles. Major challenges include the determination of genes/disorders based on the current medical system in Japan, the storage of results, prevention of misunderstanding, and collaboration of medical professionals. To overcome these challenges, we plan to conduct multilayer pilot studies, which deal with different disorders/genes. We finally chose familial hypercholesterolemia (FH) as a target disease for the first pilot study. Of the 665 eligible candidates, 33.5% were interested in the pilot study and provided consent after an educational "genetics workshop" on the basic genetics and medical facts of FH. The genetics professionals disclosed the results to the participants. All positive participants were referred to medical care, and a serial questionnaire revealed no significant psychosocial distress after the disclosure. Return of genomic results to research participants was implemented using a well-prepared protocol. To further elucidate the impact of different disorders, we will perform multilayer pilot studies with different disorders, including actionable pharmacogenomics and hereditary tumor syndromes.

A proposal on the first Japanese practical guidance for the return of individual genomic results in research settings.

Large-scale, low-cost genome analysis has become possible with next-generation sequencing technology, which is currently used in research and clinical practice. Many attempts of returning individual genomic results have commenced not only in clinical practice, but also in research settings of several countries. In Japan, the government guidelines include a section on the disclosure of genetic information regarding genome analysis in research. However, no practical guidance for the return of individual genomic results in research settings (ROGRR) currently exists. We propose practical guidance regarding ROGRR in Japan based on extensive research, including a literature review of related previous studies, an examination of the relevant legislation in Japan, and interviews with stakeholders. The guidance we developed consists of "Points to consider" and "Issues for further discussion and consideration." The "Points to consider" were divided into five parts, from preliminary review before discussion of policy, to the actual return and follow-up process, in the order of the assumed ROGRR process. It is anticipated that a situation will arise where numerous research projects will consider ROGRR carefully and realistically in the future, and in the process of drafting such practical guidance, various issues requiring continuous discussion will emerge. The necessities of continuous discussion concerning ROGRR in Japan's context is increasing, particularly in terms of the ethical, legal, and social implications. We believe such discussions and considerations may contribute to creating a new system that will increase availability of personalized medicine and prevention using genetic information, allowing them to become useful to the broader population.

A training and education program for genome medical research coordinators in the genome cohort study of the Tohoku Medical Megabank Organization.

BACKGROUND: Genome cohort studies are used to analyze interactions between genetic and environmental factors, providing valuable information for personalized healthcare. Large-scale and long-term cohort studies require a number of specially trained personnel, of whom those involved in obtaining informed consent play a vital role, especially during the initial phase of such studies. The Japanese Society of Human Genetics (JSHG) previously established a certification system for genome medical research coordinators (GMRCs) responsible for obtaining written consent via face-to-face explanation. Meanwhile, in the Tohoku Medical Megabank Organization (ToMMo), GMRCs are expected to play important roles not only in obtaining informed consent and conducting various assessments, but also in communicating with participants throughout the long-term follow-up. Based on the JSHG program, we therefore developed a specific education and training program for ToMMo GMRCs consisting of 17 lectures, one practical training session on the informed consent procedure, and written and interview examinations. Re-education workshops aimed at self-improvement are also carried out following certification. In this study, we evaluated the education and training program in terms of overall understanding, usefulness, and satisfaction using an anonymous questionnaire. METHODS: An anonymous questionnaire addressing each aspect of the education and training program (understanding, usefulness, and satisfaction) was distributed among 152 qualified ToMMo GMRCs. Responses were received from 94 participants (61.8%). RESULTS: There was a significant association between the level of overall understanding of lectures and medical qualification (nurse or clinical laboratory technologist), but not with age or educational background. The level of understanding and overall usefulness were lower in sessions related to genetics and epidemiology than those dealing with ToMMo practices. In the re-education workshops, GMRCs showed a preference for and hoped to learn more about both background knowledge and research progress in the ToMMo. CONCLUSIONS: The results of our questionnaire suggest that not all ToMMo GMRCs are able to understand everything during the initial education and training program, especially in terms of genomic medicine. Continuous re-education is therefore vital in improving knowledge, skills and motivation, and preparing GMRCs for a specialist role in community-based personalized healthcare.

Ethical and Social Issues for Health Care Providers in the Intensive Care Unit during the Early Stages of the COVID-19 Pandemic in Japan: a Questionnaire Survey.

This questionnaire-based observational study was conducted in July 2020 with the aim of understanding the ethical and social issues faced by health care providers (HCPs) registered with the Japanese Society of Intensive Care Medicine in intensive care units (ICUs) during the coronavirus disease (COVID-19) pandemic. There were 200 questionnaire respondents, and we analyzed the responses of 189 members who had been involved in COVID-19 treatment in ICUs. The ethical and social issues that HCPs recognized during the pandemic were difficulties in the decision-making process with patients' families, limitations of life-sustaining treatment, lack of palliative care, and inadequate mental support for patients' families and HCPs. Regarding decision-making on issues of clinical ethics during the pandemic, more than half of the respondents thought they had failed to provide sufficient palliative care to patients and responded that they experienced moral distress. The free-text responses on moral distress revealed issues such as unusual treatment and care, restricted visits, challenging situations for HCPs, and psychological burden. Additionally, 38.1% of respondents experienced episodes of social prejudice or discrimination and 4.7% experienced a shortage of medical resources. Our study result shows that the moral distress of HCPs was caused by difficulties in patient-centered decision-making and insufficient medical care to patients and their families. These were caused mainly by a lack of communication due to the stronger implementation of infection control measures. We believe that it is important to address ethical and social issues during a pandemic in order to provide appropriate medical care and prevent burnout among HCPs. Supplementary Information: The online version contains supplementary material available at 10.1007/s41649-021-00194-y.

Institutional and Social Issues Surrounding Genetic Counselors in Japan: Current Challenges and Implications for the Global Community.

In recent years, genetic counseling has started playing a major role in the field of genomic medicine. There are currently about 7,000 genetic counselors in more than 28 countries, with 267 certified genetic counselors in Japan alone (about 2 per million population, as of April 2020). While the rapid advancement of genomic medicine has expanded this field, the challenges genetic counselors face are also evolving. This article aims to provide an overview of the institutional and social issues surrounding genetic counselors in Japan and discuss implications for the global community. In Japan, with the rapid changes in genomic medicine and the establishment of a delivery mechanism within the healthcare system, several issues need to be discussed. First, many genetic testing, counseling, and preventive healthcare programs are not covered by public health insurance. Second, reducing human resource shortages for genetic counseling is an urgent issue. Third, the lack of a national qualification in the profession is critically important issue in the field. Fourth, research on the role and value of genetic counselors is still limited. To address these issues, discussions among relevant stakeholders, including genetic counselors, professionals in genomic medicine, and lawmakers, are necessary. Additionally, we believe that research by genetic counselors to evaluate and improve their practice and examine institutional and social issues is crucial for developing their profession's activities and delivering high-quality healthcare to many people. To establish the position and role of the relatively new profession of genetic counselor, sharing information and collaborating on institutional and social challenges faced by genetic counselors globally will be beneficial.

One-pot beta-substitution of enones with alkyl groups to beta-alkyl enones.

Vinylic hydrogens at the beta-position of enones were effectively substituted with alkyl groups in a one-pot procedure to afford beta-alkyl enones in good to high isolated yields by conjugate addition of higher-order dialkyl cyanocuprates to enones, followed by a reaction with N-tert-butylbenzenesulfinimidoyl chloride at -78 degree C.