Parents of a child with epilepsy: Views and expectations on receiving genetic results from Whole Genome Sequencing.

PURPOSE: The use of Next Generation Sequencing technologies (NGS), such as Whole Genome Sequencing (WGS), is expected to improve the often complex and protracted course of treatment of patients with epilepsy by providing an earlier and more accurate diagnosis. As part of the "Personalized medicine in the treatment of epilepsy" project, which aimed to determine whether WGS could be used as a valuable "diagnostic tool" in pharmacoresistant epilepsies, we examined parents' expectations, hopes, and concerns upon receiving results related to their child's epilepsy, comorbidities, resistance to medication, and genetic information on unrelated conditions, and how these results could impact their and their child's life. METHODS: Parents of 32 children participating in the genetic study completed either paper or online questionnaires. A descriptive analysis of responses and comments was conducted regarding parents' experience with their child's epilepsy, as well as their views on WGS, and expectations and concerns surrounding such test results. RESULTS: Most respondents had trouble explaining the medical causes of their child's epilepsy (n = 27), and a majority (n = 26) feared that their child may be treated unjustly because of their epilepsy, although some acknowledged that their child had never actually been treated unjustly (n = 13). A majority of respondents had also experienced feelings of guilt due to their child's epilepsy (n = 23), and some expected WGS results to have an impact on those feelings. The anticipation of benefits for their child was the parents' primary reason to get involved in a genomic research project, closely followed by altruism. A majority expressed strong intentions to receive as many WGS results as possible, considering that any could be beneficial for them and their child, even when mutations were not found. Respondents were divided as to how and when to tell their child that they might have newly discovered predispositions to develop another disease. In proportion, more parents expressed concerns about sharing unexpected results with their family members compared with sharing results linked to epilepsy, comorbidities, and pharmacoresistance. CONCLUSION: Our results reinforce the importance of having clear guidelines to help parents manage their expectations and better navigate the complexities of receiving and sharing WGS results. Despite the small size of our sample, we believe that our results are meaningful to clinical practice.

Exploring neurologists' perspectives on the return of next generation sequencing results to their patients: a needed step in the development of guidelines.

BACKGROUND: The use of Next Generation Sequencing such as Whole Genome Sequencing (WGS) is a promising step towards a better understanding and treatment of neurological diseases. WGS can result into unexpected information (incidental findings, IFs), and information with uncertain clinical significance. In the context of a Genome Canada project on 'Personalized Medicine in the Treatment of Epilepsy', we intended to address these challenges surveying neurologists' opinions about the type of results that should be returned, and their professional responsibility toward recontacting patients regarding new discovered mutations. METHODS: Potential participants were contacted through professional organizations or direct invitations. RESULTS: A total of 204 neurologists were recruited. Fifty nine percent indicated that to be conveyed, WGS results should have a demonstrated clinical utility for diagnosis, prognosis or treatment. Yet, 41% deemed appropriate to return results without clinical utility, when they could impact patients' reproductive decisions, or on patients' request. Current use of targeted genetic testing and age of patients influenced respondents' answers. Respondents stated that analysis of genomics data resulting from WGS should be limited to the genes likely to be relevant for the patient's specific medical condition (69%), so as to limit IFs. Respondents felt responsible to recontact patients and inform them about newly discovered mutations related to the medical condition that triggered the test (75%) for as long as they are following up on the patient (55%). Finally, 53.5% of the respondents felt responsible to recontact and inform patients of clinically significant, newly discovered IFs. CONCLUSION: Our results show the importance of formulating professional guidelines sensitive to the various - and sometimes opposite - viewpoints that may prevail within a same community of practice, as well as flexible so as to be attuned to the characteristics of the neurological conditions that triggered a WGS.

The elusive ideal of inclusiveness: lessons from a worldwide survey of neurologists on the ethical issues raised by whole-genome sequencing.

The anticipation of ethical issues that may arise with the clinical use of genomic technologies is crucial to envision their future implementation in a manner sensitive to local contexts. Yet, populations in low- and middle-income countries are underrepresented in studies that aim to explore stakeholders' perspectives on the use of such technologies. Within the framework of a research project entitled "Personalized medicine in the treatment of epilepsy", we sought to increase inclusiveness by widening the reach of our survey, inviting neurologists from around the world to share their views and practices regarding the use of whole-genome sequencing in clinical neurology and its associated ethics. We discuss herein the compelling scientific and ethical reasons that led us to attempt to recruit neurologists worldwide, despite the lack, in many low- or middle-income countries, of access to genomic technologies. Recruitment procedures and their results are presented and discussed, as well as the barriers we faced. We conclude that inclusive recruitment remains a challenging, albeit necessary and legitimate, endeavour.

Is human enhancement also a personal matter?

Emerging technologies are increasingly used in an attempt to "enhance the human body and/or mind" beyond the contemporary standards that characterize human beings. Yet, such standards are deeply controversial and it is not an easy task to determine whether the application of a given technology to an individual and its outcome can be defined as a human enhancement or not. Despite much debate on its potential or actual ethical and social impacts, human enhancement is not subject to any consensual definition. This paper proposes a timely and much needed examination of the various definitions found in the literature. We classify these definitions into four main categories: the implicit approach, the therapy-enhancement distinction, the improvement of general human capacities and the increase of well-being. After commenting on these different approaches and their limitations, we propose a definition of human enhancement that focuses on individual perceptions. While acknowledging that a definition that mainly depends on personal and subjective individual perceptions raises many challenges, we suggest that a comprehensive approach to define human enhancement could constitute a useful premise to appropriately address the complexity of the ethical and social issues it generates.

Experiences of adults living with refractory epilepsy and their views and expectations on receiving results from whole genome sequencing.

INTRODUCTION: Researchers, clinicians and patients are turning to new innovations in research and clinical practice to further their knowledge in the genetic domain and improve diagnostics or treatment. However, with increased knowledge in genetics, societal issues may arise. Being conscious of these issues is crucial in order to implement standardized and efficient testing on a wider scale that is accessible to a greater number of individuals while simultaneously returning test results, including incidental findings, in a timely manner. METHODS: Within the framework of a genomics research project, we invited 20 participants who suffer from refractory epilepsy to provide insight on their personal experiences with epilepsy, as well as their thoughts on receiving Whole Genome Sequencing (WGS) results and with whom they would feel comfortable sharing these results with. RESULTS: All participants had their own unique experience with epilepsy, such as how they handled their diagnosis, their struggles following the diagnosis, the healthcare services they received, how they shared their diagnosis with others, and how they managed stigmatization from others. Most participants would be eager to know their WGS results, whether the results be related to epilepsy (n = 19), response to pharmaceutical drugs including AEDs (n = 16), comorbidities (n = 19) and incidental findings (n = 15). CONCLUSION: Our findings reinforce the need to improve access to genetic testing for epilepsy patients in clinical settings. Furthermore, while acquiring more genetic knowledge (i.e. WGS) about epilepsy can provide answers for the affected population, it also requires the simultaneous involvement of several medical disciplines, with greater emphasis on genetic and psychological counseling.

Opinion, experience and educational preferences concerning pharmacogenomics: an exploratory study of Quebec pharmacists.

Aim: To evaluate the current opinion, experience and educational preferences of pharmacists in Quebec concerning pharmacogenomics. Method: A web-based survey containing 25 questions was sent to all Quebec pharmacists. Results: Most pharmacists were willing to advise patients (81%) and physicians (84%) on treatment choices based on pharmacogenomic test results after proper training. Only 31% had been previously exposed to pharmacogenomic test results, and 91% were favorable to pharmacogenomics training, with e-learning through interactive video sessions (69%). The preferred training session length was between 1 and 3 h (59%). Hospital pharmacists were more often exposed to pharmacogenomic tests (p < 0.0001) and more frequently advised patients on treatment choices (p < 0.001) than community pharmacists. Conclusion: Pharmacists remain favorable toward pharmacogenomics, but its use in clinical practice stays limited. Identifying the educational preferences of pharmacists may help in the development of educational programs to help them integrate pharmacogenomics in their clinical practice.

Correction: Ethical issues in the development and implementation of nutrition-related public health policies and interventions: A scoping review.

[This corrects the article DOI: 10.1371/journal.pone.0186897.].

Ethical considerations in the implementation of nutrigenetics/nutrigenomics.

Awareness of ethical issues that may be raised by the implementation of nutrigenetic/nutrigenomic (NGx) testing and personalized nutrition, at an individual or a public health level, is crucial to ensure the latter's sound and effective implementation. NGx tests that are currently offered or developed have different natures and scopes. We provide an example of NGx testing on the MTHFR gene to illustrate the current challenges when it comes to grasp the meaning of the results of such testing. In addition, NGx testing is developed within an evolving landscape of new genomic technologies and occurs at a time when public health policies mainly focus on preventive and predictive healthcare, with an emphasis on increased individual responsibility. The ethical issues raised by such a context and the genetic nature of NGx testing both should be carefully evaluated.

Practices and views of neurologists regarding the use of whole-genome sequencing in clinical settings: a web-based survey.

The use of Whole-Genome Sequencing (WGS) in clinical settings has brought up a number of controversial scientific and ethical issues. The application of WGS is of particular relevance in neurology, as many conditions are difficult to diagnose. We conducted a worldwide, web-based survey to explore neurologists' views on the benefits of, and concerns regarding, the clinical use of WGS, as well as the resources necessary to implement it. Almost half of the 204 neurologists in the study treated mostly adult patients (48%), while the rest mainly children (37.3%), or both (14.7%). Epilepsy (73%) and headaches (57.8%) were the predominant conditions treated. Factor analysis brought out two profiles: neurologists who would offer WGS to their patients, and those who would not, or were not sure in which circumstances it should be offered. Neurologists considering the use of WGS as bringing more benefits than drawbacks currently used targeted genetic testing (P<0.05) or treated mainly children (P<0.05). WGS' benefits were directed towards the patients, while its risks were of a financial and legal nature. Furthermore, there was a correlation between respondents' current use of genetic tests and an anticipation of increased use in the future (P<0.001). However, over half of respondents did not feel sufficiently informed to use WGS in their practice (53.5%). Our results highlight gaps in education, organization, and funding to support the use of WGS in neurology, and draw attention to the need for resources that could strongly contribute to more straightforward diagnoses and possibly better treatment of neurological conditions.

Ethical issues in the development and implementation of nutrition-related public health policies and interventions: A scoping review.

BACKGROUND: The limited integration of ethics in nutrition-related public health policies and interventions is one major concern for those who have the task of implementing them. Ethical challenges that are overlooked during the development of such interventions could raise serious ethical issues during their implementation and even after. As a result, these decision makers need technical support and ethical guidance for adaptation of interventions to local (cultural, social, economic, etc.) contexts. AIM: The goal of this scoping review is to delineate and "map" the range of ethical issues in nutrition-related public health interventions, as well as the range of the various fields in which they may arise. METHODS: A scoping review of empirical research and conceptual literature was conducted following the framework of Arksey and O'Malley. Searches using PubMed with Medical Subject Headings (MeSH) categories and Advanced Search Builder as well as in the Global Health Library were performed. The final sample consists of 169 publications. RESULTS: The ethics of public health prevention or treatment of obesity and non-communicable diseases is the most explicitly and frequently discussed subject. In comparison, ethical issues raised by public health interventions in the fields of undernutrition, breastfeeding, vitamin/mineral supplementation and food fortification, food security, food sustainability and food safety are addressed in a lower proportion of the sample. The results illustrate the various natures, types, and scopes of existing public health nutrition-related interventions, and the various ethical issues that may be raised by these interventions, in addition to the numerous and different contexts in which they may be implemented. DISCUSSION: The ethical issues faced in the development and implementation of nutrition-related public health interventions are varied and cannot be equated with, nor generalized about, when dealing with specific activities in this field. More importantly, these ethical issues cannot be managed without a careful consideration for the complexity of contexts in which nutrition-related interventions are expected to be implemented. These interventions engage a variety of actors with diverse perspectives and interests. We discuss these challenges and also comment on the importance of considering ethical impacts in the monitoring and evaluation of such interventions. CONCLUSION: General ethical frameworks or recommendations-although useful-cannot be expected to provide policy makers, implementators and other public health personnel with sufficient practical ethical guidance as they cannot consider and anticipate the particularities of all specific nutrition-related public health interventions and the complexity of the contexts in which they are implemented. Further research is needed in order to develop more targeted ethical frameworks.

Guidelines for disclosing genetic information to family members: from development to use.

This paper presents the existing legal frameworks, professional guidelines and other documents related to the conditions and extent of the disclosure of genetic information by physicians to at-risk family members. Although the duty of a physician regarding disclosure of genetic information to a patient's relatives has only been addressed by few legal cases, courts have found such a duty under some circumstances. Generally, disclosure should not be permitted without the patient's consent. Yet, due to the nature of genetic information, exceptions are foreseen, where treatment and prevention are available. This duty to warn a patient's relative is also supported by some professional and policy organizations that have addressed the issue. Practice guidelines with a communication and intervention plan are emerging, providing physicians with tools that allow them to assist patients in their communication with relatives without jeopardizing their professional liability. Since guidelines aim to improve the appropriateness of medical practice and consequently to better serve the interests of patients, it is important to determine to what degree they document the 'best practice' standards. Such an analysis is an essential step to evaluate the different approaches permitting the disclosure of genetic information to family members.

Evaluation of a cartoon-based knowledge dissemination intervention on scientific and ethical challenges raised by nutrigenomics/nutrigenetics research.

CONTEXT: The push for knowledge translation on the part of health research funding agencies is significant in Canada, and many strategies have been adopted to promote the conversion of knowledge into action. In recent years, an increasing number of health researchers have been studying arts-based interventions to transform knowledge into action. This article reports on the results of an online questionnaire aimed at evaluating the effectiveness of a knowledge dissemination intervention (KDI) conveying findings from a study on the scientific and ethical challenges raised by nutrigenomics-nutrigenetics (NGx) research. The KDI was based on the use of four Web pages combining original, interactive cartoon-like illustrations accompanied by text to disseminate findings to Canadian Research Ethics Boards members, as well as to NGx researchers and researchers in ethics worldwide. METHODS: Between May and October 2012, the links to the Web pages were sent in a personal email to target audience members, one thematic Web page at a time. On each thematic Web page, members of the target audience were invited to answer nine evaluation questions assessing the effectiveness of the KDI on four criteria, (i) acquisition of knowledge; (ii) change in initial understanding; (iii) generation of questions from the findings; and (iv) intent to change own practice. FINDINGS: Response rate was low; results indicate that: (i) content of the four Web pages did not bring new knowledge to a majority of the respondents, (ii) initial understanding of the findings did not change for a majority of NGx researchers and a minority of ethics respondents, (iii) although the KDI did raise questions for respondents, it did not move them to change their practice. CONCLUSIONS: While target end-users may not feel that they actually learned from the KDI, it seems that the findings conveyed encouraged reflection and raised useful and valuable questions for them. Moreover, the evaluation of the KDI proved to be useful to gain knowledge about our target audiences' views since respondents' comments allowed us to improve our understanding of the disseminated knowledge as well as to modify (and hopefully improve) the content of the Web pages used for dissemination.

Disclosure of individual pharmacogenomic results in research projects: when and what kind of information to return to research participants.

In the growing field of genomics, the utility of returning certain research results to participants has become a highly debated issue. Existing guidelines are not explicit as to the kind of genomic information that should be returned to research participants. Moreover, very few current recommendations and articles in the literature address the return of pharmacogenomic results. Although genetics and pharmacogenomics have many similarities, the circumstances in which disclosure could have a benefit for the participants are different. This review aims to describe the conditions in which disclosure of pharmacogenomic results is appropriate.

An evaluation of pharmacists' expectations towards pharmacogenomics.

BACKGROUND: Given their expertise in pharmacotherapy, pharmacists are well positioned to play a leading role in the implementation of pharmacogenomics in clinical practice. However, little is known about the opinions of pharmacists towards pharmacogenomics or their willingness to integrate this new field in their practice. METHODS: We conducted a survey of 284 pharmacists practicing in the province of Québec (Canada) to describe the opinions, expectations and concerns of pharmacists toward pharmacogenomics. RESULTS: Pharmacists were very hopeful regarding the potential role of pharmacogenomics. Moreover, more than 95% of responders would be willing to recommend pharmacogenomic testing. Nevertheless, only 7.7% of pharmacists currently felt comfortable advising patients based on pharmacogenomic test results. Accordingly, the majority of responders (96.6%) indicated that they would like to undertake continuing education related to pharmacogenomics. CONCLUSION: Pharmacists are extremely hopeful towards pharmacogenomic testing. Furthermore, a vast majority is willing to integrate these tests as part of their clinical practice. Proper education will be required if the integration of pharmacogenomics in patient care is to be optimal.