With transformative initiatives like the UK's 100,000 Genomes Project underway, vast amounts of data from genome sequencing are being generated. Genomic results are being actively returned to participants, although policies around their management remain inconsistent and a subject of debate. Secondary findings (SF) have been of particular concern - variants associated with health conditions other than the indication for sequencing, which may or may not be medically actionable. I have conducted a mixed methods study to explore the current transitional period and the issue of secondary findings, and inform future management. Following a narrative review of the literature around SF in genome sequencing and a focused systematic review of primary studies on stakeholder views towards the subject (Part I), gaps in the current literature were identified. These were, chiefly: (1) the need for diverse stakeholder views based on experience making actual decisions around SF; and, (2) empirical data - phenotypic, psychological, behavioural - on actual returned SF. Thus, taking advantage of the local programme of translational genome sequencing, I conducted qualitative studies involving genomic healthcare professionals and genome sequencing participants, to explore their views towards genomic medicine and SF (Part II). Following this, I detail a case study illustrating the process and challenges of returning an SF, as well as outline a study designed to collect empirical data on actual returned SF and present preliminary data to this end (Part III). I illustrate that secondary findings will be a part of tomorrow's genomic medicine: cautious optional screening of actionable SF (including treatable conditions and carrier status information) appears favourable. However, if SF are to be a part of the genomic medicine paradigm, several barriers must be considered: insufficient connectivity between specialties, variant interpretation, clinical interpretation and management, and overpromise and expectations (including recontact in light of new information). In order to overcome these challenges, individuals in unselected populations must be prospectively phenotyped to derive more accurate estimates of population-level penetrance and better understand the full phenotypic spectrum, and we must explore the downstream impact of disclosure. As genome sequencing is mainstreamed, clear evidence-based guidelines for SF in genome sequencing will be essential if harms are to be minimised and benefits are to be maximised, both for participants and the healthcare system at large. At this point, albeit cautiously, we must 'learn by doing'.

Background: Major depressive disorder (MDD) is commonly treated with antidepressants, but many patients undergo trial-and-error to find the medication best suited for them. Pharmacogenomic (PGx) testing was developed to provide prescribing guidance for a variety of medications including antidepressants. PGx testing is not yet part of standard depression care in Canada, but clinical implementation efforts are ongoing. Patient perspectives, as well as the views of people with professional expertise about this technology, are critical to health technology assessment (HTA) and policy decisions, and can inform implementation. Methods: This dissertation produces actionable patient and key informant (i.e., clinician, scientists, policy actor, industry member) perspectives evidence for future HTA and policy- making through three independent studies: a systematic review and qualitative meta-synthesis of patient experiences of treatment-resistant depression (TRD), and two qualitative description studies about patient and key informant perspectives on PGx testing to guide antidepressant prescribing. Results: Trial-and-error of medications often leaves patients feeling hopeless but desperate to get better. Patients and key informants both felt the main benefit of PGx testing is its potential to reduce the time between diagnosis and successful treatment. The main findings of this research were concrete suggestions for how PGx testing may be integrated in the health system. Participants preferred this technology be deployed in primary care, with patients with TRD identified as a possible priority population. The ideal PGx test would incorporate genetic variants common in non-white populations to ensure equity of health outcomes, and mechanisms to facilitate equity of access (eg., public funding) were considered important. Conclusions: Patients and key informants both described benefits of PGx testing to guide antidepressant prescribing. Patients typically raised more concerns than key informants. Future research is needed around some of the ethical and social issues related to PGx testing, as well as to address feasibility questions. / Dissertation / Doctor of Philosophy (PhD) / Pharmacogenomic (PGx) testing may facilitate targeted prescribing of antidepressants by identifying genetic factors that play a role in how a person responds to these drugs. However, this technology is not yet widely or systematically used in clinical care. This dissertation focuses on how PGx testing might be implemented in primary care in Ontario, Canada. It examines which patients this type of genetic testing may be most appropriate for, and collects and analyzes the views of patients with depression and experts on PGx testing about this technology. The main benefit of PGx testing was its potential to help people get better faster, and primary care was uniformly considered an appropriate care setting for the use of this technology. There were some concerns that people may not fully understand the limitations of PGx testing. Future research is needed to understand how this technology might fit into clinician workflows across the healthcare system.

Trata-se de um estudo descritivo, exploratório, de natureza histórico-social e ético-legal, desenvolvido a partir da análise documental como parte do método histórico. As bases de dados nacionais e internacionais pesquisadas foram CINAHL, LILACS, MEDLINE, PeriEnf e PubMed, com os descritores: enfermagem, atendimento pré-hospitalar e aspectos ético-legais, publicados nos últimos 10 anos. O método histórico estuda os fatos sociais e suas relações, a partir de documentos, surgidos de fontes, contextos e momentos distintos, e envolve a reconstrução do conhecimento e novas interpretações dos fatos. A escassez de literatura específica, sobre os aspectos ético-legais no atendimento pré-hospitalar (APH) e a inserção do enfermeiro nesta modalidade de serviço, motivou a realização deste estudo. Igualmente, a experiência profissional como enfermeiro e a vivência de situações críticas no Grupo de Resgate e Atendimento de Urgências (GRAU - RESGATE 193), despertaram o interesse pelo tema e as bases para a incursão no campo do Direito. Com este estudo pretendeu-se fazer um resgate histórico do surgimento do APH e a inserção do enfermeiro com os objetivos de levantar a legislação e as funções do enfermeiro no atendimento pré-hospitalar; identificar os desafios éticos e legais do enfermeiro no exercício profissional nesse atendimento; e, traçar o tipo de enfermeiro profissional necessário para o atendimento pré-hospitalar / This is a descriptive, exploratory study of historical-social and ethical-legal nature, developed through a documentary analysis as part of the historical method. National and international data basis were searched at CINAHL, LILACS, MEDLINE, PeriEnf e PubMed utilizing the following descriptors: nursing, pre-hospital care, and ethical-legal aspects, published in the last ten years. The historical method studies social facts and its relations, from documents found in sources, contexts and distinct moments, and involve the knowledge reconstruction and new interpretation of facts. Lack of specific literature on ethical-legal aspects within pre-hospital care and the nurse´s insertion into this kind of service, has motivated this study. Also, the professional experience as nurse and having lived critical situations within the Rescue Group for Urgent Care (GRAU-Resgate 193), has created the interest on the theme and the basis for this into the Law field. This study aimed at making an historical rescue about the emergence of pre-hospital care and the nurse´s insertion in it with the objectives: to survey the legislation and the nurses´ functions in this service; to identify the nurses´ ethical and legal challenges at professional practice; and, to outline the kind of nurse needed for pre-hospital care

Trata-se de um estudo descritivo, exploratório, de natureza histórico-social e ético-legal, desenvolvido a partir da análise documental como parte do método histórico. As bases de dados nacionais e internacionais pesquisadas foram CINAHL, LILACS, MEDLINE, PeriEnf e PubMed, com os descritores: enfermagem, atendimento pré-hospitalar e aspectos ético-legais, publicados nos últimos 10 anos. O método histórico estuda os fatos sociais e suas relações, a partir de documentos, surgidos de fontes, contextos e momentos distintos, e envolve a reconstrução do conhecimento e novas interpretações dos fatos. A escassez de literatura específica, sobre os aspectos ético-legais no atendimento pré-hospitalar (APH) e a inserção do enfermeiro nesta modalidade de serviço, motivou a realização deste estudo. Igualmente, a experiência profissional como enfermeiro e a vivência de situações críticas no Grupo de Resgate e Atendimento de Urgências (GRAU - RESGATE 193), despertaram o interesse pelo tema e as bases para a incursão no campo do Direito. Com este estudo pretendeu-se fazer um resgate histórico do surgimento do APH e a inserção do enfermeiro com os objetivos de levantar a legislação e as funções do enfermeiro no atendimento pré-hospitalar; identificar os desafios éticos e legais do enfermeiro no exercício profissional nesse atendimento; e, traçar o tipo de enfermeiro profissional necessário para o atendimento pré-hospitalar / This is a descriptive, exploratory study of historical-social and ethical-legal nature, developed through a documentary analysis as part of the historical method. National and international data basis were searched at CINAHL, LILACS, MEDLINE, PeriEnf e PubMed utilizing the following descriptors: nursing, pre-hospital care, and ethical-legal aspects, published in the last ten years. The historical method studies social facts and its relations, from documents found in sources, contexts and distinct moments, and involve the knowledge reconstruction and new interpretation of facts. Lack of specific literature on ethical-legal aspects within pre-hospital care and the nurse´s insertion into this kind of service, has motivated this study. Also, the professional experience as nurse and having lived critical situations within the Rescue Group for Urgent Care (GRAU-Resgate 193), has created the interest on the theme and the basis for this into the Law field. This study aimed at making an historical rescue about the emergence of pre-hospital care and the nurse´s insertion in it with the objectives: to survey the legislation and the nurses´ functions in this service; to identify the nurses´ ethical and legal challenges at professional practice; and, to outline the kind of nurse needed for pre-hospital care

Made available in DSpace on 2016-04-26T20:21:00Z (GMT). No. of bitstreams: 1 Alberto de Amorim Micheli.pdf: 832453 bytes, checksum: 0ff26cb458269607b30febb0363210a7 (MD5) Previous issue date: 2012-06-01 / This work has been developed in order to provide a critical approach concerning the role of Ethics and Law within the ambit of the Judiciary s political activity. We intend to demonstrate that the Judiciary does not always act in the strict observance of ethical and legal principles when it comes to the political activity of disciplinary control against judges. We therefore selected a case, which took place a few years ago in the Judiciary of the State of São Paulo and was rather controversial interna corporis, in which several possible violations of ethical-legal principles might be found. Finally we outline that the purpose of the this work is not to generalize, but yet to show that it is easier to find such problems in the course of an administrative process of disciplinary control than in a judicial process / O presente trabalho foi elaborado com a finalidade de efetuarmos uma abordagem crítica em relação à questão da incidência da Ética e do Direito na esfera da atividade político-disciplinar do Poder Judiciário. De fato, de acordo com o que pretendemos demonstrar, na atuação política de controle disciplinar (respectivamente a magistrados) o Poder Judiciário algumas vezes não atua com o mesmo rigor, na observância de preceitos éticos e legais, que emprega em sua atividade jurisdicional. Bem por isso, selecionamos um caso ocorrido há poucos anos na magistratura paulista, que causou certo rumor interna corporis, daí o interesse em abordá-lo, no qual podem ser questionados diversos aspectos éticos-legais verificados. Por fim, entendemos aqui também oportuno destacar que o objetivo do trabalho não é generalizar, mas apenas demonstrar que é mais fácil encontrar esse tipo de problema num processo disciplinar do que num processo judicial