Thesis (Ph. D.)--University of Washington, 1984. / Vita. Bibliography: leaves [124]-128.

Thesis (M.S.)--University of Wisconsin--Madison, 1982. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 54-58).

In 2009, two large genome wide association studies (GWAS) found associations between common single nucleotide polymorphisms (SNPs) at three loci (CLU, PICALM and CR1) and Alzheimer’s disease (AD) risk. The causal variants underlying these associations and how these impact on AD susceptibility remain unclear. Target enrichment and next generation sequencing (NGS) were used to completely resequence the three associated loci in 96 AD patients in an attempt to uncover potentially causative and rare variants that may explain the observed association signals. A pipeline was developed for the handling of pooled NGS data following a comparison of several different combinations of programs. 33 exonic SNPs were found within the three genes, along with over 1000 non-coding variants. To identify the variants most likely to be affecting AD risk, a two pronged approach was adopted. The variants were imputed in a large case-control cohort (2067 cases, 7376 controls) to test for association with AD, and the likely functional consequences of the variants were assessed using in silico resources. Several of the analysed variants showed suggestive or significant association with AD in the imputed data, and/or were predicted to have consequences on the function or regulation of the genes, suggesting avenues for future research in AD genetics. The whole method of pooled, targeted NGS and prioritisation using imputed data for association testing and in silico resources for functional analysis represents a new strategy for tracking down the illusive causation of GWAS signals.

This thesis explores doctors’ and medical students’ attitudes toward older patients in UK hospital settings. There have been regular and strong assertions in the grey literature and the news media that negative attitudes toward older patients may contribute to the inequality of healthcare service provision and treatment for older patients, compared to younger patients (those aged under 65 years), in UK hospital settings. However, much of the evidence does not investigate or explore these attitudes using a theoretical framework of attitudes outlined in the scientific research literature. This thesis comprises three studies. Firstly, a systematic search and review (Study 1) was undertaken in order to determine how attitudes toward older patients had been explored to date in the English-language, scientific research literature. Results demonstrated that previous studies had focused on attitude measurement rather than exploring the content of attitudes toward older patients. In fact, there was little evidence that previous research had ever explored these attitudes, despite the number of studies attempting to measure them. Furthermore, the review indicated the lack of research emanating from UK settings. In Study 2, attitudes toward older patients and their care were explored in twenty-five in-depth interviews with medical students and doctors in a UK NHS Hospital trust. Data were thematically analysed and findings indicated that attitudes toward older patients and their care could be conceptualised as: (1) attitudes toward older patients and their healthcare needs, and (2) attitudes toward providing care for older patients (e.g. the social and organisational barriers and facilitators). Within these two domains, the themes, subthemes and nodes, which represent attitude content with increasing levels of specificity, are presented. The findings from Study 2 mark one of the first attempts in this research area to explore and describe the content of attitudes in line with a theoretical framework of attitudes. The final study, Study 3, explored the devaluation and unpopularity of the specialty of geriatric medicine as a future career choice in a sample of junior doctors. Having identified, in Study 2, that geriatric medicine was not highly regarded in a range of doctors and medical students, Study 3 aimed to ascertain whether this was due to the organisational and working environment or due to older patient-related factors in a recently-qualified sample of doctors. The findings indicated that organisational and work-related factors serve to discourage junior doctors from pursuing geriatric medicine, rather than factors related to the older patients treated on geriatric wards. This thesis contributes to the research literature in two main ways. Firstly, this thesis outlines the research gaps in the worldwide English-language scientific research. Secondly, this thesis presents a conceptualisation of doctors’ and medical students’ attitudes toward older patients in a UK hospital setting. Importantly, this conceptualisation provides research that is relevant to UK settings and is in line with a theoretical framework of attitudes that has been identified from the scientific research literature. The strengths and limitations of this work are discussed.

Master of Science / Department of Statistics / Abigail Jager / A discrete-time Markov chain with stationary transition probabilities is often used for the purpose of investigating treatment programs and health care protocols for chronic disease. Suppose the patients of a certain chronic disease are observed over equally spaced time intervals. If we classify the chronic disease into n distinct health states, the movement through these health states over time then represents a patient’s disease history. We can use a discrete-time Markov chain to describe such movement using the transition probabilities between the health states. The purpose of this study was to investigate the case when the observation interval coincided with the cycle length of the Markov chain as well as the case when the observational interval and the cycle length did not coincide. In particular, we are interested in how the estimated transition matrix behaves as the ratio of observation interval and cycle length changes. Our results suggest that more estimation problems arose for small sample sizes as the length of observational interval increased, and that the deviation from the known transition probability matrix got larger as the length of observational interval increased. With increasing sample size, there were fewer estimation problems and the deviation from the known transition probability matrix was reduced.

The increased influence of digitalizing in the Swedish healthcare is a change that some people find it hard to adapt to. For most youths and people from the younger generations this is not considered a problem, since they have been exposed to different aspects of digitalization throughout their lives. However, how do older people and especially older people with chronic diseases feel about the digitalization and the changes it brings? The purpose of this study is to explore how people with chronic diseases experience this progresses in the society that has contributed to the digitalization within healthcare and the increased utilization of digital platforms. Previous studies indicate that both the change in the doctor-patient relationship and the increased possibilities for patient to access health information from their homes, is an effect of the digitalization. In this study, which is conducted with a qualitative method, we come to understand that older people with chronic diseases find it difficult to adapt to the digitalization. None of the participants are opposing it, rather they experience the changes as complicated. Furthermore, the participants stress the prerequisite of the physical contact with a doctor to enable a correct medical assessment. Whether or not this means that health centers will be dismantled is still unknown. However, our study shows that there is no resistance to digitalization among the participants, provided it is executed in a correct and trustworthy manner.

Dissertation submitted to the Faculty of Health Sciences, University of Witwatersrand in fulfillment of the Master of Science in Medicine in the School of Physiology / Introduction: The changing socio-economic landscape in Africa has brought with it unique health challenges previously uncommon in people of African ancestry. Noncommunicable diseases such as coronary artery disease and stroke have emerged as pressing public health concern highlighting the need to find more on-target diagnostic tools as well as therapeutic interventions. Although ambulatory blood pressure (AMBP) has in many studies conducted in the western world proved to be an independent predictor of carotid intima-media thickness (C-IMT), such results cannot outright be imputed to people of African ancestry living in Africa. That is because people of African ancestry living in Africa are not only of a different ethnicity but are still in the early phases of an epidemiological transition while people in the western countries who are mostly Caucasians, are believed to be in the middle to late phases of an epidemiological transition. Methods: The relationship between the intima-media thickness of the common carotid artery (SonoCalcTM IMT version 3.4) and AMBP (Space labs model 90207) was determined in 320 randomly selected participants of African descent living in an urban developing community in South Africa. Relationships were determined after adjustment for (clinic blood pressure) BPc, age, gender, alcohol and tobacco use, the presence or absence of diabetes mellitus or inappropriate blood glucose control measured by glycated hemoglobin (ghb), antihypertensive therapy and menopausal status. III Results: Mean age for the study population was 43.7± 16.0 years. Both BPc and AMBP parameters were strongly associated with C-IMT (p<0.001) in univariate analysis. In multivariate analysis with BPc. and AMBP entered into separate models and after adjusting for cofounders, BPc. and AMBP maintained significant associations with CIMT. [BPc (partial r=0.0648, p< 0.1612), systolic blood pressure 24 (SBP24) (partial r= 0.236, p< 0.001), systolic blood pressure day (SBPd) (partial r= 0.302, p<0.05), systolic blood pressure night (SBPn) (partial r= 0.0983, p<0.05)]. When adjustments were made with BPc. and SBP24 entered into the same model, BPc lost its association with C-IMT, [SBP24 (partial r=0.236, p<0.001) SBPd (partial r=0.149, p<0.05), SBPn (partial r=0.172, p<0.05)]. Importantly the relationship between SBP24 and C-IMT persisted independent of body mass index (BMI), BPc and age. SBP24 had the highest significant association with C-IMT. Conclusion: SBP24 independently predicts C-IMT even in a model that includes conventional systolic blood pressure (SBPc) leading to the conclusion that AMBP is a more effective tool at diagnosing C-IMT alterations while BPcdoes not have an independent relationship C-IMT.

Considerando a espiritualidade como parte do conceito de saúde do indivíduo e suas repercussões no viver a doença crônica, realizou-se o presente estudo. Trata-se de um estudo exploratório, com metodologia quanti-qualitativa que teve como objetivo principal identificar e compreender o papel da espiritualidade no manejo da doença crônica do idoso. Procurou-se ainda conhecer o perfil dos idosos participantes do estudo, as mudanças de vida ocasionadas pelo diagnóstico da doença crônica e a compreensão de como a religião/espiritualidade/fé interfere neste processo. O método da análise de conteúdo de Bardin foi escolhido para interpretação dos discursos. O estudo foi realizado com 20 idosos portadores de doença crônica atendidos no Instituto Paulista de Geriatria e Gerontologia José Ermírio de Moraes (IPGG), instituição que tem como missão promover o envelhecimento saudável e a integração social do idoso. A coleta de dados foi realizada em outubro de 2010, através de entrevistas semiestruturadas. Os idosos possuíam entre 60 e 81 anos, sendo 65% mulheres e 35% homens, 65% casados, 20% viúvos e 15% divorciados. Quanto à ocupação, 80% são aposentados, 10% do lar/donas de casa, 10% estão ativos no mercado de trabalho. Com relação às condições de moradia, 85% residem em casa própria, 10% em casas de familiares e 5% em casa alugada, 50% residem com cônjuge e filhos ou netos, 35% apenas com cônjuge, 10% moram sozinhos e 5% apenas com filho. Quando questionados quanto às crenças religiosas, todos os participantes referiram pertencer a uma doutrina religiosa e dentre as religiões 75% declarou-se católico, 20% evangélico e 5% espírita. A doença crônica mais prevalente foi a Hipertensão Arterial Sistêmica (HAS), referida por 45% dos participantes, seguida do diabetes mellitus, presente em 35% dos idosos. A análise dos discursos resultou nos seguintes temas centrais: impacto multidimensional da doença crônica, enfrentamento e expectativas dos idosos. Na análise do impacto multidimensional da doença crônica, identificaram-se as seguintes unidades temáticas: impacto no estilo de vida, impacto emocional e impacto socioeconômico. Com relação ao enfrentamento da doença crônica, foram analisados o enfrentamento individual, o suporte social e a espiritualidade/religiosidade/fé. Quanto às expectativas, as unidades temáticas identificadas foram expectativas quanto à saúde e quanto ao sentido da vida. Os resultados evidenciaram as mudanças trazidas pelo diagnóstico da doença crônica e suas implicações na adaptação ao novo modo de vida. O manejo destas alterações é complexo e diversos fatores influenciam positivamente e negativamente no modo de lidar com a nova condição. Os resultados mostraram que a espiritualidade/religiosidade/fé interfere de maneira positiva no enfrentamento dos obstáculos e dificuldades da vida, fortalece a resiliência do paciente, melhorando assim, sua qualidade de vida. Para que o manejo da doença crônica seja bem sucedido, o profissional de saúde atuante na assistência ao idoso portador de doença crônica deve ter a sensibilidade de compreender o idoso dentro de seu contexto cultural e fortalecer o entendimento e responsabilização do paciente quanto a sua condição crônica. / This study was carried out considering spirituality as part of the concept of health and its impacts on living with a chronic disease. It is an exploratory study with quanti-qualitative methodology that aimed to identify and understand the role of spirituality in the management of chronic disease of the elderly, by identifying the profile of individual participating in the study, the life changes caused by diagnosis of chronic disease and how religion/spirituality/faith interferes in this process. The technique of contents analysis of Bardin was chosen for the interpretation of discourse. The study was conducted with 20 elderly patients with chronic disease treated at the Instituto Paulista de Geriatria e Gerontologia José Ermírio de Moraes (IPGG), an institution whose mission is to promote healthy aging and social integration of the elderly. Data collection was conduted in October 2010, through semi-structured interviews. The elderly had between 60 and 81 years, being 65% women and 35% men, 65% married, 20% widowed and 15% divorced. As to occupation, 80% are retired, 10% housewives, 10% are active in the labor market. About the conditions of living, 85% live in their own home, 10% in relatives house and 5% in rented accommodation, 50% live with spouse and children or grandchildren, 35% with spouse, 10% living alone and 5% living with children. When asked about their religious beliefs, all participants reported belonging to a religious doctrine, 75% declared themselves Catholic, 20% Protestant and 5% Spiritualist. The most prevalent chronic disease was High Blood Pressure, reported by 45% of the respondents, followed by Diabetes, present in 35% of the elderly. The discourse analysis resulted in the following themes: the multidimensional impact of chronic disease, coping and expectations of the elderly. In the analysis of the multidimensional impact of chronic disease, we identified the following thematic units: impact on lifestyle, emotional impact and economic impact. When regarding to coping with chronic illness, we analyzed the individual coping, social support and spirituality/ religion/ faith. As for expectations, thematic units identified were expectations about health and expectations about the meaning of life. The results demonstrate the changes brought by the diagnosis of chronic disease and its implications for adaptation to the new way of life. Management of these changes is complex and many factors influence both positively and negatively in dealing with the new condition. The results show that spirituality/religion/faith interferes positively in addressing the obstacles and difficulties of life, strengthen the resilience of the patient, thus improving their quality of life. For chronic disease management to be successful, health professionals active in assistance of the elderly with chronic illness should have the sensitivity to understand the elderly within their cultural context and strengthen their understanding and their accountability about the chronic condition.

O presente estudo busca lançar luz ao significado de ser uma pessoa diabética sob a ótica de quem vivencia essa situação. Para tanto, dirigiu-se para as experiências vividas por essas pessoas, em seu conviver com a doença. Fundamentada no referencial teórico-metodológico da investigação fenomenológica, a pesquisa direcionou-se para essas pessoas, entrevistandoas e obtendo depoimentos à uma pergunta norteadora: \"O que é isto, ser uma pessoa diabética? Descreva para mim.\" Na busca pela subjetividade do existir dessas pessoas, o estudo propôs, assim, a um deslocamento de análise da diabetes sob a ótica de um fato para a de um fenômeno. A coleta de dados ocorreu na cidade de San Luis Potosí, no México,no Instituto Mexicano de Seguro Social \"Francisco Padrón Poyuo\", envolvendo pacientes que participavam de um grupo de apoio. A análise dos depoimentos foi realizada conforme o preconizado pelos fundamentos da fenomenologia, possibilitando a construção de categorias temáticas que apontaram para a essência do significado do conviver com a doença. Os resultados abrem perspectivas para transformações em várias esferas de assistência a essas pessoas, o que inclui o resgate da subjetividade, o repensar a formação dos profissionais de saúde e posturas mais efetivas de acolhimento e construção de políticas de saúde. / The present study aims to throw a light on the meaning of the diabetic person, from the standpoint of who lives that situation. Therefore, he went to look for the experiences these people, the living with the disease. Grounded in the theoretical - methodological reference of phenomenological research, the research looked at people the disease, and getting the interview narratives Blasting starting with a question: Could you describe for me What is this, to be a diabetic person?. In the quest for subjectivity to exist of these people, the study suggested, a movement analysis of the experiences of diabetes mellitus, from the standpoint of an event into a phenomenon. Obtaining the information was held in the city of San Luis Potosi, Mexico, the Mexican Institute of Social Security, \"Francisco Padron Poyou\" with patients participating in a support group. Data analysis was performed according to the fundamentals of phenomenology, there by enabling the construction of thematic categories that enabled get to the essence of the meaning of living with the disease. The findings offer prospects for change in several areas of assistance to these individuals, who allow the rescue of subjectivity, or rethink the training of health professionals as well as a more effective care and construction of health policies.

Este estudo teve como objetivos realizar a adaptação cultural do Family Management Measure (FaMM) para a língua portuguesa do Brasil; avaliar a confiabilidade da versão adaptada do Family Management Measure (FaMM) verificando a consistência interna de seus itens em amostra de família de crianças e adolescentes com doença crônica. Na realidade brasileira, não se localizou qualquer outro instrumento que tivesse objetivos iguais, nem semelhantes aos propostos pelo FaMM, além de haver uma lacuna no que diz respeito à maneira como a família maneja a situação de doença crônica da criança. Consiste de um estudo metodológico com abordagem quantitativa a fim de alcançar os objetivos propostos, seguindo as seguintes etapas: tradução, adaptação transcultural do Family Management Measure para o português e validação das propriedades de medida do instrumento adaptado. Para tanto, utilizou-se a metodologia proposta por Guillemin para tradução e adaptação transcultural de instrumentos (Guillemin 1993, 2002), composta pelo seguinte processo: permissão dos autores para a adaptação transcultural e validação do Family Management Measure (FaMM); tradução para língua portuguesa do Family Management Measure; obtenção do primeiro consenso das versões traduzidas; avaliação pelo Comitê de Especialistas; retrotradução - (Back translation); pré-teste; tratamentos dos dados. A população da pesquisa foi composta por 72 famílias de crianças e adolescentes com doenças crônicas em atendimento em um ambulatório de especialidades de hospital-escola público no município de Londrina. A confiabilidade interna medida através do Alfa de Cronbach foi de 0,8660 para o instrumento todo e variou de 0,4430 a 0,7908 entre as dimensões do instrumento. Houve a eliminação do item 35 da dimensão Esforço de manejo. Concluiu-se que o Family Management Measure (FaMM) apresenta-se adaptado para a língua portuguesa do Brasil e recomenda-se a realização de outros estudos junto a outros familiares de crianças. / This study aimed to realize the cultural adaptation of the Family Management Measure (FaMM) for the Portuguese language of Brazil, to evaluate the reliability of the adapted version of the Family Management Measure (FaMM) by verifying the internal consistency of the items from a family sample of children and adolescents with a chronic disease. In Brazil, no other instrument having the same goals was located, nor were any similar to those proposed by FaMM, moreover there is a gap regarding how the family handles the child\'s chronic illness. This was a methodological study with a quantitative approach attempting to achieve the proposed objectives, following these steps: translation and cultural adaptation of the Family Management Measure to Portuguese; validation of the measurement properties of the adapted instrument. For this purpose, the methodology proposed by Guillemin was used for the translation and the cultural adaptation of instruments (Guillemin 1993, 2002) consisting of the following process: Permission of the authors for the cultural adaptation and validation of the Family Management Measure (FaMM) Translation into Portuguese the Family Management Measure; Obtaining the consent of the first translated versions; Evaluation Committee of Experts; Retro-translation - (Back translation); Pre-test; Treatment of the data. The study population consisted of 72 families with children and adolescents who have chronic diseases being attended in specialty outpatient clinic in a public teaching hospital in Londrina. The internal reliability measured with Cronbach\'s alpha was 0.8660 for the entire instrument and varied from 0.4430 to 0.7908 between the dimensions of the instrument. There was an elimination of item 35 in the dimension \"Stress management. It can be concluded that the Family Management Measure (FaMM) appears to adapt well to the Portuguese language in Brazil and it is recommended that further studies be performed with other families with children.