INTRODUÇÃO: Delirium é um problema médico frequente em idosos e está potencialmente associado a desfechos desfavoráveis, como prolongamento da hospitalização, declínio funcional e cognitivo, e maior mortalidade. Contudo, considerando que, geralmente, ocorre em situações de grande complexidade clínica, o efeito ajustado de delirium e seus subtipos motores sobre o prognóstico de pacientes acometidos ainda não foi suficientemente explorado. OBJETIVOS: Investigar em idosos agudamente enfermos hospitalizados: (1) a associação independente entre ocorrência de delirium e tempo para óbito intra-hospitalar, e em 12 meses de seguimento; (2) a associação independente entre subtipos motores de delirium e tempo para óbito intra-hospitalar, e em 12 meses de seguimento. MÉTODOS: Estudo de coorte prospectivo realizado em uma enfermaria de geriatria de um hospital universitário terciário, em São Paulo, Brasil. Foram incluídas internações de pacientes agudamente enfermos, com idade igual ou superior a 60 anos, hospitalizados entre junho de 2009 e maio de 2014. Delirium foi detectado pelo Confusion Assessment Method e classificado de acordo com o subtipo motor em hipoativo, hiperativo, ou misto. Os desfechos primários foram tempo para óbito intra-hospitalar, e tempo para óbito em 12 meses (para a amostra que recebeu alta). Os pacientes foram avaliados na admissão seguindo modelo de avaliação geriátrica ampla que incluiu variáveis sociodemográficas, clínicas, funcionais, cognitivas, e laboratoriais. Informações adicionais sobre a hospitalização foram registradas na alta ou no óbito. As análises multivariadas foram realizadas por meio de modelos de riscos proporcionais de Cox. Foi examinada a presença de modificação do efeito de delirium sobre os desfechos por análises de interação com outros fatores clínicos. RESULTADOS: Incluímos 1.034 hospitalizações, com uma média de idade de 80 anos. Na amostra geral, 61% eram mulheres, e 35% tinham demência. A mortalidade intra-hospitalar foi de 22%, com uma mortalidade cumulativa de 44% em 12 meses. Delirium ocorreu em 52% das internações, e o subtipo motor predominante foi o hipoativo (53%). Nas hospitalizações com delirium, 32% dos idosos faleceram no hospital, com uma taxa de óbitos cumulativa de 59% em 12 meses. Verificamos que delirium teve associação independente com tempo até óbito intra-hospitalar (HR=1,63 IC95%=1,11-2,40), porém não encontramos associação estatisticamente significante com sobrevida em 12 meses após ajuste para as covariáveis selecionadas. Constatamos, ainda, que os subtipos hipoativo e misto se associaram independentemente com o desfecho intra-hospitalar (HR=1,87 IC95%=1,24-2,83; HR=1,65 IC95%=1,022,67), mas não houve associação estatisticamente significante com o desfecho em 12 meses. O efeito de delirium sobre o tempo até óbito intrahospitalar não foi modificado de modo significativo por sua interação com idade, câncer, desnutrição, ou valores de albumina sérica. CONCLUSÕES: Um terço dos idosos agudamente enfermos internados que tiveram delirium faleceu ainda no hospital. Delirium se associou a menor tempo de sobrevida intra-hospitalar, mesmo após ajuste para características clínicas coexistentes. Além disso, profissionais da saúde devem ter especial atenção com os subtipos hipoativo e misto de delirium, que também se associaram independentemente com maior mortalidade intra-hospitalar em idosos / BACKGROUND: Delirium in older adults is common and potentially associated with unfavorable outcomes, such as longer hospital stay, functional and cognitive decline, and higher mortality. However, given that it usually occurs in a context of great clinical complexity, the adjusted effect of delirium and its motor subtypes on the prognosis of affected patients has not been sufficiently explored. OBJECTIVES: To investigate in acutely ill hospitalized older adults: (1) the independent association between delirium and time to death in the hospital, and in a 12-month follow-up; (2) the independent association between delirium motor subtype and time to death in the hospital, and in a 12-month follow-up. METHODS: Prospective cohort study completed in a geriatric ward of a tertiary university hospital, in Sao Paulo, Brazil. We included admissions of acutely ill patients aged 60 years and over, who were hospitalized from June 2009 to May 2014. Delirium was detected using the Confusion Assessment Method and classified according to its motor subtype in hypoactive, hyperactive, or mixed. Primary outcomes were time to death in the hospital, and time to death in 12 months (for the discharged sample). Patients were evaluated at admission according to a comprehensive geriatric assessment model that included socio-demographic, clinical, functional, cognitive, and laboratory variables. Further clinical data were documented upon death or discharge. Multivariate analyses were performed using Cox proportional hazards models. We investigated the potential modification of the effect of delirium on outcomes including an interaction term between delirium and other clinical variables. RESULTS: We included 1,034 hospitalizations, with a mean age of 80 years. Overall, 61% were women, and 35% had dementia. The proportion of in-hospital deaths was of 22%, with a cumulative mortality of 44% in 12 months. Delirium ensued in 52% of the admissions, and the predominant motor subtype was hypoactive (53%). In-hospital death occurred in 32% of the cases with delirium, while cumulative 12-month mortality reached 59% in this group. We verified that delirium was independently associated with time to in-hospital death (HR=1.63 95%CI=1.11-2.40), but did not find statistically significant association with 12month survival after adjusting for selected covariates. We additionally found that hypoactive and mixed motor subtypes were independently associated with in-hospital death (HR=1.87 95%CI=1.24-2.83; HR=1.65 95%CI=1.02-2.67), but there were no significant associations with 12-month mortality. The effect of delirium on time to in-hospital death was not significantly modified by its interaction with age, cancer, malnutrition, or serum albumin levels. CONCLUSIONS: One third of acutely ill hospitalized older adults who suffered delirium died in the hospital. Delirium was associated with decreased survival in the hospital, even after adjusting for coexistent clinical characteristics. In addition, health care providers should be attentive for the hypoactive and mixed subtypes of delirium, as they were also independently associated with poorer in-hospital outcomes in older adults

O Acidente Vascular Cerebral (AVC) é a principal causa de morbimortalidade no mundo, sendo prevalente entre a população idosa. Sofrer AVC é um episódio inesperado com alto potencial para ser vivenciado como estressante, uma vez que representa ameaça ao controle pessoal. Os objetivos do estudo foram caracterizar os idosos com AVC, avaliar o déficit neurológico, a independência funcional, os sintomas depressivos e o estresse percebido deles, assim como a relação entre o déficit neurológico, a independência funcional, sintomas depressivos e o estresse percebido. Trata-se de um estudo analítico e transversal dos idosos com diagnóstico médico de primeiro evento de AVC, atendidos na Unidade de Emergência do Hospital das Clínicas de Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo. Foram utilizados os seguintes instrumentos: Roteiro estruturado para caracterização dos idosos, Mini-Exame do Estado Mental (MEEM), Escala de AVC do National Institutes Health (NIHSS), Medida da Independência Funcional (MIF), Escala de Depressão Geriátrica (EGD) e Escala de Estresse Percebido (EEP). A técnica de estatística descritiva foi utilizada para todas as variáveis, incluindo a medida de tendência central (média e mediana) e de dispersão (desvio padrão), para variáveis quantitativas; análise univariada (tabelas de frequência) e bivariada (tabelas de contingência), para variáveis qualitativas. As médias das variáveis categóricas foram analisadas pelo T de Student para comparação entre dois grupos. Já a comparação das médias de mais de dois grupos foi realizada por meio da ANOVA e teste de Bonferroni (post-hoc). A regressão linear múltipla foi utilizada para ajustar as associações entre a variável resposta e as variáveis exploratórias. Do total de 90 idosos com diagnóstico do primeiro AVC, que se caracterizaram pela média de 71,2 anos, 56,7% eram do sexo masculino, 53,3% casados, 55,6% estudaram de 1 a 4 anos, 56,7% com restrição da participação nas atividades, 50% com cuidador familiar, 92,2% com AVC isquêmico, 68,7% com AVC leve, 56,7% com 2 ou 3 comorbidades, 70% com independência modifica ou completa, 26,7% com sintomas depressivos. A média do escore da Escala de Estresse Percebido foi de 14,04 (8,5) [IC 95%: 12,2 - 15,83]. Maior estresse percebido estava associado à presença do cuidador (p < 0,001), a restrição da participação das atividades após AVC (p < 0,001), maior gravidade do AVC (p < 0,001), maior dependência funcional (p < 0,001) e com maior número de sintomas depressivos (p < 0,001). No modelo da regressão linear múltipla, as variáveis presença do cuidador, independência funcional e sintomas depressivos explicaram 63% da variação do escore da escala de estresse, o que foi significante (F3;86 = 51,48; p < 0,001). Os idosos após o AVC parecem vivenciar o retorno para casa de forma estressante, sendo a percepção do estresse influenciada pela dependência funcional e sintomas depressivos apresentados por eles. Estudos longitudinais devem ser conduzidos a fim de identificar os preditores de estresse. Além disso, estudos qualitativos podem aprofundar a análise para a compreensão e significado do estresse vivenciado pelos idosos no retorno para casa após a alta hospitalar. / Stroke is the main cause of morbidity and mortality around the world, and is prevalent in the elderly population. Being a stroke victim is an unexpected episode with great potential to be experienced as a stressful event, as it represents a threat to personal control. The study aims were to characterize elderly stroke victims, to assess their neurological deficit, functional independence, depressive symptoms and perceived stress. An analytic and cross-sectional study was developed among elderly patients medically diagnosed with a first stroke episode and attended at the Emergency Unit of the University of São Paulo at Ribeirão Preto Medical School Hospital das Clínicas. The following instruments were used: Structured script to characterize the elderly, Mini-Mental State Examination (MMSE), National Institute of Health Stroke Scale (NIHSS), Functional Independence Measure (FIM), Geriatric Depression Scale (GDS) and Perceived Stress Scale (PSS). Descriptive statistics were applied to all variables, including central trend (mean and median) and dispersion (standard deviation) for quantitative variables; and univariate (frequency tables) and bivariate analyses (contingency tables) for qualitative variables. Student\'s t-test to compare two groups was used to analyze the means of the categorical variables. To compare the means of more than two groups, ANOVA and Bonferroni\'s test (post-hoc) were used. Multiple linear regression served to adjust associations between the response variable and the exploratory variables. The 90 elderly diagnosed with a first stroke episode were characterized as follows: mean age 71.2 years, 56.7% were male, 53.3% married, 55.6% between 1 and 4 years of education, 56.7% with restricted participation in activities, 50% with family caregiver, 92.2% with ischemic stroke, 68.7% with mild stroke, 56.7% with two or three comorbidities, 70% with modified or complete independence, 26.7% with depressive symptoms. The mean score on the Perceived Stress Scale was 14.04 (8.5) [95% CI: 12.2 - 15.83]. Higher levels of perceived stress were associated with the presence of a caregiver (p < 0.001), restricted participation in activities after the stroke (p < 0.001), more severe stroke (p < 0.001), greater functional dependence (p < 0.001) and a higher number of depressive symptoms (p < 0.001). In the multiple linear regression model, the variables presence of the caregiver, functional independence and depressive symptoms explained 63% of the variation in the stress scale score, which was significant (F3;86 = 51.48; p < 0.001). After the stroke, the elderly seemed to experience their return home as stressful, and the perceived stress was influenced by their functional dependence and depressive symptoms. Longitudinal studies are needed to identify stress predictors. In addition, qualitative studies can deepen the analysis in order to understand and grasp the meaning of the stress elderly patients experience when they return home after discharge.

Bakgrund Antalet äldre som behöver hemsjukvård ökar. Sjuksköterskan är omvårdnadsledare som ska leda teamet i strävan att uppnå personcentrerad vård hos den äldre. Syfte Syftet med denna uppsats var att sammanställa forskning om sjuksköterskans ledarskap med fokus på faktorer som påverkar personcentrerade processer inom hemsjukvård av äldre. Metod Metoden var en litteraturstudie där artiklar söktes i databaserna CINAHL, PudMed och PsycINFO. Efter diskussion om artiklarnas innehåll, kvalitetsgranskades relevanta artiklar och sju artiklar valdes ut och analyserades. Resultat Resultatet beskrivs utifrån tre kategorier som var att öka medvetenheten om personcentrerad vård, gensvar av personcentrerad vård och hinder i ledarskapet. Resultatet visar att sjuksköterskans ledarskap har inverkan på huruvida en personcentrerad vård uppnås eller inte. Slutsats Litteraturstudien visar att sjuksköterskans ledarskap kan påverka genomförandet av personcentrerad vård. Mer kunskap och utbildning samt tillgång till ett ramverk behövs hos all vårdpersonal för att kunna förstå vad personcentrerat arbetssätt innebär.

O rápido envelhecimento populacional faz com que a saúde mental da população geriátrica venha tomando uma importância cada vez maior na saúde pública. Os objetivos deste estudo foram:(1) investigar a prevalência de transtornos mentais ao longo da vida, analisando possíveis fatores sócio-demográficos associados (2) pesquisar a possível relação entre prevalência de transtorno mental ao longo da vida e desempenho cognitivo. Foram estudados 82 sujeitos acima de 60 anos da área de captação do Hospital das Clínicas da cidade de São Paulo. O instrumento utilizado para investigação diagnóstica foi o Composite International Diagnostic Interview (CIDI), sendo a avaliação do desempenho cognitivo obtida através do Mini Exame do Estado Mental (MEEM) e do Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Os resultados mostraram que os transtornos mentais de maior prevalência ao longo da vida foram Depressão (16%), Transtorno de Humor Recorrente (10%) e Transtorno de Ansiedade Generalizada (8,5%). Os demais transtornos observados foram Distimia (6%), Transtorno Doloroso Persistente (5%), Uso Nocivo de Álcool (5%) e Transtorno Dissociativo (2,4%). Não foram identificados casos de Transtorno Afetivo Bipolar, Esquizofrenia e outras psicoses, assim como dependência de Álcool ou de psicotrópicos. Apesar de haver uma maior prevalência nas mulheres dos quadros de Depressão (18,5%), Transtorno de Humor Recorrente (12%), Distimia (6%), Transtorno Doloroso Persistente (7%) e Transtorno Dissociativo (3,5%), e por outro lado uma maior prevalência de Abuso de Álcool (9%) e Transtorno de Ansiedade Generalizada (9%) nos homens, não houve correlação estatisticamente significativa entre gênero e transtornos mentais. Na amostra, os sujeitos de maior escolaridade demonstraram maior associação com prevalência de distimia (p=0,01) e transtorno de ansiedade generalizada (p=0,03). Houve maior associação entre baixa escolaridade (p=0,000) e idade mais avançada (p=0,007) com pior desempenho cognitivo pelo MEEM. A presença de disfunção cognitiva pelo MEEM foi de 11% e pelo IQCODE 16%. Não foi identificada asssociação entre prevalência de transtornos mentais ao longo a vida e pior desempenho cognitivo. Os resultados da prevalência de transtornos mentais ao longo da vida desta amostra foi similar aos achados de outros estudos que utilizaram o CIDI, exceto pela maior prevalência de Transtorno do Humor Recorrente no presente estudo que nos demais. Maior atenção deve se dar a associação entre maior escolaridade e prevalência de distimia e transtornos de ansiedade generalizada ao longo da vida em populações idosas de regiões urbanas / With a rapidly aging society, geriatric mental health is emerging as important public health concern.The study objectives were: (1) investigate the lifetime prevalence of psychiatric illnesses and the association between sociodemografic characteristics (2) investigate the possible relationship between the prevalence of mental disorder throughout life and cognitive performance. We studied 82 subjects over 60 years older from the catchment area of Hospital das Clínicas de São Paulo. The instrument used for diagnostic investigation was the Composite International Diagnostic Interview (CIDI), and the assessment of cognitive performance achieved by the Mini Mental State Examination (MMSE) and Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). The results showed that the most prevalent lifetime ICD-10/CIDI disorders were major depression (16%), followed by recurrent mood disorder (10%), and generalized anxiety disorder (8,5%). Other disorders were observed such as dysthymia (6%), persistent pain disorder (5%), alcohol abuse (5%) and dissociative disorders (2.4%). There were no identified cases of bipolar affective disorder, schizophrenia and other psychoses, as well as dependence on alcohol or psychotropic substances. Women had higher prevalence of depression (18.5%), recurrent mood disorders (12%), dysthymia (6%), persistent pain disorder (7%) and dissociative disorder (3.5%). On the other hand, men have higher prevalence alcohol (9%) and generalized anxiety disorder (9%). However, these differences were not statistically significant. In this sample, subjects with higher education showed an association with prevalence of dysthymia (p = 0.01) and generalized anxiety disorder (p = 0.03). There was a higher association between low education (p = 0.000) and older age (p = 0.007) with worse cognitive performance by the MMSE. The presence of cognitive impairment evaluated by the MMSE was 11% and the result based on the IQCODE was 16%. There was not a relationship between lifetime prevalence of mental disorders and impaired cognitive performance. The results of lifetime prevalence of mental disorders in this sample were similar to the findings of other studies using the CIDI, except for a higher prevalence of recurrent mood disorder in this study than the others. Close attention are required to address the relationships between higher educational level and dysthymia and generalized anxiety disorder in urban elderly population

Dado o acelerado processo de envelhecimento populacional vivenciado no Brasil e no mundo, é importante identificar quais as melhores maneiras de avaliar a saúde da pessoa idosa inserida na comunidade ou institucionalizada. Neste sentido, a Organização Mundial de Saúde preconiza a avaliação desta população por meio da condição funcional. Diferentes instrumentos se propõem a este fim, seja evidenciando o desempenho de atividades ou capacidade funcional, por métodos aferido ou referido. No entanto, existe grande diferença entre estas possíveis maneiras de avaliação da pessoa idosa e poucos estudos que abordem este tema. Objetivo: comparar a avaliação de atividades básicas de vida diária (ABVD) por meio do desempenho referido e aferido em pessoas idosas residentes na comunidade. Método: Estudo transversal que avaliou 40 idosos que realizavam tratamento ou acompanhamento médico em dois ambulatórios (clínica médica e ortopedia) no município de Londrina (PR). Esta amostra foi avaliada frente desempenho funcional por meio da Medida de Independência Funcional (MIF) e o desempenho referido foi verificado a partir da utilização de um questionário padronizado. Ao todo, 12 atividades básicas de vida diária foram avaliadas por ambos os métodos. Para possibilitar a comparação entre as respostas obtidas em cada instrumento, houve um processo de categorização no qual cada idoso era classificado como independente; tendo dificuldade ou utilizando adaptação para realizar a atividade; ou necessitando de ajuda. Foi utilizado o teste do coeficiente de Kappa e teste de correlação de Spearman para comparar a concordância entre os métodos de avaliação da condição funcional. Resultados: Os idosos residentes na comunidade apresentavam média etária de 71,6 anos (IC 95% 72,8;79,4) e maior proporção de mulheres (52,5) e a maioria dos participantes não apresenta comprometimento da função cognitiva. Dentre as atividades avaliadas, aquelas relacionadas ao uso e acesso ao vaso sanitário foram as que a presentaram menor concordância. Já locomoção, alimentação, controle de fezes, banho e vestir-se são aquelas mais comparáveis. Pela comparação entre os métodos de avaliação foi possível observar que a avaliação de modo aferido evidencia indivíduos com menor nível funcional frente a avaliação autorreferida das mesmas atividades. As dificuldades aferidas e referidas estiveram relacionadas com a condição de saúde do idoso avaliado, sendo que idosos provindos do ambulatório ortopédico apresentavam maior comprometimento de atividades que comprometiam membros superiores ou inferiores. Foi possível concluir que a avaliação de ABVD utilizando desempenho referido ou aferido apresenta respostas similares para maioria das atividades avaliadas, com grau de concordância substancial. No entanto, as respostas obtidas pelo método de avaliação autorreferido devem ser interpretadas com cautela, principalmente quando da avaliação do uso e acesso ao vaso sanitário. Os métodos de avaliação avaliados são complementares e quando possível ambos devem ser aplicados para avaliação funcional de pessoas idosas. / About the accelerated ageing process experienced in Brazil and the world, it is important to identify the best ways to check the health of the older persons inserted in the community. In this sense, the World Health Organization indicates the assessment of functional condition as good option to evaluate this population. Different instruments are proposed and it can be done by the assessment of capacity or performance, by measured or (self) reported methods. However, these methods are different and there are few studies that address this issue. Objective: To compare the evaluation of activities of daily living (ADL) by reported or measured performance in older adults living in community. Methods: Cross-sectional study that evaluated 40 subjects who were undergoing treatment or medical care at two clinics (generical medicine and orthopedics) in Londrina (PR). This sample was evaluated from the functional performance through the Functional Independence Measure (FIM) and reported performance was observed from the use of a standardized questionnaire. Twelve ADL were assessed by both methods. To enable a comparison of obtained responses with each instrument, the subjects were classified as independent; with difficulty or using adaptation to perform the activity; or who needing help. We used the Kappa coefficient test to compare the agreement among the methods to assess functional condition. Results: community-dwelling older adults had a mean age of 71.6 years (95% CI 72.8; 79.4) and higher proportion of women (52.5) and most of the participants does not have impaired cognitive function. Among the activities evaluated, those related to the use and access to the toilet showed the least agreement. Already locomotion, feeding, control stool, bathing and dressing are those more comparable. In the comparison process, it was observed that the older adults had lower functional level when the assessment is made by measured performance against reported assessment of the same activities. The measured and reported difficulties were related to the health condition of the evaluated elderly, and older persons in treatment of orthopedic clinic had greater commitment in activities involving the arms or legs, structures in rehabilitation process. When we evaluated community-dwelling elderly, there was a higher level of agreement between measured functional condition and reported performance. We concluded that the evaluation of ABVD using measured or reported performance shows similar responses to most of the activities evaluated, with substantial degree of agreement. However, the responses obtained by self-reported assessment method should be interpreted with caution, especially when assessing the use of and access to toilet. The methods of this evaluation are complementary and it is a better option when both can be applied for functional assessment of elderly.

年齡相關性黃斑變性（AMD）是發展國家高齡人群中不可逆盲的首要原因。在AMD患者中，即使在改變生活模式或進行治療后，其滲出性亞型仍導致超過80% 的病例出現嚴重視力喪失及法定盲。息肉狀脈絡膜血管病變 （PCV）是一種與滲出性AMD在臨床表型上存在相同之處的黃斑病變，它的典型病變被定性為眼底血管螢光造影時出現息肉狀的病灶。近年PCV被認為是滲出性AMD亞型中的一種，因為兩者共享相同的基因成份及環境因素。然而，PCV曾經被認為是與滲出性AMD截然不同的一種疾病，由於兩者的臨床表現並不一致。另外，PCV病人相對年輕，多為亞洲人，以及對光動力治療和抗血管內皮生長因子治療存在不同的反應。一個明確的鑒別診斷可以更好的輔助臨床醫生對患有這些疾病的老年病人進行管理，然而兩者是相同還是不同的疾病種類仍是一個具爭議性的議題。 / CFH 基因和ARMS2/HTRA1位點已被全基因組相關性研究及相關的分子學研究定位為AMD候選基因。鑒於FPR1基因的協調吞噬性白細胞激活及遷移的功能，它可能是一個新的AMD候選基因。本論文評估在滲出性AMD和PCV中FPR1作為一個新的疾病基因基因的可能，獲取滲出性AMD和PCV病人中的CFH，ARMS2，HTRA1和FPR1基因檔案，同時研究在ARMS2/HTRA1位點中基因型和疾病表型的關聯性，以此從基因學方面鑑別滲出性AMD與PCV。 / 本研究在滲出性AMD，PCV病例和對照人群中使用聚合酶鏈反應和直接測序法進行ARMS2， HTRA1， CFH 和FPR1基因篩查。本研究發現滲出性AMD和PCV之間存在不同的基因型分佈，關聯模式以及基因效應值。 / 在HTRA1的多態性中，rs11200638，rs2672598, rs1049331 和 rs2293870 在滲出性AMD和PCV之間表現出鑒別性關聯 （p < 0.001）。其中rs11200638 (p = 1.48×10⁻⁴) and rs2672598 (p = 2.27×10⁻³) 在滲出性AMD病人中相互校正后仍保持各自的顯著性，但rs2672598 未能在PCV病人中保持顯著性(p = 0.20)。並且本研究發現攜帶rs11200638和 rs2672598聯合基因型AA-CC 的病人更傾向是滲出性AMD病人，與PCV相比幾率高11.7倍。 / 在ARMS2中，有11個基因多態性與滲出性AMD和PCV存在顯著性的相關。在與rs11200638校正后，rs10490924保持和滲出性AMD的顯著相關性(p = 0.011)，但PCV中未能保持(p = 0.077)。同時，元分析結果顯示ARMS2 rs10490924和HTRA1 rs11200638不同人群的PCV中的等位基因相關性是一致的。 / 在FPR1中，rs78488639與滲出性AMD (p = 0.049, 比值比 (OR) = 2.05, 95% 信賴區間（CI）: 1.014.14)和PCV (p = 0.016, OR = 2.27, 95%CI: 1.154.47)的疾病風險存在顯著的相關性。多態性rs104229的G等位基因純合子和滲出性AMD存在顯著相關(p = 0.039, OR = 2.27, 95%CI: 1.084.74)，但在PCV中未發現相關性(p = 0.24)。多態性rs2070746 AMD (p = 0.021, OR = 0.57, 95%CI: 0.35 0.91)和rs867229 (p = 0.0091, OR = 0.54, 95%CI: 0.340.86) 的雜合子基因型與滲出性AMD相關，但在PCV中未發現相關性。與此同時，本研究在上述多態性中發現滲出性AMD和PCV之間不同的基因型分佈。 / 本研究發現在滲出性AMD和PCV病人中FPR1 rs78488639和CFH rs800292存在顯著的相互作用（ORs > 4）。兩個多態性之間的相互作用提高滲出性AMD和PCV的疾病風險，而不是僅對其中之一起作用。 / ARMS2 多態性 rs10490924 (A69S, 205G>T, pAMD = 1.01×10⁻²⁹ OR = 7.91, 95% CI: 4.93 - 12.67; pPCV = 8.25×10⁻⁷, OR = 3.51, 95% CI: 1.98 - 5.03), HTRA1 多態性rs11200638 (-625G>A, pAMD = 9.88×10⁻²⁸, OR = 6.95, 95% CI: 4.37 - 11.06; pPCV = 8.02×10⁻⁶, OR = 2.82, 95%CI: 1.77 - 4.47), CFH 多態性rs800292 (V62I, 184G>A, pAMD = 9.00×10⁻⁴ , OR = 0.58, 95% CI: 0.42 0.79; pPCV = 0.011, OR = 0.66, 95% CI: 0.49 0.90) and FPR1 多態性rs78488639 (L97M, 289C>A, pAMD = 0.049, OR = 2.05, 95% CI: 1.01 - 4.14; pPCV = 0.016, OR = 2.27, 95% CI: 1.15 - 4.47)代表各自基因的最強相關性。此外，元分析揭示了在不同種族人群PCV中的等位基因相關性顯著並且一致(ORtotal = 2.14, 95% CI: 1.97 2.33, ORtotal = 2.34, 95% CI: 1.98 2.76 and ORtotal = 0.49, 95% CI: 0.44 0.56)。表型-基因型分析發現ARMS2/HTRA1 的風險基因型和較差的治療反應呈正相關性(p = 0.04)。另外，本研究在滲出性AMD中發現HTRA1 rs11200638和吸煙的聯合作用。然而，在PCV中未觀察到次聯合作用，這可能提示兩者間存在不同的疾病機制。 / 本論文提出FPR1基因是一個新的滲出性AMD和PCV候選基因，揭示了ARMS2，HTRA1，CFH和FPR1在滲出性AMD和PCV間顯著並且一致的相關性， 提供鑒別兩者的基因學證據，闡明了ARMS2/HTRA1 的風險基因型和較差的治療反應之間的相關性以及顯示了吸煙在滲出性AMD和PCV之間的不同影響。然而，由於兩者間基因關聯的趨勢一致，目前尚未能清晰界定兩者的不同。因此，要進一步明確鑒別滲出性AMD和PCV，還需要進行不同種族的複製研究，以及更重要的是，尋找特定的PCV基因以鑒別兩個不同疾病。 / Age-related macular degeneration (AMD) is the leading cause of irreversible blindness for the elderly in developed countries. Its exudative subtype accounts for more than 80% of severe visual loss or legal blindness in AMD patients regardless of modified lifestyle and therapeutic treatments. Polypoidal choroidal vasculopathy (PCV) is a macular disorder characterized by typical polypoidal lesions on fundus angiograhpy and sharing similar phenotype with exudative AMD. PCV was suggested as a distinct disease from exudative AMD based on different clinical features in ophthalmic imaging. Furthermore, PCV patients tend to be younger and more prevalent in Asian, and have different responses to photo-dynamic therapy and anti-vascular endothelial growth factor treatments, compared to exudative AMD patients. Howerver, it has also been suggested that PCV could be a subtype of exudative AMD mainly because of their common genetic and environmental factors. Therefore, genetic differentiation between exudtive AMD and PCV might assist clinicans to determine the condition. / The complement factor H (CFH) gene, and age-related maculopathy susceptibility 2 (ARMS2)/high temperature requirement factor A1 (HTRA1) locus have been mapped for AMD by genome-wide association studies (GWAS) and subsequent molecular investigations. The formyl peptide receptor 1 (FPR1) gene, which mediates trafficking and activation of phagocytic leukocytes, is related to the AMD-associated inflammatory condition. This thesis aims to evaluate FPR1 as a novel disease gene for exudative AMD and PCV, to compare the genetic profiles of ARMS2, HTRA1, CFH, and FPR1 in exudative AMD and PCV, to investigate the correlation of ARMS2/HTRA1 genotypes with disease phenotypes, and to differentiate these two disorders throught the genomic compositions. / Case-control association studies were conducted on ARMS2, HTRA1, CFH and FPR1 in exudative AMD and PCV patients of our Hong Kong Chinese cohort using polymerase chain reaction and direct sequencing. We observed different genotypic distributions (p < 0.05), association patterns and effect sizes between these two diseases. / In HTRA1 polymorphisms, rs11200638, rs2672598, rs1049331 and rs2293870 showed differential associations between exudative AMD and PCV (p < 0.001). Both rs11200638 (p = 1.48×10⁻⁴) and rs2672598 (p = 2.27×10⁻³) remained significant after adjusting for each other in exudative AMD, whereas rs2672598 was not significantly associated with PCV (p = 0.20). The joint genotype AA-CC constructed by the risk alleles of these rs11200638 and rs2672598 were prone to exudative AMD, conferring an 11.7-fold higher risk (p = 4.00×10⁻³) when compared to PCV. / In ARMS2, 11 single nucleotide polymorphisms (SNPs) showed significant associations with both exudative AMD and PCV. After adjusting for rs11200638, ARMS2 rs10490924 remained significantly associated with exudative AMD (p = 0.011), but not with PCV (p = 0.077). / In FPR1, SNP rs78488639 significantly increased the risk to exudative AMD (p = 0.049, odds ratio (OR) = 2.05, 95% confidence interval (CI): 1.014.14) and PCV (p = 0.016, OR = 2.27, 95%CI: 1.154.47). The homozygous G allele of rs1042229 was associated with exudative AMD (p = 0.039, OR = 2.27, 95%CI: 1.084.74), but not with PCV (p = 0.24). The heterozygous genotypes of rs2070746 and rs867229 were associated with exudative AMD (p = 0.021, OR = 0.57, 95%CI: 0.35 0.91; p = 0.0091, OR = 0.54, 95%CI: 0.340.86, respectively), but not with PCV. / Significant interaction was identified between FPR1 rs78488639 and CFH rs800292, with joint ORs > 4 folds for both exudative AMD and PCV. Interactions between FPR1 rs78488639 with CFH rs800292 enhance risks to both AMD and PCV, not just one of them. / Overall, the ARMS2 rs10490924 (A69S, 205G>T, pAMD = 1.01×10⁻²⁹, OR = 7.91, 95% CI: 4.93 - 12.67; pPCV = 8.25×10⁻⁷, OR = 3.51, 95% CI: 1.98 - 5.03), HTRA1 rs11200638 (-625G>A, pAMD = 9.88×10⁻²⁸, OR = 6.95, 95% CI: 4.37 - 11.06; pPCV = 8.02×10⁻⁶, OR = 2.82, 95%CI: 1.77 - 4.47), CFH rs800292 (V62I, 184G>A, pAMD = 9.00×10⁻⁴ , OR = 0.58, 95% CI: 0.42 0.79; pPCV = 0.011, OR = 0.66, 95% CI: 0.49 0.90) and FPR1 rs78488639 (L97M, 289C>A, pAMD = 0.0487, OR = 2.05, 95% CI: 1.01 - 4.14; pPCV = 0.0161, OR = 2.27, 95% CI: 1.15 - 4.47) were responsible for the strongest association in each gene. Moreover, meta-analysis revealed a consistent and significant association of the ARMS2/HTRA1 locus with PCV in different ethnic cohorts (OR{U+209C}{U+2092}{U+209C}{U+2090}{U+2097} = 2.14, 95% CI: 1.97 2.33, OR{U+209C}{U+2092}{U+209C}{U+2090}{U+2097} = 2.34, 95% CI: 1.98 2.76 and {U+209C}{U+2092}{U+209C}{U+2090}{U+2097} = 0.49, 95% CI: 0.44 0.56, respectively). The phenotype-genotype analysis implicated a positive correlation between ARMS2/HTRA1 risk genotype and a worse response to treatment (p = 0.04) in our exudative AMD patients. In addition, joint effects between cigarette smoking and HTRA1 rs11200638 was found in exudative AMD group. However, this effect was not significant in PCV group, which might implicate a different disease mechanism. / This thesis attempts to dissect the genetic profiles of exudative AMD and PCV. Results in this thesis suggest FPR1 as a novel candidate gene for exudative AMD and PCV, reveal a significant and consistent association of ARMS2, HTRA1, CFH and FPR1 with both exudative AMD and PCV, provide evidences for genetic differentiation of these two disorders, demonstrate a significant correlation between ARMS2/HTRA1 genotypes and response to treatment, and indicate different influence of smoking in exudative AMD and PCV. However, definite differentiation between exudative AMD and PCV was limited because of the same trend of associations between these two disorders. Therefore, replication studies in other enthic populations are necessary, and identification of PCV-specific genes/polymorphisms could further differentiate PCV from exudative AMD. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Liang, Xiaoying. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 124-143). / Abstract also in Chinese. / Title page --- p.i / Abstract --- p.iii / 摘要 --- p.vii / Acknowledgements --- p.xii / Table of Contents --- p.xiii / List of Figures --- p.xix / List of Tables --- p.xxi / Abbreviations --- p.xxiv / Publications --- p.xxvii / Conference Presentations --- p.xxviii / Chapter Chapter 1: --- Introduction / Chapter 1.1. --- Normal retinal architecture --- p.1 / Chapter 1.2. --- Age-related retinal changes --- p.3 / Chapter 1.3. --- Age-related macular degeneration (AMD) --- p.7 / Chapter 1.3.1. --- Classification, clinical manifestation and disease course --- p.7 / Chapter 1.3.2. --- Exudative AMD and therapeutic strategies --- p.9 / Chapter 1.3.3. --- Pathology of AMD --- p.10 / Chapter 1.3.4. --- Risk factors and associated pathogenesis --- p.12 / Chapter 1.3.4.1. --- Age --- p.12 / Chapter 1.3.4.2. --- Ethnicity --- p.13 / Chapter 1.3.4.3. --- Oxidative stress --- p.13 / Chapter 1.3.4.3.1. --- Reactive oxygen species and AMD --- p.14 / Chapter 1.3.4.3.2. --- Antioxidants --- p.15 / Chapter 1.3.4.3.3. --- Association of oxidation genes with AMD --- p.16 / Chapter 1.3.4.4. --- Inflammation --- p.16 / Chapter 1.3.4.4.1. --- Complement in AMD --- p.17 / Chapter 1.3.4.4.2. --- The potential role of formyl peptide receptor 1 (FPR1) in AMD --- p.19 / Chapter 1.3.4.5. --- Genetic predisposition --- p.19 / Chapter 1.3.4.5.1. --- Complement factor H --- p.21 / Chapter 1.3.4.5.2. --- The 10q26 locus --- p.22 / Chapter 1.3.4.5.3. --- Phenotype-genotype correlation --- p.23 / Chapter 1.4. --- Comparisons between exudative AMD and Polypoidal choroidal vasculopathy --- p.24 / Chapter 1.4.1. --- History --- p.25 / Chapter 1.4.2. --- Natural course --- p.26 / Chapter 1.4.3. --- Epidemiological factors --- p.27 / Chapter 1.4.3.1. --- Ethnicity --- p.27 / Chapter 1.4.3.2. --- Gender --- p.27 / Chapter 1.4.3.3. --- Age --- p.28 / Chapter 1.4.3.4. --- Risk factors --- p.28 / Chapter 1.4.4. --- Clinical manifestation and histopathological features --- p.29 / Chapter 1.4.5. --- Genetic determinants --- p.29 / Chapter 1.4.5.1. --- Genes with common associations --- p.30 / Chapter 1.4.5.2. --- Genes not have common association --- p.32 / Chapter 1.4.6. --- Response to treatments --- p.32 / Chapter 1.5. --- Objectives and research prospects --- p.33 / Chapter Chapter 2: --- Materials and Methods / Chapter 2.1. --- Polymorphism identification in ARMS2, HTRA1, FPR1 and CFH --- p.39 / Chapter 2.1.1. --- Study subjects --- p.39 / Chapter 2.1.1.1. --- Diagnostic features of AMD and PCV --- p.39 / Chapter 2.1.1.2. --- Control subjects --- p.40 / Chapter 2.1.2. --- Laboratory methods --- p.40 / Chapter 2.1.2.1. --- DNA extraction and quantification --- p.40 / Chapter 2.1.2.2. --- Genotyping --- p.41 / Chapter 2.1.2.2.1. --- Polymerase chain reaction (PCR) and agrose gel electrophoresis --- p.41 / Chapter 2.1.2.2.2. --- DNA sequencing --- p.42 / Chapter 2.1.3. --- Statistical analysis --- p.43 / Chapter 2.1.3.1. --- Genotypic association analysis --- p.43 / Chapter 2.1.3.2. --- Haplotype association analysis --- p.43 / Chapter 2.1.3.3. --- Logistic regression analysis --- p.44 / Chapter 2.1.3.4. --- Joint effect analysis --- p.44 / Chapter 2.1.3.5. --- Meta-analysis --- p.45 / Chapter 2.1.3.6. --- Statistical power calculation and sample size --- p.45 / Chapter 2.2. --- Phenotype-genotype correlation in ARMS2/HTRA1 locus --- p.46 / Chapter 2.2.1. --- Patient recruitment --- p.46 / Chapter 2.2.2. --- Genotyping --- p.46 / Chapter 2.2.3. --- Outcome measurement --- p.46 / Chapter 2.2.4. --- Statistical analysis --- p.47 / Chapter Chapter 3: --- Results / Chapter 3.1. --- The age and gender distribution in study subjects --- p.57 / Chapter 3.2. --- The HTRA1 sequencing in exudative AMD and PCV --- p.57 / Chapter 3.2.1. --- Polymorphism identification and genotypic association --- p.57 / Chapter 3.2.2. --- Haplotype structure and Haplotype-based association analysis --- p.59 / Chapter 3.2.3. --- Joint genotype analysis --- p.59 / Chapter 3.3. --- Differential association of exudative AMD and PCV with the ARMS2/HTRA1 locus --- p.60 / Chapter 3.3.1. --- Genotypic association --- p.60 / Chapter 3.3.2. --- Haplotype analysis --- p.62 / Chapter 3.3.3. --- Logistic regression --- p.63 / Chapter 3.3.4. --- Meta-analysis of ARMS2/HTRA1 association with PCV --- p.64 / Chapter 3.3.5. --- In-position OR plot --- p.64 / Chapter 3.4. --- FPR1 and CFH in exudative AMD and PCV --- p.65 / Chapter 3.4.1. --- Polymorphism identification and genotypic association --- p.65 / Chapter 3.4.2. --- Haplotype analysis of FPR1 --- p.66 / Chapter 3.4.3. --- The association of CFH rs800292 --- p.67 / Chapter 3.4.4. --- Joint effect analysis of the CFH and FPR1 genes --- p.67 / Chapter 3.4. --- Phenotype-genotype correlation in ARMS2/HTRA1 locus --- p.68 / Chapter 3.4.1. --- Distribution of age and bilaterality --- p.69 / Chapter 3.4.2. --- Greatest linear dimension of CNV lesion in exudative AMD --- p.69 / Chapter 3.4.3. --- Response to treatment in exudative AMD --- p.69 / Chapter 3.4.4. --- Recurrence in PCV --- p.70 / Chapter 3.4.5. --- Smoking status --- p.70 / Chapter Chapter 4: --- Discussion / Chapter 4.1. --- Age and gender distribution --- p.104 / Chapter 4.2. --- Genetic differentiation in ARMS2/HTRA1 locus --- p.S104 / Chapter 4.2.1. --- SNPs with common association --- p.106 / Chapter 4.2.2. --- SNPs with different association S --- p.106 / Chapter 4.2.3. --- Comparison with previous studies C --- p.107 / Chapter 4.2.4. --- Sample size S --- p.109 / Chapter 4.3. --- The FPR1 gene in exudative AMD and PCV --- p.110 / Chapter 4.4. --- Interaction between FPR1 and CFH --- p.112 / Chapter 4.5. --- Correlation between phenotypes and genotypes --- p.113 / Chapter 4.6. --- Common and rare variants for complex disease --- p.114 / Chapter 4.6.1. --- The debate of common disease common variant versus common disease rare variant --- p.115 / Chapter 4.6.2. --- Candidate gene screening versus geno-wide association study --- p.117 / Chapter 4.6.3. --- Common variants versus rare variants in 10q26 locus --- p.118 / Chapter 4.6.3.1. --- Common variants --- p.119 / Chapter 4.6.3.2. --- Rare variants --- p.120 / Chapter Chapter 5: --- Conclusions and future prospects --- p.122 / Chapter Chapter 6: --- References --- p.124

Introdução: a vulnerabilidade é um conceito que visa ampliar a compreensão da condição de saúde do ser humano. Posto isto, o objetivo geral deste estudo foi analisar a vulnerabilidade individual, social e programática entre idosos que vivem no domicílio e sua associação com os desfechos adversos relacionados aos indicadores da condição de saúde, e mapeá-los espacialmente. Método: trata-se de um estudo epidemiológico de base populacional, do tipo inquérito domiciliar, transversal e observacional, desenvolvido no município de Uberaba (MG). Constituíram a amostra final 701 idosos selecionados por meio da amostragem por conglomerado em múltiplo estágio. Para avaliação do componente individual recorreu-se ao fenótipo de fragilidade; o programático por meio de um indicador de acesso e utilização do serviço de saúde; o social mediante a distribuição espacial dos setores censitários do município deste estudo. Procedeu-se análise descritiva, análise de componentes principais, teste qui-quadrado e modelos de regressão logística, logística multinomial e linear (p<0,05). A análise espacial foi realizada por meio de mapas temáticos. Resultados: constatou-se que 32,0 % dos idosos apresentava as três condições de vulnerabilidade (individual, social e programática) concomitantemente. Evidenciaram-se como fatores associados à condição de fragilidade física: sexo feminino (p=0,015) e faixas etárias de 70 a 79 anos (p=0,013) e 80 anos ou mais (p<0,001). Para condição de elevada/muito elevada vulnerabilidade social predominaram: faixas etárias de 60+ 70 anos (p=0,009) e 70+ 80 anos (p=0,039); ausência de escolaridade (p<0,001) (p<0,001) e 1+4 anos de estudo (p=0,001); e renda mensal < 1 salário mínimo (p=0,007), 1 salário (p=0,013) e 1+3 salários (p=0,027). Já os fatores associados à moderada vulnerabilidade programática foram: faixa etária 70+ 80 anos (p=0,039); não possuir escolaridade (p=0,017), 1+4 anos de estudo (p=0,003) e 4+9 anos de estudo (p=0,029). Na análise de associação entre os componentes da vulnerabilidade, constatou-se menor proporção de idosos frágeis com elevada vulnerabilidade programática quando comparados aos pré-frágeis e não frágeis (p=0,011). Na distribuição espacial dos desfechos adversos de saúde segundo a vulnerabilidade social, houve maior ocorrência de quedas, dependência para AIVD e péssima/má autopercepção de saúde entre idosos residentes em áreas de elevada/muito elevada vulnerabilidade social comparados aos demais. Em relação à associação entre os componentes de vulnerabilidade e os desfechos de saúde, observou-se associação da fragilidade física com todos os desfechos analisados (quedas, hospitalização, dependência para ABVD e AIVD, autopercepção de saúde e número de morbidade). O componente social associou-se à dependência para ABVD e AIVD e à autopercepção de saúde. Já o componente programático permaneceu associado apenas ao maior número de morbidade. Conclusão: os resultados evidenciaram que os idosos estão sujeitos às condições de vulnerabilidade sob as perspectivas biológica, social e no acesso e utilização de serviços de saúde. Infere-se que os componentes individual, social e programático de vulnerabilidade podem influenciar nas condições de saúde de idosos, sendo que a fragilidade física se relacionou a todos os desfechos analisados / Vulnerability is a concept intended to broaden understanding regarding the health condition of people. This study\'s general objective was to analyze the individual, social and programmatic vulnerability of elderly individuals living in the community and its association with adverse outcomes related to health status indicators, in addition to mapping them spatially. Method: This population-based, cross-sectional and observational epidemiological study included a survey conducted in the individuals\' homes in the city of Uberaba, MG, Brazil. The final sample included 701 elderly individuals selected through multistage cluster sampling. The fragility phenotype was used to assess the individual component; the programmatic component was verified through an indicator for access and attendance to health services; and the social component was verified through the spatial distribution of the census sector of the city under study. Descriptive analysis, principal components analysis, and the Chi-square test, in addition to logistic regression models and multinomial logistic regression (p<0.05) were performed. Spatial analysis was conducted using thematic maps. Results: 32.0% of the elderly individuals concomitantly presented three vulnerability conditions (individual, social and programmatic). The factors that appeared associated with a physically frail condition were: being a woman (p=0.015), aged from 70 to 79 years old (p=0.013) or 80 years old or older (p<0.001). The following predominated for conditions of high social vulnerability: aged from 60+ 70 years old (p=0.009) and 70+ 80 years old (p=0.039); no formal education (p<0.001) (p<0.001) and 1+4 years of schooling (p=0.001); and monthly income < 1 times the minimum wage (p=0.007), 1 times the minimum wage (p=0.013) and 1+3 times the minimum wage (p=0.027). The factors associated with moderate programmatic vulnerability were: ages between 70+ 80 (p=0.039); no formal education (p=0.017), 1+4 years of schooling (p=0,003) and 4+9 years of schooling (p=0,029). Analysis of association among vulnerability components revealed a lower proportion of frail elderly individuals with high programmatic vulnerability when compared to their pre-frail and non-frail counterparts (p=0.011). The spatial distribution of adverse health outcomes according to social vulnerability revealed a greater occurrence of falls, dependency for IADLs, and poor/very poor self-perception of health status among those living in areas of high/very high social vulnerability compared to their counterparts. In regard to association among vulnerability components and health outcomes, physical frailty was associated with all outcomes (falls, hospitalization, dependency for ADLs and IADLs, self-perception of health and number of morbidities). The social component was associated with ADL and IADL dependency and self-perception of health. The programmatic component remained associated only with a greater number of morbidities. Conclusion: The results evidenced that elderly individuals are subject to vulnerable conditions from a biological and social perspective also considering access and use of health services. The results suggest that individual, social and programmatic components of vulnerability influence the health conditions of elderly individuals, while physical frailty was related to all the outcomes under study

The purpose of this qualitative pilot study is to explore the patient perspectives about what it is like to receive a bed bath. Examining studies of bath basins versus alternative methods has shown a decrease in the spread of nosocominal infections. However, there is not sufficient evidence evaluating the patient perspectives of assistive bed bathing and interactions with nurses and nursing support staff. This information can provide healthcare providers, especially nurses, with a better understanding of patient perspectives and values. It also supports the national healthcare approach towards patient-centered care.

Define the SLP role with patients commonly seen in primary care Duplicate SLP knowledge to help in primary care Evaluate the role of the SLP as part of the multidisciplinary team

Thesis (M. OPT.) -- University of Limpopo, 2001 / Refer to document