INTRODUÇÃO: As infecções causadas pela neutropenia severa são as causas mais frequentes de morbidade em pacientes submetidos à quimioterapia e Transplante de Células Tronco Hematopéticas (TCTH). Além da neutropenia prolongada vários fatores como o uso de dispositivos intravenosos, mucosite, condições clinicas prévias, tipo de tratamento e tempo de internação também contribuem para o desenvolvimento de infecções. A classe socioeconômica parece influenciar em uma série de desfechos no tratamento do câncer. A análise destas correlações é importante para determinar um melhor desfecho clinico para estes pacientes. OBJETIVO: verificar a relação entre perfil clinico e condições econômicas com o desenvolvimento de complicações infecciosas em pacientes submetidos a quimioterapia e TCTH. MÉTODO: Foi realizado um estudo de coorte prospectivo com 89 pacientes adultos e crianças submetidos a quimioterapia e/ou TCTH que internaram na Unidade de Ambiente Protegido (UAP) do Hospital de Clinicas de Porto Alegre (HCPA). O período de coleta de dados foi de Abril de 2011 a Maio de 2012, e o método foi através de acompanhamento clínico diário e análise de prontuário eletrônico. Foram analisados os desfechos de infecções correlacionados com o perfil clinico e status econômico. RESULTADO: Pacientes com comorbidades foram 35(39,3%). A classe econômica foi classificada A+B igual (37) 41,6% e classe C+D igual (52) 58,6%. Dos pacientes analisados 85,4% apresentaram algum tipo de infecção, sendo as bacterianas as mais frequentes (37) 41,6% e mucosite verificada em (79) 88,8%. Em relação à classe econômica, o grupo C+D apresentou RR 1,2 e P 0,005 para o desfecho infecção. CONCLUSÃO: constatamos que pacientes submetidos à quimioterapia e/ou TCTH com comorbidades apresentam maior risco para infecções, e que o grupo de classe econômica A+B foi associada a menor incidência de infecções e de tempo de internação que a classe C + D durante o período de tratamento. / INTRODUCTION: The infections caused by severe Neutropenia are the most frequent causes of morbidity and mortality in patients undergoing chemotherapy and Hematopoietic Stem Cell Transplantation (HSCT). Besides the extended Neutropenia, other factors like the use of intravenous devices, mucositis, previous clinical conditions, kind of treatment, economic class and length of stay in hospital contribute to the development of infections. The present analysis of these correlations is important to establish the best clinical outcome for these patients. OBJECTIVE: The objective of this study is to verify the clinical profile, the economic conditions and the infectious complications in patients undergoing chemotherapy and HSCT. METHOD: A prospective cohort study was performed with 89 patients, adults and children, undergoing chemotherapy and/or HSCT admitted at the Unit of Protected Environment (UAP) at the Hospital de Clínicas de Porto Alegre (HCPA). The data were collected from April 2011 to May 2012, through the method of a daily monitoring and analysis of the electronic medical records. The outcomes of infections correlated to the clinical profile and economic status were analyzed. RESULT: Patients with comorbidity represented 39,3%. The economic class was ranked as: A+B equal to 41,6% and class C+D equal to 58,6%. From the analyzed patients, 84,5 % presented some kind of infection, with more frequency to the bacterial infection (41,6%) and mucositis representing 88,8%. In relation to the economic class the C+D group presented RR 1,2 and P 0,005 to the outcome of the infection. CONCLUSION: We concluded that patients undergoing chemotherapy and/or HSCT with comorbidities presented a higher risk of infection, and that the A+B economic class was associated to a lower incidence of infections and length of stay in hospital than the class C+D during the period of treatment.

Base teórica: A infecção pelo HIV tornou-se uma doença crônica com o uso de terapia antiretroviral combinada, e a expectativa de vida de pessoas vivendo com HIV aproxima-se da população geral. Entretanto, à medida que a população com HIV envelhece, um número elevado de comorbidades crônicas é descrito. Objetivo: comparar a prevalência de multimorbidade entre indivíduos HIV-positivos e controles HIV-negativos. Métodos: Em um estudo transversal, pacientes HIV-positivos com idade superior a 50 anos foram selecionados no Hospital de Clínicas de Porto Alegre (HCPA) e pareados a controles da Unidade Básica de Saúde do HCPA. A prevalência de multimorbidade e o número de comorbidades crônicas foi comparada entre os grupos. Um modelo de regressão foi utilizado para analisar fatores associados a ocorrência de multimorbidade na amostra de pacientes com HIV Resultados: Foram incluídos 416 pacientes no estudo. A prevalência de multimorbidade foi maior em pacientes com HIV (63% vs 43%, p<0.001). O número médio de comorbidades nos pacientes HIV-positivos e HIV-negativos foi de 2 e 1.4, respectivamente (p<0.001). A quantidade de comorbidades crônicas em pacientes com HIV foi comparável a controles 10 anos mais velhos. Duração de infecção pelo HIV (p=0.02) e de terapia antiretroviral (p=0.015) foram associadas a maior prevalência de multimorbidade, após ajuste para idade. Conclusão: Demonstramos maior prevalência de multimorbidade em pacientes com HIV. Além disso, as comorbidades estão presentes em pacientes com HIV em idades inferiores em comparação aos controles. Duração da terapia antiretroviral e de infecção pelo HIV estão associadas à ocorrência de multimorbidade. Uma rede de cuidado necessitará ser construída para manejo adequado da população que envelhece com HIV. / Background: HIV became a chronic disease with the use of combined antiretroviral therapy (cART), with life expectancy approaching that of general population. However, as HIV individuals are ageing, a large number of chronic comorbidities are being reported. Objective: The aim of this study was to compare disease burden between HIV-positive individuals with non-HIV matched controls in Brazil. Methods: In a cross-sectional study, 1:1 ratio, HIV-positive patients older than 50 years of age were enrolled at Hospital de Clínicas de Porto Alegre. HIV negative controls were from the Health Basic Unit. Prevalence of multimorbidity and number of non-AIDS related comorbidities were compared between groups. A regression model was used to analyze multimorbidity risk factors in HIV individuals Results: A total of 416 individuals were recruited. Multimorbidity prevalence was higher in HIV-positive patients (63% vs 43%, p<0.001). The mean number of comorbidities in HIV population and in HIV-negative controls was 2 and 1.4, respectively (p<0.001). Disease burden in HIV patients was comparable to that of patients 10 years older in the control group. After adjusting for age, duration of HIV infection (p=0.02) and time on ART (p=0.015) were associated with greater prevalence of multimorbidity in HIV-positive individuals. Conclusion: We demonstrate a high multimorbidity prevalence in HIV-positive patients. Furthermore, these comorbidities were present at younger age compared to non-HIV controls. Length of cART exposure and duration of HIV infection were associated with multimorbidity in HIV individuals. The world will need to construct a network to deal with the ageing of HIV population.

L’épidémiologie du VIH est en train de changer. Une nouvelle population, vieillissant avec le VIH, émerge et devrait prendre une place considérable dans les années futures. Les comorbidités liées à l’âge (CLA) sont nombreuses dans cette population et peu d’études évaluent leur impact conjointement. La création d’index pronostique dans cette population est une priorité de recherche. Les objectifs de cette thèse étaient donc d’étudier chez les patients vivant avec le VIH (PVVIH) âgés de 60 ans ou plus, la prévalence des principales CLA, d’identifier celles prédictives de la mortalité globale ou de l’excès de mortalité liée au VIH sur 5 ans, et de construire et réaliser la validation interne d’un score prédictif de mortalité sur 5 ans associant CLA et facteurs liés au VIH. Pour cela nous avons constitué une cohorte de 1415 PVVIH âgés de 60 ans ou plus, suivis entre 2008 et 2013 issus de la cohorte nationale française Dat’AIDS. Nous montrons que les CLA sont nombreuses chez les PVVIH âgés, et qu’elles impactent la mortalité globale ainsi que la mortalité liée au VIH. Les maladies cardiovasculaires et la maladie rénale chronique méritent une attention toute particulière du fait de leur prévalence et de leur impact. Le développement d’un score de comorbidités prédictif de la mortalité sur 5 ans, simple et discriminant, concernant une population qui sera considérable dans les années futures, pourra sous réserve de sa validation externe être utile au clinicien pour l’évaluation du rapport bénéfice-risque, et au chercheur pour stratifier une population par groupe de risque de mortalité ou pour évaluer l’impact d’une intervention dans un groupe particulier. / The epidemiology of HIV is changing. A new population, aging with HIV, is emerging and is expected to take a significant place in future years. Age-related comorbidities (ARC) are numerous in this population and few studies evaluate their impact simultaneously. The validation of prognostic indexes in this population is a research priority. The objectives of this thesis were therefore to study, in people living with HIV (PLHIV) aged 60 or over, the prevalence of the main CLAs, to identify those predictive of overall mortality or HIV-related excess mortality over 5 years, and to construct and carry out the internal validation of a 5-year mortality prediction score associating CLA and HIV-related factors. For this purpose, we selected, from the French national Dat'AIDS cohort, 1415 PLHIV aged 60 or older followed between 2008 and 2013. We showed that CLA are numerous in older PHAs, and that they impact overall mortality as well as HIV-related mortality. Cardiovascular disease and chronic renal disease deserve special attention because of their prevalence and impact. The development of a simple and discriminating 5-year mortality comorbidity-based prediction score for a population that will be considerable in future years may, once externally validated, be useful to the clinician for the evaluation of the risk-benefit ratio, and to the researcher to stratify a population by mortality-risk groups or to assess the impact of an intervention in a particular group.

A epidemia do HIV/AIDS vive o final de sua terceira década acompanhada de avanços importantes na terapia e na sobrevida dos pacientes infectados. Com o advento das drogas antiretrovirais altamente ativas transformou-se em uma condição crônica capaz de ser controlada por muito tempo. Com isso surgiram mudanças no quadro clínico geral e oral dos pacientes. Algumas comorbidades e alterações hematológicas passaram tornaram-se mais prevalentes nessa população, enquanto que as manifestações bucais oportunistas passaram a ser mais raras. Uma vez que o paciente HIV positivo hoje no Brasil vive mais tempo, espera-se que a demanda destes pacientes aumente nos consultórios odontológicos. Torna-se importante que o cirurgião dentista conheça o atual perfil do paciente HIV positivo, as condições bucais e as comorbidades mais freqüentes, especialmente as que exigem mudanças no manejo clínico odontológico. Desta forma, os objetivos deste trabalho foram determinar as prevalências de comorbidades, alterações hematológicas e manifestações bucais em pacientes HIV positivos atendidos no CAPE-FOUSP, correlacionando-as entre si na busca de marcadores bucais para alterações sistêmicas e verificar a correlação entre as prevalências encontradas com os dados demográficos e com o estado imunológico do paciente. Para tanto, estudamos prospectivamente 138 pacientes HIV positivos atendidos no Centro de Atendimento a Pacientes especiais da FOUSP. A presença de comorbidades foi relatada por 92% dos pacientes. O hemograma solicitado revelou alterações hematológicas, que muitas vezes eram desconhecidas por eles. Pelo menos uma manifestação orofacial relacionada com a infecção pelo HIV foi observada em 54% dos pacientes, sendo a mais freqüente o aumento de glândulas salivares, observado em 16,7% dos pacientes. Leucoplasia pilosa e candidíase bucal ainda podem ser considerados importantes marcadores da progressão da doença. Xerostomia e cáries pareceram ter relação com maiores prevalências de hipertensão e desordens psiquiátricas, respectivamente, sugerindo que possam ser marcadores bucais para estas comorbidades. / HIV/AIDS epidemic lives the end of its third decade followed by important advances in the therapy and life expetancy of the infected patients. With the advent of highly active antiretroviral therapy (HAART), HIV/AIDS was been transformed into a chronic condition that can be managed over time. Consequently, several changes in the general and oral clinical status were observed. Some comorbidities and hematological alterations became more prevalent in this population, while opportunist buccal manifestations had started to be rare. Once Brazilian HIV-positive patients are living more time, is expected that the demand of these patients increases in the dental office. Is important for the dentist to know the current profile of HIV-positive patient, which includes: the associated oral conditions and the most frequent comorbities, specially that ones that demand changes in the dental management. Based on this, the objectives of this research were to identify buccal alterations, comorbidities and hematological alterations, searching for correlation between them, to analize them according to demographic data and immunologic status. For this study, 138 HIV-positive patients of Special Care Dentistry Center of Sao Paulo University (CAPE-FOUSP) were analized prospectively. The presence of comorbidities was related by 92% of the patients. The requested hematological exams disclosed several hematologic alterations, many times unknown by them. At least one HIV-related orofacial manifestation was observed in 54% of the patients. Hairy leukoplakia and oral candidiasis still can be considered important markers of the progression of HIV infection. Xerostomia and dental caries was more often observed in patients with hypertension and psychiatric desorders, respectively, suggesting that they can be buccal markers for these comorbidities.

A síndrome de Down (SD) é a mais comum doença de origem genética, causada pela trissomia do cromossomo 21 e caracterizada por comprometimento intelectual, alterações físicas e várias comorbidades sistêmicas. O objetivo deste trabalho foi de avaliar as alterações sistêmicas e comportamentais de interesse odontológico nos pacientes com SD e discutir a adequação no manejo odontológico frente às comorbidades apresentadas. Foram analisados 52 pacientes com SD em atendimento no CAPE-FOUSP. Os responsáveis foram entrevistados com relação às alterações sistêmicas, com base em um questionário desenvolvido especificamente para esta pesquisa. Foram pesquisadas as seguintes alterações: cardíacas, respiratórias, neurológicas e comportamentais, imunológicas, hematológicas, endócrinas (disfunção da glândula tireóide e diabetes mellitus), doenças infecciosas e articulares. Os pacientes realizaram exames complementares, como a aferição da pressão arterial, do IMC e da glicemia capilar e os seguintes exames laboratoriais: hemograma, coagulagrama, hormônio tireotrófico (TSH), tri-iodotironina total (T3 total), tiroxina livre (T4 livre), tiroxina total (T4 total), colesterol total e frações, triglicerídeos, hemoglobina glicosilada, sorologia para hepatite B e C, aspartato aminotransferase (AST), alanina aminotransferase (ALT). Os resultados mostram que as alterações sistêmicas mais freqüentes foram as respiratórias, sendo a pneumonia a mais comum e sua incidência era inversamente proporcional à idade dos pacientes, seguida pelas alterações cardíacas, sendo que 13 pacientes apresentaram apenas uma, e 4 apresentaram múltiplas alterações; e o sopro foi a doença cardíaca mais relatada. Dentro das alterações neurológicas e comportamentais, 37 pacientes apresentavam pelo menos uma das características do início da doença de Alzheimer. Dez pacientes apresentaram hipotireodismo, 7 pacientes hipotireoidismo subclínico, 3 pacientes estado de pré-diabetes, dois pacientes estado de pré-hipertensão. Os níveis de colesterol total estavam dentro dos padrões desejáveis em 36 pacientes, assim como os triglicerídeos em 42 pacientes, com correlação inversa ao índice de massa corporal que apresentou 37 pacientes com sobrepeso ou algum grau de obesidade. Analisando o hemograma, foi observado 5 pacientes com anemia e 10 com leucopenia. Pesquisando a vacinação contra hepatite A e B, 24 pacientes foram vacinados para hepatite A, 26 para hepatite B onde 12 pacientes não apresentaram soroconversão frente a vacina. Um paciente foi diagnosticado com hepatite C. Quanto a presença de instabilidade atlato-axial, 8 pacientes relataram sua presença. Podemos concluir que muitas das alterações sistêmicas citadas na literatura estão presentes nos pacientes atendidos no CAPE, mostrando a necessidade de conhecermos a história médica dos pacientes com SD antes de atendê-los no consultório odontológico, e adequando o tratamento de acordo com cada alteração apresentada pelos pacientes tornando seu tratamento seguro e eficaz. / Downs syndrome (DS) is the most common genetic disorder and it is caused by the trissomy of 21 chromosome. It is characterized by mental retardation, physical alterations and several systemic co morbidities. The aim of this study was to evaluate behavior and systemic alterations with dental implications in DS patients and discuss the dental management of these patients. We evaluate 52 patients with DS under dental treatment at the Special Care Dentistry Center of the School of Dentistry, University of São Paulo. The guardians were interviewed about systemic co morbidities based on a special chart developed for this research. The following systemic alterations were analyzed: cardiac, respiratory, neurological and behavior, immunological, hematological, endocrine (thyroid disorders and diabetes), infeccious diseases and joint alterations. Patients were submitted to complementary exams such as : blood pressure and glucose levels, body mass index, CBC, coagulagrama hormone (TSH), total triiodothyronine (T3), free thyroxine (FT4), total thyroxine (T4), total cholesterol and fractions, triglycerides, glycated hemoglobin, serology for hepatitis B and C, aspartate aminotransferase (AST), alanine aminotransferase (ALT). The results show that the most frequent systemic alterations were respiratory alterations, pneumonia being the most common and its incidence was inversely proportional to the age of the patients, followed by cardiac abnormalities, while 13 patients had only one, and four had multiple abnormalities, and the heart murmur was the most frequent cardiac alterations. Within the neurological and behavioral disorders, 37 patients had at least one characteristic of early Alzheimer\'s disease. Ten patients had hypothyroidism, 7 patients had subclinical hypothyroidism, 3 patients state of pre-diabetes, two patients a state of pre-hypertension. The total cholesterol levels were desirable in 36 patients, and triglycerides in 42 patients, with inverse correlation to body mass index. 37 patients showed some degree of overweight or obesity. CBC showed 5 patients with anemia and 10 with leukopenia. 24 patients were vaccinated for hepatitis A, and 26 for hepatitis B, but 12 patients did not show seroconversion against the vaccine. One patient was diagnosed with hepatitis C. As the presence of atlanto-axial instability, eight patients reported their presence. We can conclude that many of the systemic alterations reported in the literature are present in patients with DS seen at CAPE. It is necessary for the dentist to know the medical history of patients with SD before the dental treatment, and it is necessary to adjust the treatment according to each systemic alterations presented by patients in order to provide a safe and effective treatment.

A síndrome de Down (SD) é a mais comum doença de origem genética, causada pela trissomia do cromossomo 21 e caracterizada por comprometimento intelectual, alterações físicas e várias comorbidades sistêmicas. O objetivo deste trabalho foi de avaliar as alterações sistêmicas e comportamentais de interesse odontológico nos pacientes com SD e discutir a adequação no manejo odontológico frente às comorbidades apresentadas. Foram analisados 52 pacientes com SD em atendimento no CAPE-FOUSP. Os responsáveis foram entrevistados com relação às alterações sistêmicas, com base em um questionário desenvolvido especificamente para esta pesquisa. Foram pesquisadas as seguintes alterações: cardíacas, respiratórias, neurológicas e comportamentais, imunológicas, hematológicas, endócrinas (disfunção da glândula tireóide e diabetes mellitus), doenças infecciosas e articulares. Os pacientes realizaram exames complementares, como a aferição da pressão arterial, do IMC e da glicemia capilar e os seguintes exames laboratoriais: hemograma, coagulagrama, hormônio tireotrófico (TSH), tri-iodotironina total (T3 total), tiroxina livre (T4 livre), tiroxina total (T4 total), colesterol total e frações, triglicerídeos, hemoglobina glicosilada, sorologia para hepatite B e C, aspartato aminotransferase (AST), alanina aminotransferase (ALT). Os resultados mostram que as alterações sistêmicas mais freqüentes foram as respiratórias, sendo a pneumonia a mais comum e sua incidência era inversamente proporcional à idade dos pacientes, seguida pelas alterações cardíacas, sendo que 13 pacientes apresentaram apenas uma, e 4 apresentaram múltiplas alterações; e o sopro foi a doença cardíaca mais relatada. Dentro das alterações neurológicas e comportamentais, 37 pacientes apresentavam pelo menos uma das características do início da doença de Alzheimer. Dez pacientes apresentaram hipotireodismo, 7 pacientes hipotireoidismo subclínico, 3 pacientes estado de pré-diabetes, dois pacientes estado de pré-hipertensão. Os níveis de colesterol total estavam dentro dos padrões desejáveis em 36 pacientes, assim como os triglicerídeos em 42 pacientes, com correlação inversa ao índice de massa corporal que apresentou 37 pacientes com sobrepeso ou algum grau de obesidade. Analisando o hemograma, foi observado 5 pacientes com anemia e 10 com leucopenia. Pesquisando a vacinação contra hepatite A e B, 24 pacientes foram vacinados para hepatite A, 26 para hepatite B onde 12 pacientes não apresentaram soroconversão frente a vacina. Um paciente foi diagnosticado com hepatite C. Quanto a presença de instabilidade atlato-axial, 8 pacientes relataram sua presença. Podemos concluir que muitas das alterações sistêmicas citadas na literatura estão presentes nos pacientes atendidos no CAPE, mostrando a necessidade de conhecermos a história médica dos pacientes com SD antes de atendê-los no consultório odontológico, e adequando o tratamento de acordo com cada alteração apresentada pelos pacientes tornando seu tratamento seguro e eficaz. / Downs syndrome (DS) is the most common genetic disorder and it is caused by the trissomy of 21 chromosome. It is characterized by mental retardation, physical alterations and several systemic co morbidities. The aim of this study was to evaluate behavior and systemic alterations with dental implications in DS patients and discuss the dental management of these patients. We evaluate 52 patients with DS under dental treatment at the Special Care Dentistry Center of the School of Dentistry, University of São Paulo. The guardians were interviewed about systemic co morbidities based on a special chart developed for this research. The following systemic alterations were analyzed: cardiac, respiratory, neurological and behavior, immunological, hematological, endocrine (thyroid disorders and diabetes), infeccious diseases and joint alterations. Patients were submitted to complementary exams such as : blood pressure and glucose levels, body mass index, CBC, coagulagrama hormone (TSH), total triiodothyronine (T3), free thyroxine (FT4), total thyroxine (T4), total cholesterol and fractions, triglycerides, glycated hemoglobin, serology for hepatitis B and C, aspartate aminotransferase (AST), alanine aminotransferase (ALT). The results show that the most frequent systemic alterations were respiratory alterations, pneumonia being the most common and its incidence was inversely proportional to the age of the patients, followed by cardiac abnormalities, while 13 patients had only one, and four had multiple abnormalities, and the heart murmur was the most frequent cardiac alterations. Within the neurological and behavioral disorders, 37 patients had at least one characteristic of early Alzheimer\'s disease. Ten patients had hypothyroidism, 7 patients had subclinical hypothyroidism, 3 patients state of pre-diabetes, two patients a state of pre-hypertension. The total cholesterol levels were desirable in 36 patients, and triglycerides in 42 patients, with inverse correlation to body mass index. 37 patients showed some degree of overweight or obesity. CBC showed 5 patients with anemia and 10 with leukopenia. 24 patients were vaccinated for hepatitis A, and 26 for hepatitis B, but 12 patients did not show seroconversion against the vaccine. One patient was diagnosed with hepatitis C. As the presence of atlanto-axial instability, eight patients reported their presence. We can conclude that many of the systemic alterations reported in the literature are present in patients with DS seen at CAPE. It is necessary for the dentist to know the medical history of patients with SD before the dental treatment, and it is necessary to adjust the treatment according to each systemic alterations presented by patients in order to provide a safe and effective treatment.

Les thérapeutiques antirétrovirales ont permis d’augmenter la survie des personnes vivant avec le VIH (PVVIH). Cependant, de nombreuses comorbidités non liées au VIH émergent et sont une préoccupation majeure dans la prise en charge des patients. L’activation, l’inflammation et l’immunosénescence pourraient jouer un rôle majeur dans ce processus. De nombreux marqueurs existent pour mesurer ces dysfonctionnements et ils ont souvent été considérés sans prendre en compte leurpossible interdépendance. Les objectifs de cette thèse était i) de proposer une combinaison de ces marqueurs, ii) d’évaluer l’association entre la combinaison de ces marqueurs et la présence des comorbidités, et iii) d’évaluer l’association entre la combinaison de ces marqueurs, et le risque de survenue des comorbidités et de la mortalité chez des PVVIH inclus dans la sous étude CIADIS de la cohorte ANRS CO3 Aquitaine. Nous avons identifié deux scores : le score CIADIS cellulaire et soluble. Le score cellulaire était plutôt associé à la multimorbidité et à la survenue d’une nouvelle comorbidité quelle qu’elle soit. Le profil des dysfonctionnements immunitaires sous-jacent était différent lorsque l’on s’intéressait aux comorbidités séparément. Ces résultats soutiennent l’hypothèse que différents profils d’activation, d’inflammation et de sénescence sous-jacents pourraient être impliqués dans le développement de différentes comorbidités. Nos résultats montrent que des analyses intégrant de nouveaux biomarqueurs pourraient accroître la compréhension des comorbidités. Nous allons continuer de travailler sur l’identification des profils de dysfonctionnements immunitaires pour des comorbidités spécifiques. / Antiretroviral therapies have improved the survival of HIV-infected people. However, many non-HIVrelated comorbidities occur and represent a major concern in patient care. Activation, inflammation and immunosenescence could play a major role in this process. Many markers can measure those dysfunctions and they are often used without accounting for their possible interdependency. The objectives of this thesis were i) proposing a combination of those markers, ii) assessing the association between the combination of markers and the presence of comorbidities and iii) assessing the association between the combination of markers and the risk of occurrence of comorbidities and mortality in HIV-infected patients included in the sub-study CIADIS from cohort ANRS CO3 Aquitaine. We identified two scores: the cellular and the soluble CIADIS scores. The cellular score was mostly to multimorbidity and occurrence of any kind of new comorbidity. The profile of underlying immune dysfunctions was different when looking separately at the comorbidities. These results support the assumption that several underlying profiles of activation, inflammation and senescence could be involved in the development of different comorbidities. Our results show that integrating new biomarkers in analyses could improve the understanding of comorbidities. We will continue to work on the identification of profiles of immune dysfunctions for some specific comorbidity.

Identifying depressive symptoms in community-dwelling elders has been problematic, due to a lack of resources and training for health clinicians. Previous researchers have indicated that older adults who engage in physical activities can prevent, or mitigate depression, but no model has included this variable in conjunction with factors such as lifestyle or sociodemographic characteristics. In this study, a predictive design was used with a regression analysis. The purpose of this quantitative study was to investigate the relationship between depressive symptoms and the different factors identified in the literature as significant contributors to its prevalence among older community-dwelling adults. Erikson's theory of psychosocial development, Beck's cognitive model of depression, and the learned helplessness model were used as the theoretical foundations to determine whether lifestyle activities, perceived social support, sociodemographic variables, and comorbidities can predict depressive symptoms. The sample consisted of 156 older adults who were 60 years of age and older and living in Northern Louisiana. Pearson correlation analysis and multiple regression analyses were used to investigate whether (a) daily lifestyle activities, (b) community setting (rural or urban), (c) gender, (d) perceived social support, (e) marital status, and (f) comorbidities can predict depressive symptoms. The 2 primary predictors of depression among older adults were low activity levels and low perceived social support. Positive social implications include improving counselors' and mental health practitioners' knowledge of the ways to lessen the depressive symptoms experienced by the elderly population.

Background: Diabetic foot ulcers are the result of multiple complications from hyperglycemia and lead to poor quality of life and high healthcare costs. The annual diabetes foot screening exam (ADFSE) and prevention interventions can reduce DFUs up to 75%. In 2015, 71% of the US population received the ADFSE. Objectives: The main objectives of this dissertation were: 1) to determine the association between adherence to diabetes self-management behaviors and the ADFSE, 2) to determine the association between concordant and discordant comorbidities and the ADFSE and 3) to determine the association between the performance of diabetes preventive care processes, number of office visits for diabetes and the completion of the ADFSE. Methods: Three cross-sectional studies used data from the 2015 Behavioral Risk Factor Surveillance System. Logistic regression models were evaluated to assess the association between the self-management behaviors and the ADFSE. Structural equation modeling (SEM) was used to assess the simultaneous, direct effects of concordant and discordant comorbidity loads on the ADFSE and the performance of diabetes preventive care processes and the number of office visits for diabetes care on the ADFSE. Results: In 2015, between 78.2% and 80.4% of the US population with diabetes received the ADFSE. Performance of the ADFSE was 77% less likely (OR: 0.33, 95%CI: 0.25-0.44) in those who do not perform self-foot inspections and 40% (OR: 0.59, 95%CI: 0.45-0.76) less likely in those who have never received the pneumococcal vaccination. Receiving the ADFSE was 50-80% less likely in patients who do not self-monitor blood glucose at least one time per day, depending on insulin use and receipt of diabetes education. Neither concordant comorbidities (β=0.226, p=0.086) nor discordant comorbidities (β=0.080, p=0.415) had a direct association with the performance of the ADFSE. The collection of preventive care processes demonstrated a 7% (OR: 1.07, 95% CI: 1.05-1.10) increase in the likelihood the ADFSE was performed Conclusions: Performance of the ADFSE may be improved through multiple types of interventions. Patient-based interventions to increase adherence to self-management behaviors is one route. Programs to improve overall diabetes care in the clinical setting may also help to further improve completion of the ADFSE.

Development of a Tool for Pressure Ulcer Risk Assessment and Preventive Interventions in Ancillary Services Patients Monica S. Messer Abstract The incidence of nosocomial pressure ulcers has increased 70 percent in U.S. hospitals over the past 15 years despite implementation of preventive guidelines and the wide-spread use of validated risk assessment tools. Most preventive efforts have been focused primarily on patients who are bed-ridden or immobile for extended periods. What has not been well studied or identified is the risk for pressure injury to patients undergoing diagnostic procedures in hospital ancillary units where extrinsic risk factors such as high interface pressures on procedure tables and friction and shear from positioning and transport can greatly magnify the effect of patient-specific intrinsic risk factors which might not otherwise put these patients at high risk on an inpatient unit. The purpose of this study was to develop a risk assessment tool designed explicitly to quantify the combination of these intrinsic and extrinsic risk factors in individual patients undergoing ancillary services procedures, and to identify targeted preventive interventions based on the individual level of risk. Empirically and theoretically-derived risk factors for the tool were tested in a nation-wide hospital database of over 6 million patient discharge records using bivariate and multivariate analysis to identify significant predictors of pressure ulcer outcomes. The statistically significant factors emerging were then used to develop the risk assessment scale. These predictors included; advanced age, diabetes, human immunodeficiency virus infection, sepsis, and fever. The scale was tested for internal validity using the split-sample cross-validation method, and for accuracy using the area under the Receiver Operating Characteristics curve. The optimum score cut point was identified to provide a predictive accuracy of 71 percent. Interventions for the tool were identified from national clinical practice guidelines and aligned in sets based on patient levels of risk identified by the scoring portion of the tool. The entire tool was evaluated for content validity by a panel of five international nurse experts in pressure ulcer prevention and tool development. The content validity index calculated from their ratings was .91 indicating excellent agreement on content validity.