Introduction: Research suggests that patients with head and neck cancer from poorer backgrounds are more likely to have recurrences or die earlier than similar patients from affluent backgrounds. Survival is influenced by tumour characteristics on presentation and a range of individual factors such as socioeconomic status and comorbidity. Deprived patients of more advanced age have a higher likelihood of having comorbidity; this may be due to high-risk lifestyle behaviours such as smoking and drinking. Therefore, it seems reasonable to assume that survival will be lower in these deprived patients which can be attributed to comorbidity compared to index diseases such as the head and neck cancer itself. Survival rates for head and neck cancer patients are approximately 50% in the first five years in Scotland. This is dependent on a range of individual and tumour-related factors such as head and neck cancer sub-type and stage at diagnosis. The risk of head and neck cancer developing in deprived patients has been likened to that of developing head and neck cancer in heavy smokers. While the relationship between deprivation and comorbidity in head and neck cancer has been established, how both factors affect survival is yet to be explored. Reviewing these two factors individually has demonstrated the need to assess how both interact with each other in determining clinical presentation and survival. Aim: The aims of this thesis are:- 1. To investigate the roles and interrelationship between comorbidity and deprivation on the survival of HNC patients. 2. To investigate whether there are differences in HNC presentation based on comorbidity and deprivation. 3. To ascertain whether patients from deprived backgrounds with comorbidity present with more advanced cancers. Methods: In order to answer the research questions, this project began by describing the index disease, HNC and how comorbidity and deprivation are placed within the epidemiology of this disease using systematic review methods. The rationale for embarking upon this study was highlighted. Data linkage of administrative datasets We used anonymised patient data that was accessed through an encrypted repository held by the Health Informatics Centre. The data that was used in the retrospective cohort analysis was obtained from a prospective dataset collected by the Fife Head and Neck cancer Specialist Nurse (Fife data) and a retrospective case note review from the Tayside oncology records held by the Ear Nose and Throat Department and the Oral and Maxillofacial Surgery team. Thereafter we matched the patient data with that from routine medical datasets such the Scottish Morbidity Records, SMR01- inpatient discharges and SMR06 – Cancer Registry data. We conducted survival analysis methods with the intent of assessing the impact of both comorbidity and deprivation in determining survival. Results: The systematic review found that worsening levels of comorbidity were linked to reduced survival whereas patients with low incomes and poor educational attainment also had poor survival outcomes. Being young and having severe comorbidity appeared to also be associated with poorer survival. In the retrospective cohort analysis, the level of association between risk of death with comorbidity and deprivation could not be clearly ascertained in the patients from Fife. The Tayside data to a larger extent supported the systematic review findings particularly for the comorbidity measures with clearly defined measures of association for the Scottish Index of Multiple Deprivation income and education domains. Conclusions: This thesis was able to use evidence triangulation by way of a systematic review of the literature followed by a retrospective cohort analysis to investigate what influence on prognosis both comorbidity and deprivation posed in patients with head and neck cancer. There was substantiation of both factors interacting with head and neck cancer to cause a significantly reduced impact on survival. The inherent difficulties of measuring socioeconomic status and comorbidity encountered in this thesis may go some way towards illustrating the complexity and multifaceted nature of both comorbidity and socioeconomic status; particularly the quite complex interplay between socioeconomic status, comorbidity, stage at diagnosis, and access to care in head and neck cancer, and these factors’ ultimate impact on survival. We found that socioeconomic status i.e. deprivation, comorbidity, stage at diagnosis, access to care, and survival are all potentially causally related. Future work directed at using administrative data linked to medical records would not be sufficient; there is need for epidemiological and clinical studies to unravel the survival disadvantage. To this end clinical cohorts could be nested within larger registry based studies which would allow for uniform interventions based on clinical practice guidelines, uniform SES measurement and ascertainment of comorbidity using a head and neck cancer comorbidity index, i.e. the Washington University Head and Neck Cancer Index.

Anualmente são realizadas mais de 234 milhões de cirurgias no mundo com taxas de morbi e mortalidade relativamente elevadas. Os dados nacionais disponíveis de registros de operações não cardíacas são escassos e deficientes. O objetivo do nosso estudo foi avaliar o perfil epidemiológico dos pacientes submetidos a operações não cardíacas e a sua evolução nos últimos anos no Brasil. Selecionamos a partir do banco de dados de DATASUS, as informações de sistema público de saúde em caráter nacional para descrição epidemiológica de operações não cardíacas realizadas no país. As variáveis estudadas foram: número total de internações, gasto total por internação, gasto com transfusões sanguíneas, número de óbitos e tempo de internação hospitalar. O período estudado compreendeu os anos de 1995 a 2007. No período de 13 anos, foram realizadas 32.659.513 operações não cardíacas no país e houve um incremento de 20,42% no número de procedimentos realizados. De forma semelhante, os gastos hospitalares relacionados a estas cirurgias apresentaram aumento importante neste período (~ 200%), com gasto anual superior a 2 bilhões de reais. As despesas relacionadas às transfusões sanguíneas no perioperatório tiveram um aumento superior a 100%, com um gasto anual acima de 17 milhões de reais ao ano. A mortalidade hospitalar encontrada é bastante elevada no nosso país, com média de 1,77% e o aumento registrado foi mais de 30% no período. A única variável que apresentou redução ao longo dos últimos anos foi o tempo de internação hospitalar, com a média de permanência de 3,83 dias. Concluímos que há uma tendência no aumento de intervenções cirúrgicas no país. Apesar do aumento dos gastos hospitalares relacionados a estas cirurgias, a taxa de mortalidade encontrada ainda é bastante elevada. Estudos futuros são necessários para maior investigação e elaboração de estratégias complementares para melhorar os resultados cirúrgicos / Worldwide, there were performed about 234 millions of surgeries annually with a relatively high surgical morbidity and mortality. Registry and information about non-cardiac operations in Brazil are scarce and deficient. The purpose of our study was to describe the epidemiological data of non-cardiac surgeries performed in Brazil in the last years. This is a retrospective cohort study that investigated the time-window from 1995 to 2007. We collected information from DATASUS, a national public health system database. The variables studied were: number of surgeries, in-hospital expenses, blood transfusion related costs, length of stay and case fatality rates. There were 32.659.513 non-cardiac surgeries performed in Brazil in thirteen years. An increment of 20.42% was observed in the number of surgeries in this period. The cost of these procedures has increased tremendously in the last years. The increment of surgical cost was almost 200% and the yearly cost of surgical procedures to public health system was superior to 1.2 billions of dollars (2 billions of reais). The cost of blood transfusion had an increment superior to 100% and annually approximately 10 millions of dollars (17 millions of reais) were spent in perioperative transfusion. Actually, in 2007, the surgical mortality in Brazil was 1.77% and it had an increment of 31.11% in the period of 1995 to 2007. The length of stay was the unique variable which had a reduction of its numbers in the period. In average, the mean time of surgical hospitalization was 3.83 days. We concluded that the volume of surgical procedures has increased substantially in Brazil through the past years. The expenditure related to these procedures and its mortality has also increased as the number of operations. Better planning of public health resource and strategies of investment are needed to supply the crescent demand of surgery in Brazil

Submitted by Rosina Valeria Lanzellotti Mattiussi Teixeira (rosina.teixeira@unisantos.br) on 2015-04-06T13:58:03Z No. of bitstreams: 1 Jacqueline Barauna.pdf: 1067134 bytes, checksum: cdefd02bc846a4c5ece8b033aa28624a (MD5) / Made available in DSpace on 2015-04-06T14:02:50Z (GMT). No. of bitstreams: 1 Jacqueline Barauna.pdf: 1067134 bytes, checksum: cdefd02bc846a4c5ece8b033aa28624a (MD5) Previous issue date: 2014-08-18 / Foods have the purpose of providing energy to the human body and the material for the formation and maintenance of tissues , while governing the functioning of the organs. The regions Cubatao( pylons and center ), Saint Vincent and Guaruja houses an industrial center with numerous basic industries. Through improper disposal, eventually releasing chemical origin of environmental contaminants in air , water and soil , that only in the 1980s , were detected and identified as : heavy metals , organochlorines , dioxins and furans. These contaminants can cause harmful effects and adverse acute (short-term), chronic ( ong term) and late ( through generations) to human health . The aim of this study was to evaluate the use of terrestrial and aquatic food from contaminated areas of the 4 regions: Drumsticks (Cubatao), Centro (Cubatao) , São Vicente , Guarujá and Bertioga (control region) , and its association with the prevalence of morbidity above. This cross-sectional study in 820 households per study area , considering the number of households per census tract . The test of proportions for qualitative variables and descriptive analysis of the sociodemographic variables was applied. There was a statistically significant difference in the consumption of food from contaminated and morbidities mainly in foods of aquatic origin, which undergo bioaccumulation and biomagnification through the food chain areas. / Os alimentos possuem a finalidade de fornecer ao corpo humano a energia e o material destinados à formação e manutenção dos tecidos, ao mesmo tempo em que regulam o funcionamento dos órgãos.As regiões de Cubatão (Pilões e Centro), São Vicente e Guarujá abriga um polo industrial com inúmeras indústrias de base. Através de descarte inadequado, acabaram por lançar contaminantes ambientais de origem química no ar, água e solo, que somente na década de 1980, foram detectados e identificados como: metais pesados, organoclorados, dioxinas e furanos. Estes contaminantes podem causar efeitos danosos e adversos agudos (curta duração), crônicos (longa duração) e tardios (atravessa gerações)á saúde humana. O objetivo deste estudo foi avaliar o consumo de alimentos terrestres e aquáticos provenientes de áreas contaminadas das 4regiões: Pilões (Cubatão), Centro (Cubatão), São Vicente, Guarujá e Bertioga (região controle), e sua associação com a prevalência de morbidade referida. Trata-se de estudo transversal feito em 820 domicílios por área estudada, considerando o número de domicílios existentes por setor censitário. Foi aplicado o teste de proporções para as variáveis qualitativas e análise descritiva das variáveis sóciodemográficas. Houve diferença estatisticamente significativa para o consumo de alimentos provenientes de áreas contaminadas e morbidades referidas principalmente em alimentos de origem aquática, os quais sofrem bioacumulação e biomagnificação através da cadeia alimentar. Palavras-Chave: alimentos contaminados, morbidade referida

Submitted by Rosina Valeria Lanzellotti Mattiussi Teixeira (rosina.teixeira@unisantos.br) on 2016-08-11T15:01:51Z No. of bitstreams: 1 Vanessa Luna Araujo Teotonio.pdf: 1901452 bytes, checksum: a6084bb09e1976d5f834c827781a1d4f (MD5) / Made available in DSpace on 2016-08-11T15:01:51Z (GMT). No. of bitstreams: 1 Vanessa Luna Araujo Teotonio.pdf: 1901452 bytes, checksum: a6084bb09e1976d5f834c827781a1d4f (MD5) Previous issue date: 2016-05-25 / New HIV-positive cases enhanced 11% from 2005 to 2013 in Brazil. However, there was difference in distribution and evolution between Brazilian regions from 2003 to 2014, increasing 79.7% in Northern region, 30% in Northeastern region, 6.4% in Southern region and 6% in the Midwestern- region; decreasing 26.5% in Southeastern region. According to DATASUS 2014 database, is was also observed an increase in the incidence of tuberculosis (TB) associated with HIV in Brazil. There were 4,905 new registered coinfected cases in 2000, and 6,821 new cases in 2012. HIV infection is one of the main risk factors of TB latent reactivation, due lacking immune response. TB/HIV coinfection induces higher mortality than isolated HIV infection. Given the importance of TB/HIV co-infection, we aimed to analyze space-temporal distribution of TB/HIV coinfection in Brazilian regions from 2003 to 2013. The methods used the ecological study from SINAN secondary data of patients reported with TB/HIV in Brazil in the 2003-2013 periods. The dependent variables were incidence and prevalence rates; proportions of deaths caused by the TB, of tuberculosis cure and of TB treatment dropout among coinfected TB/HIV; and as independent variables, were used socio-demographic characteristics such as gender and age group. The analysis was performed with the estimate of the relative risk for Poisson multilevel analysis, with significance level of 5%. The identification of spatial and space-temporal clusters were conducted through ArcGis 10.1. developed by Esri. The results detected 8% TB/HIV coinfection in Brazil. The highest averages of the incidence and prevalence rates were, respectively, in Southern region (5.92; 8.86 cases/100.000habitants) and Southeastern region (4.38;5.95cases/100.000 habitants). The incidence and prevalence were positively associated to male sex (RR = 3.06) and age 20-59 years old (RR = 11.4), p< 0,001. The highest proportion of death caused by TB in coinfected occurred in Northern region (6.23%), and the lowest in Southern region (2.37%). The TB cure proportion average in TB/HIV coinfection was 46% in Brazil. The highest average of TB cure proportion occurred in Northern region (50%) and the lowest in Northeastern region (41%). The average of TB treatment dropout proportion was 16.5%. The highest average of TB treatment dropout proportion occurred in Northeastern region (18%) and Midwest region had the lowest 13%. The TB cure and TB treatment abandon proportions were negatively associated to the age 20-39 years old (RR = 0.66) and 40-59 years old (RR = 0.71) in relation to younger people. The other group of old people didn¿t present significant statistical association. We conclude that the highest detection rates from TB/HIV coinfection and the worst outcome treatment proportions from TB/HIV coinfection occurred in regions with the worst social and economic levels. After these unfavorable results with regional differences, this study will be useful for planning public health policy in all Brazilian regions. / No Brasil, houve um aumento de 11% dos casos novos de HIV de 2005 a 2013. No entanto, observa-se diferença na distribuição e evolução entre as regiões brasileiras, entre 2003 e 2014, com aumento de 79,7% na região Norte, 30% no Nordeste e 6,4% no Sul e 6% no Centro-Oeste; e redução de 26,5% na região Sudeste. De acordo com dados do DATASUS 2014, observa-se também um aumento na incidência de tuberculose (TB) associada ao HIV no Brasil, com 4.905 casos novos notificados em 2000 e 6.821 em 2012. A infecção por HIV é um dos mais importantes fatores de risco na reativação da primoinfecção por TB, em razão da supressão imunológica. A coinfecção TB/HIV resulta em taxas de mortalidade mais altas do que a infecção isolada do HIV. Diante da relevância da coinfecção TB/HIV, objetivamos analisar a distribuição espaço-temporal da coinfecção TB-HIV nas macrorregiões brasileiras no período de 2003 a 2013. Os métodos utilizados foram por meio de estudo ecológico, a partir dos dados secundários do SINAN, dos pacientes notificados com a coinfecção tuberculose-AIDS no Brasil, no período de 2003-2013. As variáveis de desfecho foram as taxas de incidência, de prevalência, as proporções de óbitos por TB, cura da TB e abandono do tratamento de TB entre os coinfectados TB/HIV; e como variáveis independentes, as características sócio-demográficas como sexo, faixa etária. A estimativa do Risco Relativo foi analisada com modelo multinível de Poisson, com nível de significância adotado de 5%. A identificação dos aglomerados espaciais e espaçotemporais foi feita por meio da ArcGis 10.1 desenvolvido pela Esri. Os resultados encontrados detectaram 8% de coinfecção TB/HIV no Brasil. As maiores médias das taxas de incidência e prevalência, respectivamente, da coinfecção TB/HIV ocorreram nas regiões Sul (5,92; 8,86 casos/100.000hab.) e Sudeste (4,38; 5,95casos/100.000hab.). A incidência e prevalência se associaram positivamente ao sexo masculino (RR = 3,06) e faixa etária 20-59 anos (RR = 11,4), com p < 0,001. A maior proporção de óbito por TB na coinfecção TB/HIV ocorreu na região Norte (6,23%) e a menor na região Sul (2,37%). A média da proporção de cura da tuberculose nos coinfectados no Brasil foi 46%. A maior média da proporção de cura ocorreu na região Norte (50%) e a menor no Nordeste (41%). A média da proporção de abandono do tratamento da tuberculose nos coinfectados do Brasil foi 16,5%, a região com maior proporção de abandono foi a Nordeste (18%) e a menor no Centro-Oeste (13%). As proporções de cura a abandono foram associadas negativamente com idade de 20 a 39 anos (RR = 0,66) e 40 a 59 anos (RR = 0,71) em relação aos mais jovens. As duas categorias de pessoas mais idosas não tiveram associação estatisticamente significativa. Conclui-se que taxas mais altas de detecção da coinfecção são encontradas em regiões com maior nível socioeconômico, piores taxas no desfecho do tratamento da TB na coinfecção ocorreram também em regiões com pior nível socioeconômico. Diante das elevadas taxas de coinfecção por HIV e TB, com desfechos desfavoráveis no tratamento, e das diferenças regionais, a pesquisa servirá de subsídio para o planejamento das políticas públicas nas diversas regiões do Brasil.

Introdução: Os acidentes de transporte terrestre (ATT) são responsáveis por milhares de óbitos e lesões em todo o mundo. Muitas dessas lesões resultam em sequelas que comprometem a capacidade funcional das vítimas desses agravos. As internações e as sequelas representam importante impacto nos serviços de saúde e na sociedade. Entretanto, não é conhecida a prevalência das sequelas decorrentes de ATT e nem os fatores associados às mesmas. Em 2010, a Organização das Nações Unidas estabeleceu o período de 2011 a 2020 como a Década de Segurança Viária, com a meta de estabilizar ou reduzir as mortes decorrentes de ATT nos países membros. Objetivo: Descrever um panorama sobre os ATT ocorridos no Brasil, caracterizando as internações, as sequelas e os óbitos por esta causa, com vistas a contribuir para a vigilância destes agravos. Métodos: Foram realizados quatro estudos: a) estimativa do tempo de permanência e dos gastos das internações em 2013 e análise da morbidade hospitalar no triênio 2011-2013; b) uma revisão sistemática nas bases de dados eletrônicas sobre prevalência de sequelas; c) ecológico de série temporal sobre as internações por ATT com diagnóstico sugestivo de sequelas físicas de 2000 a 2013; e d) descritivo sobre mortalidade por ATT em 2013 e estimativa dos anos potenciais de vida perdidos. Resultados: Ocorreram, em 2013, 170.805 internações por ATT, maior no sexo masculino, na faixa etária de 20 a 39 anos, entre os motociclistas e nas regiões Centro-Oeste e Nordeste. Os gastos em 2013 foram de R$ 231.469.333,13, com 1.072.557 dias de permanência e média de 6,3 dias. As taxas de internação por ATT foram 77,8 (2011), 79,9 (2012) e 85,0 (2013) internações/100 mil habitantes. Foram incluídos quatro artigos na revisão sistemática. A prevalência de sequelas decorrentes do ATT variou de 19 por cento em Yorkshire/Inglaterra a 49,5 por cento em Teresina/Piauí. As referências analisadas não apresentaram caracterização do perfil epidemiológico das vítimas com sequelas por ATT. De 2000 a 2013, ocorreram 1.747.191 internações por ATT. Destas 410.448 pessoas (23,5 por cento ) apresentaram diagnóstico sugestivo de sequelas físicas, sendo a maioria do sexo masculino, da faixa etária de 20 a 29 anos, residentes na Região Sudeste, pedestres e motociclistas. A tendência foi de aumento nas internações por ATT com diagnóstico sugestivo de sequela certeza no sexo masculino e nas regiões Norte e Centro-Oeste. A taxa de mortalidade em 2013 foi de 21,0 óbitos por 100 mil habitantes para o país. A região Centro-oeste apresentou a taxa mais elevada (29,9 óbitos por 100 mil habitantes). A maioria dos óbitos por ATT foi observada no sexo masculino, na raça/cor da pele negra, nos adultos jovens, em indivíduos com baixa escolaridade e entre motociclistas. A taxa de mortalidade no triênio 2011 a 2013 reduziu 4,1 por cento , mas aumentou entre os motociclistas. Em todo o país, mais de um milhão de anos potenciais de vida foram perdidos em 2013 devido aos ATT, especialmente na faixa etária de 20 a 29 anos. Conclusão: O Brasil ainda precisa avançar na temática que envolve os ATT, desde a sua prevenção à reabilitação de suas vítimas. Ressalta-se que para o alcance da meta da Década de Ação para Segurança Viária é necessário que as iniciativas deixem de ser pontuais e sigam para além do setor saúde, pois requerem atuações intersetoriais priorizadas no plano de governo e na agenda da sociedade. / Introduction: Traffic Accidents are responsible for thousands of deaths and injuries in all world. Many these injuries provoke sequelae that compromise the functional capacity of the traffic accidents victims. Hospitalizations and sequelae represent significant impact on health services and society. However, prevalence of sequelae due to traffic accident and his association factors is not known. Objective: Describe a perspective on traffic accidents in Brazil, characterizing hospitalizations, sequelae and deaths due to this event, in order to contribute to traffic accidents surveillance. In 2010, the United Nations established the period 2011-2020 as the \"Decade of Action for Road Safety\" with a goal to stabilize or reduce deaths from traffic accidents in member countries. Methods: Four studies were carried out: a) an estimation of the time and spending on hospitalization in 2013 and an analysis of hospital morbidity during 2011-2013; b) a systematic review of the electronic databases about sequelae prevalence; c) an ecological time series about hospitalizations due to traffic accidents with suggestive diagnostic of physical sequelae, from 2000 to 2013; and d) an descriptive approach about mortality due to traffic accidents and an estimation of years of potential life lost. Results: In 2013, there were 170,805 hospitalizations for traffic accidents, higher in male, 20 to 39 years old, motorcycles and Central-West and Northeast Regions. Direct costs were R$ 231,469,333.13 in 2013, the duration of hospitalization was 1,072,557 days e average permanence in hospital was 6.3 days. Hospitalization rates for traffic accidents were 77.8 (2011), 79.9 (2012) e 85.0 (2013) hospitalization/ 100,000 inhabitants. Four papers were included in this review. The prevalence of physical sequelae among victms of traffic accidents ranged from 19 per cent , in Yorkshire/England, to 49,5 per cent in Teresina/Piauí. The articles studied did not show epidemiological profile of victims with physical sequelae of traffic accident. From 2000 to 2013, there were 1,747,191 hospitalizations due to traffic accidents, whose 410,448 people (23.5 per cent ) showed suggestive diagnostic of physical sequelae, the majority was male, 20 to 29 years old, residents in Southeast Region, pedestrian and motorcyclists. there were significant rising trends in the rates of hospitalizations for confirmed sequel among men and in North and Central-West regions. Mortality rate was 21.0 deaths per 100.000 habitants for the country as a whole. The Central West Region showed the highest rate (29.9 deaths per 100,000 habitants). Most of deaths for traffic accidents were male, black, young adults, low levels of schooling and motorcyclists. Mortality rate in the periods of 2011 to 2013 showed a decrease (- 4.1 per cent ), however this rate increased among motorcyclists. In Brazil, years of potential life lost amounted to 1 million in 2013, mainly in the 20-29 years age group. Conclusion: Brazil needs to make progress in traffic accidents issues, for their prevention and rehabilitation for victims. It is emphasized that to achieve the Decade of Action for Road Safety\'s goal is necessary that initiatives are no transitories and go beyond the health sector, because these strategies require intersectoral actions that are prioritized in the government plan and society agenda.

Les femmes représentent un tiers des personnes vivant avec le VIH en France. Les trois parties de cette thèse visent à explorer les principaux aspects cliniques de la maladie (causes de décès, morbidité grave) ou de la vie des femmes (ménopause) afin d’identifier des recommandations spécifiques pour la prise en charge des femmes dans un contexte d’accès aux soins similaire à celui des hommes.Les causes de décès des femmes infectées par le VIH ont été décrites grâce à l’enquête nationale ANRS EN19, Mortalité 2005. Les femmes décédaient plus fréquemment que les hommes de causes liées au sida (43% vs. 34% chez les hommes). Elles décédaient moins souvent de causes hépatiques (13 % vs. 16%), de cancers non sida-non hépatiques (14% vs. 17%) et de maladies cardiovasculaires (6% vs. 9%). La morbidité grave des patients infectés par le VIH a été étudiée au sein de la Cohorte ANRS CO3-Aquitaine, entre 2000 et 2008. Le taux d’incidence annuelle d’hospitalisation a diminué de moitié entre 2000 et 2008 (146 à 69 pour 1000 PA). Globalement, ce taux ne différait pas entre les femmes et les hommes. Les causes les plus fréquentes de morbidité grave conduisant à une hospitalisation étaient : les infections bactériennes, les événements sida, psychiatriques, hépatiques, hématologiques, infections virales, événements digestifs, infections parasitaires et les événements cardiovasculaires. Toutes ces causes ont eu une baisse de leur incidence annuelle entre 2000 et 2008 chez les hommes et les femmes, exceptés les événements hématologiques (de 2,5 à 15,1 pour 1000 PA), hépatiques (2,5 à11,5) et cardiovasculaires (6,3 à 14,2) qui ont augmenté chez les femmes. L’âge de survenue de la ménopause étudié grâce à une enquête menée au sein de la Cohorte ANRS CO3-Aquitaine était de 49 ans en médiane et 12% des femmes ont eu une ménopause précoce, survenant avant l’âge de 40 ans. L’origine africaine (RR : 8,2) et l’antécédent de toxicomanie IV (RR : 2,5) étaient liés à la survenue plus précoce de la ménopause. En conclusion, les femmes infectées par le VIH en France décèdent plus souvent de sida, mais présentent une morbidité grave caractérisée par une prédominance de complications non classant sida. Dans un contexte d’accès aux soins similaires à celui des hommes infectés par le VIH, les femmes ont un profil de maladies associées traduisant à la fois leurs co-morbidités (co-infections par les hépatites) ou l’inflammation chronique du VIH (maladies cardio-vasculaires) qui nécessitent d’être détectées précocement et prises spécifiquement en charge. / Women represent one third of HIV-infected patients in France. The objective of this thesis was to study the clinical features (causes of death and severe morbidity) and the age and determinants of menopause of these patients in a context of equal access to care for all HIV-infected patients.Causes of death of HIV-infected women were identified in 2005, in a nation-wide survey (ANRS EN19, Mortalité 2005). Women died more often than men from AIDS-related causes (43% vs. 34%) and less frequently from hepatic (13% vs. 16%), non-AIDS non-hepatic cancers (14% vs. 17%) and cardiovascular diseases (6% vs. 9%). Severe morbidity was studied within the ANRS CO3-Aquitaine Cohort between 2000 and 2008. Annual incidence rates of hospitalization globally decreased for men and women from 146 per 1000 PY in 2000 to 69 in 2008. The most frequent causes of severe morbidity leading to hospitalization were: bacterial infections, AIDS events, psychiatric, hepatic, hematologic events, viral infections, digestive events, parasitical infections and cardiovascular events. All events had decreased between 2000 and 2008 in men and women excepted for hematologic (2.5 to 15.1 per 1000 PY), hepatic (2.5 to 11.5) and cardiovascular (6.3 à 14.2) events that increased overtime in women. Age at onset and associated factors of menopause were determined within the ANRS CO3-Aquitaine Cohort. Median age at menopause was 49 years and 12% reached menopause before 40 years (premature menopause). African origin (HR: 8.2) and history of injecting drug use (HR: 2.5) were associated with earlier menopause.In conclusion, HIV infected women in France, die more often from AIDS events but present with a predominantly non-AIDS severe morbidity. In a context of similar access to care than men, women’s health care should take into account their co-morbidities (hepatitis co-infections) and the cardiovascular complications of a long term HIV infection.

Trisomy 21 (T21), trisomy 18 (T18) and trisomy 13 (T13) represent the most common autosomal trisomies detected in live-born infants. Previous studies have addressed interventions, morbidities and survival in term or near-term infants with T21, T18 or T13, or were limited by a small number of patients. However, the combination of one of these chromosomal anomalies and very low birth weight (VLBW) presents greater challenges. Data from the NICHD Neonatal Research Network (NRN) and from the Vermont Oxford Network (VON) databases were used to examine the frequency, interventions, risk of mortality and neonatal morbidities, including patent ductus arteriosus (PDA), necrotizing enterocolitis (NEC), late onset sepsis (LOS), retinopathy of prematurity (ROP), and bronchopulmonary dysplasia (BPD), among VLBW infants with T21, T18 or T13 compared to VLBW infants without major birth defects (BD) and VLBW infants with non-chromosomal BD. Anthropometric VON charts for the assessment of birth weight for gestational age among 22 week to term infants with T21, T18 or T13 were also developed. In the VON database (n=539,509), the frequency of VLBW infants diagnosed with T21 was 1681 (0.31%), with T18 was 1416 (0.27%), and with T13 was 435 (0.08%). Major surgery was reported for 30.4% of infants with T21, 9.2% with T18, and 6.8% with T13. In-hospital mortality occurred for 33.1% of infants with T21, 89.0% with T18, and 92.4% with T13. Median survival time was 4 days (95% CI: 3-4) among infants with T18 and 3 days (95% CI: 2-4) among infants with T13. Birth weight for gestational age charts were created using VON data with a total of 5147 infants with T21 aged 22-41 weeks, 1053 infants with T18 aged 22-41 weeks, and 613 infants with T13 aged 22-40 weeks. Among the three groups, infants with T18 were the most likely to be growth restricted while infants with T21 were the least likely to be growth restricted. The new anthropometric VON charts for infants with T21 were also compared to the Lubchenco and Fenton charts and both showed frequent misclassification of infants with T21 as small or large for gestational age. In the NICHD NRN database (n=52,259), 133 (0.26%) VLBW infants were diagnosed with T21, 132 (0.25%) with T18 and 40 (0.08%) with T13. The adjusted relative risk, estimated using Poisson regression models with robust variance estimators, showed an increased risk of death, PDA, NEC, LOS, and BPD among infants with T21 relative to infants with no BD. Relative to infants with non-chromosomal BD, infants with T21 were at increased risk of PDA and NEC. A trend toward a lower risk of ROP was observed among infants with T21 compared to infants with non-chromosomal BD and infants without major BD. Infants with T13, but not infants with T18, were less likely to be mechanically ventilated than infants with T21 and infants without BD. Infants with T18 had increased risk of PDA compared to infants with T13, infants with T21 and infants without BD and increased risk of BPD compared to infants with T21 and infants without BD. The current studies evaluated the largest cohorts of VLBW infants with T21, T18 or T13. These data are important to help families and care providers make informed decisions involving the care of their VLBW infants with these chromosomal anomalies.

The worldwide eradication of lymphatic filariasis has recently started with two strategies, interruption of transmission and morbidity control. One of the most endemic countries, Haiti has experienced successful interventions through national and international efforts, but the morbidity control is still hindered by a lack of adequate information on quality of life (QOL) issues among those suffering from the chronic manifestations of the disease such as lymphedema. In addition, previous interventions have been focused primarily in a single community where an established lymphedema treatment clinic serves as a national reference center, so it is critical to expand programs to other areas in Haiti. The purpose of the study was to understand the issues of morbidity control and QOL among lymphedema patients due to lymphatic filariasis in three rural Haitian towns. Secondary data (n = 316) collected in an ongoing filariasis support group project was analyzed in terms of socio-demographic characteristics, including gender age, and regional perspectives. Also, two different commercial QOL instruments (EuroQol, CDC Healthy Days) and a subjective well-being assessment tool (CES-D) were introduced to describe their QOL and mental health status, respectively. The reliability and validity of the measurements were established at the same time. Regional differences were evident in patients illness history, knowledge of the illness, self-care and self-efficacy for legs, and major QOL indicators related to physical and mental health. Age of patients also influenced foot size, illness stage, and the QOL scores. However, other socio-demographic factors were poorly associated with filariasis related variables, including gender. The commercial QOL instruments and a standardized mental health tool satisfied a reasonable level of reliability and validity. Though additional discussion is needed regarding the validation of the mental health scales between EuroQol and the other instruments, they nevertheless offer utility for enhancing the quality of morbidity control programs. These findings offer a significant contribution for the development of filariasis prevention programs such as community-based morbidity control and support group activities in Haiti, as well as other areas of the filariasis-endemic world.

Affecting 6-8% of all pregnancies, preeclampsia is the leading cause of maternal morbidity in the western world and is charactensed by hypertension, proteinuria, edema and platelet aggregation. Despite its prevalence and severity, no comprehensive theory or single factor has been suggested to explain the pathophysiology of this multi system disorder of pregnancy, with the only therapies being bed rest, pharmacological symptom management and if necessary early delivery. Oxidative stress plays an important role in the pathophysiology of preeclampsia, resulting from defective trophoblast invasion, reductions in placental perfusion and placental hypoxia/reoxygenation. The inability of endogenous antioxidant systems up regulated in normal pregnancy, to control increased levels of oxidative stress, is suggested as a possible factor in the feed forward generation of reactive oxygen species and placental oxidative stress. That in turn may stimulate increased syncytiotrophoblast apoptosis, endothelial cell activation and the maternal hyper immune response characteristic of preeclampsia. Analysis of the research literature revealed that previous evaluations of placental oxidation and antioxidant enzyme activity in preeclampsia were by no means comprehensive, and exhibited significant inter-study variations. It was the aim of this thesis to clarify the placental oxidative state and the endogenous antioxidant activity of glutathione peroxidase, thioredoxin reductase, thioredoxin and superoxide dismutase in human placentae in an attempt to determine if variations in antioxidant function were due to changes in gene expression or protein oxidation. The findings reported in this thesis indicate the presence of increased levels of oxidative stress in the preeclamptic placenta, associated with significant reductions in antioxidant enzyme capacity. Quantitative real-time PCR analysis of placental samples revealed that deceases in antioxidant capacity in the placenta are more likely to be related to the significant oxidative burden within the tissue rather than reductions in gene expression. A number of animal models exist to investigate components of preeclampsia pathophysiology, however the ability of these models to mimic the oxidative and antioxidant features of preeclampsia remains unclear. The exposure of pregnant rats to N(G)-nitro-L-arginine methyl ester is a widely used model of endothelial cell dysfunction during preeclampsia. It was the aim of this thesis to determine the biochemical characteristics of this model in an attempt to assess its effectiveness in mimicking oxidative changes in the preeclamptic placenta. Although this model is capable of producing a syndiome in rats similar to the disorder in terms of physiology, this is not manifest in terms of placental biochemistry. The importance of selenium in the synthesis of selenobased antioxidants such as glutathione peroxidase and thioredoxin reductase is well documented. Increasing demand for selenium by the developing fetus may be linked to reductions in selenium status during pregnancy. Considering preeclampsia is associated with significant reductions in selenium status it may be hypothesised that reductions in antioxidant function may be linked to selenium inadequacy. The modulation of dietary selenium in pregnant rats was used to determine the importance of selenium during pregnancy and its effect on antioxidant function and placental oxidative stress. The results of this analysis revealed that selenium deficiency causes a pregnancy specific condition similar to preeclampsia. This condition was found to be associated with increased placental oxidative stress and significant reductions in the systemic activity of selenobased antioxidants that could be modified through selenium supplementation. In summary, data obtained in this thesis indicate that placental oxidative stress and reduced antioxidant enzyme activity play a significant role in the pathogenesis of preeclampsia. These studies support the hypothesis that antioxidant sufficiency is crucial in the maintenance of oxidative balance and that antioxidant dysfunction may result in damage to the placenta and the progression of the disease. These novel data further our understanding of the pathophysiology of preeclampsia and provide new insight into the pathogenesis of clinical complications exhibited in this condition, suggesting antioxidant therapy as a possible means for improving the health outcomes of both mother and baby.

<p>Syftet med studien var att undersöka hur anställda inom en polismyndighet i Sverige skattade sina levnadsvanor och hälsa samt om det finns någon skillnad mellan grupperna; poliser med yttre tjänstgöring, poliser med inre tjänstgöring och civilanställda. Ytterligare ett syfte var att studera sambandet mellan levnadsvanor och hälsa. Studien hade en kvantitativ ansats med en beskrivande, korrelativ och jämförande design. De medverkande var 153 personer. Stratifierat urval och randomiseringstabell har använts. Två instrument/enkäter har använts från folkhälsoinstitutet och livsmedelsverket. Resultatet visade att deltagarna bedömer sig stressade men skattar sitt hälsotillstånd som relativt gott.<strong> </strong>Över 50 procent av deltagarna hade besvär av värk i axlar och över 43 procent besväras av värk i ryggen. Deltagarna bedömde sig ha ringa besvär från sjukdomar som högt blodtryck, diabetes och astma. Användandet av tobak varierade mellan deltagargrupperna. Poliserna rökte minst, detta även jämfört med befolkningen i övrigt men snusade mest. Sambandsanalyser visade att deltagare med värk var tröttare, hade svårare att sova och kände sig mer stressade.</p>