Background: Venous thromboembolism (VTE), comprising the conditions of deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common acute cardiovascular event associated with increased long-term morbidity, functional disability, all-cause mortality, and high rates of recurrence. Major advances in identification, prophylaxis, and treatment over the past 3-decades have likely changed its clinical epidemiology. However, there are little published data describing contemporary, population-based, trends in VTE prevention and management. Objectives: To examine recent trends in the epidemiology of clinically recognized VTE and assess the risk of recurrence after a first acute episode of VTE. Methods: We used population-based surveillance to monitor trends in acute VTE among residents of the Worcester, Massachusetts, metropolitan statistical area (WMSA) from 1985 through 2009, including in-hospital and ambulatory settings. Results: Among 5,025 WMSA residents diagnosed with acute PE and/or lower-extremity DVT between 1985 and 2009 (mean age = 65 years), 46% were men and 95% were white. Age- and sex-adjusted annual event rates (per 100, 000) of clinically recognized acute first-time and recurrent VTE was 142 overall, increasing from 112 in 1985/86 to 168 in 2009, due primarily to increases in PE occurrence. During this period, non-invasive diagnostic VTE testing increased, vi while treatment shifted from the in-hospital (chiefly with warfarin and unfractionated heparin) to out-patient setting (chiefly with low-molecular-weight heparins and newer anticoagulants). Among those with community-presenting first-time VTE, subsequent 3-year cumulative event rates of key outcomes decreased from 1999 to 2009, including all-cause mortality (41% to 26%), major bleeding episodes (12% to 6%), and recurrent VTE (17% to 9%). Active-cancer (with or without chemotherapy), a hypercoagulable state, varicose vein stripping, and Inferior vena cava filter placement were independent predictors of recurrence during short- (3-month) and long-term (3-year) follow-up after a first acute episode of VTE. We developed risk score calculators for VTE recurrence based on a 3-month prognostic model for all patients and separately for patients without active cancer. Conclusions: Despite advances in identification, prophylaxis, and treatment between 1985 and 2009, the disease burden from VTE in residents of central Massachusetts remains high, with increasing annual events. Declines in the frequency of major adverse outcomes between 1999 and 2009 were reassuring. Still, mortality, major bleeding, and recurrence rates remained high, suggesting opportunities for improved prevention and treatment. Clinicians may be able to use the identified predictors of recurrence and risk score calculators to estimate the risk of VTE recurrence and tailor outpatient treatments to individual patients.

L'objectif principal de ce travail est d’étudier en profondeur certaines techniques biostatistiques avancées en recherche évaluative en chirurgie cardiaque adulte. Les études ont été conçues pour intégrer les concepts d'analyse de survie, analyse de régression avec “propensity score”, et analyse de coûts. Le premier manuscrit évalue la survie après la réparation chirurgicale de la dissection aigüe de l’aorte ascendante. Les analyses statistiques utilisées comprennent : analyses de survie avec régression paramétrique des phases de risque et d'autres méthodes paramétriques (exponentielle, Weibull), semi-paramétriques (Cox) ou non-paramétriques (Kaplan-Meier) ; survie comparée à une cohorte appariée pour l’âge, le sexe et la race utilisant des tables de statistiques de survie gouvernementales ; modèles de régression avec “bootstrapping” et “multinomial logit model”. L'étude a démontrée que la survie s'est améliorée sur 25 ans en lien avec des changements dans les techniques chirurgicales et d’imagerie diagnostique. Le second manuscrit est axé sur les résultats des pontages coronariens isolés chez des patients ayant des antécédents d'intervention coronarienne percutanée. Les analyses statistiques utilisées comprennent : modèles de régression avec “propensity score” ; algorithme complexe d'appariement (1:3) ; analyses statistiques appropriées pour les groupes appariés (différences standardisées, “generalized estimating equations”, modèle de Cox stratifié). L'étude a démontrée que l’intervention coronarienne percutanée subie 14 jours ou plus avant la chirurgie de pontages coronariens n'est pas associée à des résultats négatifs à court ou long terme. Le troisième manuscrit évalue les conséquences financières et les changements démographiques survenant pour un centre hospitalier universitaire suite à la mise en place d'un programme de chirurgie cardiaque satellite. Les analyses statistiques utilisées comprennent : modèles de régression multivariée “two-way” ANOVA (logistique, linéaire ou ordinale) ; “propensity score” ; analyses de coûts avec modèles paramétriques Log-Normal. Des modèles d’analyse de « survie » ont également été explorés, utilisant les «coûts» au lieu du « temps » comme variable dépendante, et ont menés à des conclusions similaires. L'étude a démontrée que, après la mise en place du programme satellite, moins de patients de faible complexité étaient référés de la région du programme satellite au centre hospitalier universitaire, avec une augmentation de la charge de travail infirmier et des coûts. / The main objective of this work is to study in depth advanced biostatistical techniques in adult cardiac surgery outcome research. The studies were designed to incorporate the concepts of survival analysis, regression analysis with propensity score, and cost analysis. The first manuscript assessed survival, and cardiovascular specific mortality, following surgical repair of acute ascending aortic dissection. The statistical analyses included survival analyses with multiphase parametric hazard regression and other parametric (exponential, Weibull), semi-parametric (Cox) or non-parametric models (Kaplan Meier), comparison with the survival of a matched cohort for age, gender and race using State lifetables, and modelization with bootstrapping and multinomial logit models. The study showed that the early and late survival following surgical repair has improved progressively over 25 years in association with noticeable changes in surgical techniques and preoperative diagnostic testing. The second manuscript focused on outcomes following isolated coronary artery bypass grafting in patients with a history of percutaneous coronary intervention. The statistical analyses included multivariable regression models with propensity score, complex matching algorithm (1:3) and appropriate statistical analyses for matched groups (standardized differences, generalized estimating equations, and survival analyses with stratified proportional hazards models). The study showed that remote prior percutaneous coronary intervention more than 14 days before coronary artery bypass grafting surgery was not associated with adverse outcomes at short or long-term follow-up. The third manuscript evaluated the financial consequences and the changes in case mix that occurred at an academic medical center subsequent to the implementation of a satellite cardiac surgery program. The statistical analyses included two-way ANOVA multivariable regression models (logistic, linear or ordinal), propensity score, and cost analyses using Log-Normal parametric models. “Survival” analyses models were also explored, using “cost” instead of “time” as the outcome of interest, and led to similar conclusions. The study showed that, after implementation of the satellite cardiac surgery program, fewer patients of lower complexity came to the academic medical center from the satellite program area, with a significant increase in nursing workload and costs.

Contexte : Un accès adéquat aux aliments sains dans les environnements résidentiels peut contribuer aux saines habitudes alimentaires. Un tel accès est d’autant plus important pour les personnes âgées, où les changements associés au vieillissement peuvent accentuer leur dépendance aux ressources disponibles dans le voisinage. Cependant, cette relation n’a pas encore été établie chez les aînés. Objectifs : La présente thèse vise à quantifier les associations entre l’environnement alimentaire local et les habitudes alimentaires de personnes âgées vivant à domicile en milieu urbain. La thèse s’est insérée dans un projet plus large qui a apparié les données provenant d’une cohorte d’aînés québécois vivant dans la région métropolitaine montréalaise avec des données provenant d’un système d’information géographique. Trois études répondent aux objectifs spécifiques suivants : (1) développer des indices relatifs de mixité alimentaire pour qualifier l’offre d’aliments sains dans les magasins d’alimentation et l’offre de restaurants situés dans les quartiers faisant partie du territoire à l’étude et en examiner la validité; (2) quantifier les associations entre la disponibilité relative de magasins d’alimentation et de restaurants près du domicile et les habitudes alimentaires des aînés; (3) examiner l’influence des connaissances subjectives en nutrition dans la relation entre l’environnement alimentaire près du domicile et les habitudes alimentaires chez les hommes et les femmes âgés. Méthodes : Le devis consiste en une analyse secondaire de données transversales provenant de trois sources : les données du cycle 1 pour 848 participants de l’Étude longitudinale québécoise « La nutrition comme déterminant d’un vieillissement réussi » (2003-2008), le Recensement de 2001 de Statistique Canada et un registre privé de commerces et services (2005), ces derniers regroupés dans un système d’information géographique nommé Mégaphone. Des analyses bivariées non paramétriques ont été appliquées pour répondre à l’objectif 1. Les associations entre l’exposition aux commerces alimentaires dans le voisinage et les habitudes alimentaires (objectif 2), ainsi que l’influence des connaissances subjectives en nutrition dans cette relation (objectif 3), ont été vérifiées au moyen d’analyses de régression linéaires. Résultats : Les analyses ont révélé trois résultats importants. Premièrement, l’utilisation d’indices relatifs pour caractériser l’offre alimentaire s’avère pertinente pour l’étude des habitudes alimentaires, plus particulièrement pour l’offre de restaurants-minute. Deuxièmement, l’omniprésence d’aspects défavorables dans l’environnement, caractérisé par une offre relativement plus élevée de restaurants-minute, semble nuire davantage aux saines habitudes alimentaires que la présence d’opportunités d’achats d’aliments sains dans les magasins d’alimentation. Troisièmement, un environnement alimentaire plus favorable aux saines habitudes pourrait réduire les écarts quant à la qualité de l’alimentation chez les femmes ayant de plus faibles connaissances subjectives en nutrition par rapport aux femmes mieux informées. Conclusion : Ces résultats mettent en relief la complexité des liens entre l’environnement local et l’alimentation. Dans l’éventualité où ces résultats seraient reproduits dans des recherches futures, des stratégies populationnelles visant à résoudre un déséquilibre entre l’accès aux sources d’aliments sains par rapport aux aliments peu nutritifs semblent prometteuses. / Context: Adequate access to healthful foods in residential environments may contribute to healthful dietary practices. Such access is important for older adults where changes associated with aging may accentuate their dependence on resources available in their residential neighborhood. However, this relationship has not been established for seniors. Objectives: This thesis aims to quantify associations between the local food environment and dietary patterns of independent urban-dwelling older adults. The thesis is part of a larger project involving the linkage of data from a cohort of Québec seniors living in the Montréal metropolitan area and data from a geographic information system. Three studies addressed the following specific objectives: (1) to develop relative indices of local-area food sources outlets to qualify stores potentially selling healthful foods and supply of restaurants in neighborhoods that were part of the study area, (2) to quantify associations between the relative availability of food stores and restaurants in residential area and dietary patterns of members of the cohort, (3) to examine the influence of subjective nutrition knowledge in the relationship between the residential food environment and dietary patterns among older men and women. Methods: Cross-sectional analysis of data from three different sources was performed: (1) person-level data on 848 participants from cycle 1 of the Québec Longitudinal Study on Nutrition and Successful Aging , (2) 2001 Census data from Statistics Canada and (3) data from private businesses and services registry (2005), these two gathered in a geographic information system called Megaphone. Nonparametric bivariate analyses were applied to address objective 1. Associations between exposure to residential-area food sources and dietary patterns (objective 2), as well as moderating effect of nutrition knowledge (objective 3), were tested using linear regression analyses. Results: Analyses revealed three important results. First, the use of relative indices to characterize availability of local-area food sources is relevant to the study of dietary patterns, particularly regarding the supply of fast food restaurants. Second, the ubiquity of unfavorable aspects in the food environment, characterized by relatively higher fast food restaurants offer seem more detrimental to healthful eating habits that the presence of opportunities to buy healthful foods in food stores. Third, a residential food environment more favorable to healthful dietary patterns could reduce disparities in diet quality between women with low nutrition knowledge compared to women more knowledgeable. Conclusion: These results highlight the complex links between local environment and diet. If findings can be replicated in future research, population-based strategies to address an imbalance between accessibility to healthful food sources relative to unhealthful food sources, would be promising.

L'augmentation et la dissémination de la résistance aux antibiotiques chez les bactéries à gram-negatif, particulièrement les Entérobactéries, les bactéries du genre Pseudomonas et Acinetobacter, représentent un problème majeur de santé publique au niveau mondial. Les infections nosocomiales causées par les bactéries multi-résistantes (BMR) ont conduit non seulement à une augmentation de la mortalité, de la morbidité, et du coût de traitement, mais aussi continuent de mettre en danger la vie des patients surtout immunodéprimés en milieu hospitalier. Bien entendu, l'utilisation abusive et non contrôlée des antibiotiques a grandement contribué à la large diffusion des déterminants de la résistance; cependant, des études récentes ont démontré que ces déterminants de la résistance pouvaient émerger à partir de sources anciennes et/ou environnementales. Ainsi, face à cette préoccupation mondiale, plusieurs études ont été rapportées avec des recommandations importantes de conduire des études épidémiologiques, moléculaires, et génomiques afin de contrôler la diffusion et l'augmentation de la résistance aux antibiotiques. De plus, durant ces 10 dernières années, nous avons assisté à l'emergence et au développement de nouvelles technologies de séquençage à haut débit coïncidant avec une augmentation exponentielle du nombre de genomes bactériens séquencés. / The increase and spread of multidrug-resistant (MDR) gram-negative bacteria especially Enterobacteriaceae, Pseudomonas, and Acinetobacter (E.P.A) species have become a major concern worldwide. The hospital-acquired infections caused by MDR bacteria have led not only to an increase in mortality, morbidity, and cost of treatment, but also continue to endanger the life of patients, especially those immunocompromised. Although the frequent misuse of antibiotic drug has greatly contributed to worldwide dissemination and resistance to antibiotics; recent studies have shown that these resistance determinants could emerge from ancient or environmental sources. Front of this worldwide concern, several studies have been reported with significant recommendations to conduct molecular epidemiology, and genomic studies, in order to control the increase and the dissemination of the antibiotic resistance. Moreover, during these last 10 years, we are witnessing the emergence and development of new technologies of high throughput sequencing and coinciding with an exponential increase of number of bacterial genomes sequenced today. Therefore, it is in this context that the project of this thesis was conducted with three essential objectives: (i) the genome sequencing of clinical MDR bacteria, the analysis and the identification of the mechanisms and the genetic determinants of antimicrobial resistance (ii) the achievement of molecular epidemiology studies from clinical MDR bacteria responsible of outbreak (iii) the development and implementation of molecular tools for monitoring and diagnosis of potential MDR bacteria.

Introdução:A mortalidade materna é um dos melhores indicadores do desenvolvimento socioeconômico de um país. O Brasil implementou políticas públicas para redução da mortalidade materna até 2015. A região do Grande ABC Paulista no Brasil apresenta grande heterogeneidade socioeconômica entre seus municípios, podendo refletir a desigualdade social do país, porém apresentando dimensões que permitem maior controle de dados da mortalidade. Objetivo: Avaliar a tendência da mortalidade materna na região do Grande ABC Paulista no período de 1997 a 2011. Metodologia: Estudo ecológico de série temporal, cujos dados foram obtidas no banco de dados do Departamento de Informática do Sistema Único de Saúde do Brasil (DATASUS) do Ministério da Saúde do Brasil (MS). Os dados foram transformados em Índices da Mortalidade Materna Direta (IMMD), estratificados por municípios, índices de desenvolvimento humano (IDH), causas de óbito materno segundo Classificação internacional de doenças (CID-10), local e período de ocorrência do óbito, dados sóciodemográficos e submetidos a comparações (teste U de Mann-whitney, teste de Kruskal-Wallis e teste de Dunn) e associações pela regressão linear, com significância de 5%. Resultados: Os IMMD predominaram em mulheres solteiras, entre 20-34 anos de idade, brancas, escolaridade entre 4-7 anos, intra-hospitalar, no puerpério imediato, por hemorragias/tromboses/embolias e eclâmpsias. Não houve diferença nos IMMD em relação ao grupo IDH. Rio Grande da Serra atingiu IMMD alto (OMS) na maioria das covariáveis analisadas. Apenas São Caetano do Sul apresentou IMMD baixo (OMS), alto IMMI (p=0,03), queda nos IMMD no período de 1997 a 2011 (beta= -0,67/ano, p=0,03) e tendência neste milênio (2000 a 2011, beta=-0,55/ano, p=0,07) com estimativa de queda de 65,1% até 2015. A soma dos óbitos não investigados, não se aplica e de fichas sem investigação para qualquer variável analisada ultrapassa 50%. Conclusão: Os índices da Mortalidade Materna Direta na região do Grande ABC Paulista apresentaram níveis altos e queda discreta no tempo. Apenas o município de São Caetano do Sul apresentou queda expressiva de IMMD nos 15 anos de estudo e tendência a queda neste milênio com estimativa de atingir 65,1% até 2015. Descritores: Mortalidade materna; Políticas públicas; Mulheres; Saúde da mulher/estatística & dados numéricos; Complicações na gravidez/mortalidade; Mortalidade; Sistema Único de Saúde; Estudos epidemiológicos; Saúde da mulher/estatística & dados numéricos; Período pós-parto; Objetivos de desenvolvimento do milênio; Brasil/epidemiologia / Introduction: Maternal mortality is one of the best indicators of socioeconomic development of a country. Brazil has implemented public policies to reduce maternal mortality by 2015. The Grande ABC Paulista region in Brazil shows great socioeconomic heterogeneity among its municipalities, which can reflect the country social inequality, however presenting dimensions that allow greater control of mortality data. Objective: To evaluate the trend of maternal mortality in the Grande ABC Paulista region in the period of 1997-2011. Methodology: Ecological time series, where data was obtained from the database of the Information Technology Department of the Public Health Care System (DATASUS) of the Health Ministry of Brazil (MS). The data was transformed into direct maternal mortality indices (DMMI), stratified by municipalities, Human Development Indices (HDI), causes of maternal death according to the International Classification of Diseases (ICD-10), period and local of maternal death, socio-demographic parameters. Data were submitted to comparison tests (Mann-Whitney U test, Kruskal-Wallis test, followed by Dunn\'s multiple comparisons test) and association tests (linear regression) when applied and a significance of 5%. Results: The DMMI predominated in single women, aged 20-34 years old, white, 4 to 7 school age, in-hospital, postpartum, by bleeding / thrombosis / embolism and eclampsia. There was no difference in DMMI when comparing by HDI group. The Municipality of Rio Grande da Serra reached high DMMI values in the most of the analyzed covariates. São Caetano do Sul presented the lowest DMMI values and was the only municipality which presented decrement in the DMMI during the 15 years of the studied period (beta = - 0.67/year, p=0.03) and a trend in this millennium (2000-2011, beta- 0.55/year, p=0.07) with an estimated fall of 65.61% by 2015. The sum of not investigated, not applied and files without investigation for any analyzed variable exceeded 50%. Conclusion: The DMMI in the Grande ABC Paulista showed high levels and downward trend in time. São Caetano do Sul was the sole municipality where the DMMR dropped in 15 years of study and presented a tendency to decrease in this millennium with an estimated fall of 65.1% by 2015

Por apresentarem mecanismos de transmissão superponíveis, a infecção concomitante pelo vírus da hepatite C (VHC) e pelos vírus linfotrópicos de células T humanas dos tipos 1 (HTLV-1) e 2 (HTLV-2) é esperada. Considerando a relevância dessas infecções em nosso meio e a existência de lacunas no conhecimento da coinfeção VHC/HTLV, conduziu-se este estudo transversal, com o objetivo de comparar uma série de pacientes coinfectados, com indivíduos infectados pelo VHC isoladamente, no tocante a características sócio-demográficas e de exposição aos agentes virais, alterações clínicas e laboratoriais, bem como alterações histológicas do parênquima hepático. Selecionaram-se, com base em algoritmos de diagnóstico sorológico e de biologia molecular, pacientes adultos assistidos em ambulatórios do Hospital das Clínicas da FMUSP entre janeiro de 1993 e agosto de 2005, que apresentaram viremia pelo VHC, associada, ou não, a infecção por HTLV-1 ou HTLV-2, excluindo-se da amostra os coinfectados pelo VHB ou HIV. Coletaram-se dos pacientes selecionados características sócio-demográficas, informações acerca de exposição a vírus de transmissão sexual ou sangüínea, sinais e sintomas clínicos relacionados às infecções causadas pelo VHC ou HTLV, bem como dados laboratoriais hematológicos e de função hepática. Procedeu-se ainda à revisão sistemática dos achados histopatológicos do parênquima hepático, seguindo-se a classificação de Ishak. Compararam-se, então, os grupos VHC, VHC/HTLV-1 e VHC/HTLV-2, empregando-se o teste de X2 para as variáveis categóricas e o teste de Kruskal-Wallis para as variáveis contínuas. Em seguida, pela análise discriminante linear de Fischer, definiram-se funções classificatórias com variáveis que conjuntamente diferenciassem os grupos estudados. Finalmente, a acurácia discriminatória das funções classificatórias foi avaliada por validação cruzada, empregando-se a técnica leave-one-out. Compuseram a população estudada 85 pacientes, sendo 55 no grupo VHC, 24 no grupo VHC/HTLV-1 e 6 no grupo VHC/HTLV-2. À análise bivariada, não se observou diferença significativa entre os grupos no tocante a características sócio-demográficas, hábito de fumar, fatores de exposição às infecções virais, tais como transfusão sangüínea, tatuagem, acupuntura, ou número de parceiros sexuais. Ao contrário, o relato de uso de álcool, drogas endovenosas, ou cocaína inalatória, bem como a parceria sexual com UDEV foi mais freqüente entre os pacientes do grupo VHC/HTLV-2, enquanto o relato de parceiro sexual com hepatite predominou no grupo VHC. Do ponto de vista clínico, apenas a queixa de dor abdominal apresentou-se em freqüência significativamente diferente entre os grupos, sendo mais prevalente no grupo VHC. Em relação aos achados laboratoriais, apesar de contida nos intervalos de normalidade, houve diferença significativa na contagem de plaquetas em sangue periférico, com valores medianos mais elevados nos grupos de coinfectados. As concentrações séricas de aminotransferases e de GGT foram mais altas no grupo VHC. Apesar de freqüentemente encontradas alterações sugestivas de hepatopatia pelo VHC, como fibrose hepática e atividade necroinflamatória, a análise histopatológica não mostrou diferença significativa entre os grupos. À análise discriminante de Fischer, definiram-se funções classificatórias que melhor diferenciam os pacientes estudados, incluindo as variáveis sexo, faixa etária, relato de uso de drogas endovenosas e parceria sexual com indivíduo com hepatite. Por meio de validação cruzada, verificou-se que a acurácia discriminante das funções classificatórias foi alta (87,3%) para a identificação dos infectados pelo VHC isoladamente e intermediária (66,7%) para os coinfectados VHC/HTLV-2. O método não se mostrou, contudo, clinicamente útil na distinção de pacientes com coinfecção VHC/HTLV-1. / Co-infection with hepatitis C virus (HCV) and human T-lymphotropic virus types 1 (HTLV-1) and 2 (HTLV-2) is expected, as these viruses share common infection routes. Due to the relevance of these viral infections in Brazil and the existing gaps in knowledge about HCV/HTLV co-infection, we carried out this cross-sectional survey. A cohort of co-infected patients was compared to HCV-infected subjects, in regard to socio-demographic features, risk factors for viral acquisition, clinical and laboratory data, as well as liver histopathologic findings. Based on established serologic and molecular diagnostic algorithms, we selected HCV-viremic adult patients who attended the Hospital das Clínicas-FMUSP outpatient clinic from January 1993 to August 2005, whether or not they presented co-infection with HTLV-1 or HTLV-2. HBV and HIV-infected individuals were excluded from the sample. We collected patients\' sociodemographic characteristics, risk of exposure to blood-borne or sexually-transmitted viral agents, signs and symptoms related to HCV or HTLV disease, as well as laboratory data that included hematologic counts and liver function tests. Histopathologic findings were systematically reviewed, in accordance to the Ishak\'s scoring system. Patients from the HCV, HCV/HTLV-1 and HCV/HTLV-2 groups, were then compared by means of the X2 or Kruskal-Wallis tests for categorical or continuous variables, respectively. In addition, Fischer\'s linear discriminant analysis was applied to define classification functions that better identified the combined effect of variables important for discrimination of the study groups. Finally, the discriminating accuracy of the model was evaluated by cross-validation, using the leave-one-out technique. The study sample comprised 85 patients, 55 in the HCV group, 24 in the HCV/HTLV-1 group and 6 in the HCV/HTLV-2 group. In bivariable analysis, no significant difference was found among groups in regard to socio-demographic features, smoking, risk factors for viral acquisition, such as blood transfusion, tattooing, acupuncture, or number of sexual partners. In contrast, alcohol consumption, use of intravenous drugs or inhaled cocaine and sexual partnership with an intravenous drug user were more frequent in the HCV/HTLV-2 group, whereas patients in the HCV group more often reported a sexual partner with hepatitis. As far as clinical data are concerned, abdominal pain was the only variable to be reported differently, being more prevalent in the HCV group. Even though within normal ranges, co-infected patients presented higher median platelet counts, whereas aminotransferase and GGT levels were higher among HCV-infected subjects. No significant difference was seen in liver histopathologic findings, though HCV liver disease-associated abnormalities, such as fibrosis and necroinflammatory activity were often found in patients from the three groups. Classification functions, defined by discriminating analysis included as relevant variables sex, age, intravenous drug use and sexual partner with hepatitis. Cross-validation yielded high (87.3%) and intermediate (66,7%) discriminating accuracies for the HCV and HCV/HTLV-2 functions. However, this method was not shown clinically useful to distinguish HCV/HTLV-1 co-infected patients.

INTRODUÇÃO: Em 1999 e 2000, a ocorrência de surtos de rubéola, com maior acometimento entre adultos jovens, refletiu no aumento da síndrome da rubéola congênita. Como estratégia de controle da doença, foram realizadas campanhas de vacinação contra a rubéola em mulheres em idade fértil em vários Estados do País. Em razão das controvérsias existentes na literatura geradas quanto ao emprego da vacina de vírus vivos atenuados em gestantes, não se recomendou sua utilização durante a gravidez e até um mês após a aplicação da vacina. No entanto, 6.473 mulheres foram inadvertidamente vacinadas no Estado de São Paulo, sendo encaminhadas a serviços de referência para acompanhamento dessas gestações, dentre eles, o HCFMUSP. OBJETIVO: Este estudo buscou descrever as características clínicas e epidemiológicas das gestantes atendidas no HCFMUSP e obter os resultados dessas gestações. MÉTODO: Foi realizado um estudo epidemiológico descritivo, utilizando-se como fonte de dados as notificações das gestantes inadvertidamente vacinadas contra a rubéola e atendidas no HCFMUSP entre novembro de 2001 a dezembro de 2002. Para obter o desfecho das gestações, utilizou-se a base de dados dos nascidos vivos do Município de São Paulo (SINASC). RESULTADOS: No HCMFUSP, foram atendidas e notificadas 409 gestantes. Destas, 49,1% foram vacinadas no primeiro mês de gravidez e 26,2% engravidaram até um mês após a vacinação. Em relação a condição sorológica durante o pré-natal, 16,9% das gestantes apresentaram sorologia reagente para rubéola. Do relacionamento com a base de dados do SINASC, foram localizados os dados do parto de 63,3% das gestantes, sendo detectadas duas malformações congênitas no SINASC e um abortamento, porém, não se pode atribuir estes resultados à vacina, pois, as sorologias das mães não permitem determinar se estas mulheres eram realmente suscetíveis. CONSIDERAÇÕES FINAIS: O estudo apresentou o fluxo de informação estabelecido frente a um evento inusitado. Além disso, o uso de bases de dados secundárias contribuiu para o aprimoramento dos dados coletados, resultando na melhora da qualidade das informações. Os Núcleos de Epidemiologia Hospitalar são fundamentais na articulação entre a equipe assistencial e o Sistema de Vigilância e colaboram para discussão na padronização de Sistemas de Informação para permitir melhor integração entre as informações geradas pelos Serviços de Saúde. / INTRODUCTION: In the years 1999 and 2000, rubella outbreaks reaching mostly young adults resulted in an increased number of cases of Congenital Rubella Syndrome in Brazil. State Vaccination Campaigns aiming at women at childbearing age were promoted around the country to control the disease, recommending that vaccination of pregnant women should be avoided and pregnancy should be postponed for at least a month after vaccination. Despite the recommendations, 6.473 pregnant women were accidentally vaccinated in the State of São Paulo and therefore sent to reference obstetrical services for prenatal care. A study was conducted to describe the cases assisted at the University of São Paulo, School of Medicine, General Hospital and notified to Public Health and also to obtain information on the pregnancy outcomes. METHODS: This descriptive epidemiological study used notification by the Hospital Epidemiology Service as source of information on pregnant women accidentally vaccinated against rubella that received care from November 2001 to December 2002 at the School of Medicine, General Hospital. The City of São Paulo Newborn Database was searched for pregnancy outcomes. RESULTS: Among the 409 notified cases, 49,1% were women accidentally vaccinated during fist trimester of pregnancy and 26,2% women that became pregnant within less than a month after vaccination. Positive serological tests were found in 16,9% of women during prenatal care. Newborn data base search yielded pregnancy outcome for 63,3%. The findings of 2 cases of Congenital Rubella Syndrome and 1miscarriage cannot be surely attributed to vaccination because immediate previous immunization status was unknown. CONCLUSIONS: The study described the information flow established for an unexpected adverse event and the use of secondary data to improve quality of information. Hospital Epidemiology Services have a fundamental role in connecting health assisting professionals to Public Surveillance Systems and in setting standards for information generated by Health Assistance.

Made available in DSpace on 2016-01-26T12:51:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-03-31 / Acute respiratory infections, especially upper respiratory tract infections (URTI), are the most frequent causes of infantile morbidity in the world. Day-care facilities are closed, with great circulation of people and infectious agents as well, being therefore prone to the spreading of viral respiratory infections. Mathematical epidemic models are quantitative analysis methods that might be used for understanding and predicting the transmission dynamics of infectious diseases. Objective: Verify the monthly incidence of URTI, of 8 respiratory viruses, and to simulate a mathematical model, evaluating its qualitative and quantitative behavior regarding true data from URTI in school of infantile education in integral period children. Casuistic and Methods: From July 2003 to July 2004, all children (173) in the school of infantile education in integral period were followed from 1.6 to 12 months. Them presenting signs of respiratory infections were examined and their nasopharyngeal aspirate specimen was collected, in a total of 255 analyses. Soon after, specific multiplex trial of reverse transcription, followed by the polymerase chain reaction (multiplex RT-PCR), was accomplished for identification of the 8 viruses related to respiratory infections. Results and Conclusions: The average incidence of URTI was 2.33 episodes per child-year. URTI was observed throughout the year of study, especially in the fall and winter, lowering during spring and presenting few cases in summer. Rhinovirus presented the greatest incidence, being observed throughout the period of study. Influenza B, respiratory syncytial virus (RSV), and metapneumovirus presented lower incidence, especially during fall and winter. URTI caused by other analyzed viruses - influenza A, parainfluenza 1, 2, and 3 were rare. The evaluation of the mathematical model through simulations has provided promising results, as it was possible to get true data reproduction. The model is promising. Having its suppositions adequate, it might be useful for understanding the dynamics and spreading of diseases, planning and evaluating prevention and immunization strategies in epidemics. / As infecções respiratórias agudas, em especial as infecções das vias aeríferas superiores (IVAS), são as causas mais freqüentes de morbidade infantil no mundo. As creches são ambientes fechados, onde há grande circulação de pessoas e também de agentes infecciosos, sendo então favoráveis à disseminação de infecções respiratórias virais. Os modelos epidemiológicos matemáticos são métodos de análise quantitativos e podem ser usados para compreensão e predição da dinâmica de transmissão de uma doença infecciosa. Objetivo: Verificar a incidência mensal de IVAS, de 8 vírus respiratórios, e simular um modelo matemático, avaliando seu comportamento qualitativo e quantitativo em relação aos dados reais de IVAS nas crianças da Escola de Educação Infantil em período integral. Casuística e Método: Todas as crianças (173) que freqüentaram a escola no período de julho de 2003 a julho de 2004 foram acompanhadas por 1,6 a 12 meses. Elas apresentaram sinais de IVAS foram examinadas e tiveram coletado espécime de aspirado de nasofaringe, perfazendo um total de 255 análises. Em seguida, foi realizado ensaio específico multiplex de transcrição reversa seguida da reação em cadeia de polimerase (multiplex RT-PCR) para identificação dos 8 vírus relacionados às IVAS. Resultados e Conclusões: A incidência média de IVAS foi de 2,33 episódios por criança-ano. As IVAS incidiram durante todo o período do estudo, principalmente no outono e inverno, decaindo na primavera e com poucos casos no verão. O rinovírus teve maior incidência tendo sido observado em todos os períodos em que ocorreram episódios de IVAS. Influenza B, vírus sincicial respiratório (VSR) e metapneumovírus ocorreram com menor incidência, principalmente no outono e inverno. IVAS causadas pelos outros vírus analisados influenza A, parainfluenza 1, 2 e 3 foram raras. A avaliação do modelo matemático, por meio de simulações, forneceu resultados animadores, visto que se conseguiu a reprodução dos dados reais. O modelo é promissor. Com a adequação das suas suposições, pode ser útil para a compreensão das dinâmicas de disseminação de doenças, planejamento e avaliação de estratégias de prevenção e de imunização em epidemias.

Introdução:A mortalidade materna é um dos melhores indicadores do desenvolvimento socioeconômico de um país. O Brasil implementou políticas públicas para redução da mortalidade materna até 2015. A região do Grande ABC Paulista no Brasil apresenta grande heterogeneidade socioeconômica entre seus municípios, podendo refletir a desigualdade social do país, porém apresentando dimensões que permitem maior controle de dados da mortalidade. Objetivo: Avaliar a tendência da mortalidade materna na região do Grande ABC Paulista no período de 1997 a 2011. Metodologia: Estudo ecológico de série temporal, cujos dados foram obtidas no banco de dados do Departamento de Informática do Sistema Único de Saúde do Brasil (DATASUS) do Ministério da Saúde do Brasil (MS). Os dados foram transformados em Índices da Mortalidade Materna Direta (IMMD), estratificados por municípios, índices de desenvolvimento humano (IDH), causas de óbito materno segundo Classificação internacional de doenças (CID-10), local e período de ocorrência do óbito, dados sóciodemográficos e submetidos a comparações (teste U de Mann-whitney, teste de Kruskal-Wallis e teste de Dunn) e associações pela regressão linear, com significância de 5%. Resultados: Os IMMD predominaram em mulheres solteiras, entre 20-34 anos de idade, brancas, escolaridade entre 4-7 anos, intra-hospitalar, no puerpério imediato, por hemorragias/tromboses/embolias e eclâmpsias. Não houve diferença nos IMMD em relação ao grupo IDH. Rio Grande da Serra atingiu IMMD alto (OMS) na maioria das covariáveis analisadas. Apenas São Caetano do Sul apresentou IMMD baixo (OMS), alto IMMI (p=0,03), queda nos IMMD no período de 1997 a 2011 (beta= -0,67/ano, p=0,03) e tendência neste milênio (2000 a 2011, beta=-0,55/ano, p=0,07) com estimativa de queda de 65,1% até 2015. A soma dos óbitos não investigados, não se aplica e de fichas sem investigação para qualquer variável analisada ultrapassa 50%. Conclusão: Os índices da Mortalidade Materna Direta na região do Grande ABC Paulista apresentaram níveis altos e queda discreta no tempo. Apenas o município de São Caetano do Sul apresentou queda expressiva de IMMD nos 15 anos de estudo e tendência a queda neste milênio com estimativa de atingir 65,1% até 2015. Descritores: Mortalidade materna; Políticas públicas; Mulheres; Saúde da mulher/estatística & dados numéricos; Complicações na gravidez/mortalidade; Mortalidade; Sistema Único de Saúde; Estudos epidemiológicos; Saúde da mulher/estatística & dados numéricos; Período pós-parto; Objetivos de desenvolvimento do milênio; Brasil/epidemiologia / Introduction: Maternal mortality is one of the best indicators of socioeconomic development of a country. Brazil has implemented public policies to reduce maternal mortality by 2015. The Grande ABC Paulista region in Brazil shows great socioeconomic heterogeneity among its municipalities, which can reflect the country social inequality, however presenting dimensions that allow greater control of mortality data. Objective: To evaluate the trend of maternal mortality in the Grande ABC Paulista region in the period of 1997-2011. Methodology: Ecological time series, where data was obtained from the database of the Information Technology Department of the Public Health Care System (DATASUS) of the Health Ministry of Brazil (MS). The data was transformed into direct maternal mortality indices (DMMI), stratified by municipalities, Human Development Indices (HDI), causes of maternal death according to the International Classification of Diseases (ICD-10), period and local of maternal death, socio-demographic parameters. Data were submitted to comparison tests (Mann-Whitney U test, Kruskal-Wallis test, followed by Dunn\'s multiple comparisons test) and association tests (linear regression) when applied and a significance of 5%. Results: The DMMI predominated in single women, aged 20-34 years old, white, 4 to 7 school age, in-hospital, postpartum, by bleeding / thrombosis / embolism and eclampsia. There was no difference in DMMI when comparing by HDI group. The Municipality of Rio Grande da Serra reached high DMMI values in the most of the analyzed covariates. São Caetano do Sul presented the lowest DMMI values and was the only municipality which presented decrement in the DMMI during the 15 years of the studied period (beta = - 0.67/year, p=0.03) and a trend in this millennium (2000-2011, beta- 0.55/year, p=0.07) with an estimated fall of 65.61% by 2015. The sum of not investigated, not applied and files without investigation for any analyzed variable exceeded 50%. Conclusion: The DMMI in the Grande ABC Paulista showed high levels and downward trend in time. São Caetano do Sul was the sole municipality where the DMMR dropped in 15 years of study and presented a tendency to decrease in this millennium with an estimated fall of 65.1% by 2015

Por apresentarem mecanismos de transmissão superponíveis, a infecção concomitante pelo vírus da hepatite C (VHC) e pelos vírus linfotrópicos de células T humanas dos tipos 1 (HTLV-1) e 2 (HTLV-2) é esperada. Considerando a relevância dessas infecções em nosso meio e a existência de lacunas no conhecimento da coinfeção VHC/HTLV, conduziu-se este estudo transversal, com o objetivo de comparar uma série de pacientes coinfectados, com indivíduos infectados pelo VHC isoladamente, no tocante a características sócio-demográficas e de exposição aos agentes virais, alterações clínicas e laboratoriais, bem como alterações histológicas do parênquima hepático. Selecionaram-se, com base em algoritmos de diagnóstico sorológico e de biologia molecular, pacientes adultos assistidos em ambulatórios do Hospital das Clínicas da FMUSP entre janeiro de 1993 e agosto de 2005, que apresentaram viremia pelo VHC, associada, ou não, a infecção por HTLV-1 ou HTLV-2, excluindo-se da amostra os coinfectados pelo VHB ou HIV. Coletaram-se dos pacientes selecionados características sócio-demográficas, informações acerca de exposição a vírus de transmissão sexual ou sangüínea, sinais e sintomas clínicos relacionados às infecções causadas pelo VHC ou HTLV, bem como dados laboratoriais hematológicos e de função hepática. Procedeu-se ainda à revisão sistemática dos achados histopatológicos do parênquima hepático, seguindo-se a classificação de Ishak. Compararam-se, então, os grupos VHC, VHC/HTLV-1 e VHC/HTLV-2, empregando-se o teste de X2 para as variáveis categóricas e o teste de Kruskal-Wallis para as variáveis contínuas. Em seguida, pela análise discriminante linear de Fischer, definiram-se funções classificatórias com variáveis que conjuntamente diferenciassem os grupos estudados. Finalmente, a acurácia discriminatória das funções classificatórias foi avaliada por validação cruzada, empregando-se a técnica leave-one-out. Compuseram a população estudada 85 pacientes, sendo 55 no grupo VHC, 24 no grupo VHC/HTLV-1 e 6 no grupo VHC/HTLV-2. À análise bivariada, não se observou diferença significativa entre os grupos no tocante a características sócio-demográficas, hábito de fumar, fatores de exposição às infecções virais, tais como transfusão sangüínea, tatuagem, acupuntura, ou número de parceiros sexuais. Ao contrário, o relato de uso de álcool, drogas endovenosas, ou cocaína inalatória, bem como a parceria sexual com UDEV foi mais freqüente entre os pacientes do grupo VHC/HTLV-2, enquanto o relato de parceiro sexual com hepatite predominou no grupo VHC. Do ponto de vista clínico, apenas a queixa de dor abdominal apresentou-se em freqüência significativamente diferente entre os grupos, sendo mais prevalente no grupo VHC. Em relação aos achados laboratoriais, apesar de contida nos intervalos de normalidade, houve diferença significativa na contagem de plaquetas em sangue periférico, com valores medianos mais elevados nos grupos de coinfectados. As concentrações séricas de aminotransferases e de GGT foram mais altas no grupo VHC. Apesar de freqüentemente encontradas alterações sugestivas de hepatopatia pelo VHC, como fibrose hepática e atividade necroinflamatória, a análise histopatológica não mostrou diferença significativa entre os grupos. À análise discriminante de Fischer, definiram-se funções classificatórias que melhor diferenciam os pacientes estudados, incluindo as variáveis sexo, faixa etária, relato de uso de drogas endovenosas e parceria sexual com indivíduo com hepatite. Por meio de validação cruzada, verificou-se que a acurácia discriminante das funções classificatórias foi alta (87,3%) para a identificação dos infectados pelo VHC isoladamente e intermediária (66,7%) para os coinfectados VHC/HTLV-2. O método não se mostrou, contudo, clinicamente útil na distinção de pacientes com coinfecção VHC/HTLV-1. / Co-infection with hepatitis C virus (HCV) and human T-lymphotropic virus types 1 (HTLV-1) and 2 (HTLV-2) is expected, as these viruses share common infection routes. Due to the relevance of these viral infections in Brazil and the existing gaps in knowledge about HCV/HTLV co-infection, we carried out this cross-sectional survey. A cohort of co-infected patients was compared to HCV-infected subjects, in regard to socio-demographic features, risk factors for viral acquisition, clinical and laboratory data, as well as liver histopathologic findings. Based on established serologic and molecular diagnostic algorithms, we selected HCV-viremic adult patients who attended the Hospital das Clínicas-FMUSP outpatient clinic from January 1993 to August 2005, whether or not they presented co-infection with HTLV-1 or HTLV-2. HBV and HIV-infected individuals were excluded from the sample. We collected patients\' sociodemographic characteristics, risk of exposure to blood-borne or sexually-transmitted viral agents, signs and symptoms related to HCV or HTLV disease, as well as laboratory data that included hematologic counts and liver function tests. Histopathologic findings were systematically reviewed, in accordance to the Ishak\'s scoring system. Patients from the HCV, HCV/HTLV-1 and HCV/HTLV-2 groups, were then compared by means of the X2 or Kruskal-Wallis tests for categorical or continuous variables, respectively. In addition, Fischer\'s linear discriminant analysis was applied to define classification functions that better identified the combined effect of variables important for discrimination of the study groups. Finally, the discriminating accuracy of the model was evaluated by cross-validation, using the leave-one-out technique. The study sample comprised 85 patients, 55 in the HCV group, 24 in the HCV/HTLV-1 group and 6 in the HCV/HTLV-2 group. In bivariable analysis, no significant difference was found among groups in regard to socio-demographic features, smoking, risk factors for viral acquisition, such as blood transfusion, tattooing, acupuncture, or number of sexual partners. In contrast, alcohol consumption, use of intravenous drugs or inhaled cocaine and sexual partnership with an intravenous drug user were more frequent in the HCV/HTLV-2 group, whereas patients in the HCV group more often reported a sexual partner with hepatitis. As far as clinical data are concerned, abdominal pain was the only variable to be reported differently, being more prevalent in the HCV group. Even though within normal ranges, co-infected patients presented higher median platelet counts, whereas aminotransferase and GGT levels were higher among HCV-infected subjects. No significant difference was seen in liver histopathologic findings, though HCV liver disease-associated abnormalities, such as fibrosis and necroinflammatory activity were often found in patients from the three groups. Classification functions, defined by discriminating analysis included as relevant variables sex, age, intravenous drug use and sexual partner with hepatitis. Cross-validation yielded high (87.3%) and intermediate (66,7%) discriminating accuracies for the HCV and HCV/HTLV-2 functions. However, this method was not shown clinically useful to distinguish HCV/HTLV-1 co-infected patients.