A utilização de bases de dados para estudos epidemiológicos, avaliação da qualidade e quantidade dos serviços de saúde vem despertando a atenção dos pesquisadores no contexto da Saúde Pública. No Brasil, as bases de dados do Sistema Único de Saúde (SUS) são exemplos de repositórios importantes que reúnem informações fundamentais sobre a Saúde. Entretanto, apesar dos avanços em termos de coleta e de ferramentas públicas para a pesquisa nessas bases de dados, tais como o TABWIN e o TABNET, esses recursos ainda não fazem uso de técnicas mais avançadas para a produção de informação gerencial, como as disponíveis em ferramentas OLAP (On Line Analytical Processing) e de mineração de dados. A situação é extremamente agravada pelo fato dos dados da Saúde Pública, produzidos por vários sistemas isolados, não estarem integrados, impossibilitando pesquisas entre diferentes bases de dados. Consequentemente, a produção de informação gerencial torna-se uma tarefa extremamente difícil. Por outro lado, a integração dessas bases de dados pode constituir um recurso indispensável e fundamental para a manipulação do enorme volume de dados disponível nesses ambientes e, assim, possibilitar a produção de informação e conhecimento relevantes, que contribuam para a melhoria da gestão em Saúde Pública. Acompanhar o seguimento de pacientes e comparar diferentes populações são outras importantes limitações das atuais bases de dados, uma vez que não há um identificador unívoco do paciente que possibilite executar tais tarefas. Esta Tese teve como objetivo a construção de um armazém de dados (data warehouse), a partir da análise de dez anos (período de 2000 a 2009) das principais bases de dados do SUS. Os métodos propostos para coleta, limpeza, padronização das estruturas dos bancos de dados, associação de registros ao paciente e integração dos sistemas de informação do SUS permitiram a identificação e o seguimento do paciente com sensibilidade de 99,68% e a especificidade de 97,94%. / The use of databases for epidemiologic studies, quality and quantity evaluation of health services have attracted the attention of researchers in the context of Public Health. In Brazil, the databases of the Sistema Único de Saúde (SUS) are examples of important repositories, which store fundamental information about health. However, despite of the advances in terms of load and public tools for research in those databases, such as TABWIN and TABNET, these resources do not use advanced techniques to produce management information as available in OLAP (On Line Analytical Processing) and data mining tools. The situation is drastically increased for the fact that data in public health, produced for different systems, are not integrated. This makes impossible to do research between different databases. As a consequence, the production of management information is a very difficult task. On the other hand, the integration of these databases can offer an important and fundamental resource to manipulate the enormous volume of data available in those environments and, in this way, to permit the production of relevant information and knowledge to improve the management of public health. The patient follow up and the comparison of different populations are other important limitations of the available databases, due to the absence of a common patient identifier. The objective of this Thesis was the construction of a data warehouse to analyze ten years (period from 2000 to 2009) of the principal databases of SUS. The proposed methods to load, clean, database structure standardization, patient record linkage and SUS information systems integration have been permitted patient identification and follow up with sensitivity of 99.6% and specificity of 97.94%.

Im ersten Aufsatz dieser Dissertation analysiere ich, wie sich ein negativer Arbeitsmarktnachfrage-Schock auf Fertilität auswirkt. Ich analysiere dies anhand des ostdeutschen Fertilitätsrückgangs nach dem Mauerfall und nutze unerwartete, exogene, und permanente Anpassungen der Arbeitsnachfrage, welche von industriellen Restrukturierungsprozessen resultierten. Ostdeutsche Frauen, die stärker vom negativen Arbeitsnachfrage-Schock betroffen waren, haben in den 1990er Jahren relativ mehr Kinder bekommen als jene Frauen, die von dem Schock weniger stark betroffen waren. Der Schock hat somit nicht nur das aggregierte Fertilitätsniveau gesenkt, sondern auch die Zusammensetzung der Mütter beeinflusst. Der zweite Aufsatz untersucht den Einfluss staatlicher Hilfen auf den späteren ökonomischen Erfolg junger Flüchtlinge. Wir untersuchen dies anhand von ostdeutschen Flüchtlingen, die von 1946 bis 1961 nach Westdeutschland geflohen sind. Nur „politische Flüchtlinge“ hatten ab 1953 Anspruch auf Flüchtlingshilfen. Somit können wir Identifikations-Probleme adressieren, die durch Selektion entstehen. Es zeigen sich positive Effekte der Flüchtlingshilfen auf die Bildung, Jobs, und das Einkommen von Flüchtlingen, die als junge Erwachsene migriert sind. Wir finden keine vergleichbaren Effekte für Flüchtlinge, die als Kinder migriert sind. Das letzte Kapitel präsentiert Ergebnisse eines Projektes, das partiell die Lücke schließt, welche derzeit für Ostdeutsche in den deutschen Sozialversicherungsdaten existiert. Durch die Verknüpfung letzterer mit dem „Datenspeicher Gesellschaftliches Arbeitsvermögen“ der DDR von 1989 haben wir einen neuen Datensatz geschaffen, welcher Analysen von Phänomenen wie Arbeitslosigkeit, beruflicher und regionaler Mobilität ermöglicht. Der neue Datensatz kann auch dazu beitragen, das existierende Wissen über die individuellen Arbeitsmarktkonsequenzen des Mauerfalls zu erweitern. / In the first essay of this dissertation, I analyze how a negative labor demand shock impacts fertility. I analyze this question in the context of the East German fertility decline after the fall of the Berlin Wall in 1989. I exploit differential pressure for restructuring across East German industries which led to unexpected, exogenous, and permanent changes to labor demand. I find that throughout the 1990s, women more severely impacted by the demand shock had relatively more children than their less-severely-impacted counterparts. Thus, the demand shock not only depressed the aggregate fertility level, but also changed the composition of mothers. The second essay explores the question of how refugee-specific aid impacts the medium-term economic success of young refugees. We address this question in the context of German Democratic Republic (GDR) refugees who escaped to West Germany between 1946 and 1961, exploiting that only the subgroup of "political refugees" was granted refugee-targeted aid, and that this only occurred after 1953. The quasi-experiment allows us to address identification difficulties resulting from the fact that refugees eligible for aid are both self-selected and screened by local authorities. We find positive effects of aid-eligibility on educational attainment, job quality and income among the refugees who migrated as young adults. We do not find similar effects of aid-eligibility for refugees who migrated as children. The final chapter of this thesis presents results of a project which partially closes a gap that currently exists for East Germans in the German social security data. By linking these data with the GDR's "Data Fund of Societal Work Power" from 1989, we have created a new data set that permits the analysis of phenomena such as unemployment, job mobility, and regional mobility. The new data set can also be used to refine existing knowledge of the individual-level labor market consequences of German reunification.

Introdução: A associação entre a infecção pelo vírus da imunodeficiência humana (HIV) e o câncer tem sido documentada desde os primórdios da epidemia da síndrome da imunodeficiência adquirida (Aids). A introdução da highly active antirretroviral therapy (HAART) alterou, profundamente, o curso da epidemia da Aids, reduzindo, drasticamente, a incidência de manifestações definidoras da síndrome, incluindo cânceres. No entanto, existem informações limitadas sobre a incidência de câncer em crianças e adolescentes com Aids vivendo em países em desenvolvimento. Objetivo: Descrever a epidemiologia do câncer em crianças e adolescentes com Aids no Município de São Paulo, no período de 1997 a 2012. Métodos: Trata-se de um estudo de base populacional, utilizando as bases de dados do Registro de Câncer de Base Populacional do Município de São Paulo e do Sistema de Informações de Agravos de Notificação (SINAN). As crianças e adolescentes (< 20 anos) com Aids e câncer foram identificadas por meio de um processo de linkage probabilístico entre as bases de dados supracitadas. Foram calculadas as taxas de incidência brutas e ajustadas por milhão de habitantes. Para comparar a incidência de câncer na população com Aids e a população geral foi calculada a razão de incidência padronizada (RIP) e respectivos intervalos de confiança de 95 por cento (IC 95 por cento ). A análise de tendência foi feita por meio do cálculo do annual percent change (APC) e IC 95 por cento correspondentes. A análise da sobrevida global de cinco anos após o câncer entre pacientes com Aids e na população geral foi calculada por meio do estimador produto limite de Kaplan-Meier e modelos univariados de riscos proporcionais de Cox. Mapas coropléticos em escalas monocromáticas foram gerados para descrever a distribuição de casos no Município. Resultados: Foram identificados 24 casos de câncer em pacientes com Aids menores de 20 anos, sendo 62,5 por cento cânceres definidores de Aids. Os cânceres mais incidentes foram o linfoma não Hodgkin, incluindo o linfoma de Burkitt (12; 50,0 por cento ), o linfoma de Hodgkin (6; 25,0 por cento ) e o sarcoma de Kaposi (3; 12,5 por cento ). A taxa bruta de incidência foi de 1.461,3 casos/milhão. A análise de tendência revelou redução significativa da incidência para todos os cânceres (APC= -14,5), influenciada pela queda nos cânceres definidores de Aids (APC= -17,0). O risco para câncer se mostrou aumentado (RIP= 3,9), sobretudo para o linfoma não Hodgkin, excluindo linfoma de Burkitt (RIP= 22,5), linfoma de Burkitt (RIP= 29,7) e linfoma de Hodgkin (RIP= 18,7). A probabilidade acumulada de sobrevida aos cinco anos foi de 56,3 por cento em crianças e adolescentes com Aids versus 87,5 por cento na população geral. A hazard ratio para óbito foi 5,2 (IC 95 por cento = 2,0; 13,6). O mapa da distribuição geográfica mostrou concentração dos casos nas áreas de classes sociais mais baixas do Município. Conclusão: Houve redução acentuada da incidência de cânceres definidores de Aids, como provável resultado da introdução da HAART. No entanto, crianças e adolescentes com Aids permanecem sob risco aumentado para o desenvolvimento de câncer quando comparadas à população geral. Para aquelas que desenvolveram câncer, o risco para óbito também se mostrou substancialmente elevado / Introduction: The association between human immunodeficiency virus (HIV) infection and cancer has been documented since the beginning of the epidemic of the acquired immunodeficiency syndrome (AIDS). The introduction of the highly active antiretroviral therapy (HAART) has profoundly altered the course of the AIDS epidemic, drastically reducing the incidence of AIDS-defining manifestations, including cancers. Nevertheless, there is limited information on the incidence of cancer in children and adolescents with AIDS living in developing countries. Objective: To describe the cancer epidemiology in children and adolescents with AIDS in the Municipality of São Paulo from 1997 to 2012. Methods: It is a population-based study, using the databases of the Population-based Cancer Registry of São Paulo and the Notifiable Diseases Information System (SINAN). Children and adolescents (< 20 years) with AIDS and cancer have been identified by means of a probabilistic record linkage process between the aforementioned databases. Crude and age-standardized incidence rates per million inhabitants were calculated. To compare the incidence of cancer in people with AIDS and that of the general population, standardized incidence ratio (SIR) and respective 95 per cent confidence intervals (95 per cent CI) were calculated. We examined trends by calculating the annual percent change (APC) and corresponding 95 per cent CI. The analyses of the overall five-year survival after cancer diagnosis among children and adolescents with AIDS and that of the general population were based on the Kaplan-Meier product limit estimator and univariate Cox proportional hazards models. Choropleth maps on monochromatic scales were generated to describe the distribution of cases across the Municipality. Results: We identified 24 cases of cancer in patients with AIDS aged 20 years and younger, of which, 62.5 per cent were AIDS-defining malignancies. The most incident cancers were non-Hodgkin\'s lymphoma, including Burkitt\'s lymphoma (12; 50.0 per cent ), Hodgkin\'s lymphoma (6; 25.0 per cent ) and Kaposi sarcoma (3; 12.5 per cent ). The age-standardized incidence rate was 1,461.3 cases/million. The trend analyses revealed a significant reduction in the incidence of all cancers (APC= -14.5), driven by the decrease in AIDS-defining cancers (APC= -17.0). The overall risk for cancer was significantly increased (SIR= 3.9), especially for non-Hodgkin lymphoma, excluding Burkitts lymphoma (SIR= 22.5), Burkitt\'s lymphoma (SIR= 29.7) and Hodgkin\'s lymphoma (SIR= 18.7). The overall probability of survival at five years after cancer was 56.3 per cent in children and adolescents with AIDS versus 87.5 per cent in the general population. The hazard ratio for death was 5.2 (95 per cent CI= 2.0, 13.6). The map of the geographical distribution showed a concentration of cases in the low-income areas of the Municipality. Conclusion: There was a marked reduction in the incidence of AIDS-defining cancers, likely to be a result of the introduction of HAART. However, children and adolescents with AIDS remain at increased risk for the development of cancer when compared to the general population. For those who developed cancer, the risk of death was also significantly higher

In questo studio, attraverso la realizzazione di un’indagine longitudinale basata su dati amministrativi, sono stati ricostruiti i redditi delle famiglie residenti nel comune di Brescia per gli anni 2005-2008, in una prospettiva trasversale e longitudinale, individuando situazioni di disuguaglianza, di disagio e povertà economica di alcune fasce della popolazione. L’indagine longitudinale è stata realizzata mediante il record-linkage tra i dati amministrativi provenienti dall’Anagrafe comunale e quelli fiscali del Sistema Interscambio Anagrafe Tributaria Enti Locali dell’Agenzia delle Entrate (SIATEL) per il comune di Brescia. La peculiarità e l’importanza di questo lavoro risiedono sia nell’utilizzare dati di fonte amministrativa fiscale e anagrafica nella stima sui redditi e povertà delle famiglie, sia nella possibilità di ottenere stime a livello comunale o small-area, ampliando il campo della ricerca sociale sul tema oggetto di studio. L’approccio teorico di riferimento adottato è quello unidimensionale, basato sul reddito, e relativo, in cui la povertà è definita in relazione allo standard di benessere raggiunto dalla popolazione di riferimento nel suo complesso. Pertanto, anziché la soglia di povertà nazionale, che tende a sottostimare la povertà nel nord d’Italia, è stata adottata una soglia di povertà locale, pari al 60% del reddito mediano equivalente delle famiglie residenti. / In this study the incomes of the families residing in the town of Brescia for the years 2005-2008 have been simulated in a cross-section and longitudinal perspective, through the creation of a Panel based on administrative data. The research aimed at identifying situations of inequality, dislocation and economic poverty of certain population groups. The Panel was carried out on the basis of the record-linkage administrative data from Registry Office and ” Informatics’ System of Local Italian Revenue Agency” (SIATEL), for the town of Brescia. The uniqueness and importance of this work is the use of live data in estimating income and family poverty using fiscal and personal data from registry office sources, as well as in the availability of estimates at the municipal level or small-area, thus expanding the social research on the subject of study. The theoretical approach adopted by reference is one-dimensional (based on income) and relative, in which poverty is defined in relation to the standards being achieved by the reference population as a whole. Therefore, instead of the national poverty line, which tends to underestimate poverty in northern Italy, a local poverty threshold was adopted, equal to 60% of equivalised median income of the families residing in the town of Brescia.

Introdução: A associação entre a infecção pelo vírus da imunodeficiência humana (HIV) e o câncer tem sido documentada desde os primórdios da epidemia da síndrome da imunodeficiência adquirida (Aids). A introdução da highly active antirretroviral therapy (HAART) alterou, profundamente, o curso da epidemia da Aids, reduzindo, drasticamente, a incidência de manifestações definidoras da síndrome, incluindo cânceres. No entanto, existem informações limitadas sobre a incidência de câncer em crianças e adolescentes com Aids vivendo em países em desenvolvimento. Objetivo: Descrever a epidemiologia do câncer em crianças e adolescentes com Aids no Município de São Paulo, no período de 1997 a 2012. Métodos: Trata-se de um estudo de base populacional, utilizando as bases de dados do Registro de Câncer de Base Populacional do Município de São Paulo e do Sistema de Informações de Agravos de Notificação (SINAN). As crianças e adolescentes (< 20 anos) com Aids e câncer foram identificadas por meio de um processo de linkage probabilístico entre as bases de dados supracitadas. Foram calculadas as taxas de incidência brutas e ajustadas por milhão de habitantes. Para comparar a incidência de câncer na população com Aids e a população geral foi calculada a razão de incidência padronizada (RIP) e respectivos intervalos de confiança de 95 por cento (IC 95 por cento ). A análise de tendência foi feita por meio do cálculo do annual percent change (APC) e IC 95 por cento correspondentes. A análise da sobrevida global de cinco anos após o câncer entre pacientes com Aids e na população geral foi calculada por meio do estimador produto limite de Kaplan-Meier e modelos univariados de riscos proporcionais de Cox. Mapas coropléticos em escalas monocromáticas foram gerados para descrever a distribuição de casos no Município. Resultados: Foram identificados 24 casos de câncer em pacientes com Aids menores de 20 anos, sendo 62,5 por cento cânceres definidores de Aids. Os cânceres mais incidentes foram o linfoma não Hodgkin, incluindo o linfoma de Burkitt (12; 50,0 por cento ), o linfoma de Hodgkin (6; 25,0 por cento ) e o sarcoma de Kaposi (3; 12,5 por cento ). A taxa bruta de incidência foi de 1.461,3 casos/milhão. A análise de tendência revelou redução significativa da incidência para todos os cânceres (APC= -14,5), influenciada pela queda nos cânceres definidores de Aids (APC= -17,0). O risco para câncer se mostrou aumentado (RIP= 3,9), sobretudo para o linfoma não Hodgkin, excluindo linfoma de Burkitt (RIP= 22,5), linfoma de Burkitt (RIP= 29,7) e linfoma de Hodgkin (RIP= 18,7). A probabilidade acumulada de sobrevida aos cinco anos foi de 56,3 por cento em crianças e adolescentes com Aids versus 87,5 por cento na população geral. A hazard ratio para óbito foi 5,2 (IC 95 por cento = 2,0; 13,6). O mapa da distribuição geográfica mostrou concentração dos casos nas áreas de classes sociais mais baixas do Município. Conclusão: Houve redução acentuada da incidência de cânceres definidores de Aids, como provável resultado da introdução da HAART. No entanto, crianças e adolescentes com Aids permanecem sob risco aumentado para o desenvolvimento de câncer quando comparadas à população geral. Para aquelas que desenvolveram câncer, o risco para óbito também se mostrou substancialmente elevado / Introduction: The association between human immunodeficiency virus (HIV) infection and cancer has been documented since the beginning of the epidemic of the acquired immunodeficiency syndrome (AIDS). The introduction of the highly active antiretroviral therapy (HAART) has profoundly altered the course of the AIDS epidemic, drastically reducing the incidence of AIDS-defining manifestations, including cancers. Nevertheless, there is limited information on the incidence of cancer in children and adolescents with AIDS living in developing countries. Objective: To describe the cancer epidemiology in children and adolescents with AIDS in the Municipality of São Paulo from 1997 to 2012. Methods: It is a population-based study, using the databases of the Population-based Cancer Registry of São Paulo and the Notifiable Diseases Information System (SINAN). Children and adolescents (< 20 years) with AIDS and cancer have been identified by means of a probabilistic record linkage process between the aforementioned databases. Crude and age-standardized incidence rates per million inhabitants were calculated. To compare the incidence of cancer in people with AIDS and that of the general population, standardized incidence ratio (SIR) and respective 95 per cent confidence intervals (95 per cent CI) were calculated. We examined trends by calculating the annual percent change (APC) and corresponding 95 per cent CI. The analyses of the overall five-year survival after cancer diagnosis among children and adolescents with AIDS and that of the general population were based on the Kaplan-Meier product limit estimator and univariate Cox proportional hazards models. Choropleth maps on monochromatic scales were generated to describe the distribution of cases across the Municipality. Results: We identified 24 cases of cancer in patients with AIDS aged 20 years and younger, of which, 62.5 per cent were AIDS-defining malignancies. The most incident cancers were non-Hodgkin\'s lymphoma, including Burkitt\'s lymphoma (12; 50.0 per cent ), Hodgkin\'s lymphoma (6; 25.0 per cent ) and Kaposi sarcoma (3; 12.5 per cent ). The age-standardized incidence rate was 1,461.3 cases/million. The trend analyses revealed a significant reduction in the incidence of all cancers (APC= -14.5), driven by the decrease in AIDS-defining cancers (APC= -17.0). The overall risk for cancer was significantly increased (SIR= 3.9), especially for non-Hodgkin lymphoma, excluding Burkitts lymphoma (SIR= 22.5), Burkitt\'s lymphoma (SIR= 29.7) and Hodgkin\'s lymphoma (SIR= 18.7). The overall probability of survival at five years after cancer was 56.3 per cent in children and adolescents with AIDS versus 87.5 per cent in the general population. The hazard ratio for death was 5.2 (95 per cent CI= 2.0, 13.6). The map of the geographical distribution showed a concentration of cases in the low-income areas of the Municipality. Conclusion: There was a marked reduction in the incidence of AIDS-defining cancers, likely to be a result of the introduction of HAART. However, children and adolescents with AIDS remain at increased risk for the development of cancer when compared to the general population. For those who developed cancer, the risk of death was also significantly higher

To increase medicine safety, researchers use adverse event reports to assess causal relationships between drugs and suspected adverse reactions. VigiBase, the world's largest database of such reports, collects data from numerous sources, introducing the risk of several records referring to the same case. These duplicates negatively affect the quality of data and its analysis. Thus, efforts should be made to detect and clean them automatically.  Today, VigiBase holds more than 3.8 million COVID-19 vaccine adverse event reports, making deduplication a challenging problem for existing solutions employed in VigiBase. This thesis project explores methods for this task, explicitly focusing on records with a COVID-19 vaccine. We implement Jaccard similarity, TF-IDF, and BERT to leverage the abundance of information contained in the free-text narratives of the reports. Mean-pooling is applied to create sentence embeddings from word embeddings produced by a pre-trained SapBERT model fine-tuned to maximise the cosine similarity between narratives of duplicate reports. Narrative similarity is quantified by the cosine similarity between sentence embeddings.  We apply a Gradient Boosted Decision Tree (GBDT) model for classifying report pairs as duplicates or non-duplicates. For a more calibrated model, logistic regression fine-tunes the leaf values of the GBDT. In addition, the model successfully implements a ruleset to find reports whose narratives mention a unique identifier of its duplicate. The best performing model achieves 73.3% recall and zero false positives on a controlled testing dataset for an F1-score of 84.6%, vastly outperforming VigiBase’s previously implemented model's F1-score of 60.1%. Further, when manually annotated by three reviewers, it reached an average 87% precision when fully deduplicating 11756 reports amongst records relating to hearing disorders.

No description available.

Objective: To determine if paternal preconception exposure to ionizing radiation through uranium mining increases the risk of congenital anomaly (CA) in offspring. Methods: A population-based matched case-control study was conducted. Cases were infants with CAs recorded in the Canadian Congenital Anomalies Surveillance System and born alive in Ontario 1979-86 (ICD-9 codes 740-759); controls were liveborn infants without CAs identified from Ontario birth certificates and individually matched to cases (case-control file {CCF}). Exposed fathers were identified through the linkage of the CCF to the Mining Master File or the National Dose Registry file, which include those who worked in Ontario uranium mines 1952-1986. For men who linked with a case or control child, radon, gamma and total gonadal doses were estimated for three preconception periods: entire, 3-months and 6-months. Odds ratios were estimated using conditional logistic regression. Results: Linkage of 28,991 uranium miners and 40,482 case-control pairs of fathers and offspring in the CCF identified 431 discordant pairs. There was no evidence of increased risk of a child having a CA if the father was ever a uranium miner before conception of the child (OR=0.89, 95% CI=0.74–1.08). Since gamma radiation (especially during the 6-month preconception period) is more biologically relevant to gonads than radon, further analyses were performed on 117 discordant pairs where data on gamma exposures were available. When ever/never miner, exposed to gamma (yes/no), and gamma dose-response variables were all in the model, there was no ever/never miner effect (OR=1.20, 95% CI=0.85–1.69, p-value=0.30), an inverse association for exposure to gamma (OR=0.42, 95% CI=0.25–0.71, p-value=0.001), but most importantly, there was no statistically significant dose-response relationship between gamma dose during the 6-month preconception period and all CAs (OR=1.15 per loge {mSv+0.01}, 95% CI=0.83–1.59, p-value=0.40). Similarly, no dose-response relationship was observed for exposure to gamma radiation in the 3-month preconception period, or for radon or total gonadal radiation in the 3- or 6-month preconception periods. Conclusion: There was no increased risk of a CA among liveborn children of Ontario uranium miners who were exposed to radon, gamma or total radiation during the 3- or 6-month periods before conception.

Objective: To determine if paternal preconception exposure to ionizing radiation through uranium mining increases the risk of congenital anomaly (CA) in offspring. Methods: A population-based matched case-control study was conducted. Cases were infants with CAs recorded in the Canadian Congenital Anomalies Surveillance System and born alive in Ontario 1979-86 (ICD-9 codes 740-759); controls were liveborn infants without CAs identified from Ontario birth certificates and individually matched to cases (case-control file {CCF}). Exposed fathers were identified through the linkage of the CCF to the Mining Master File or the National Dose Registry file, which include those who worked in Ontario uranium mines 1952-1986. For men who linked with a case or control child, radon, gamma and total gonadal doses were estimated for three preconception periods: entire, 3-months and 6-months. Odds ratios were estimated using conditional logistic regression. Results: Linkage of 28,991 uranium miners and 40,482 case-control pairs of fathers and offspring in the CCF identified 431 discordant pairs. There was no evidence of increased risk of a child having a CA if the father was ever a uranium miner before conception of the child (OR=0.89, 95% CI=0.74–1.08). Since gamma radiation (especially during the 6-month preconception period) is more biologically relevant to gonads than radon, further analyses were performed on 117 discordant pairs where data on gamma exposures were available. When ever/never miner, exposed to gamma (yes/no), and gamma dose-response variables were all in the model, there was no ever/never miner effect (OR=1.20, 95% CI=0.85–1.69, p-value=0.30), an inverse association for exposure to gamma (OR=0.42, 95% CI=0.25–0.71, p-value=0.001), but most importantly, there was no statistically significant dose-response relationship between gamma dose during the 6-month preconception period and all CAs (OR=1.15 per loge {mSv+0.01}, 95% CI=0.83–1.59, p-value=0.40). Similarly, no dose-response relationship was observed for exposure to gamma radiation in the 3-month preconception period, or for radon or total gonadal radiation in the 3- or 6-month preconception periods. Conclusion: There was no increased risk of a CA among liveborn children of Ontario uranium miners who were exposed to radon, gamma or total radiation during the 3- or 6-month periods before conception.

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2016-09-28T11:44:16Z No. of bitstreams: 2 Dissertação - Lísia Gomes Martins de Moura Tomich - 2016.pdf: 2901743 bytes, checksum: 22cd41bfc4499cfd4754d856635357af (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2016-09-28T11:44:45Z (GMT) No. of bitstreams: 2 Dissertação - Lísia Gomes Martins de Moura Tomich - 2016.pdf: 2901743 bytes, checksum: 22cd41bfc4499cfd4754d856635357af (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2016-09-28T11:44:45Z (GMT). No. of bitstreams: 2 Dissertação - Lísia Gomes Martins de Moura Tomich - 2016.pdf: 2901743 bytes, checksum: 22cd41bfc4499cfd4754d856635357af (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2016-08-15 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / INTRODUCTION: Routine infant immunization with meningococcal C conjugate vaccine (MenC-V) started in Brazil in November 2010, administered at three, five and 12 months of age with no catch-up for older age-groups. However, by March 2010, a vaccination campaign with MenC-V was performed in Salvador in individuals under five years-old, and from 10 to 24 yearsold. In São Paulo state, the outbreaks occurred in teenagers and young adults prompting one-time vaccination campaign from 2010 to 2014 targeting these age-groups. OBJECTIVE: To assess the direct and indirect impact (herd effect) of vaccination on invasive meningococcal disease (MD) for capsular group C (MenC) four years after the introduction of MenC-V in three scenarios: i) Brazil as a whole (routine vaccination in childhood only); ii) Brazil except for Salvador (vaccination campaign with teenagers during the year of MenC-V introduction); and iii) São Paulo state (vaccination campaign for adolescents and young adults during 2010-2014 to control outbreaks). METHODS: We performed an ecological quasi-experimental design from 2008 to 2014 using data from the National Reference Laboratory for Meningitis, and data from the National Information System for Notifiable Diseases. A deterministic linkage was performed between the two databases to improve the accuracy of the detection of MD, especially in capsular groups. An interrupted time-series analysis was conducted using the Holt-Winters technique to control for pre-existing trends and seasonal variations. The MenC vaccination impact was evaluated as the percentage of reduction in the incidence rates of MenC in the post-vaccination period (2012 to 2014), using the pre-vaccination period (2008 to 2010) to estimate what would be expected on the post-vaccination period, whether the vaccination had not been introduced. For Salvador, we analyzed the effect of the vaccination on the number of MenC cases. RESULTS: A total of 18,136 invasive MD cases were analyzed. For Brazil as a whole, the vaccination reduced 67.4% (lower 95%CI 42.5%) the rates for MenC for infants under 12 months, 92.3% (lower 95%CI 77.7%) for the age-group 12-23 months, and 65.7% (lower 95%CI 28%) for children aged 2-4 years. Indirect impact (20-24.7%) was observed in the age-group 5-19 years. When excluding Salvador from the analysis of Brazil, the indirect impact was observed only for children in the age-group 5-9 years. In the scenario of São Paulo state, similarly to Brazil, significant impact was observed in the target age-groups, in addition to indirect impact in the age group 5-9 years. In Salvador, in addition to the effect on the vaccinated population a sharp and sustainable decline of MenC cases was observed in all age-groups not target for vaccination. Overall, 1,170 cases of MenC were averted in Brazil after the introduced of Men-C vaccination. CONCLUSION: The strategy of catch-up for adolescents and young adults, especially during the year of MenC-V introduction may lead to rapid and sustainable herd effect. / A vacina meningocócica conjugada contra o grupo capsular C (MenC-V) foi introduzida no calendário de imunização infantil brasileiro em novembro de 2010, sendo administrada aos três, cinco e 12 meses de idade sem catch-up para os demais grupos etários. Entretanto, em março de 2010, uma campanha de vacinação com MenC-V foi realizada em Salvador para indivíduos menores de cinco anos de idade e de 10 a 24 anos. No estado de São Paulo os surtos ocorreram em adolescentes e adultos jovens, determinando campanhas de vacinações de bloqueio nessa faixa etária nos anos de 2010 a 2014. OBJETIVO: Avaliar o impacto direto e indireto (rebanho) da vacinação nas taxas de incidência de doença meningocócica (DM) invasiva pelo grupo capsular C (MenC) após quatro anos da introdução da MenC-V em três cenários: i) Brasil como um todo (imunização de rotina somente de crianças); ii) Brasil exceto Salvador (campanha de vacinação em adolescentes no ano de introdução da MenCV); e iii) estado de São Paulo (vacina de rotina na infância e vacinações de bloqueio em adolescentes e adultos jovens para controlar surtos). MÉTODOS: Foi realizado um estudo ecológico quasi-experimental para avaliar o impacto da vacinação em série histórica de 2008 a 2014 usando os bancos de dados do Laboratório Nacional de Referência para Meningites Bacterianas, Instituto Adolfo Lutz (IAL) e o Sistema de Informação de Agravos de Notificação (Sinan). Um processo de vinculação (linkage) determinístico entre as duas bases foi realizado para melhorar a acurácia da detecção de casos de DM, especialmente de grupo capsulares. Uma análise de série temporal interrompida foi conduzida utilizando a técnica de Holt-Winters para controlar por tendência pré-existente e variações sazonais. O desfecho foi taxa de MenC. O impacto da vacinação foi avaliado pelo percentual de redução da incidência de MenC no período pós-vacinal (2012 a 2014), utilizando o período pré-vacinal (2008 a 2010) para estimar o que seria esperado no período pós-vacinal, caso a vacinação não tivesse sido introduzida. Para Salvador foi analisado o efeito da MenC-V no número de casos de MenC. RESULTADOS: Um total de 18.136 casos de DM invasiva foram analisados. Para o Brasil como um todo, a vacinação reduziu significativamente a DM por MenC na faixa etária alvo, com redução de 67,4% (limite inferior do IC95% 42,5%) em menores de 12 meses, 92,3% (limite inferior do IC95% 77,7%) para faixa etária de 12-23 meses e 65,7% (limite inferior do IC95% 28%) em crianças de 2-4 anos, e efeito rebanho foi observado na faixa etária de 5 a 19 anos com 20-24,7%. Quando se exclui Salvador na análise do Brasil, impacto indireto significativo foi observado somente em crianças de 5-9 anos. No cenário São Paulo, semelhante ao Brasil, observou-se impacto estatisticamente significante nas faixas etárias alvo do PNI, além do efeito rebanho na faixa etária de 5-9 anos de idade. Para Salvador, o impacto da vacinação apresentou um declínio acentuado e sustentável em todas as faixas etárias fora do alvo da vacinação. Ao todo, 1.170 casos de MenC foram evitados no período estudado. CONCLUSÃO: A estratégia de vacinação de catch-up em adolescentes e adultos jovens, especialmente no ano de introdução da MenC-V, promoveu um rápido e sustentável rebanho.