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Riscos competitivos : uma aplicação na sobrevida de pacientes com câncerGiordani, Natalia Elis January 2015 (has links)
A quantidade de novos casos de câncer, o número de mortes causadas por ele e a quantidade de pessoas convivendo com a doença (cinco anos após o diagnóstico) têm crescido em todo o mundo. Em função disso, analisar dados de pacientes com câncer torna-se uma ferramenta necessária para avaliar os programas de tratamento e monitorar o progresso das iniciativas de controle da doença. No que tange a análise, a mortalidade é um dos parâmetros utilizados para avaliar os resultados dessa área e as metodologias tradicionalmente utilizadas compreendem o método de Kaplan-Meier e o modelo de Cox. Ambos, porém, desprezam que um paciente com câncer pode vir a óbito por um câncer diferente do primeiro diagnosticado ou, até mesmo, por causas não relacionadas à doença. Portanto, propomos a utilização e entendimento de métodos de análise de sobrevivência que consideram eventos competitivos a fim avaliar incidências, letalidades e fatores associados ao óbito de pacientes com câncer primário atendidos no Hospital de Clínicas de Porto Alegre entre 2002 e 2009. Os resultados obtidos permitiram um melhor conhecimento dos tipos de cânceres com maiores incidências (pele (1.920 casos), próstata (1.080 casos), brônquios e pulmões (950 casos), mama (893 casos), sistema hematopoiético e reticuloendotelial (654 casos), cólon (573 casos), esôfago (497 casos), estômago (422 casos), neoplasia maligna secundária e não especificada dos gânglios linfáticos (360 casos) e colo do útero (328 casos)) e letalidades (pâncreas (145 óbitos; 57,1%), brônquios e pulmões (527 óbitos; 55,5%) e esôfago (262 óbitos, 52,7%)), considerando os eventos competitivos. Em função das vantagens do método, recomenda-se aos pesquisadores que não desprezem, em seus estudos, situações com eventos competitivos, uma vez que há softwares e diversos materiais disponíveis que auxiliam e facilitam sua aplicação. / The amount of new cancer cases, the number of deaths caused by it, and the number of people living with the disease (five years after the diagnosis) have grown around the world. Due that, analyzing cancer patient’s data becomes a necessary tool for evaluating treatment programs and monitor the progress of the disease control initiatives. Regarding the analysis, mortality is one of the parameters used to evaluate the results of this area and the methodologies traditionally used include the Kaplan-Meier and Cox model. However, these methodologies do not consider the fact that the death of a cancer patient can be caused by a different cancer diagnosed or even by causes unrelated to the disease. Therefore, we propose the use and understanding of survival analysis methods that consider competing events in order to assess incidence, lethality and factors associated with death in patients with primary cancer attended at Hospital de Clínicas de Porto Alegre from 2002 to 2009. The results allowed a better understanding of the types of cancers with higher incidence (skin (1,920 cases), prostate (1,080 cases), bronchi and lungs (950 cases), breast (893 cases), hematopoietic and reticuloendothelial system (654 cases), colon (573 cases), esophagus (497 cases), stomach (422 cases), second malignancy and not specified lymph nodes (360 cases) and cervix (328 cases)) and lethality (pancreas (145 deaths; 57.1%), bronchi and lungs (527 deaths; 55.1%) and esophagus (262 deaths; 52.7%)), considering the competing events. In addition, we also evaluated how gender and age contribute to the risk of death from some cancers: women has bigger risk of death for esophageal cancer, while age was associated with the risk of death for prostate cancer. This study allowed characterizing the profile of cancers attended by the hospital by considering the competing events into the estimates methods. Due the advantages of the method, we recommend to researchers do not despise, in their studies, situations with competing events, since there are many softwares and materials available to help and facilitate its implementation.
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Sobrevida de mulheres com câncer de mama atendidas em um serviço de reabilitação / Survival of women with breast cancer treated at a rehabilitation serviceLais Corsino Durant 25 November 2016 (has links)
O câncer de mama apresenta alta incidência na população feminina, sendo considerado uma das principais causas de morte por câncer entre mulheres em diversos países; devido a isso, tornam-se essenciais estudos de sobrevivência na área oncológica, para avaliar resultados, fatores relacionados e delinear o comportamento da doença. Este estudo teve como objetivo avaliar a taxa de sobrevida em mulheres com câncer de mama atendidas em um serviço de reabilitação de mulheres mastectomizadas, tratadas em hospital universitário de nível terciário, localizado no interior da região Sudeste do país. A coorte foi identificada a partir de busca de atendimentos realizados no núcleo de reabilitação de 1989 a 2014. A coleta foi realizada em dados secundários, complementado por busca no banco do Sistema de Informação sobre Mortalidade (SIM), contato telefônico e distribuição de cartas. As principais variáveis analisadas foram as sociodemográficas: idade ao diagnóstico, cor da pele, estado civil e procedência; as clínicas e de tratamento: tamanho do tumor, estadiamento, marcadores tumorais, hormonioterapia, cirurgia e radioterapia, entre outras. Os dados foram apresentados de maneira descritiva por meio de números absolutos, medidas de tendência central e de variabilidade. As funções de sobrevida foram calculadas por meio do método de Kaplan- Meier, e para comparação entre as curvas foi utilizado o teste Log Rank. O nível de significância considerado para o estudo foi de 0,05. Não foi realizado neste estudo o modelo de riscos proporcionais de Cox. Os resultados deste estudo indicam que a sobrevida global em 60 meses desta população foi de 78,5%. E a sobrevida livre de doença (SLD) foi 75,8% em 60 meses. Apresentaram diferenças significativas em relação à ocorrência ao desfecho analisado, que foi o óbito, das características sociodemográficas, apenas as variáveis estado civil (p < 0,007) e escolaridade (p < 0,000). Na análise das curvas de sobrevivência, identificamos uma sobrevivência menor para aquelas mulheres que tiveram até 4 anos de estudo. Referente às características clínicas, o tipo histológico mais frequente foi o CDI com (82,2%); 49,9% apresentavam tumor entre 2 e 5 cm e o estádio clínico predominante no diagnóstico foi o IIA (25,7%), o estadiamento e presença de receptor de hormônio estrógeno e progesterona positivos, apresentaram uma relação estatisticamente significativa com a ocorrência do óbito (p < 0,000) e diferenças significativas nas curvas de sobrevivência. Aquelas que não desenvolveram metástase à distância apresentaram sobrevida de 96,9% em cinco anos, comparado com aquelas que tiveram metástase em 5 anos (50%). Houve significância pelo teste de Log-rank (p<0,000) nessa variável. Os resultados deste estudo fortalecem a importância do diagnóstico precoce através do rastreamento por meio do exame clínico das mamas e de mamografia, aliado ao tratamento eficaz. A análise da sobrevivência dessas mulheres possibilitou conhecer o perfil de mulheres atendidas em um serviço público de saúde, de nível terciário/quaternário, de alta complexidade e de referência. Estas informações são extremamente úteis para os gestores de saúde adotarem medidas voltadas para a prevenção e controle da doença, assim como para avaliações da qualidade do cuidado prestado e acessibilidade ao sistema de saúde / Breast cancer has a high incidence in the female population and is considered a major cause of cancer death among women in many countries, there fore it is essential more survival studies in oncology to evaluate results, related factors and outline the behavior disease. This study aimed to evaluate the survival rate of women treated in a rehabilitation service of mastectomies at the university hospital of tertiary level, located in the Southeast region of the country. The cohort was identified from search services performed in the rehabilitation center from 1989 to 2014. The data were collected on secondary data, complemented by search the database of the Mortality Information System (MIS), telephone call and distribution of cards. The main demographic variables were: age at diagnosis, skin color, marital status and origin, clinical and treatment: tumor size, stage, tumor markers, hormone therapy, surgery and radiation, among others. The data were presented descriptively by absolute numbers, measures of central tendency and variability. Survival functions were calculated using the Kaplan-Meier method and to compare the curves we used the log rank test. The level of significance for the study was 0.05. It was not done in this study the model of Cox proportional hazards. The results indicated that overall survival at 60 months of this population was 78.5%, and the specific-survival was 75.8% in 60 months. Only the variables marital status (p <0.007) and education (p <0.000), the sociodemographic characteristics, showed significant differences in the occurrence analyzed the outcome, which was death. In the analysis of the survival curves we identified a lower survival for those women who had up to 4 years of study. Regarding the clinical features, the most common histological type was with CDI (82.2%); 49.9% had tumors between 2 and 5 cm and the predominant clinical stage at diagnosis was the IIA (25.7%), the staging and the presence of the hormone estrogen and progesterone receptor positive showed a statistically significant related to the occurrence of death (p <0.000) and significant differences in survival curves. Those who did not develop distant metastases had a survival rate of 96.9% in five years compared with those who had metastasis in 5 years (50%). There were significant by log-rank test (p <0.000) in this variable. The results of this study reinforce the importance of early diagnosis through screening by clinical breast examination and mammography combined with effective treatment. The analysis of the survival of these women showed the profile of women in reference a public health service, tertiary / quaternary level, high complexity. These informations are extremely useful for health managers to adopt measures aimed at preventing and controlling the disease, as well as the quality of service and accessibility to health care system assessments
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Riscos competitivos : uma aplicação na sobrevida de pacientes com câncerGiordani, Natalia Elis January 2015 (has links)
A quantidade de novos casos de câncer, o número de mortes causadas por ele e a quantidade de pessoas convivendo com a doença (cinco anos após o diagnóstico) têm crescido em todo o mundo. Em função disso, analisar dados de pacientes com câncer torna-se uma ferramenta necessária para avaliar os programas de tratamento e monitorar o progresso das iniciativas de controle da doença. No que tange a análise, a mortalidade é um dos parâmetros utilizados para avaliar os resultados dessa área e as metodologias tradicionalmente utilizadas compreendem o método de Kaplan-Meier e o modelo de Cox. Ambos, porém, desprezam que um paciente com câncer pode vir a óbito por um câncer diferente do primeiro diagnosticado ou, até mesmo, por causas não relacionadas à doença. Portanto, propomos a utilização e entendimento de métodos de análise de sobrevivência que consideram eventos competitivos a fim avaliar incidências, letalidades e fatores associados ao óbito de pacientes com câncer primário atendidos no Hospital de Clínicas de Porto Alegre entre 2002 e 2009. Os resultados obtidos permitiram um melhor conhecimento dos tipos de cânceres com maiores incidências (pele (1.920 casos), próstata (1.080 casos), brônquios e pulmões (950 casos), mama (893 casos), sistema hematopoiético e reticuloendotelial (654 casos), cólon (573 casos), esôfago (497 casos), estômago (422 casos), neoplasia maligna secundária e não especificada dos gânglios linfáticos (360 casos) e colo do útero (328 casos)) e letalidades (pâncreas (145 óbitos; 57,1%), brônquios e pulmões (527 óbitos; 55,5%) e esôfago (262 óbitos, 52,7%)), considerando os eventos competitivos. Em função das vantagens do método, recomenda-se aos pesquisadores que não desprezem, em seus estudos, situações com eventos competitivos, uma vez que há softwares e diversos materiais disponíveis que auxiliam e facilitam sua aplicação. / The amount of new cancer cases, the number of deaths caused by it, and the number of people living with the disease (five years after the diagnosis) have grown around the world. Due that, analyzing cancer patient’s data becomes a necessary tool for evaluating treatment programs and monitor the progress of the disease control initiatives. Regarding the analysis, mortality is one of the parameters used to evaluate the results of this area and the methodologies traditionally used include the Kaplan-Meier and Cox model. However, these methodologies do not consider the fact that the death of a cancer patient can be caused by a different cancer diagnosed or even by causes unrelated to the disease. Therefore, we propose the use and understanding of survival analysis methods that consider competing events in order to assess incidence, lethality and factors associated with death in patients with primary cancer attended at Hospital de Clínicas de Porto Alegre from 2002 to 2009. The results allowed a better understanding of the types of cancers with higher incidence (skin (1,920 cases), prostate (1,080 cases), bronchi and lungs (950 cases), breast (893 cases), hematopoietic and reticuloendothelial system (654 cases), colon (573 cases), esophagus (497 cases), stomach (422 cases), second malignancy and not specified lymph nodes (360 cases) and cervix (328 cases)) and lethality (pancreas (145 deaths; 57.1%), bronchi and lungs (527 deaths; 55.1%) and esophagus (262 deaths; 52.7%)), considering the competing events. In addition, we also evaluated how gender and age contribute to the risk of death from some cancers: women has bigger risk of death for esophageal cancer, while age was associated with the risk of death for prostate cancer. This study allowed characterizing the profile of cancers attended by the hospital by considering the competing events into the estimates methods. Due the advantages of the method, we recommend to researchers do not despise, in their studies, situations with competing events, since there are many softwares and materials available to help and facilitate its implementation.
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Vida residual em pacientes com insuficiência cardíaca: uma abordagem semiparamétrica / Residual life on heart failure pacients: a semiparametric approachVictor Gonçalves Duarte 12 June 2017 (has links)
Usualmente a análise de sobrevivência considera a modelagem da função da taxa de falha ou função de risco. Uma alternativa a essa visão é estudar a vida residual, que em alguns casos é mais intuitiva do que a função de risco. A vida residual é o tempo de sobrevida adicional de um indivíduo que sobreviveu até um dado instante t0. Este trabalho descreve técnicas semiparamétricas e não paramétricas para estimar a média e a mediana de vida residual em uma população, testes para igualdade dessas medidas em duas populações e também modelos de regressão. Tais técnicas já foram testadas anteriormente em dados com baixa presença de censura; aqui elas são aplicadas a um conjunto de dados de pacientes com insuficiência cardíaca que possui uma alta quantidade de observações censuradas. / Usually, survival analysis is based on the modeling of the hazard function. One alternative approach is to consider the residual life, which would be more intuitive than the hazard function. Residual lifetime is the remaining survival time of a person given he or she survived a given time point t0. We describe semiparametric and non-parametric techniques for mean and median residual life estimation in a one-sample population, as well as tests for two-sample cases and regression models. Such techniques were previously tested for moderate censored data; here we apply them to heart-failure patients data with a high rate of censoring.
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Análise de sobrevida de pacientes coinfectados HIV/HCV de um centro de referência em DST/AIDS no município de São Paulo / Survival analysis of HIV/HCV co-infected patients at a STD/AIDS reference center in the city of São PauloWong Kuen Alencar 16 September 2011 (has links)
Introdução: A estimativa de sobrevida de pacientes com HIV/aids aumentou após a terapia antirretroviral de alta potência: no entanto, a mortalidade por doenças hepáticas também cresceu. Objetivos: Estimar a probabilidade acumulada de sobrevida após o diagnóstico de aids entre pacientes coinfectados HIV/HCV e realizar análise exploratória para investigar fatores relacionados à sobrevida desses pacientes. Metodologia: Estudo de coorte não concorrente, utilizando sistemas de Informações: o de Agravos de Notificação, o de informação laboratorial e o de informação da vigilância epidemiológica do Centro de Referência e Treinamento DST/AIDS-SP, de pacientes com aids maiores de 13 anos, acompanhados no ambulatório geral. As variáveis estudadas foram: hepatite C, hepatite B, categoria de exposição, contagem de células T CD4+, faixa etária, escolaridade, cor, sexo e períodos de diagnóstico de aids: 1986 a 1993, 1994 a 1996, 1997 a 2002 e 2003 a 2010. Foi utilizado o estimador de Kaplan-Meier, o modelo de Cox e as estimativas das hazard ratio (HR) com os respectivos intervalos de confiança (IC 95 por cento ). Resultados: De um total de 2.864 pessoas incluídas, com idade mediana de 35 anos, 219 foram a óbito (7,5 por cento ). De 358 (12,5 por cento ) coinfectados, 159 (45,1 por cento ) eram usuários de drogas injetáveis (UDI) e de 2.506 não coinfectados, 96 (3,9 por cento ) eram UDI. A probabilidade acumulada de sobrevida entre coinfectados, a partir do diagnóstico de aids, foi 100 por cento aos 60 meses no período de 1986 a 1993; 27,8 por cento aos 168 meses no período de 1994 a 1996; 76,3 por cento aos 168 meses no período de 1997 a 2002 e 92,8 por cento aos 96 meses no período de 2003 a 2010. As curvas de sobrevida foram diferentes entre coinfectados e não coinfectados no período de 1994 a 1996 (log rank = 19,8; p < 0,001) e no período de 1997 a 2002 (log rank = 38,8; p < 0,001). No modelo de Cox multivariado, mostraram-se preditores de óbito, independentemente das outras variáveis: ter hepatite C (HR = 2,9; IC 2,1-3,9), ter hepatite B (HR = 2,5; IC 1,7-3,6), ter até 3 anos de estudo (HR = 2,3; IC 1,5-3,6), ter 50 anos ou mais de idade (HR = 2,1; IC 1,3-3,2). Ter diagnóstico de aids no período entre 1997 a 2002 mostrou-se fator de proteção ao óbito (HR = 0,4; IC 0,3-0,5). Conclusões: Coinfectados HIV/HCV apresentaram menor sobrevida quando comparado com não coinfectados nos períodos de diagnóstico de aids 1994 a 1996 e 1997 a 2002. A partir do período 1994 a 1996, observou-se aumento significativo na probabilidade acumulada de sobrevida entre coinfectados, sendo que no período 2003 a 2010, essa probabilidade foi semelhante entre coinfectados e não coinfectados, refletindo possível impacto do tratamento da hepatite C / Introduction: The estimated survival of patients with HIV/AIDS has increased after highly active antiretroviral therapy; mortality due to liver diseases, however, has also increased. Objectives: To estimate the accumulated probability of survival after AIDS diagnosis among HIV/HCV co-infected individuals and to perform an exploratory analysis to investigate factors related to the survival of these patients. Method: Non-concurrent cohort study, using data from the National Disease Reporting Information System, the laboratory and epidemiological surveillance information systems of the SP-STD Reference and Training Center-CRT, of patients over 13 years of age, followed at the general outpatient clinic. The following variables were studied: hepatitis C, hepatitis B, exposure category, T CD4+ cell count, age group, schooling, color, sex, and AIDS diagnostic periods: 1986 to 1993, 1994 to 1996, 1997 to 2002 and 2003 to 2010. Survival analysis was performed using the Kaplan-Meier estimator and the Cox model, with estimates of the hazard ratio (HR) and respective confidence intervals (95 per cent CI). Results: Of a total of 2,864 individuals included, with a median age of 35 years, 219 died (7.5 per cent ). Of the 358 (12.5 per cent ) HIV/HCV co-infected individuals, 159 (45.1 per cent ) were injecting drug users (IDU), and of the non-co-infected 2,506, 96 (3.9 per cent ) were IDU. The accumulated probability of survival among HIV/HCV co-infected individuals at 60, 168, 168 and 96 months as of AIDS diagnosis, was 100 per cent in the 1986 -1993 period; 27,8 per cent in the 1994-1996 period; 76,3 per cent in the 1997-2002 period; and 92,8 per cent in the 2003-2010 period. The survival curves were different between co-infected and non-co-infected individuals in the 1994-1996 (log rank = 19,8; p < 0,001) and in the 1997-2002 (log rank = 38,8; p < 0,001). In the multivariate model, regardless of other variables, the following were predictors of death: having hepatitis C (HR = 2.9; CI 2.1-3.9); having hepatitis B (HR = 2.5; CI 1.7-3.6); being 50 years old or over (HR = 2.1; CI 1.3-3.2) and having up to 3 years of schooling (HR = 2.3; CI 1.5-3.6). AIDS diagnosis between 1997 and 2010 was shown to be a protective factor for death (HR = 0.4; CI 0.3-0.5). Conclusions: HIV/HCV co-infected individuals had shorter survival, when compared to non-co-infected individuals in the 1994-1996 and in the 1997-2002 AIDS diagnostic periods. As of the 1994-1996 period, a significant increase in the accumulated probability of survival among HIV/HCV co-infected individuals was observed. In the 2003-2010 period, the probability was similar between co-infected and non-coinfected individuals, showing the possible impact of hepatitis treatment
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Modelos de sobrevivência para estimação do período de latência do câncer / Survival models to estimate the latency period of cancerBárbara Beltrame Bettim 29 June 2017 (has links)
O câncer é responsável por aproximadamente 13% de todas as mortes no mundo, sendo que elas ocorrem principalmente em pessoas que são diagnosticadas tardiamente e em estágios avançados. Devido às suas características devastadoras e à prevalência cada vez maior da doença, é inquestionável a necessidade de investigações e pesquisas constantes na área, no sentido de aprimorar a detecção precoce e auxiliar em sua prevenção e tratamento. Dentre as diversas abordagens existentes, uma alternativa é a criação de técnicas para estimar o período de crescimento \"silencioso\" do câncer, que significa conhecer o momento do início do processo cancerígeno, também chamado de período de latência. A partir da revisão da literatura realizada, foi verificada uma escassez de modelos que estimam a latência do câncer, indicando a necessidade de estudo sobre o tema. Nesse contexto, métodos de análise de sobrevivência surgem como uma ferramenta útil para a construção desses modelos. No presente trabalho, é apresentada uma revisão de um modelo já existente, bem como sua formulação e métodos de estimação. Além disso, apresenta-se uma aplicação em um conjunto de dados reais e uma discussão dos resultados obtidos.Foi identificada a necessidade da formulação de um novo modelo, visto que o método estudado apresenta algumas limitações. Com isso são apresentadas 3 alternativas de modelos que solucionam os pontos apresentados na discussão, com respectivas aplicações. / Cancer is responsible for about 13% of all deaths in the world occuring mainly in people who are late diagnosed and in advanced stages. Due to its devastating characteristics and the growing prevalence of the disease, it is unquestionable the need of constant investigation and research in this area, in order to improve the early detection and to help in its prevention and treatment. Among the existing approaches, one alternative is the creation of techniques to estimate the \"silent\" growth period of cancer, which means to know the beginning moment of the carcinogen period, also known as latency period. In a literature review, it was found an shortage of models that estimate the latency of cancer, indicating the need of study about this theme. In this context, survival analysis methods appear as an useful tool to build these models. In this study, a review of an existing model is presented, as well as its formulation and estimation methods. Furthermore, an application on real data and a discussion of the obtained results are made. As a result, it was identified the need to formulate a new model, because of the limitations of the studied one. We present 3 alternative models that solve the points presented in the discussion, with applications.
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Investigation on Genetic Modifiers of Age at Onset of Major Depressive DisorderGedik, Huseyin 01 January 2017 (has links)
Major Depressive Disorder (MDD) is a complex multifactorial disorder, which would lead to disability. Environmental and genetic factors are involved in MDD etiology. The aim of this project was to identify loci modifying age at onset (AAO) of MDD using survival models after adjusting for Childhood Sexual Abuse (CSA). To achieve this aim, a dataset was made available by the China Oxford and VCU Experimental Research on Genetic Epidemiology (CONVERGE) consortium. The study population had 5,220 controls and 5,282 cases with MDD. We performed two univariate association analyses using Cox Proportional Hazard (Cox PH) models. These two are Full Sample (FS), cases and controls, and only the Case Cohort (CC). No genome-wide significant associations were found in univariate analyses. Subsequent gene set enrichment analysis showed that there were significant enrichments in neurological Gene Ontology terms and some novel non-neural pathways. These findings may allow us to better understand MDD pathology.
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DEFINITIVE PRIMARY THERAPY IN PATIENTS PRESENTING WITH OLIGOMETASTATIC NON-SMALL CELL LUNG CANCER (NSCLC)Parikh, Ravi B 01 November 2014 (has links)
Background: Although palliative chemotherapy is the standard of care for patients diagnosed with stage IV NSCLC, patients with a small metastatic burden, “oligometastatic” disease, may benefit from definitive local therapy.
Methods: We identified 186 patients (26% of Stage IV patients) prospectively enrolled in our institutional database from 2002-2012 with oligometastatic disease, which we defined as five or fewer distant metastatic lesions at diagnosis. Univariable and multivariable Cox proportional hazards models were used to identify patient and disease factors associated with improved survival. Using propensity score methods, we investigated the effect of definitive local therapy to the primary site on overall survival.
Results: Median age at diagnosis was 61 years, 51% of patients were female, 12% had squamous histology, and 33% had N0-1 disease. On multivariable analysis, ECOG performance status ≥2 (hazard ratio [HR] 2.43), nodal status N2-3 (HR 2.16), squamous pathology, and metastases to multiple organs (HR 2.11) were associated with a greater hazard of death (all p<0.01). Number of metastatic lesions and size of primary were not significantly associated with overall survival. Definitive local therapy to the primary tumor was associated with prolonged survival (HR 0.65, p=0.043).
Conclusions: Definitive local therapy to the primary tumor appears to be associated with improved survival in patients with oligometastatic NSCLC. Select patient and tumor characteristics, including good performance status, non-squamous histology, and limited nodal disease, may predict for improved survival in these patients.
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Risk assessment for osteoporotic fractures among men and women from a prospective population study : the EPIC-Norfolk studyMoayyeri, Alireza January 2012 (has links)
Osteoporotic fractures are a major and increasing clinical and public health concern internationally. Identification of individuals at high risk for fragility fractures may enable us to target preventive interventions more effectively. In this thesis, I aimed to evaluate novel risk factors for osteoporosis and develop a fracture risk assessment model among the middle-aged and older people. I used data from the European Prospective Investigation into Cancer (EPIC)-Norfolk study, which is a large population-based prospective study started in 1993. About 25,000 men and women were assessed at baseline and about 15,000 of them returned for a second examination 4 years later. All participants are followed up to the present for clinical events including fractures. My work is in two parts. For the first part, I examined the risk of fracture associated with some novel or less well studied risk factors. These risk factors included change in height over time, respiratory function, physical activity and body fat mass. We found that men and women with annual height loss >0.5 cm are at increased risk of hip and any fracture (relative risk=1.9 (95% CI 1.3-2.7) per cm/year height loss). One litre lower forced expiratory volume in 1 second (FEV1) was associated with a 2-fold risk of hip fracture in men and women. We also observed a non-linear association, independent of body mass index, between increasing body fat mass and lower fracture risk in women but not in men. I performed a systematic review and meta-analysis of studies evaluating the association between physical activity and hip fractures. Using a new validated questionnaire in EPIC-Norfolk, we observed varying relationships between physical activity in different domains of life and fracture risk in men and women. For the second part of the thesis, I developed a biostatistical model to calculate 10-year risk of developing a fracture among EPIC-Norfolk study participants. This model incorporates clinical and radiological assessments known to be associated with fractures and can be extended to other risk factors assessed in other prospective cohorts. This helps clinicians to achieve a better estimate of the prospective risk of fracture in their patients. I applied this model to compare the predictive value of two different clinical assessment methods for osteoporosis, namely dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS). We found that that the predictive power of QUS is comparable to, and independent of, predictive power of DXA. In summary, my studies have added to our knowledge about some novel and easy-to-use risk factors of osteoporosis and proposed a practical method to merge and utilise data from different risk factors for estimation of fracture risk in individuals.
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Délka doktorského studia na Fakultě informatiky a statistiky / Length of doctoral studies at the Faculty of Informatics and StatisticsHybšová, Aneta January 2011 (has links)
This thesis describes the survival analysis, exactly Kaplan-Meier estimate. A main part of the thesis deals with the problem of censored data, which is typical for survival analysis. The empirical part describes lenght of PhD studies at the Faculty of Informatics and Statistics and their "survival" in studies by Kaplan-Meier curves. First are analyzed uncensored data and then the whole data set (censored and uncensored data).
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