Thesis (M.A.)--University of South Florida, 2006. / Title from PDF of title page. Document formatted into pages; contains 71 pages. Includes bibliographical references.

Orientador: Djalma de Carvalho Moreira Filho / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-26T22:55:22Z (GMT). No. of bitstreams: 1 Ferraz_RosemeiredeOlanda_D.pdf: 2711370 bytes, checksum: b4966f4c4ea3b88daffa54c0576bd307 (MD5) Previous issue date: 2015 / Resumo: O objetivo deste estudo é identificar os fatores associados ao tempo de sobrevida do câncer de mama, como idade, estadiamento e extensão do tumor, utilizando modelos de riscos proporcionais de Cox e de riscos competitivos de Fine-Gray. E também propor um modelo de regressão paramétrico para ajustar o tempo de sobrevida na presença dos riscos competitivos. É um estudo de coorte retrospectivo de base-populacional referente a 524 mulheres diagnosticadas com câncer de mama no período de 1993 a 1995, acompanhadas até 2011, residentes no município de Campinas/SP. Um ponto de corte para a variável contínua da idade foi escolhido utilizando-se modelos de Cox. Nos ajustes de modelos simples e múltiplo de Fine-Gray e de Cox, a idade não foi significativa quando o óbito por câncer de mama foi o evento de interesse. As curvas de sobrevivências estimadas por Kaplan-Meier evidenciaram diferenças expressivas nas probabilidades comparando-se os óbitos por câncer de mama e por riscos competitivos. As curvas de sobrevida por câncer de mama não apresentaram diferenças significativas quando comparadas as categorias de idades, segundo teste de log rank. Os modelos de Fine-Gray e Cox identificaram praticamente as mesmas covariáveis influenciando no tempo de sobrevida para ambos eventos de interesse, óbitos por câncer de mama e óbitos por riscos competitivos. Foram comparados os modelos exponencial, de Weibull e lognormal com o modelo gama generalizada e conclui-se que o modelo de regressão de Weibull foi o mais adequado para ajustar o tempo de sobrevida na presença dos riscos competitivos, conforme resultados dos testes de razões de verossimilhanças / Abstract: The aim of this study is to identify associated factors to time failure survival of breast cancer such as age, stage and extent of the tumor using Cox's proportional hazards and Fine-Gray competing risks models. It is a retrospective cohort study of population-based concerning to 524 women diagnosed with breast cancer in the period 1993-1995, followed until 2011, living in the city of Campinas, São Paulo State, Brazil. The cutoff age variable has been defined using Cox models. In the settings of simple and multiple models of Fine-Gray and Cox age was not significant when the death from breast cancer was the outcome of interest. The survival curves estimated by Kaplan-Meier showed significant differences in the odds comparing the deaths from breast cancer and competing risks. The survival curves for breast cancer showed no significant differences when comparing age groups, according to the logrank test. The Fine-Gray and Cox models identified the same covariates influencing the survival time for both events of interest: deaths from breast cancer and deaths from competing risks. The exponential, Weibull and lognormal regression models were compared with generalized gamma model and it is concluded that the Weibull regression model was the most appropriate to adjust the survival time in the presence of competing risks, according to results of the ratio likelihood tests / Doutorado / Epidemiologia / Doutora em Saúde Coletiva

No description available.

Diversos modelos têm sido propostos na literatura com o objetivo de analisar dados de sobrevivência em que a população sob estudo é assumida ser uma mistura de indivíduos suscetíveis (em risco) e não suscetíveis a um específico evento de interesse. Tais modelos são usualmente denominados modelos com sobreviventes de longa duração ou modelos com fração de cura. Neste trabalho, diversos desses modelos (nos contextos paramétrico e semi-paramétrico) foram considerados para analisar os dados de um ensaio clínico aleatorizado conduzido com o objetivo de comparar três estratégias terapêuticas (cirurgia, angioplastia e medicamentoso) utilizadas no tratamento de pacientes com doença coronariana multiarterial. Em todos os modelos, as funções de ligação logito e complemento log-log foram utilizadas para modelar a proporção de sobreviventes de longa duração (indivíduos não suscetíveis). Quanto à função de sobrevivência dos indivíduos suscetíveis, foram utilizados os modelos de Weibull e de Cox. Covariáveis foram consideradas tanto na proporção de sobreviventes de longa duração quanto na função de sobrevivência dos indivíduos suscetíveis. De modo geral, os modelos considerados se mostraram adequados para analisar os dados do ensaio clínico aleatorizado, indicando a cirurgia como a estratégia terapêutica mais eficiente. Indicaram também, que as covariáveis idade, hipertensão e diabetes mellitus exercem influência na ocorrência do óbito cardíaco, mas não no tempo até a ocorrência deste óbito nos pacientes suscetíveis. / Several models have been proposed in the literature with the aim of analyzing survival data when the population under study is assumed to be a mixture of susceptible (at risk) and not susceptible individuals to a specific event of interest. Such models are usually called long-term survivors models or cure rate models. In this work, several of these models (under both parametric and semi-parametric approaches) were considered to analyze the data from a randomized clinical trial conducted in order to compare three therapeutic strategies (surgery, angioplasty and medicine) used in the treatment of patients with multivessel coronary artery disease. For all models the logit and complementary log-log link functions were used to model the proportion of long-term survivors (not susceptible individuals). In regards to the survival function of the susceptible individuals, the Weibull and Cox models were used. Covariates were considered both in the proportion of longterm survivors and in the survival function of the susceptible individuals. Overall, the models considered were suitable for analyzing the data from the randomized clinical trial indicating surgery as the most effective therapeutic strategy. They also indicated that the covariates age, hypertension and diabetes mellitus exhibit influence on the occurrence of cardiac death, but not on the time to the occurrence of this death in susceptible patients.

Introdução: O câncer de orofaringe representa 10 a 12 % entre todos os tumores malignos do trato aero digestivo superior com incidência crescente nos Estados Unidos e Europa. O Papillomavírus humano (HPV) está associado aos tumores de orofaringe em até 63%, promovendo uma evolução e prognóstico melhor. Objetivo: Descrever a prevalência do HPV em carcinomas de células escamosas de orofaringe tratados por cirurgia. Analisar a associação entre a presença do HPV e as características demográficas, clínicas, patológicas e terapêuticas. Avaliar a importância da presença do HPV na sobrevida livre de doença e sobrevida global. Método: Pesquisamos a presença do Papillomavirus humano, por PCR, no anátomo patológico. A descrição da amostra foi realizada através de média, frequência absoluta e relativa. Foi estimada a prevalência do HPV e seu respectivo intervalo de 95% de confiança. A análise da associação entre a presença de HPV e as características demográficas, clínicas e patológicas, foi feita pelo teste de associação pelo quiquadrado. A análise da sobrevida livre de doença e sobrevida global foi feita pelo estimador produto limite de Kaplan-Meier e modelos de risco proporcionais de Cox. Resultados: Os pacientes apresentavam idade variando de 34 a 78 anos, com uma média de 56,9 anos. Apenas 10 mulheres no estudo, totalizando com 76 homens. A maioria dos pacientes eram brancos (83,7%). Até 6 meses foi o tempo que a maioria dos pacientes apresentaram como início dos sintomas (69,0%). O sintoma mais comum foi a odinofagia (38,4%). A amígadala foi a localização mais frequente (69,8%). Quanto ao estádio clínico, o III e o IV apresentavam a maior frequência (71,4%). Forma realizadas cirurgias amplas como as bucofaringectomias em 76 pacientes (88,4%). O esvaziamento cervical ipsilateral foi realizado em 81 pacientes (94,2%) e no contralateral em apenas 21 (24,4%). A prevalência do HPV foi de 57%, e o tipo mais comum foi o 16, em 83,6%. A única associação estatisticamente significativa entre as variáveis do estudo com o HPV, foi o tabagismo, onde todos os não fumantes apresentavam HPV. As taxas de sobrevida livre de doença foram 73,9%, 65,9 e 57,9% respectivamente para 12, 24 e 60 meses. Houve diferença estatisticamente significativa com piores taxas, para idade menor que 55 anos e margens comprometidas. A presença do HPV não influenciou a sobrevida livre de doença, nem a sobrevida global. As taxas de sobrevida global foram 75,6%, 54,7% e 43,0%, respectivamente aos 12, 24 e 60 meses. Houveram piores taxas para o paciente etilista e com recidiva.Conclusão:A presença do HPV não se mostrou importante, como fator prognóstico, nessa série cirúrgica se o paciente for etilista e ou tabagista / Introduction:Oropharynx cancer is considered to enact approximately 10 to 12% of the cases among all malignant tumors from the upper aero digestive tract showing significant growth in its frequency rate in The United States and Europe. Human papillomavirus (HPV) is associated to oropharynx cancer in up to 63% of the cases, promoting better evolution and prognostic.Objective:Describe the prevalence of the HPV in oropharynx squamous cells carcinoma submitted to surgery. Investigate the association between HPV presence and the demographic, clinical, pathologic and therapeutic features. Estimate the importance of the HPV existence on the diseasefree survival and overall survival. Material andMethods: The existence of Human papillomavirus was studied through the use of PCR. The sample account was conducted through average, absolute and relative frequency. It has been estimated the prevalence of HPV and its corresponding 95% confidence interval. The association analysis between the presence of HPV and the demographic, clinical and pathological features was completed by the Qui-square association test. The disease-free survival timeline and the overall survival were estimated using the product limit estimator Kaplan-Meier and Cox proportional hazards model. Results: The studied patients were aged between 34 and 78, showing an average of 56.9 years of age. There were only 10 women in the study, thus presenting 76 men. Most of the patients were white (83.7%). It has been ascertained that 69.0% of the patients presented the symptoms onset up to the sixth month of the disease. The most common symptom among 38.4% of the cases was odinophagy. In regards to the tumor location 69.8% were found in the amygdala.Clinical stagings III and IV were found to be the ones with greater representation among patients (71.4%). Extensive surgeries such as bucopharyngectomy were performed in 76 patients (88.4%). In order to treat ipsilateral neck 81 patients underwent neck dissection (94.2%). Contralateral neck dissection was applied in 21 patients (24.4%). The prevalence of HPV was of 57%, and the most common type was 16, present in 83.6% of the cases. It was possible to notice smoking as the only statistically significant association, which showed all nonsmoking having HPV. The disease-free survival rates were of 73.9%, 65.9% and 57.9% to 12, 24 and 60 months respectively. The study has shown significant statistical difference with worse rates, to the ones under 55 years of age and presenting compromised margins. HPV presence did not influence the disease-free survival timeline, or the overall survival. The overall survival rates were of 75.6%, 54.7% and 43.0% to 12, 24 and 60 months respectively. Worse rates were found in alcoholic patients as well as in relapse cases. Conclusion: In these surgical series, HPV existence was not identified as an important prognosis factor when considering smokers and/or alcoholic patients

Many epidemiological studies assess the effects of time-dependent exposures, where both the exposure status and its intensity vary over time. The analysis of such studies poses the challenge of modelling the association between complex time-dependent drug exposure and the risk, especially given the uncertainty about the etiological relevance of doses taken in different time periods. / To address this challenge, I developed a flexible method for modelling cumulative effects of time-varying exposures, weighted by recency, represented by time-dependent covariates in the Cox proportional hazards model. The function that assigns weights to doses taken in the past is estimated using cubic regression splines. Models with different number of knots and constraints are estimated. Bootstrap techniques are used to obtain pointwise confidence bands around the weight functions, accounting for both the sampling variation of the regression coefficients, and the uncertainty at the model selection stage, i.e. the additional variance due to a posteriori selection of the number of knots. / To assess the method in simulations, I had to develop and validate a novel algorithm to generate event times conditional on time-dependent covariates and compared it with the algorithms available in the literature. The proposed algorithm extends a previously proposed permutational algorithm to include a rejection sampler. While all the algorithms generated data sets that, once analyzed, provided virtually unbiased estimates with comparable variances, the algorithm that I proposed reduced the computational time by more than 50 per cent relative to alternative methods. I used simulations to systematically investigate the properties of the weighted cumulative dose method. Six different weight functions were considered. Simulations showed that in most situations, the proposed method was able to capture the shape of the true weight functions and to produce estimates of the magnitude of the exposure effect on the risk that were close to those used to generate the data. I finally illustrated the use of the weighted cumulative dose modelling by reassessing the association between the use of selected benzodiazepines and fall-related injuries, using administrative data on a cohort of elderly who initiated their use of benzodiazepines between 1990 and 2004.

Diversos modelos têm sido propostos na literatura com o objetivo de analisar dados de sobrevivência em que a população sob estudo é assumida ser uma mistura de indivíduos suscetíveis (em risco) e não suscetíveis a um específico evento de interesse. Tais modelos são usualmente denominados modelos com sobreviventes de longa duração ou modelos com fração de cura. Neste trabalho, diversos desses modelos (nos contextos paramétrico e semi-paramétrico) foram considerados para analisar os dados de um ensaio clínico aleatorizado conduzido com o objetivo de comparar três estratégias terapêuticas (cirurgia, angioplastia e medicamentoso) utilizadas no tratamento de pacientes com doença coronariana multiarterial. Em todos os modelos, as funções de ligação logito e complemento log-log foram utilizadas para modelar a proporção de sobreviventes de longa duração (indivíduos não suscetíveis). Quanto à função de sobrevivência dos indivíduos suscetíveis, foram utilizados os modelos de Weibull e de Cox. Covariáveis foram consideradas tanto na proporção de sobreviventes de longa duração quanto na função de sobrevivência dos indivíduos suscetíveis. De modo geral, os modelos considerados se mostraram adequados para analisar os dados do ensaio clínico aleatorizado, indicando a cirurgia como a estratégia terapêutica mais eficiente. Indicaram também, que as covariáveis idade, hipertensão e diabetes mellitus exercem influência na ocorrência do óbito cardíaco, mas não no tempo até a ocorrência deste óbito nos pacientes suscetíveis. / Several models have been proposed in the literature with the aim of analyzing survival data when the population under study is assumed to be a mixture of susceptible (at risk) and not susceptible individuals to a specific event of interest. Such models are usually called long-term survivors models or cure rate models. In this work, several of these models (under both parametric and semi-parametric approaches) were considered to analyze the data from a randomized clinical trial conducted in order to compare three therapeutic strategies (surgery, angioplasty and medicine) used in the treatment of patients with multivessel coronary artery disease. For all models the logit and complementary log-log link functions were used to model the proportion of long-term survivors (not susceptible individuals). In regards to the survival function of the susceptible individuals, the Weibull and Cox models were used. Covariates were considered both in the proportion of longterm survivors and in the survival function of the susceptible individuals. Overall, the models considered were suitable for analyzing the data from the randomized clinical trial indicating surgery as the most effective therapeutic strategy. They also indicated that the covariates age, hypertension and diabetes mellitus exhibit influence on the occurrence of cardiac death, but not on the time to the occurrence of this death in susceptible patients.

Introdução: O câncer de orofaringe representa 10 a 12 % entre todos os tumores malignos do trato aero digestivo superior com incidência crescente nos Estados Unidos e Europa. O Papillomavírus humano (HPV) está associado aos tumores de orofaringe em até 63%, promovendo uma evolução e prognóstico melhor. Objetivo: Descrever a prevalência do HPV em carcinomas de células escamosas de orofaringe tratados por cirurgia. Analisar a associação entre a presença do HPV e as características demográficas, clínicas, patológicas e terapêuticas. Avaliar a importância da presença do HPV na sobrevida livre de doença e sobrevida global. Método: Pesquisamos a presença do Papillomavirus humano, por PCR, no anátomo patológico. A descrição da amostra foi realizada através de média, frequência absoluta e relativa. Foi estimada a prevalência do HPV e seu respectivo intervalo de 95% de confiança. A análise da associação entre a presença de HPV e as características demográficas, clínicas e patológicas, foi feita pelo teste de associação pelo quiquadrado. A análise da sobrevida livre de doença e sobrevida global foi feita pelo estimador produto limite de Kaplan-Meier e modelos de risco proporcionais de Cox. Resultados: Os pacientes apresentavam idade variando de 34 a 78 anos, com uma média de 56,9 anos. Apenas 10 mulheres no estudo, totalizando com 76 homens. A maioria dos pacientes eram brancos (83,7%). Até 6 meses foi o tempo que a maioria dos pacientes apresentaram como início dos sintomas (69,0%). O sintoma mais comum foi a odinofagia (38,4%). A amígadala foi a localização mais frequente (69,8%). Quanto ao estádio clínico, o III e o IV apresentavam a maior frequência (71,4%). Forma realizadas cirurgias amplas como as bucofaringectomias em 76 pacientes (88,4%). O esvaziamento cervical ipsilateral foi realizado em 81 pacientes (94,2%) e no contralateral em apenas 21 (24,4%). A prevalência do HPV foi de 57%, e o tipo mais comum foi o 16, em 83,6%. A única associação estatisticamente significativa entre as variáveis do estudo com o HPV, foi o tabagismo, onde todos os não fumantes apresentavam HPV. As taxas de sobrevida livre de doença foram 73,9%, 65,9 e 57,9% respectivamente para 12, 24 e 60 meses. Houve diferença estatisticamente significativa com piores taxas, para idade menor que 55 anos e margens comprometidas. A presença do HPV não influenciou a sobrevida livre de doença, nem a sobrevida global. As taxas de sobrevida global foram 75,6%, 54,7% e 43,0%, respectivamente aos 12, 24 e 60 meses. Houveram piores taxas para o paciente etilista e com recidiva.Conclusão:A presença do HPV não se mostrou importante, como fator prognóstico, nessa série cirúrgica se o paciente for etilista e ou tabagista / Introduction:Oropharynx cancer is considered to enact approximately 10 to 12% of the cases among all malignant tumors from the upper aero digestive tract showing significant growth in its frequency rate in The United States and Europe. Human papillomavirus (HPV) is associated to oropharynx cancer in up to 63% of the cases, promoting better evolution and prognostic.Objective:Describe the prevalence of the HPV in oropharynx squamous cells carcinoma submitted to surgery. Investigate the association between HPV presence and the demographic, clinical, pathologic and therapeutic features. Estimate the importance of the HPV existence on the diseasefree survival and overall survival. Material andMethods: The existence of Human papillomavirus was studied through the use of PCR. The sample account was conducted through average, absolute and relative frequency. It has been estimated the prevalence of HPV and its corresponding 95% confidence interval. The association analysis between the presence of HPV and the demographic, clinical and pathological features was completed by the Qui-square association test. The disease-free survival timeline and the overall survival were estimated using the product limit estimator Kaplan-Meier and Cox proportional hazards model. Results: The studied patients were aged between 34 and 78, showing an average of 56.9 years of age. There were only 10 women in the study, thus presenting 76 men. Most of the patients were white (83.7%). It has been ascertained that 69.0% of the patients presented the symptoms onset up to the sixth month of the disease. The most common symptom among 38.4% of the cases was odinophagy. In regards to the tumor location 69.8% were found in the amygdala.Clinical stagings III and IV were found to be the ones with greater representation among patients (71.4%). Extensive surgeries such as bucopharyngectomy were performed in 76 patients (88.4%). In order to treat ipsilateral neck 81 patients underwent neck dissection (94.2%). Contralateral neck dissection was applied in 21 patients (24.4%). The prevalence of HPV was of 57%, and the most common type was 16, present in 83.6% of the cases. It was possible to notice smoking as the only statistically significant association, which showed all nonsmoking having HPV. The disease-free survival rates were of 73.9%, 65.9% and 57.9% to 12, 24 and 60 months respectively. The study has shown significant statistical difference with worse rates, to the ones under 55 years of age and presenting compromised margins. HPV presence did not influence the disease-free survival timeline, or the overall survival. The overall survival rates were of 75.6%, 54.7% and 43.0% to 12, 24 and 60 months respectively. Worse rates were found in alcoholic patients as well as in relapse cases. Conclusion: In these surgical series, HPV existence was not identified as an important prognosis factor when considering smokers and/or alcoholic patients

No description available.

Indiana University-Purdue University Indianapolis (IUPUI) / Introduction: The prevalence of diabetes mellitus (DM) is rapidly increasing among the aging United States population. This poses a challenge to dental providers since DM and multiple oral conditions have been identified as comorbidities. Hypertension (HTN) is associated with more poorly controlled DM and has been identified as contributing to RCT tooth loss in prior studies. Links have also been established between DM and the survival rate of root canal treated teeth, however, previous research has focused on institutional settings despite the majority of RCT being performed in private dental practices. This study will use data from private dental practices to evaluate the survival rate of RCT teeth in patients with DM and HTN. Materials and Methods: This retrospective study evaluated the survival rate of endodontic treated teeth among patients with DM and HTN using National Dental PBRN Practice data. Electronic dental records from 42 private dental practices in the United States over a period of 15 years with a minimum 2-year follow-up comprising 11,532 root canal treated teeth were analyzed. Kaplan-Meier survival curves were used to demonstrate the effects of HTN and DM on RCT tooth survival and Cox proportional hazards survival analysis was used to evaluate the DM and HTN effects after accounting for age, gender, insurance, year of treatment, tooth type, and crown and filling placement as covariates. Results: Patients with HTN only had significantly lower risk of failure than patients with both HTN and DM (p=0.003). Patients with neither HTN nor DM had significantly lower risk of failure than patients with both HTN and DM (p=0.020). Patients with DM only did not have significantly different risk of failure than patients with both HTN and DM (p=0.223). Patients with DM only did not have significantly different risk of failure than patients with HTN only (p=0.361). Patients with neither HTN nor DM did not have significantly different risk of failure than patients with HTN only (p=0.121) or patients with DM only (p=0.800). Conclusions: Patients with both DM and HTN have an increased chance of root canal treated tooth failure while patients with only DM or only HTN do not. Evaluation of severity of DM may be more important in determining RCT failure and studies utilizing laboratory values should be considered for future research.