Dissertations / Theses on the topic 'Kaplan-Meier estimation'

Nous nous sommes intéressés dans cette étude à l'estimation de la loi de la durée de séjour en prenant en compte les individus sur lesquels l'évènement d'intérêt et la censure peuvent se produire dans un même intervalle et être observés. Pour cela, nous avons proposé deux approches d'estimation non paramétrique basées sur une approximation asymptotique quand la longueur de l'intervalle entre deux dates consécutives d'observation tend vers 0. La première est basée sur une relation intégrale et la deuxième est basée sur une restauration des durées de séjour. Nous nous sommes servis de ces approches pour monter un modèle de croissance des fruits du cacaoyer en fonction du climat. Nous avons également estimé la sensibilité (probabilité de pénétration et de réussite d'infection) des fruits en fonction de leur stade et le potentiel infectieux (nombre moyen de spores sur un fruit) par date. Ce potentiel infectieux nous permettrait de monter un modèle du potentiel infectieux en fonction des fruits attaqués. La connaissance du potentiel infectieux en fonction des fruits attaqués, de l'estimation de la sensibilité suivant les stades, de l'estimation du modèle de croissance permettra alors de monter un modèle dynamique du potentiel infectieux pour prédire le risque d'évolution de la pourriture brune des fruits du cacaoyer
We are interested in this study in estimating the lifetime distribution by taking into consideration individuals on which the interest event and the censorship can occur in the same intervaland both events were then observed. We proposed two nonparametric approaches based on an asymptotic approximation when the lengthbetween two consecutive observation days tends to 0. The first one was based on an integral relationship and the second one on a lifetime restoration. We used theses approaches to build a fruitgrowth model depending on climatic variables. We also estimated the susceptibility (success probability of attack by a spore on a fruit) of the fruit depending of its developmental stage and theinfectious potential of the disease over time.This infectious potential could help to build a model of infectious potential depending on infected fruits. The knowledge of the infectious potential depending on infected fruits, the estimation of the susceptibility of the fruit and the model of growth will allow to built a dynamic model of infectious potential to predict the evolution risk of disease progression

This thesis centers on nonparametric inferences of the cumulative hazard function of a right truncated variable. We present three variance estimators for the Nelson-Aalen estimator of the cumulative hazard function and conduct a simulation study to investigate their performances. A close match between the sampling standard deviation and the estimated standard error is observed when an estimated survival probability is not close to 1. However, the problem of poor tail performance exists due to the limitation of the proposed variance estimators. We further analyze an AIDS blood transfusion sample for which the disease latent time is right truncated. We compute three variance estimators, yielding three sets of confidence intervals. This work provides insights of two-sample tests for right truncated data in the future research.

This work introduces nonparametric models which are used in time to event data analysis. It is focused on applying these methods in medicine where it is called survival analysis. The basic techniques and problems, which can appear in survival analysis, are presented and explained here. The Kaplan -- Meier estimator of survival function is discussed in the main part. This is the most frequented method used for estimating the survival function in patients who have undergone a specific treatment. The Kaplan -- Meier estimator is also a common device in the statistical packets. In addition to estimation of survival function, the estimation of hazard function and cumulative hazard function is presented. The hazard function shows the intensity of an individual experiencing the particular event in a short time period. Special problems occur when analyzing time to event data. A distinctive feature, often present in such data, is known as censoring. That is the situation when the individual does not experience the event of interest at the time of study. The thesis covers also an empiric part, where the results of an analysis of patients with the larynx carcinoma diagnosis are shown. These patients were treated in a hospital located in České Budějovice. This analysis is based on a theory presented in the previous chapters.

Cette thèse porte sur l'étude des propriétés asymptotiques d'un estimateur non paramétrique de la densité de type Parzen-Rosenblatt, sous un modèle de données censurées à droite, vérifiant une structure de dépendance de type associé. Dans ce cadre, nous rappelons d'abord les résultats existants, avec détails, dans les cas i.i.d. et fortement mélangeant (α-mélange). Sous des conditions de régularité classiques, il est établi que la vitesse de coonvergence uniforme presque sûre de l'estimateur étudié, est optimale. Dans la partie dédiée aux résultats de cette thèse, deux résultats principaux et originaux sont présentés : le premier résultat concerne la convergence uniforme presque sûre de l'estimateur étudié sous l'hypothèse d'association. L'outil principal ayant permis l'obtention de la vitesse optimale est l'adaptation du Théorème de Doukhan et Neumann (2007), dans l'étude du terme des fluctuations (partie aléatoire) de l'écart entre l'estimateur considéré et le paramètre étudié (densité). Comme application, la convergence presque sûre de l'estimateur non paramétrique du mode est établie. Les résultats obtenus ont fait l'objet d'un article accepté pour publication dans Communications in Statistics-Theory and Methods ; Le deuxième résultat établit la normalité asymptotique de l'estimateur étudié sous le même modèle et constitute ainsi une extension au cas censuré, du résultat obtenu par Roussas (2000). Ce résultat est soumis pour publication
This thesis deals with the study of asymptotic properties of e kernel (Parzen-Rosenblatt) density estimate under associated and censored model. In this setting, we first recall with details the existing results, studied in both i.i.d. and strong mixing condition (α-mixing) cases. Under mild standard conditions, it is established that the strong uniform almost sure convergence rate, is optimal. In the part dedicated to the results of this thesis, two main and original stated results are presented : the first result concerns the strong uniform consistency rate of the studied estimator under association hypothesis. The main tool having permitted to achieve the optimal speed, is the adaptation of the Theorem due to Doukhan and Neumann (2007), in studying the term of fluctuations (random part) of the gap between the considered estimator and the studied parameter (density). As an application, the almost sure convergence of the kernel mode estimator is established. The stated results have been accepted for publication in Communications in Statistics-Theory & Methods ; The second result establishes the asymptotic normality of the estimator studied under the same model and then, constitute an extension to the censored case, the result stated by Roussas (2000). This result is submitted for publication

Les registres de population doivent donner des indications fiables et non biaisées sur les besoins de prise en charge et sur les performances du système de soins. L'étude de la survie occupe une position centrale dans la construction des indicateurs de santé. Les analyses de survie en population diffèrent de celles issues des essais thérapeutiques par les méthodes d'analyse et par des biais spécifiques qui sont étudiés dans ce travail et illustrés d'exemples. La survie relative est la méthode la plus utilisée. Dans les comparaisons, une attention particulière doit donc être portée à la mortalité utilisée dans la correction de la mortalité observée. Certains biais sont liés à la qualité de la collecte des données. Le manque d'exhaustivité sélectionne les malades de bon pronostic. L'insuffisance d'infromations conduit à créer dans les variables des catégories regroupant les informations imprécises. Ces catégories hétérogènes correspondent à des cas de mauvais pronostic peu explorés ou à des cas ordinaires mal documentés par l'enquête. Comparer des sous-groupes où la qualité de l'enquête peut varier (zones ou périodes) expose à des biais. Des problèmes, propres aux situations d'observation tels les biais d'indication, existent. La prise en compte du stade, facteur pronostic jouant un rôle majeur dans la compréhension des phénomènes observés, pose des problèmes. Un calcul décentralisé du stade peut-être à l'origine d’erreurs de classification. De plus, il existe des glissements de classification liés à une insuffisance d'exploration (faible nombre de ganglions examinés, bilan d'extension incomplet). Ces biais potentiels sont retrouvés dans l'analyse de la survie des cancers colorectaux étudiés par 6 registres français. La prise en compte de variables complémentaires, en particulier pour valider le stade, permettent d'en corriger une partie, mais les procédures de standardisation de collecte et codage sont encore insuffisantes. Faute de pouvoir utiliser les informations des certificats de décès, l'exhaustivité est difficilement évaluable dans les registres français. Malgré ces imperfections, les données fournies par les registres sont fondamentales dans la mesure des besoins. Elles permettent, par un suivi détaillé et à long terme, de calculer la prévalence (cas ayant une maladie active nécessitant des soins)

Dans cette thèse, nous étudions les propriétés asymptotiques de paramètres fonctionnels conditionnels en statistique non paramétrique, quand la variable explicative prend ses valeurs dans un espace de dimension infinie. Dans ce cadre non paramétrique, on considère les estimateurs des paramètres fonctionnels usuels, tels la loi conditionnelle, la densité de probabilité conditionnelle, ainsi que le quantile conditionnel. Le premier travail consiste à proposer un estimateur du quantile conditionnel et de prouver sa convergence uniforme sur un sous-ensemble compact. Afin de suivre la convention dans les études biomédicales, nous considérons une suite de v.a {Ti, i ≥ 1} identiquement distribuées, de densité f, censurée à droite par une suite aléatoire {Ci, i ≥ 1} supposée aussi indépendante, identiquement distribuée et indépendante de {Ti, i ≥ 1}. Notre étude porte sur des données fortement mélangeantes et X la covariable prend des valeurs dans un espace à dimension infinie.Le second travail consiste à établir la normalité asymptotique de l’estimateur à noyau du quantile conditionnel convenablement normalisé, pour des données fortement mélangeantes, et repose sur la probabilité de petites boules. Plusieurs applications à des cas particuliers ont été traitées. Enfin, nos résultats sont appliqués à des données simulées et montrent la qualité de notre estimateur
In this thesis, we study some asymptotic properties of conditional functional parameters in nonparametric statistics setting, when the explanatory variable takes its values in infinite dimension space. In this nonparametric setting, we consider the estimators of the usual functional parameters, as the conditional law, the conditional probability density, the conditional quantile. We are essentially interested in the problem of forecasting in the nonparametric conditional models, when the data are functional random variables. Firstly, we propose an estimator of the conditional quantile and we establish its uniform strong convergence with rates over a compact subset. To follow the convention in biomedical studies, we consider an identically distributed sequence {Ti, i ≥ 1}, here density f, right censored by a random {Ci, i ≥ 1} also assumed independent identically distributed and independent of {Ti, i ≥ 1}. Our study focuses on dependent data and the covariate X takes values in an infinite space dimension. In a second step we establish the asymptotic normality of the kernel estimator of the conditional quantile, under α-mixing assumption and on the concentration properties on small balls of the probability measure of the functional regressors. Many applications in some particular cases have been also given

Le risque attribuable (RA) mesure la proportion de cas de maladie qui peuvent être attribués à une exposition au niveau de la population. Plusieurs définitions et méthodes d'estimation du RA ont été proposées pour des données de survie. En utilisant des simulations, nous comparons quatre méthodes d'estimation du RA dans le contexte de l'analyse de survie : deux méthodes non paramétriques basées sur l'estimateur de Kaplan-Meier, une méthode semi-paramétrique basée sur le modèle de Cox à risques proportionnels et une méthode paramétrique basée sur un modèle à risques proportionnels avec un risque de base constant par morceaux. Nos travaux suggèrent d'utiliser les approches semi-paramétrique et paramétrique pour l'estimation du RA lorsque l'hypothèse des risques proportionnels est vérifiée. Nous appliquons nos méthodes aux données de la cohorte E3N pour estimer la proportion de cas de cancer du sein invasif attribuables à l'utilisation de traitements hormonaux de la ménopause (THM). Nous estimons qu'environ 9 % des cas de cancer du sein sont attribuables à l'utilisation des THM à l'inclusion. Dans le cas d'une exposition protectrice, une alternative au RA est la fraction préventive (FP) qui mesure la proportion de cas de maladie évités. Cette mesure n'a pas été considérée dans le contexte de l'analyse de survie. Nous proposons une définition de la FP dans ce contexte et des méthodes d'estimation en utilisant des approches semi-paramétrique et paramétrique avec une extension permettant de prendre en compte les risques concurrents. L'application aux données de la cohorte des Trois Cités (3C) estime qu'environ 9 % de cas d'accident vasculaire cérébral peuvent être évités chez les personnes âgées par l'utilisation des hypolipémiants. Notre étude montre que la FP peut être utilisée pour évaluer l'impact des médicaments bénéfiques dans les études de cohorte tout en tenant compte des facteurs de confusion potentiels et des risques concurrents
The attributable risk (AR) measures the proportion of disease cases that can be attributed to an exposure in the population. Several definitions and estimation methods have been proposed for survival data. Using simulations, we compared four methods for estimating AR defined in terms of survival functions: two nonparametric methods based on Kaplan-Meier's estimator, one semiparametric based on Cox's model, and one parametric based on the piecewise constant hazards model. Our results suggest to use the semiparametric or parametric approaches to estimate AR if the proportional hazards assumption appears appropriate. These methods were applied to the E3N women cohort data to estimate the AR of breast cancer due to menopausal hormone therapy (MHT). We showed that about 9% of cases of breast cancer were attributable to MHT use at baseline. In case of a protective exposure, an alternative to the AR is the prevented fraction (PF) which measures the proportion of disease cases that could be avoided in the presence of a protective exposure in the population. The definition and estimation of PF have never been considered for cohort studies in the survival analysis context. We defined the PF in cohort studies with survival data and proposed two estimation methods: a semiparametric method based on Cox’s proportional hazards model and a parametric method based on a piecewise constant hazards model with an extension to competing risks. Using data of the Three-City (3C) cohort study, we found that approximately 9% of cases of stroke could be avoided using lipid-lowering drugs (statins or fibrates) in the elderly population. Our study shows that the PF can be estimated to evaluate the impact of beneficial drugs in observational cohort studies while taking potential confounding factors and competing risks into account

L'analyse de durées de vie censurées est utilisée dans des domaines d'application variés et différentes possibilités ont été proposées pour la modélisation de telles données. Nous nous intéressons dans cette thèse à deux types de modélisation différents, le modèle de Cox stratifié avec indicateurs de strates aléatoirement manquants et le modèle de régression linéaire censuré à droite. Nous proposons des méthodes d'estimation des paramètres et établissons les propriétés asymptotiques des estimateurs obtenus dans chacun de ces modèles. Dans un premier temps, nous considérons une généralisation du modèle de Cox qui permet à différents groupes de la population, appelés strates, de posséder des fonctions d'intensité de base différentes tandis que la valeur du paramètre de régression est commune. Dans ce modèle à intensité proportionnelle stratifié, nous nous intéressons à l'estimation des paramètres lorsque l'indicateur de strate est manquant pour certains individus de la population. Des estimateurs du maximum de vraisemblance non paramétrique pour les paramètres du modèle sont proposés et nous montrons leurs consistance et normalité asymptotique. L'efficacité du paramètre de régression est établie et des estimateurs consistants de sa variance asymptotique sont également obtenus. Pour l'évaluation des estimateurs du modèle, nous proposons l'utilisation de l'algorithme Espérance-Maximisation et le développons dans ce cas particulier. Dans un second temps, nous nous intéressons au modèle de régression linéaire lorsque la donnée réponse est censurée aléatoirement à droite. Nous introduisons un nouvel estimateur du paramètre de régression minimisant un critère des moindres carrés pénalisé et pondéré par des poids de Kaplan-Meier. Des résultats de consistance et normalité asymptotique sont obtenus et une étude de simulations est effectuée pour illustrer les propriétés de cet estimateur de type LASSO. La méthode bootstrap est utilisée pour l'estimation de la variance asymptotique
Life data analysis is used in various application fields. Different methods have been proposed for modelling such data. In this thesis, we are interested in two distinct modelisation types, the stratified Cox model with randomly missing strata indicators and the right-censored linear regression model. We propose methods for estimating the parameters and establish the asymptotic properties of the obtained estimators in each of these models. First, we consider a generalization of the Cox model, allowing different groups, named strata, of the population to have distinct baseline intensity functions, whereas the regression parameter is shared by all the strata. In this stratified proportional intensity model, we are interested in the parameters estimation when the strata indicator is missing for some of the population individuals. Nonparametric maximum likelihood estimators are proposed for the model parameters and their consistency and asymptotic normality are established. We show the efficiency of the regression parameter and obtain consistent estimators of its variance. The Expectation-Maximization algorithm is proposed and developed for the evaluation of the estimators of the model parameters. Second, we are interested in the regression linear model when the response data is randomly right-censored. We introduce a new estimator of the regression parameter, which minimizes a Kaplan-Meier-weighted penalized least squares criterion. Results of consistency and asymptotic normality are obtained and a simulation study is conducted in order to investigate the small sample properties of this LASSO-type estimator. The bootstrap method is used for the estimation of the asymptotic variance

MOTA, Rosa Maria Salani. Respondent Driven Sampling (RDS) aplicado à população de homens que fazem sexo com homens no Brasil. 2012. 189 f. Tese (Doutorado em Saúde Pública) - Universidade Federal do Ceará. Faculdade de Medicina, Fortaleza, 2012.
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The estimators for population parameters in samples collected by sampling Respondent Driven Sampling (RDS) are sensitive to the presence of observations ignored and tends to underestimate the population parameters. The absence of a clearly defined sampling frame for the collection of samples from populations considered hidden and/or difficult access made the RDS became an important tool for biological and behavioral surveillance in these populations at higher risk for HIV, especially Brazil. Considered a method of sampling in the reference chain, RDS uses information about the connections of social networks for specific asymptotically unbiased estimators of population characteristics and accuracy of these estimators. Multicenter cross-sectional epidemiological and behavioral surveillance for MSM populations in 18 years or more was conducted in 10 cities (Manaus, Recife, Salvador, Campo Grande, Brasilia, Curitiba, Itajaí, Santos, Belo Horizonte and Rio de Janeiro) in 2009 and collected in each municipality, a sample through RDS. This study offered the rapid test for diagnosis of HIV infection to those who agreed to participate in a pre-counseling. All participants were asked about testing for HIV prior to the research and about which the diagnosis obtained. By simulating a dichotomous variable (eg, HIV serology positive or negative) without comment ignored in recruiting network in Rio de Janeiro and later recruited 18 deletions, that is, the unknown sample is evaluated from a number of observations significantly smaller than the original sample and the parameter in question (HIV prevalence) is underestimated. Still, with the allocation of single serology ignored in the descriptive context, it is observed in samples with attribution, biological markers indicating that more accurate values. Multicentre study for the group of participants who self-reported positive or negative serology for HIV rapid test and performed the research notes to self-reports, high correlation (0.88) and 100% sensitivity with gold standard rapid test for HIV diagnosis. Finally, estimating the prevalence of HIV in the samples observed by county and general, and the proposed allocation of the self-reported HIV positive and HIV serology subsequent assignment of + / - through three proposed charges: are all negative, proximity of the participants in the network recruitment and by logistic regression. It is found in samples collected from the estimated overall HIV prevalence was equal to 11.1%, by municipality, the lower prevalence in Santos (2.6%) and highest in Rio de Janeiro (17.6%).With the charges tend to increase the prevalence and the highest estimates are found with the imputation logistic regression in 7 of 9 municipalities assessed by this methodology. The estimated overall HIV logistic regression is 14.2% and, by municipality, the lower prevalence in Recife (5.2%) and highest in Brasilia (23.7%). The allocation of serology for HIV by the Logistic Regression occurs by municipality and by a model with a minimum accuracy of 70%.
Os estimadores para parâmetros populacionais em amostras coletadas pelo método de amostragem Respondent Driven Sampling (RDS) são sensíveis à presença de observações ignoradas e tendem a subestimar os parâmetros populacionais. A ausência de um quadro de amostragem bem definido para a coleta de amostras em populações consideradas escondidas e/ou de acesso difícil fez com que o RDS se tornasse uma importante ferramenta de vigilância comportamental e biológica nessas populações com maior risco para o HIV, em especial no Brasil. Considerado um método de amostragem em cadeia de referência, o RDS utiliza informações sobre as conexões das redes sociais para obter estimadores contingentes assintoticamente imparciais das características populacionais e a precisão desses estimadores. Estudo multicêntrico de corte transversal para vigilância epidemiológica e comportamental em populações de HSH com 18 anos ou mais foi realizado em dez cidades brasileiras (Manaus, Recife, Salvador, Campo Grande, Brasília, Curitiba, Itajaí, Santos, Belo Horizonte e Rio de Janeiro) no ano de 2009 e, coleta, em cada município, uma amostra pelo RDS. Neste estudo, foi oferecido o teste rápido para diagnóstico da infecção por HIV àqueles que aceitam participar de um pré-aconselhamento. Todos os participantes foram inquiridos sobre a realização de testes anti-HIV anteriores ao da pesquisa e sobre qual o diagnóstico obtido. Com a simulação de uma variável dicotômica (exemplo: sorologia para HIV positiva ou negativa) sem observações ignoradas na rede de recrutamento do Rio de Janeiro e posteriores exclusões de 18 recrutados, encontra-se que, a amostra com ignorados é avaliada com base em um número de observações significativamente menor que o da amostra original e o parâmetro em questão (prevalência do HIV) é subestimado. Ainda, com a imputação única das sorologias ignoradas, no contexto descritivo, observam-se, nas amostras com imputação, marcadores biológicos que indicam valores mais acurados. No estudo multicêntrico, para o grupo de participantes que autorrelatou sorologia positiva ou negativa para o HIV e realizou teste rápido na pesquisa, observa-se para os autorrelatos elevada concordância (0,88) e sensibilidade de 100% com o padrão-ouro teste rápido para diagnóstico do HIV. Finalmente, estimando a prevalência para o HIV nas amostras observadas por município e geral, e, com a proposta da imputação pelo autorrelato do HIV positivo e posterior atribuição de sorologia HIV +/- mediante três propostas de imputações: todos são negativos, proximidade dos participantes na rede de recrutamento e pela regressão logística. Encontra-se nas amostras coletadas a estimativa geral da prevalência do HIV igual a 11,1% sendo, por município, a menor prevalência em Santos (2,6%) e a maior no Rio de Janeiro (17,6%). Com as imputações as prevalências tendem a aumentar e as maiores estimativas são encontradas com a imputação por meio da regressão logística em sete de nove municípios avaliados por essa metodologia. A estimativa geral do HIV pela regressão logística é 14,2% sendo, por município, a menor prevalência no Recife (5,2%) e a maior em Brasília (23,7%). A imputação da sorologia de infecção por HIV pela regressão logística ocorre por município e por intermédio de um modelo com acurácia mínima igual a 70%.

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The main objective of this research is to explore economics issues that may induce impact on lifetime of small businesses during 2002 to 2006. The group of enterprises studied was selected from database of taxpayers recorded at fiscal authority of State of CearÃ. To do that, the methodology was focused on a branch of statistics which deals with survival analysis, called duration analysis or duration modeling in economics. It was applied non-linear model whose non-parametric estimator chosen was KAPLAN-MEIER. Through that methodology, it was developed sceneries based on the following attributes: county where the enterprises were established; economics activities based on national classification, fiscal version 1.0/1.1; and, finally, the relationship between State of Cearà â as fiscal authority â and enterprises. The counties were grouped applying two parameters of stratifications: gross domestic product(GDP) per capita and investment in education per capita. Before any stratification, only counties with thirty or more enterprises starting their activities in year 2002 were considered in sceneries to analysis.
A dissertaÃÃo tem o objetivo de investigar fatores econÃmicos que possam influenciar na sobrevida de micros e pequenas empresas (MEPs) contribuintes do Imposto sobre OperaÃÃes relativas à CirculaÃÃo de Mercadorias e sobre PrestaÃÃes de ServiÃos de Transporte Interestadual e Intermunicipal e de ComunicaÃÃo (ICMS) do Estado do Cearà no perÃodo de 2002 à 2006. Para isso, aplicou-se uma tÃcnica estatÃstica denominada anÃlise de sobrevivÃncia a partir de modelos nÃo lineares cujo estimador nÃo-paramÃtrico escolhido foi o de KAPLAN-MEIER. Com os dados de sobrevivÃncia devidamente modelados, buscou-se estratificÃ-los focando os municÃpios dos logradouros das MEPs; dentro do que tange as operaÃÃes do ICMS, focando as atividades econÃmicas segundo a classificaÃÃo nacional de atividades econÃmicas (CNAE) versÃo fiscal 1.0/1.1; e, finalmente, observar a relaÃÃo do Estado â enquanto autoridade fiscal â com esses pequenos estabelecimentos, restringindo temporariamente seu faturamento ou mesmo baixando sua inscriÃÃo estadual, impossibilitando a continuidade de suas atividades. Dos municÃpios, utilizou-se como Ãndice de estratificaÃÃo entre as curvas de sobrevivÃncia o produto interno bruto (PIB) per capita e os investimentos mÃdio per capita em educaÃÃo daquelas empresas localizadas em municÃpios com 30 ou mais estabelecimentos ativados no ano de 2002. Dentre outras, duas importantes observaÃÃes foram identificar o municÃpio de Fortaleza como um âoutlinerâ frente aos outros municÃpios e a forte dominÃncia da curva de sobrevivÃncia das empresas que nÃo sofreram intervenÃÃo do fisco em suas atividades sobre aquelas que tiveram.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
No Brasil, existem poucos estudos sobre longevidade de vacas de corte, principalmente utilizando ferramentas de análise de sobrevivência na estimação de parâmetros genéticos. Todavia, os critérios para avaliar esta característica são vários, tal que em alguns destes nem todos os registros das vacas nos rebanhos podem ser levados em consideração, devido à metodologia de análise utilizada. Uma variável que é de fácil mensuração e já faz parte da maioria dos controles zootécnicos das fazendas é a idade da vaca ao último parto (IVUP). Neste trabalho, objetivo foi avaliar a longevidade das vacas nos rebanhos utilizando a variável IVUP, por meio da metodologia de análise de sobrevivência. Esta variável foi utilizada mediante um critério para analisar a longevidade produtiva de vacas nos rebanhos. O critério adotado foi a diferença entre a data em relação ao último parto de cada vaca e a data do último parto de cada fazenda. Se esta diferença foi superior a 36 meses, a vaca falhou e foi considerada descartada. Caso contrário, esta vaca foi censurada, indicando que esta ainda poderia ter futuras parições. O critério de 36 meses foi proposto por ser período suficiente para a ocorrência de um novo parto. A metodologia de análise de sobrevivência foi utilizada por considerar dados censurados e não censurados. As variáveis: estação e ano de nascimento de cada vaca, a fazenda e a idade ao primeiro parto foram utilizadas para as análises da variável IVUP. Um estudo prévio por meio de curvas de Kaplan-Meier e o modelo de Cox, utilizando a distribuição gama para os touros, desconsiderando o parentesco entre eles, foram realizados. O software Survival Kit foi empregado para estimação dos parâmetros genéticos, levando em consideração o parentesco entre os animais. Verificou-se que a IVUP apresentou herdabilidade de 0,25, e que seu uso permite avaliar a...
In Brazil, there are few studies about stayability, especially using tools of survival analysis in the estimation of breeding values and heritability. The criteria for evaluating this characteristic are different, such that in some of these not all information in the herds of cows can be taken into consideration, because the method of analysis used. In addition, the definitions that consider the date of disposal of the animal affect the use of information obtained in practice, because until the cows come out of the flock may take years, thus the evaluation of their parents is impaired, since the goal is selection. A variable that is easy to measure and is already part of most controls husbandry farms are cow age at last birth (IVUP). This variable was used by one criterion to analyze the productive longevity of cows in herds. The criterion was the difference between the date from the last delivery date of each cow and the last part of each farm. If this difference was more than 36 months, the cow was considered failed and discarded. Otherwise, this cow was censored, indicating that this could still have further parities. The criterion of 36 months was proposed to be sufficient time for the occurrence of a new birth. The methodology of survival analysis was used. The variables season and year of birth of each cow, farm and age at first birth were used for analysis of variable IVUP. The objective of this study was to evaluate the performance of the variable IVUP through estimates of genetic and fixed effect, to study the longevity of cows in the herd. A previous study by Kaplan-Meier and Cox model using the gamma distribution for the bulls, disregarding the relationship between them, were performed. The Survival Kit software was used to estimate the genetic parameters, taking into account the relationship between the animals. It was found that the heritability of 0.25 for IVUP ... (Complete abstract click electronic access below)

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Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Departamento de Ensino. Programa de Pós-Graduação em Saúde da Criança e da Mulher. Rio de Janeiro, RJ, Brasil
Introdução: A fibrose cística (FC) é uma doença genética, de transmissão autossômica recessiva, que compromete múltiplos órgãos, que apresenta curso crônico e progressivo sendo considerada potencialmente letal. Objetivos: Estimar a sobrevivência dos pacientes com FC e os fatores de risco associados à redução no tempo de sobrevivência. Métodos: Tratou-se de uma coorte aberta de casos diagnosticados entre 01/01/1990 e 10/10/2009 no Centro de Referência em FC do RJ, CRFC-RJ, Brasil na qual se analisou a sobrevivência global e fatores de risco associados com a sobrevida dos pacientes. O período de risco iniciou-se na idade ao diagnóstico e terminou na idade quando ocorreu o óbito por FC, a perda de seguimento ou o fim do estudo. Os fatores analisados foram: sexo, motivo da suspeita diagnóstica, genótipo, número de órgãos comprometidos, estado nutricional, colonização bacteriana, reposição enzimática e década do diagnóstico. As curvas de sobrevivência foram estimadas pelo método Kaplan- Meier, ajustadas para truncamento à esquerda e para dados censurados à direita. A seguir, as hazard ratios (HR) foram estimadas pelo modelo de Cox, utilizando o processo de contagem, tendo a idade como escala de tempo e avaliadas pelo teste de razão de verossimilhança, e os modelos comparados pela análise de resíduos. Resultados: A população (n=177) apresentou o predomínio do sexo feminino (56%) e a idade mediana ao diagnóstico foi 14 meses. A idade mediana de sobrevivência foi 20,8 anos. Após o diagnóstico 81% sobreviveram até cinco anos; 70% até 10 anos e 61% até 14,5 anos. O modelo explicou 19,9% dos efeitos e incluiu seis covariáveis: colonização por Pseudomonas aeruginosa, isolada e associada (HR = 10,30; IC95% = 2,41-43,97), por Staphylococcus aureus (HR=4,50; IC95% = 0,93-1,85), por outras bactérias (HR=3,38; IC95% = 0,92-1,32), sexo feminino (HR=1,95; IC95% = 0,96-3,96), estado nutricional ≤ p5 (HR=1,94; IC95% = 0,94-3,98) e diagnóstico na década de 1990 (HR=4,34; IC95% = 1,50-12,52). Conclusão: Este estudo de coorte de 177 pacientes com FC mostrou uma idade mediana de sobrevivência de 20,8 anos dos pacientes no CRFC-RJ. Foram confirmados os efeitos das covariáveis que, presentes ao diagnóstico, se associaram a maior mortalidade. A intervenção nestas covariáveis promoverá a recuperação nutricional, a erradicação da Pseudomonas aeruginosa ou o adiamento da colonização crônica, dessa forma aumentando a sobrevivência.
Introduction: Cystic Fibrosis (CF) is a rare genetic disease, of autossomal recessive transmission, with multiple organ involvement, progressive course and potentially lethal. Objective: To study the CF patients survival and to find the factors associated with. Methods: In an open cohort of cases diagnosed between 01/01/1990 and 10/10/2009 in a CF reference center in Rio de Janeiro, we analyzed global survival and risk factors associated with the survival of CF patients. The at-risk period started at the age of CF diagnosis and ended at age of death, loss of follow-up or end of the study. The factors analyzed were gender, presentation mode, genotype, number of involved organs, nutritional state, bacterial colonization, enzyme replacement and decade of diagnosis. Survival curves were estimated by Kaplan-Meier (KM) adjusted for left truncation and right censored data. Hazard ratios (HR) were estimated by Cox model using counting process approach with age as time scale and evaluated by likelihood ratio test. Model diagnostic was conducted by residuals analysis. Results: The majority of the population (n=177) was female (56%) and during the study the median age at diagnosis was 14 months. The median survival was of 20.8 years. After diagnosis, 81% survived up to 5 years, 70% up to 10 and 61% up to 14.5. The model explained 19.9% of the effects and included six covariates: Pseudomonas aeruginosa colonization, isolated or associated (HR = 10.30; 95%CI = 2.41-43.97), for Staphylococcus aureus (HR = 4.50; CI95% = 0.93-1.85), for other bacteria (HR = 3.38; CI95% = 0.92-1.32), for female gender (HR = 1.95; CI95% = 0.96-3.96), for nutritional state ≤ p5 (HR = 1.94; CI95% = 0.94-3.98), and for diagnostic decade (HR = 4.34; CI95% = 1.50-12.52). Conclusion: The strength of risk factors found at diagnosis was evident in the prognosis besides indicating that interventions may reduce morbidity by nutritional recovery and by Pseudomonas aeruginosa eradication thus increasing survival.

A regressão quantílica para dados censurados é uma extensão dos modelos de regressão quantílica que, por levar em consideração a informação das observações censuradas na modelagem, e por apresentar propriedades bastante satisfatórias, pode ser vista como uma abordagem complementar às metodologias tradicionais em Análise de Sobrevivência, com a vantagem de permitir que as conclusões inferenciais sejam tomadas facilmente em relação aos tempos de sobrevivência propriamente ditos, e não em relação à taxa de riscos ou a uma função desse tempo. Além disso, em alguns casos, pode ser vista também como metodologia alternativa aos modelos clássicos quando as suposições destes são violadas ou quando os dados são heterogêneos. Apresentam-se nesta dissertação três técnicas para modelagem com regressão quantílica para dados censurados, que se diferenciam em relação às suas suposições e forma de estimação dos parâmetros. Um estudo de simulação para comparação das três técnicas para dados com distribuição normal, Weibull e log-logística é apresentado, em que são avaliados viés, erro padrão e erro quadrático médio. São discutidas as vantagens e desvantagens de cada uma das técnicas e uma delas é aplicada a um conjunto de dados reais do Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo.
Censored quantile regression is an extension of quantile regression, and because it incorporates information from censored data in the modelling, and presents quite satisfactory properties, this class of models can be seen as a complementary approach to the traditional methods in Survival Analysis, with the advantage of allowing inferential conclusions to be made easily in terms of survival times rather than in terms of risk rates or as functions of survival time. Moreover, in some cases, it can also be seen as an alternative methodology to the classical models when their assumptions are violated or when modelling heterogeneity of the data. This dissertation presents three techniques for modelling censored quantile regression, which differ by assumptions and parameter estimation method. A simulation study designed with normal, Weibull and loglogistic distribution is presented to evaluate bias, standard error and mean square error. The advantages and disadvantages of each of the three techniques are then discussed and one of them is applied to a real data set from the Heart Institute of Hospital das Clínicas, University of São Paulo.

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Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior
Among the traits of economic importance to dairy cattle livestock those related to sexual precocity and longevity of the herd are essential to the success of the activity, because the stayability time of a cow in a herd is determined by their productive and reproductive lives. In Brazil, there are few studies about the reproductive efficiency of Swiss-Brown cows and no study was found using the methodology of survival analysis applied to this breed. Thus, in the first chapter of this study, the age at first calving from Swiss-Brown heifers was analyzed as the time until the event by the nonparametric method of Kaplan-Meier and the gamma shared frailty model, under the survival analysis methodology. Survival and hazard rate curves associated with this event were estimated and identified the influence of covariates on such time. The mean and median times at the first calving were 987.77 and 1,003 days, respectively, and significant covariates by the Log-Rank test, through Kaplan-Meier analysis, were birth season, calving year, sire (cow s father) and calving season. In the analysis by frailty model, the breeding values and the frailties of the sires (fathers) for the calving were predicted modeling the risk function of each cow as a function of the birth season as fixed covariate and sire as random covariate. The frailty followed the gamma distribution. Sires with high and positive breeding values possess high frailties, what means shorter survival time of their daughters to the event, i.e., reduction in the age at first calving of them. The second chapter aimed to evaluate the longevity of dairy cows using the nonparametric Kaplan-Meier and the Cox and Weibull proportional hazards models. It were simulated 10,000 records of the longevity trait from Brown-Swiss cows involving their respective times until the occurrence of five consecutive calvings (event), considered here as typical of a long-lived cow. The covariates considered in the database were age at first calving, herd and sire (cow s father). All covariates had influence on the longevity of cows by Log-Rank and Wilcoxon tests. The mean and median times to the occurrence of the event were 2,436.285 and 2,437 days, respectively. Sires that have higher breeding values also have a greater risk of that their daughters reach the five consecutive calvings until 84 months
Dentre as caracter?sticas de import?ncia econ?mica para a pecu?ria leiteira aquelas relacionadas com a precocidade sexual e a longevidade do rebanho s?o determinantes para o sucesso da atividade, uma vez que o tempo de perman?ncia de uma vaca num rebanho ? determinado por suas vidas produtiva e reprodutiva. No Brasil, existem poucos estudos sobre a efici?ncia reprodutiva de vacas Pardo-Su??as e n?o foi encontrado nenhum estudo abordando o uso da metodologia de an?lise de sobreviv?ncia aplicada a esta ra?a. Assim, no primeiro cap?tulo deste trabalho, a idade ao primeiro parto de novilhas Pardo-Su??as foi analisada como o tempo at? o evento por meio do m?todo n?o-param?trico de Kaplan-Meier e do modelo de fragilidade compartilhado gama, sob a metodologia de an?lise de sobreviv?ncia. Foram estimadas curvas de sobreviv?ncia e de taxa de risco associadas com este evento e verificada a influ?ncia das covari?veis consideradas sobre o tempo. Os tempos m?dio e mediano ao primeiro parto foram 987,77 e 1.003 dias, respectivamente; e as covari?veis significativas pelo teste de Log-Rank, na an?lise por Kaplan-Meier, foram esta??o de nascimento, ano de parto, touro (pai da vaca) e esta??o de parto. Na an?lise pelo modelo de fragilidade, foram preditos os valores gen?ticos e as fragilidades dos touros (pais) para o parto, modelando-se a fun??o de risco de cada vaca em fun??o da covari?vel fixa esta??o de nascimento e da covari?vel aleat?ria touro. A fragilidade seguiu a distribui??o gama. Touros com valores gen?ticos positivos e altos possuem fragilidades altas, o que significa menor tempo de sobreviv?ncia de suas filhas ao evento, ou seja, redu??o na idade ao primeiro parto delas. O segundo cap?tulo teve como objetivo avaliar a longevidade de vacas leiteiras utilizando o estimador n?o-param?trico de Kaplan-Meier e os modelos de riscos proporcionais de Weibull e de Cox. Foram simulados 10.000 registros da caracter?stica longevidade de f?meas Pardo-Su??as denotando seus respectivos tempos at? a ocorr?ncia de cinco partos consecutivos (evento), considerados aqui como t?picos de uma vaca longeva. As covari?veis consideradas no banco de dados foram a idade da vaca ao primeiro parto, o rebanho e o pai da vaca. Todas as covari?veis exerceram influ?ncia sobre a longevidade das vacas de acordo com os testes de Log-Rank e Wilcoxon. Os tempos m?dio e mediano para a ocorr?ncia do evento foram de 2.436,285 e 2.437 dias. Touros com maior valor gen?tico tamb?m possuem um maior risco de que as suas filhas alcancem os cinco partos aos 84 meses

Master of Science
Department of Statistics
Paul I. Nelson
Quantiles are useful in describing distributions of component lifetimes. Data, consisting of the lifetimes of sample units, used to estimate quantiles are often censored. Right censoring, the setting investigated here, occurs, for example, when some test units may still be functioning when the experiment is terminated. This study investigated and compared the performance of parametric and nonparametric estimators of quantiles from right censored data generated from Weibull and Lognormal distributions, models which are commonly used in analyzing lifetime data. Parametric quantile estimators based on these assumed models were compared via simulation to each other and to quantile estimators obtained from the nonparametric Kaplan- Meier Estimator of the survival function. Various combinations of quantiles, censoring proportion, sample size, and distributions were considered. Our simulation show that the larger the sample size and the lower the censoring rate the better the performance of the estimates of the 5th percentile of Weibull data. The lognormal data are very sensitive to the censoring rate and we observed that for higher censoring rates the incorrect parametric estimates perform the best. If you do not know the underlying distribution of the data, it is risky to use parametric estimates of quantiles close to one. A limitation in using the nonparametric estimator of large quantiles is their instability when the censoring rate is high and the largest observations are censored. Key Words: Quantiles, Right Censoring, Kaplan-Meier estimator

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

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Introducción: La introducción de la Terapia Antirretroviral de Gran Actividad (TARGA), ha reducido la morbi-mortalidad de los pacientes con VIH/SIDA tratados, yla mejora en su calidad de vida, debido al control de la replicación viral del VIH y a lamejoría del sistema inmune, conllevando a la disminución de las infecciones oportunistas.La TARGA busca conseguir la supresión virológica del VIH, que sólo se consigue entreun 57 por cento a 78 por cento de los pacientes en TARGA. La identificación de factores asociados a falla virológica puede tener implicaciones para el tratamiento de los pacientes con antirretrovirales. Metodología: Se trata de un estudio retrospectivo de 98 pacientes nuevos que iniciaron esquema de antirretrovirales de primera línea entre Mayo del 2004a Julio del 2005 en el Programa TARGA del Hospital Nacional Hipólito Unanue ubicadoen Lima Este, Lima-Perú y que desarrollaron falla virológica. El modelo de riesgos proporcionales de Cox fue utilizado para identificar los factores asociados a fallavirológica. Resultados: De 98 pacientes en TARGA, 67.3 por cento eran varones con edad media de 35.65 años. El 94 por cento recibió AZT ó D4T +3TC+NNTR. Se encontró que el 13.2 por cento desarrollaron falla virológica. La variable régimen inicial de TARGA tuvo un nivel designificación estadística limítrofe, relacionado a la falla virológica, en el análisis multivariado de Cox. Los pacientes con el régimen inicial de DDI+3TC+NNTR (DDIfue usada en vez de AZT), tuvieron un incremento de riesgo de 7 veces mayor (HR: 7.0IC95 por cento 0.93-49.6) de desarrollar falla virológica. (AU)^ies
Introduction: The introduction of Highly Active Antiretroviral Therapy (HAART) has reduced morbidity and mortality of patients with HIV / AIDS treated, and improving their quality of life, due to the control of HIV viral replication and improvement of the immune system, leading to decreased opportunistic infections. HAART therapy seeks to achieve virologic suppression of HIV that is only achieved between 57 percent to 78 percent of patients with antirretroviral therapy. The identification of factors associated with virologic failure may have implications for the treatment of patients with antiretrovirals. Methodology: This isa retrospective study of 98 new HIV patients which starting antiretroviral therapy between May 2004 to July 2005 in the HAART Program Hipólito Unanue National Hospital in Lima East, Lima-Peru and who developed virologic failure. The proportional hazards model of Cox was used to study all factors associated with virologic failure. Results: Of 98 patients on HAART, 67.3 percent were male with mean age of 35.65 years. 94 percent received AZT ó D4T +3TC+NNTR We found that 13.2 percent developed virologic failure. The variable HAART regimen had a borderline level of statistical significance related a virologic failure, patients with initial regimen with DDI + 3TC + NNTR (DDI was useinstead of AZT), were increased 7-fold greater risk (HR: 7.0 95 percent CI 0.93-49.6) todevelop virologic failure. (AU)^ien

Resumo: No Brasil, existem poucos estudos sobre longevidade de vacas de corte, principalmente utilizando ferramentas de análise de sobrevivência na estimação de parâmetros genéticos. Todavia, os critérios para avaliar esta característica são vários, tal que em alguns destes nem todos os registros das vacas nos rebanhos podem ser levados em consideração, devido à metodologia de análise utilizada. Uma variável que é de fácil mensuração e já faz parte da maioria dos controles zootécnicos das fazendas é a idade da vaca ao último parto (IVUP). Neste trabalho, objetivo foi avaliar a longevidade das vacas nos rebanhos utilizando a variável IVUP, por meio da metodologia de análise de sobrevivência. Esta variável foi utilizada mediante um critério para analisar a longevidade produtiva de vacas nos rebanhos. O critério adotado foi a diferença entre a data em relação ao último parto de cada vaca e a data do último parto de cada fazenda. Se esta diferença foi superior a 36 meses, a vaca falhou e foi considerada descartada. Caso contrário, esta vaca foi censurada, indicando que esta ainda poderia ter futuras parições. O critério de 36 meses foi proposto por ser período suficiente para a ocorrência de um novo parto. A metodologia de análise de sobrevivência foi utilizada por considerar dados censurados e não censurados. As variáveis: estação e ano de nascimento de cada vaca, a fazenda e a idade ao primeiro parto foram utilizadas para as análises da variável IVUP. Um estudo prévio por meio de curvas de Kaplan-Meier e o modelo de Cox, utilizando a distribuição gama para os touros, desconsiderando o parentesco entre eles, foram realizados. O software Survival Kit foi empregado para estimação dos parâmetros genéticos, levando em consideração o parentesco entre os animais. Verificou-se que a IVUP apresentou herdabilidade de 0,25, e que seu uso permite avaliar a ... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: In Brazil, there are few studies about stayability, especially using tools of survival analysis in the estimation of breeding values and heritability. The criteria for evaluating this characteristic are different, such that in some of these not all information in the herds of cows can be taken into consideration, because the method of analysis used. In addition, the definitions that consider the date of disposal of the animal affect the use of information obtained in practice, because until the cows come out of the flock may take years, thus the evaluation of their parents is impaired, since the goal is selection. A variable that is easy to measure and is already part of most controls husbandry farms are cow age at last birth (IVUP). This variable was used by one criterion to analyze the productive longevity of cows in herds. The criterion was the difference between the date from the last delivery date of each cow and the last part of each farm. If this difference was more than 36 months, the cow was considered failed and discarded. Otherwise, this cow was censored, indicating that this could still have further parities. The criterion of 36 months was proposed to be sufficient time for the occurrence of a new birth. The methodology of survival analysis was used. The variables season and year of birth of each cow, farm and age at first birth were used for analysis of variable IVUP. The objective of this study was to evaluate the performance of the variable IVUP through estimates of genetic and fixed effect, to study the longevity of cows in the herd. A previous study by Kaplan-Meier and Cox model using the gamma distribution for the bulls, disregarding the relationship between them, were performed. The Survival Kit software was used to estimate the genetic parameters, taking into account the relationship between the animals. It was found that the heritability of 0.25 for IVUP ... (Complete abstract click electronic access below)
Orientador: Danísio Prado Munari
Coorientador: Claudia Cristina Paro da Paz
Coorientador: Raysildo Barbosa Lobo
Banca: João Ademir de Oliveira
Banca: Henrique Nunes De Oliveira
Banca: Roberto Carvalheiro
Banca: Lenira El Faro Zadra
Doutor

Made available in DSpace on 2014-07-22T13:16:48Z (GMT). No. of bitstreams: 2 Regina Elizabeth Müller.pdf: 4161979 bytes, checksum: 5df884fdb04b617145c35c1741e9b502 (MD5) license.txt: 1914 bytes, checksum: 7d48279ffeed55da8dfe2f8e81f3b81f (MD5) Previous issue date: 2011
Fundação Oswaldo Cruz. Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira. Rio de Janeiro, RJ, Brasil.
Introdução: A cardiopatia reumática persiste como a principal doença cardiovascular adquirida em crianças e adultos jovens em todo o mundo, sendo responsável por altas taxas de morbimortalidade e evoluindo com frequência para a necessidade de cirurgia cardíaca valvar em pacientes na fase aguda ou crônica da doença. Objetivo: Estimar os fatores associados e o tempo desde o diagnóstico até a cirurgia cardíaca valvar em crianças e adolescentes portadores de cardiopatia reumática, em um centro cardiológico de referência terciária no Rio de Janeiro. Material e Métodos: estudo observacional longitudinal de base hospitalar, utilizando metodologia de análise de sobrevivência, para estimativa do tempo até a cirurgia, e modelo de regressão de Cox, para avaliar as razões de risco associadas segundo as covariáveis. A coorte foi composta por pacientes com 3 a 20 anos, cadastrados no Instituto Nacional de Cardiologia no Rio de Janeiro entre julho de 1986 e junho de 2006 e acompanhados até setembro de 2011. O diagnóstico da lesão valvar foi confirmado pelo exame Doppler-ecocardiográfico. As covariáveis, avaliadas no início do acompanhamento, foram reunidas em três dimensões: sociodemográfica (sexo, grupo etário, cor da pele, região de moradia e década do diagnóstico); clínica (apresentação clínica, classe funcional, número de surtos anteriores, profilaxia secundária, endocardite infecciosa e fibrilação atrial); e ecocardiográfica (lesão valvar por tipo e gravidade; diâmetro do átrio esquerdo, diâmetro sistólico do ventrículo esquerdo, função ventricular esquerda, hipertensão arterial pulmonar, e ruptura de cordoalha mitral). O banco de dados foi elaborado com o programa ACCESS 2000 e a análise estatística foi realizada pelo programa R versão 2.13.1. Foi considerado significativo o valor de - 0,05. Resultados: a coorte foi composta por 348 pacientes, 58% do sexo feminino, com idade mediana ao cadastro de 12,5 anos, e de 21,5 anos ao final do acompanhamento. O tempo médio de seguimento foi de 9,0 anos (2-21 anos). O evento cirurgia cardíaca ocorreu em 39% da amostra, com tempo mediano até a cirurgia de 22,3 anos. Na análise univariada todas as covariáveis das três dimensões (socioedemográfica, clínica e ecocardiográfica) apresentaram significância estatística e risco para realização de cirurgia cardíaca (hazard ratio>1), com exceção apenas da covariável região de moradia (p>0,5). Na análise multivariada, o modelo final incluiu as variáveis: década do diagnóstico, classe funcional, número de surtos anteriores, endocardite infecciosa, lesão valvar por tipo e gravidade, diâmetro do átrio esquerdo, diâmetro sistólico do ventrículo esquerdo e ruptura de cordoalha mitral. Conclusões: A realização da cirurgia cardíaca em pacientes com cardiopatia reumática está associada a fatores sociodemográficos, clínicos e ecocardiográficos.
Introduction: Rheumatic heart disease remains as the most common acquired heart disease in children and young adults all over the world, being responsible for high mortality and morbidity rates and often demanding valve surgery in the acute or chronic phase of the disease. Objective: To estimate the time from diagnosis until valve operation and the associated factors in children and young adults with rheumatic heart disease followed up in a tertiary center for cardiovascular care in Rio de Janeiro. Methods – It is a longitudinal observational study of a hospital based population, using survival analysis methodology for time estimation and Cox regression model for hazard risk evaluation of associated variables. Cohort was composed by 3 to 20 years old patients, registered in the National Institute of Cardiology (Instituto Nacional de Cardiologia), in Rio de Janeiro, between July 1986 and June 2006, and followed up until September 2011. Valve disease diagnosis was confirmed through Doppler echocardiography examination. Variables were evaluated at the patient´s first visit and separated in three dimensions: socio demographic (gender, age group, skin color, residence region, decade of diagnosis); clinic (disease status at presentation, functional class, number of previous rheumatic episodes, secondary prophylaxis, infectious endocarditis, atrial fibrillation); echocardiographic (valve lesion and severity, left atrium diameter, systolic left ventricle diameter, left ventricle function, pulmonary hypertension, rupture of mitral chordae). The database wasbased on the program ACCESS 2000 and statistical analysis was performed using the R Program version 2.13.1. For statistical analysis was considered as significant values for  value 0.05. Results – 348 patients were included in the cohort, 58% female. Median age at the register was 12.5 years, and 21.5 years at the end of follow up. Median follow-up time was 9.0 years (2 to 21 years). 39% underwent valve operation and the median time until surgery was 22.3 years. In the univariate analysis all the variables from the three dimensions (socio demographic, clinic and echocardiographic) presented statistical significance as hazard risk in predicting valve operation (hazard ratio>1), with only one exception, that was residence region (p>0.5). In the multivariate analysis the final model included the following variables: decade of diagnosis, functional class, number of anterior rheumatic episodes, infectious endocarditis, valve lesion and severity, left atrium diameter, systolic left ventricle diameter and rupture of mitral chordate. Conclusions: Valve surgery in patients with rheumatic heart disease is associated with socio demographic, clinic and echocardiographic factors.

Contexte : Dans les analyses de survie, un risque concurrent est un événement qui empêche l'observation de l'événement d'intérêt (le décès le plus souvent). Si la probabilité de survenue d'un risque concurrent dépend de la probabilité de l'événement d'intérêt, alors il ne peut pas être traité comme une censure. Les patients ayant une insuffisance rénale chronique terminale peuvent être traités par hémodialyse, dialyse péritonéale et greffe rénale. Ces traitements sont complémentaire et les patients peuvent passer d'une modalité de traitement à une autre au cours de leur prise en charge. La dépendance entre les changements de traitement et la probabilité de décès n'a pas été étudiée et ces changements sont traités comme des censures dans les analyses de survie.Objectifs : Analyser la dépendance entre les probabilités de décès en dialyse et de greffe rénale, et entre les probabilités de décès en dialyse péritonéale et de transfert en hémodialyse. Nous démontrerons les conséquences néfastes de la non-prise en compte de cette dépendance dans les analyses de survie en dialyseMéthodes : (1) Nous avons comparé les estimations de probabilité d'événement obtenues par la méthode de Kaplan-Meier et la méthode de Kalbfleisch et Prentice sur 383 patient indicent consécutifs traités par dialyse péritonéale à Lille. (2) Nous avons analysé les données de 7318 patients incidents traités par hémodialyse en France grâce au registre national REIN. Nous avons utilisé un modèle multi-états pour analyse l'influence de l'inscription sur liste d'attente de greffe sur la probabilité de décès en dialyse. (3) Sur une cohorte de 2790 patients âgés de plus de 65 ans et traités par dialyse péritonéale issus du Registre de Dialyse Péritonéale de Langue Française (RDPLF), nous avons analysé les facteurs de contre-indication au transfert en HD en prenant en compte le décès comme risque concurrent à l'aide du modèle de Fine et Gray. Cette analyse a été complétée par un questionnaire réalisé auprès 55 des néphrologues pratiquant la dialyse péritonéale en France. Résultats : (1) La méthode de Kaplan Meier surestimait systématiquement la probabilité de décès du fait de la violation de l'hypothèse d'indépendance entre le décès et les risques concurrents. Cette méthode n'apparaît donc pas valide dans les analyses de survie en dialyse. La méthode de Kalbfleisch et Prentice était valide mais l'interprétation des incidences cumulées doit prendre en compte tous les risques concurrents. (2) La greffe rénale est un risque concurrent dépendant de la probabilité de décès des patients. Les patients inscrits sur liste d'attente de greffe avaient un risque de décès significativement plus bas que les autres patients, après ajustement sur l'âge et la présence de comorbidités. (3) Le transfert en hémodialyse est un risque concurrent qui semble dépendre de la probabilité de décès des patients. En effet, l'âge et la présence de comorbidités étaient à la fois des facteurs de risque de décès et des facteurs de contre-indications au transfert en hémodialyse. De plus, la plupart des néphrologues ayant répondu à notre enquête ont déclaré qu'une espérance de vie limitée pouvait constituer une contre-indication au transfert. Conclusion : Dans les études de cohorte de patients en insuffisance rénale chronique terminale, les analyses de survie devraient prendre en compte les changements de traitement car ce sont des risques concurrents dépendants de la probabilité de décès. Notre travail a montré que les modèles multi-états sont des outils statistiques flexibles qui permettent de bien représenter l'inter-dépendance entre les différentes modalités de traitement entre dialyse péritonéale, hémodialyse, greffe rénale et décès.

Dissertação de mestrado em Estatística
Em diversos estudos longitudinais, os indivíduos ou itens em observação podem experimentar vários eventos de interesse ao longo de um determinado período de seguimento. Quando o evento de interesse pode ocorrer mais do que uma vez num indivíduo, estes eventos são designados de eventos recorrentes. Este tipo de dados é frequentemente observado em estudos de investigação médica, economia, engenharia e sociologia. Em estudos de investigação médica, os eventos recorrentes podem corresponder a múltiplas ocorrências de hospitalização de um grupo de doentes, múltiplos episódios de recorrência em estudos de cancro, ataques cardíacos repetidos ou múltiplas recaídas de remissão de pacientes com leucemia. A análise destes dados pode ser focada no tempo entre eventos ("gap times") ou nos modelos para o tempo até aos eventos. Nestes estudos, os eventos ordenados sequencialmente e os correspondentes intervalos de tempo constituem tópicos de particular interesse. Neste trabalho, foram consideradas estimativas para a função de distribuição marginal e conjunta de dois intervalos de tempo, na presença de censura aleatória univariada pela direita. Também foram consideradas estimativas para a função de sobrevivência bivariada. A presente dissertação está dividida em seis capítulos. No primeiro capítulo são introduzidos alguns conceitos e notações fundamentais da análise de sobrevivência, que servirão de suporte para os outros capítulos. Assim, são definidas algumas quantidades de interesse, alguns conceitos de estimação pontual e o estimador de Kaplan-Meier. No segundo e terceiro capítulos são apresentados vários estimadores para a função de distribuição e sobrevivência bivariada de tempos sequenciais, na presença de censura pela direita. As extensões destes estimadores, para vários intervalos de tempo, são também discutidas. Novos estimadores para as funções conjuntas (função de distribuição bivariada e função de sobrevivência bivariada) são propostos e as suas extensões para vários intervalos de tempo são também discutidas. Os novos estimadores são baseados na abordagem "landmark" (van Houwelingen, 2007) e na função de risco cumulativa ponderada. O quarto capítulo descreve detalhadamente os estudos de simulação realizados para estudar o comportamento dos estimadores propostos. Nestes estudos de simulação, foram exploradas algumas propriedades desejáveis dos estimadores, recorrendo à média, ao desvio padrão, ao viés e ao erro quadrático médio. Também foram construídos diagramas de extremos e quartis, de forma a avaliar graficamente estes estimadores. No quinto capítulo os métodos propostos são aplicados a uma base de dados real, relativa ao cancro da mama em mulheres alemãs (German breast cancer). Por fim, no sexto capítulo são apresentadas as principais conclusões desta dissertação e são referidos alguns possíveis trabalhos, decorrentes deste estudo, que podem ser realizados.
In many longitudinal studies, the individuals and items in observation can experience multiples events of interest during their follow-up. An event of interest can occurs more than once on a individual, when this occurs we are in presence of recurrent events. This type of data is frequently observed in medical studies, economics, engineering and sociology. In medical studies, recurrent events may correspond to multiple hospitalisations of a group of patients, multiple episodes of recurrence in cancer studies, repeated cardiac attacks or multiple remissions of leukemia patients. The analysis of these data can be focused 011 the times between events ("gap times") or on the models for the events times. On this studies, the sequentially ordered events and corresponding gap times, constitute topics of particular interest. In this work, were considered methods to estimate the marginal distribution function and joint distribution function of two gap-times, in the presence of univariate right censoring. Estimators for the bivariate survival function were also considered. The present dissertation is divided in six chapters. On the first chapter some fundamental notation and concepts of survival analysis, that will support others chapters, are introduced. Therefor, are defined some quantities of interest, some concepts of point estimation and the Kaplan-Meier estimator. On the second chapter and third chapter, several estimators are presented for the bivariate distribution and bivariate survival function, under right censoring. The extension of this estimators for various gap-times are also discussed. New estimators for joint functions are proposed and their extensions for multiple gap times are also discused. The new estimators are based on the "landmark" approach and on the weighted cumulative hazard function. The fourth chapter describes in detail the simulation studies carried out to study the behavior of the proposed estimators. In these simulation studies, some desirable properties of the estimators were explored, using the mean, standard deviation, bias and mean square error. Extremes and quartile diagrams were also constructed in order to graphically evaluate these estimators. In the fifth chapter the proposed methods are applied to a real database, concerning breast cancer in German women. Finally, in the sixth chapter, the main conclusions of this dissertation are presented and some possible studies are mentioned, that can be realized.

In reliability studies, the goal is to gain knowledge about a product's failure times or life expectancy. Precedence tests do not require large sample sizes and are used in reliability studies to compare the life-time distributions from two samples. Precedence tests are useful since they provide reliable results early in a life-test and the surviving units can be used in other tests. Ng and Balakrishnan (2010) proposed a precedence-type test based on the Kaplan-Meier estimator of the cumulative distribution function. A precedence-type test based on the Nelson-Aalen estimator of the cumulative hazard function has been proposed. This test was developed for both Type-II right censoring and progressive Type-II right censoring. Numerical results, including illustrative examples, critical values and a power study have been provided. The results from this test were compared with those from the test based on the Kaplan-Meier estimator.

Health technology assessment: case study on breast carcinoma treatment in the Czech Republic Bc. Lenka Šlegerová January 4, 2019 Abstract This thesis proposes an original method for assessing total costs of med- ical treatment. It defines the semi-Markov model with four states that are associated with specific costs of the treatment, and not with patients' health statuses. This method is applied to individuals' treatment data drawn from the Czech clinical practice in the treatment of the metastatic HER2+ breast cancer. The aim is to assess the cost-effectiveness of adding medication per- tuzumab to the combination of trastuzumab+docetaxel within first-line therapy and to examine whether using individual data on Czech patients and the economic conditions leads to different results from foreign stud- ies. Furthermore, employing censored data from the clinical practice in the thesis complicates the estimation of patients' overall survival in compari- son to clinical-trials data that form random samples. Therefore, survival functions were not only estimated by the Kaplan-Meier estimator but also using the Cox proportional hazard model and the Accelerated failure time model that both control for the effects of included covariates. The addition of pertuzumab does not result in significantly longer pa- tients'...

The objective of the study was to identify the factors that affect the survival lifetime of HIV+ terminal patients in rural district hospitals of Albert Luthuli municipality in the Mpumalanga province of South Africa. A cohort of HIV+ terminal patients was retrospectively followed from 2010 to 2017 until a patient died, was lost to follow-up or was still alive at the end of the observation period. Nonparametric survival analysis and semiparametric survival analysis methods were used to analyse the data. Through Cox proportional hazards regression modelling, it was found that ART adherence (poor, fair, good), Age, Follow-up mass, Baseline sodium, Baseline viral load, Follow CD4 count by Treatment (Regimen 1) interaction and Follow-up lymphocyte by TB history (yes, no) interaction had significant effects on survival lifetime of HIV+ terminal patients (p-values<0.1). Furthermore, through quantile regression modelling, it was found that short, medium and long survival times of HIV+ patients, respectively represented by the 0.1, 0.5 and 0.9 quantiles, were not necessarily significantly affected by the same factors.
Statistics
M. Sc. (Statistics)