Modelos de sobrevivência com fração de cura e erro de medida nas covariáveis

In this work, we study the survival cure rate model proposed by Yakovlev et al. (1993), based on a competing risks structure concurring to cause the event of interest, and the approach proposed by Chen et al. (1999), where covariates are introduced to model the risk amount. We focus the measurement error covariates topics, considering the use of corrected score method in order to obtain consistent estimators. A simulation study is done to evaluate the behavior of the estimators obtained by this method for finite samples. The simulation aims to identify not only the impact on the regression coefficients of the covariates measured with error (Mizoi et al. 2007) but also on the coefficients of covariates measured without error. We also verify the adequacy of the piecewise exponential distribution to the cure rate model with measurement error. At the end, model applications involving real data are made

Modelos de sobrevivência com fração de cura e omissão nas covariáveis

In this work we study the survival cure rate model proposed by Yakovlev (1993) that are considered in a competing risk setting. Covariates are introduced for modeling the cure rate and we allow some covariates to have missing values. We consider only the cases by which the missing covariates are categorical and implement the EM algorithm via the method of weights for maximum likelihood estimation. We present a Monte Carlo simulation experiment to compare the properties of the estimators based on this method with those estimators under the complete case scenario. We also evaluate, in this experiment, the impact in the parameter estimates when we increase the proportion of immune and censored individuals among the not immune one. We demonstrate the proposed methodology with a real data set involving the time until the graduation for the undergraduate course of Statistics of the Universidade Federal do Rio Grande do Norte

Testes de hipóteses em modelos de sobrevivência com Fração de cura

Survival models deals with the modeling of time to event data. However in some situations part of the population may be no longer subject to the event. Models that take this fact into account are called cure rate models. There are few studies about hypothesis tests in cure rate models. Recently a new test statistic, the gradient statistic, has been proposed. It shares the same asymptotic properties with the classic large sample tests, the likelihood ratio, score and Wald tests. Some simulation studies have been carried out to explore the behavior of the gradient statistic in fi nite samples and compare it with the classic statistics in diff erent models. The main objective of this work is to study and compare the performance of gradient test and likelihood ratio test in cure rate models. We first describe the models and present the main asymptotic properties of the tests. We perform a simulation study based on the promotion time model with Weibull distribution to assess the performance of the tests in finite samples. An application is presented to illustrate the studied concepts

Frequência e significado clínico da expressão da glicoproteína P e da proteína relacionada a resistência a múltiplas drogas na leucemia mielóide aguda

Despite the advances in the cure rate for acute myeloid leukemia, a considerable number of patients die from their disease due to the occurrence of multidrug resistance (MDR). Overexpression of the transporter proteins P-glycoprotein (Pgp) and multidrug resistance-associated protein (MRP) confer resistance to the treatment these leukemias. OBJECTIVE: To analyze the expression of the Gpp and MRP1 in patients with AML by flow cytometry (FC) and to determine the correlation between expression and demographic and also clinical and laboratorial variables. METHODS: Bone marrow and peripheral blood samples from 346 patients with a diagnosis of AML were assessed for the expression of Pgp and MRP1 by FC. RESULTS: The expression of Pgp and MRP1 was found in 111 (32.1%) and 133 (38.4%) patients, respectively, with greater prevalence in older patients and lower in adolescents, observing also a high incidence in patients with refractory disease, recurrence and secondary in comparison with the cases of de novo AML. Regarding the laboratory findings, we observed a higher correlation statistically significant between the expression of Pgp and MRP1 in AML CD34+ and FAB AML M7, M5A and M2 and lower the M3 subtype, not observed statistically significant correlation between the phenotype MDR and other laboratory data such with hemoglobin, leukocyte count, platelet count, aberrant expression of lymphoid antigens (CD2, CD7 and CD19) and clinical signs related to the disease. CONCLUSIONS: The results showed that the detection of MDR phenotype by flow cytometry can be a molecular marker for prognosis independent patients diagnosed with AML.

Perfis e práticas dos profissionais de saúde mental em dois hospitais psiquiátricos de grande porte

In the Brazilian network of psychosocial care, health professionals are important actors in the process of transformation of mental health public policies among various services. In the reality of psychiatric hospitals, one should understand the need to expand the debate about the current context of practices developed. This study aimed at analyzing the process of psychiatric reform and the mental health policy in the State of Rio Grande do Norte (RN) from the profiles and practices of higher-level professionals in two psychiatric hospitals. This is a cross-sectional and descriptive research, with quantitative and qualitative data, conducted in two psychiatric hospitals of RN. The universe of the target population was 95 professionals, taking into account the margin of error of 8%, non-response rate and the inclusion criteria: holding effective link with the institution by means of approval in public examination for, at least, six months, being state or municipal servant; having a minimum weekly workload of 20 hours in service; participating in care and/or activities with patients and families in a direct way. The final sample consisted of 60 professionals. The tool for data collection was a questionnaire with closed and semi-open questions about socioeconomic profile, and mental health policies, practices and training. Quantitative data were tabulated in the statistical software SPSS, and simple and bivariate statistics, chi-square type, was used for analysis by adopting the significance level with the value p<0,05. In order to analyze data, the content analysis of Bardin was used. The qualitative findings obtained with the semi-open questions in Analyse Lexicale par Context d'un Ensemble de Segments de Texte (ALCESTE) were grouped into four thematic axes: Professional action in mental health; Mental health training; Scenarios of psychiatric reform and psychiatric hospitals; Mental health policies and practices: challenges for professionals in hospitals. The profile of professionals has revealed the majority of women (89,7%), nurses (36,7%), aged 50-59 years (42,9%), weekly workload of 40 hours (52,4% ), time of completion of graduation from six to 15 years (57%), and 21,4% reported to have specialization in mental health. Regarding the practices developed in individual care, it was found an association between those who do not build or partially conducts the therapeutic project and those who conduct care related to observation and annotation. In family care, it was obtained care consultation during crisis; and, in group care, recreational activities. In the analysis of thematic axes, it was noted that, despite changes identified in the profiles and practices of higher-level professionals in care services for mental health, with the implementation of new public policies for this field, the findings indicate the confluence of asymmetries and divergences in the actions of the teams in psychiatric hospitals, difficulties in managing services, frequent readmissions, reduced quantitative of available services and equipment, high demand of users, disarticulation of the network of psychosocial care, and the very shortage of skilled human resources to compose these services. Accordingly, the evidenced scenarios partially outline the current political and ideological mismatch of the national process of psychiatric reform that denies the role of care actions conducted within hospitals, although it has not gone far enough with the creation of new services that justify the total extinction of this institution

Desenvolvimento de sistemas farmacêuticos emulsionados para veiculação gênica

Broadly speaking, the concept of gene therapy involves the transfer of a genetic material into a cell, tissue, or organ in order to cure a disease or at least improve the clinical status of a patient. Making it simple, gene therapy consists in the insertion of functional genes into cells containing defective genes by substituting, complementing or inhibiting them. The achievement of a foreigner DNA expression into a population of cells requires its transfer to the target. Therefore, it is a key issue to create systems able to transfer and protect the DNA until it reaches the target, the vectors. The disadvantages related to the use of viral vectors have encouraged efforts to develop emulsions as non-viral vectors. In fact, they are easily produced, present controllable stability and enable transfection. The aim of this work was to develop an emulsion for gene therapy and evaluate its ability to compact nucleic acids by the development of a complex with the plasmid pIRES2-EGFP. The first step was to determine the Hydrophilic Lipophilic Balance (HLB) of the Captex® 355 (oily internal phase of the emulsion) through long and short term stability assays. Based on the results, emulsions composed of Captex® 355, Tween 20® and Span 60® with 10.7 HLB were produced by three different methods: phase inversion, spontaneous emulsification and sonication. The results showed that the lowest diameter and best stability of the emulsions were achieved by the sonication method. The cationic emulsions were made by adding DOTAP to the basic emulsion. Its association with pIRES2-EGFP was evaluated by electrophoresis. Several rates of emulsion and DNA were evaluated and the results showed that 100% of the complex was formed when the rate DOTAP/DNA(nmol/µg) was 130. In conclusion, the overall results show the ability of the proposed emulsion to compact pIRES2-EGFP, which is a requirement to a successful transfection. Therefore, such formulation may be considered a promising candidate for gene therapy