Aplicación de modelos paramétricos alternativos para el análisis de supervivencia de pacientes con cáncer / Application of alternative parametric models for the survival analysis of cancer patients

RESUMEN En el presente artículo se describe una metodología que permite tener un acercamiento a modelos probabilísticos alternativos para el análisis de supervivencia, con censura por la derecha, distintos a los que usualmente se estudian (distribución: exponencial, gamma, Weibull y log-normal), ya que es posible que los datos no se ajusten siempre con suficiente precisión por las distribuciones existentes. La metodología utilizada permite mayor flexibilidad de modelar observaciones extremas, ubicadas generalmente en la cola derecha de la distribución de los datos, lo cual admite que algunos eventos aún tengan la probabilidad de ocurrir, lo que no sucede con los modelos tradicionales y el estimador de Kaplan-Meier, el cual estima para los tiempos más prolongados, probabilidades de supervivencia aproximadamente iguales a cero. Para mostrar la utilidad de la propuesta metodológica, se consideró una aplicación con datos reales que relaciona tiempos de supervivencia de pacientes con cáncer de colon.

ABSTRACT This article describes a methodology that allows an approach to alternative right-censored probabilistic models for the analysis of survival, different to those usually studied (exponential, gamma, Weibull, and log-normal distribution) since it is possible that the data do not always fit with sufficient precision due to existing distributions. The methodology used allows for greater flexibility when modeling extreme observations, generally located in the right tail of data distribution, which admits that some events still have the probability of occurring, which is not the case with traditional models and the Kaplan-Meier estimator, which estimates for the longest times, survival probabilities approximately equal to zero. To show the usefulness of the methodological proposal, we considered an application with real data that relates survival times of patients with colon cancer (CC).

Low serum vitamin D is associated with an increased likelihood of acquired premature ejaculation

Abstract Purpose: To investigate the relationship between 25-hydroxyvitamin D (25 (OH) D) levels and acquired premature ejaculation (PE). Materials and Methods: A total of 97 patients with acquired PE and 64 healthy men as a control group selected from volunteers without PE attending our Andrology Outpatient Clinic between November 2016 and April 2017 were included the study. All patients were considered to have acquired PE if they fulfilled the criteria of the second Ad Hoc International Society for Sexual Medicine Committee. Premature ejaculation diagnostic tool questionnaires were used to assessment of PE and all participants were instructed to record intravaginal ejaculatory latency time. Vitamin D levels were evaluated in all participants using high performance liquid chromatography method included in the study. Results: Compared to men without PE, the patients with acquired PE had significantly lower 25 (OH) D levels (12.0 ± 4.5 ng/mL vs. 18.2 ± 7.4 ng/mL, p < 0.001). In the logistic regression analysis, 25 (OH) D was found to be an independent risk factor for acquired PE, with estimated odds ratios (95% CI) of 0.639 (0.460-0.887, p = 0.007) and the area under curve of the ROC curve of 25 (OH) D diagnosing acquired PE was 0.770 (95% CI: 0.695 to 0.844, p < 0.001). The best cut-off value was 16 ng/mL with a sensitivity of 60.9%, specificity of 83.5%, PPV of 70.9%, and NPV of 76.4% to indicate acquired PE. Conclusions: This study demonstrates that lower vitamin D levels are associated with the acquired PE. The result of our study showed that the role of serum vitamin D levels should be investigate in the etiology of acquired PE. Perhaps supplementation of vitamin D in men with acquired PE will ameliorate the sexual health of these patients.

Low serum vitamin D is associated with an increased likelihood of acquired premature ejaculation.

PURPOSE: To investigate the relationship between 25-hydroxyvitamin D (25 (OH) D) levels and acquired premature ejaculation (PE). MATERIALS AND METHODS: A total of 97 patients with acquired PE and 64 healthy men as a control group selected from volunteers without PE attending our Andrology Outpatient Clinic between November 2016 and April 2017 were included the study. All patients were considered to have acquired PE if they fulfilled the criteria of the second Ad Hoc International Society for Sexual Medicine Committee. Premature ejaculation diagnostic tool questionnaires were used to assessment of PE and all participants were instructed to record intravaginal ejaculatory latency time. Vitamin D levels were evaluated in all participants using high performance liquid chromatography method included in the study. RESULTS: Compared to men without PE, the patients with acquired PE had significantly lower 25 (OH) D levels (12.0 ± 4.5 ng/mL vs. 18.2 ± 7.4 ng/mL, p < 0.001). In the logistic regression analysis, 25 (OH) D was found to be an independent risk factor for acquired PE, with estimated odds ratios (95% CI) of 0.639 (0.460-0.887, p = 0.007) and the area under curve of the ROC curve of 25 (OH) D diagnosing acquired PE was 0.770 (95% CI: 0.695 to 0.844, p < 0.001). The best cut-off value was 16 ng/mL with a sensitivity of 60.9%, specificity of 83.5%, PPV of 70.9%, and NPV of 76.4% to indicate acquired PE. CONCLUSIONS: This study demonstrates that lower vitamin D levels are associated with the acquired PE. The result of our study showed that the role of serum vitamin D levels should be investigate in the etiology of acquired PE. Perhaps supplementation of vitamin D in men with acquired PE will ameliorate the sexual health of these patients.

Importancia del cálculo de la sensibilidad, la especificidad y otros parámetros estadísticos en el uso de las pruebas de diagnóstico clínico y de laboratorio / Importance of calculation of sensitivity, specificity, and other statistical parameters in the use of clinical and laboratory diagnostic tests

Resumen: la elección de una prueba a realizar para un paciente, así como su interpretación, es un escenario diario al cual el médico se debe enfrentar y para el cual debe aplicar su juicio crítico basado en las evidencias informadas. Es común que cuando se habla de una prueba de diagnóstico clínico o de laboratorio se describan parámetros como la sensibilidad, la especificidad y los valores predictivos positivos y negativos. Estos reflejan las características de una prueba diagnóstica y sirven para decidir en qué momento se deben utilizar (sensibilidad y especificidad de una prueba) o qué significado tiene el resultado de una prueba en un paciente en particular. Cuando se trata de comparar estos parámetros en diferentes pruebas y optar por la que es de mayor utilidad en el diagnóstico de una enfermedad determinada, es indispensable que el médico conozca y aprenda cómo se obtienen estas medidas y cuál es su interpretación para decidir la conducta más apropiada para el paciente. El objetivo de la presente revisión es ofrecer los conceptos estadísticos básicos y simples para la comprensión y aplicación de las pruebas de diagnóstico clínico y de laboratorio. (AU)

Abstract: The selection of a test to request a patient as well as their interpretation is a daily scenario in which the physician must deal and apply his critical judgment based on the reported evidences. It is common that when talking about a clinical or laboratory diagnostic test, parameters such as sensitivity, specificity and positive and negative predictive values are described. These parameters reflect the characteristics of a diagnostic test and serve to decide when should be used (sensitivity and specificity of a test) or what is the meaning of a test result in a particular patient. When it is necessary to compare these parameters in different tests and opting for the most useful for the diagnosis of a particular disease, it is essential that the physician knows and learns how these measures are obtained and their interpretation to decide the most appropriate behavior for the patient. The objective of the present review is to provide basic and simple statistical concepts for the understanding and application of clinical and laboratory diagnostic tests. (AU)

Preclinical molecular imaging: development of instrumentation for translational research with small laboratory animals / Imagem molecular pré-clínica: desenvolvimento de instrumentação para pesquisa translacional com pequenos animais

ABSTRACT Objective: To present the result of upgrading a clinical gamma-camera to be used to obtain in vivo tomographic images of small animal organs, and its application to register cardiac, renal and neurological images. Methods: An updated version of the miniSPECT upgrading device was built, which is composed of mechanical, electronic and software subsystems. The device was attached to a Discovery VH (General Electric Healthcare) gamma-camera, which was retired from the clinical service and installed at the Centro de Imagem Pré-Clínica of the Hospital Israelita Albert Einstein. The combined system was characterized, determining operational parameters, such as spatial resolution, magnification, maximum acceptable target size, number of projections, and acquisition and reconstruction times. Results: Images were obtained with 0.5mm spatial resolution, with acquisition and reconstruction times between 30 and 45 minutes, using iterative reconstruction with 10 to 20 iterations and 4 projection subsets. The system was validated acquiring in vivo tomographic images of the heart, kidneys and brain of normal animals (mice and adult rats), using the radiopharmaceuticals technetium-labeled hexakis-2-methoxy-isobutyl isonitrile (99mTc-Sestamibi), technetium-labeled dimercaptosuccinic acid (99mTc-DMSA) and technetium-labeled hexamethyl propyleneamine oxime (99mTc-HMPAO). Conclusion: This kind of application, which consists in the adaptation for an alternative objective of already existing instrumentation, resulted in a low-cost infrastructure option, allowing to carry out large scale in vivo studies with enhanced quality in several areas, such as neurology, nephrology, cardiology, among others.

RESUMO Objetivo: Apresentar o resultado da adaptação de uma gama câmara clínica para uso dedicado na obtenção de imagens tomográficas in vivo de órgãos de pequenos animais de experimentação, e de sua aplicação na obtenção de imagens cardíacas, renais e neurológicas. Métodos: Foi construída uma versão atualizada do dispositivo de adaptação miniSPECT, composto por três subsistemas: mecânico, eletrônico e de software. O dispositivo foi montado em uma câmara Discovery VH da General Electric Healthcare, retirada do serviço clínico e instalada no Centro de Imagem Pré-Clínica do Hospital Israelita Albert Einstein. O sistema combinado foi caracterizado, determinando parâmetros de funcionamento como resolução espacial, magnificação, limites de tamanho dos alvos de estudo, número de projeções, tempo de registro e tempo de reconstrução das imagens tomográficas. Resultados: Foram obtidas imagens com resolução espacial de até 0,5mm, com tempos de registro e reconstrução de 30 a 45 minutos, utilizando reconstrução iterativa com 10 a 20 iterações e 4 subconjuntos de projeções. O sistema foi validado obtendo imagens tomográficas in vivo do coração, dos rins e do cérebro de animais normais (camundongos e ratos adultos), utilizando os radiofármacos hexaquis-2-metoxi-isobutil-isonitrila marcado com 99mTc (Sestamibi-99mTc), ácido dimercaptosuccínico marcado com 99mTc (DMSA-99mTc) e hexametil-propileno-amina-oxima marcada com 99mTc (HMPAO-99mTc). Conclusão: Este tipo de aplicação, que consiste na adaptação para um objetivo alternativo de instrumentação já existente, constituiu-se em uma opção de infraestrutura de baixo custo, que permite realizar estudos in vivo em larga escala, com qualidade aprimorada, em áreas diversas, como neurologia, nefrologia, cardiologia, entre outras.

Predictive performance of BI-RADS magnetic resonance imaging descriptors in the context of suspicious (category 4) findings.

OBJECTIVE: To determine the positive predictive value (PPV) and likelihood ratio for magnetic resonance imaging (MRI) characteristics of category 4 lesions, as described in the Breast Imaging Reporting and Data System (BI-RADS(®)) lexicon, as well as to test the predictive performance of the descriptors using multivariate analysis and the area under the curve derived from a receiver operating characteristic (ROC) curve. MATERIALS AND METHODS: This was a double-blind review study of 121 suspicious findings from 98 women examined between 2009 and 2013. The terminology was based on the 2013 edition of the BI-RADS. RESULTS: Of the 121 suspicious findings, 53 (43.8%) were proven to be malignant lesions, with no significant difference between mass and non-mass enhancement (p = 0.846). The PPVs were highest for masses with a spiculated margin (71%) and round shape (63%), whereas segmental distribution achieved a high PPV (80%) for non-mass enhancement. Kinetic analyses performed poorly, except for type 3 curves applied to masses (PPV of 73%). Logistic regression models were significant for both patterns, although the results were better for masses, particularly when kinetic assessments were included (p = 0.015; pseudo R(2) = 0.48; area under the curve = 90%). CONCLUSION: Some BI-RADS MRI descriptors have high PPV and good predictive performance-as demonstrated by ROC curve and multivariate analysis-when applied to BI-RADS category 4 findings. This may allow future stratification of this category.

OBJETIVO: Determinar o valor preditivo positivo (VPP) e a razão de verossimilhança positiva de características de ressonância magnética (RM) de lesões da categoria 4, como descritas no léxico do Breast Imaging Reporting and Data System (BI-RADS®), e testar o desempenho preditivo dos descritores por meio de análise multivariada e área sob a curva derivada da curva receiver operating characteristic (ROC). MATERIAIS E MÉTODOS: Foi realizado um estudo revisional duplo-cego de 121 achados suspeitos em 98 mulheres examinadas entre 2009 e 2013. A terminologia foi baseada na edição de 2013 do BI-RADS. RESULTADOS: Dos 121 achados suspeitos, 53 (43,8%) eram de fato lesões malignas, sem diferença significativa entre nódulos e realce não nodular (p = 0,846). Nódulos com margem espiculada (71%) e forma redonda (63%) apresentaram os maiores VPPs, ao passo que a distribuição segmentar teve alto VPP para realce não nodular (80%). Apenas a curva cinética do tipo 3 teve bom desempenho quando aplicada a nódulos (VPP = 73%). Modelos de regressão logística foram significantes para os dois padrões principais, embora os nódulos tenham apresentado resultados melhores, particularmente com a introdução da análise cinética (p = 0,015; pseudo-R2 = 0,48; área sob a curva = 90%). CONCLUSÃO: Alguns descritores de RM do BI-RADS têm alto VPP e bom desempenho preditivo - demonstrado por curva ROC e análise multivariada - quando aplicados a achados da categoria 4 segundo o BI-RADS. Isso pode permitir futura estratificação dessa categoria.

Predictive performance of BI-RADS magnetic resonance imaging descriptors in the context of suspicious (category 4) findings / Desempenho preditivo dos descritores de ressonância magnética do BI-RADS no contexto de achados suspeitos (categoria 4)

Abstract Objective: To determine the positive predictive value (PPV) and likelihood ratio for magnetic resonance imaging (MRI) characteristics of category 4 lesions, as described in the Breast Imaging Reporting and Data System (BI-RADS®) lexicon, as well as to test the predictive performance of the descriptors using multivariate analysis and the area under the curve derived from a receiver operating characteristic (ROC) curve. Materials and Methods: This was a double-blind review study of 121 suspicious findings from 98 women examined between 2009 and 2013. The terminology was based on the 2013 edition of the BI-RADS. Results: Of the 121 suspicious findings, 53 (43.8%) were proven to be malignant lesions, with no significant difference between mass and non-mass enhancement (p = 0.846). The PPVs were highest for masses with a spiculated margin (71%) and round shape (63%), whereas segmental distribution achieved a high PPV (80%) for non-mass enhancement. Kinetic analyses performed poorly, except for type 3 curves applied to masses (PPV of 73%). Logistic regression models were significant for both patterns, although the results were better for masses, particularly when kinetic assessments were included (p = 0.015; pseudo R2 = 0.48; area under the curve = 90%). Conclusion: Some BI-RADS MRI descriptors have high PPV and good predictive performance-as demonstrated by ROC curve and multivariate analysis-when applied to BI-RADS category 4 findings. This may allow future stratification of this category.

Resumo Objetivo: Determinar o valor preditivo positivo (VPP) e a razão de verossimilhança positiva de características de ressonância magnética (RM) de lesões da categoria 4, como descritas no léxico do Breast Imaging Reporting and Data System (BI-RADS®), e testar o desempenho preditivo dos descritores por meio de análise multivariada e área sob a curva derivada da curva receiver operating characteristic (ROC). Materiais e Métodos: Foi realizado um estudo revisional duplo-cego de 121 achados suspeitos em 98 mulheres examinadas entre 2009 e 2013. A terminologia foi baseada na edição de 2013 do BI-RADS. Resultados: Dos 121 achados suspeitos, 53 (43,8%) eram de fato lesões malignas, sem diferença significativa entre nódulos e realce não nodular (p = 0,846). Nódulos com margem espiculada (71%) e forma redonda (63%) apresentaram os maiores VPPs, ao passo que a distribuição segmentar teve alto VPP para realce não nodular (80%). Apenas a curva cinética do tipo 3 teve bom desempenho quando aplicada a nódulos (VPP = 73%). Modelos de regressão logística foram significantes para os dois padrões principais, embora os nódulos tenham apresentado resultados melhores, particularmente com a introdução da análise cinética (p = 0,015; pseudo-R2 = 0,48; área sob a curva = 90%). Conclusão: Alguns descritores de RM do BI-RADS têm alto VPP e bom desempenho preditivo - demonstrado por curva ROC e análise multivariada - quando aplicados a achados da categoria 4 segundo o BI-RADS. Isso pode permitir futura estratificação dessa categoria.

Fecundidad y participación de la mujer en el mercado laboral en la Costa Caribe y en Colombia / Fertilidade e participação feminina no mercado de trabalho no Litoral Caribenho, e na Colômbia / Fertility and female participation in the labor market in Colombia and its Caribbean Coast

El objetivo del presente artículo es identificar los determinantes que explican las diferencias en las tasas de participación laboral de las mujeres –con y sin hijos– en la Costa Caribe y en Colombia. Para tal propósito se realizaron modelos probit de los determinantes de la participación de cada grupo de mujeres, y se implementó el método de descomposición microeconométrica aplicado a los modelos de elección binaria. Los resultados sugieren a que tanto en la Costa Caribe como en Colombia las variables que explican dichas diferencias son: la escolaridad, la no tenencia de pareja y, en menor medida, la riqueza.

The aim of this article is to identify the determinants of the differences in the labor supply rates between the women with and without children in Colombia and its Caribbean Coasty. In order to achieve this, Probit models about the determinants of the labor supply rate for each group of women were estimated and the microeconometric decomposition method was applied to the binary models. The results suggest that in the Caribbean Coast of Colombia –as well as in the rest of the country- the main variables to explain such differences are: education, being single and wealth in a lesser degree.

O objetivo deste artigo é identificar os fatores que explicam as diferenças nas taxas de participação das mulheres, com e sem filhos, no mercado de trabalho do litoral Caribenho e na Colômbia. Para esse propósito foram elaboradores modelos probit dos fatores determinantes da participação de cada grupo de mulheres, e implementou-se o método de decomposição microeconométrica aplicado aos modelos de escolha binária. Os resultados mostram que tanto no litoral Caribenho como na Colômbia as variáveis que explicam tais diferenças são: a escolaridade, não ter companheiro e, em menor escala, a riqueza.

O modelo de regressão linear misto para dados longitudinais: uma aplicação na análise de dados antropométricos desbalanceados / Mixed linear regression model for longitudinal data: application to an unbalanced anthropometric data set

Os dados provenientes de estudos longitudinais se caracterizam pela seqüência de duas ou mais observações em cada indivíduo. Nos estudos de coorte, esses dados geralmente apresentam estrutura desbalanceada. Uma casuística que envolve a avaliação longitudinal de crescimento de lactentes nascidos de mães infectadas pelo HIV foi acompanhada no ambulatório de AIDS pediátrica do Hospital das Clínicas da Universidade Federal de Minas Gerais, Minas Gerais, Brasil. O objetivo deste estudo é demonstrar a aplicação do modelo linear misto na análise de dados longitudinais desbalanceados provenientes dessa coorte. Os resultados mostram que, aos seis meses de idade, os meninos eram, em média, 1,8cm maiores que as meninas e as crianças sororrevertoras eram, em média, 2,9cm maiores que as infectadas. Aos 12 meses, a diferença na altura entre meninos e meninas passou a ser, em média, de 2,4cm enquanto a diferença entre infectados e sororrevertores passou a ser, em média, de 3,5cm. Além de descrever o comportamento longitudinal do crescimento, o modelo também permite estimar a velocidade de crescimento das crianças por sexo e grupo.

A longitudinal data set is characterized by a time sequence of two or more observations from each individual. In cohort studies, these data are usually not balanced. A data set related to longitudinal height measurements in children of HIV-infected mothers was recorded at the university hospital of the Federal University in Minas Gerais, Brazil. The objective was to assess the application of the mixed effect model to this unbalanced data set. At six months of age, on average boys were 1.8cm taller than girls, and seroreverter infants were 2.9cm taller than their HIV+ peers. At 12 months of age, on average boys were 2.4cm taller than girls and seroreverter children were 3.5cm taller than HIV+ ones. In addition to describing longitudinal height behavior, this model also includes the growth rate estimation for this infant population by gender and group.