Tratamiento de Artritis reumatoide con antagonistas del factor de necrosis tumoral alfa y su asociación con el desarrollo de melanoma cutáneo: revisión sistemática de la literatura y meta-análisis.

Introducción: El tratamiento con antagonistas del factor de necrosis tumoral alfa (anti TNF) ha impactado el pronóstico y la calidad de vida de los pacientes con artritis reumatoide (AR) positivamente, sin embargo, se interroga un incremento en el riesgo de desarrollar melanoma. Objetivo: Conocer la asociación entre el uso de anti TNF y el desarrollo de melanoma maligno en pacientes con AR. Metodología: Se realizó una búsqueda sistemática en MEDLINE, EMBASE, COCHRANE LIBRARY y LILACS para ensayos clínicos, estudios observacionales, revisiones y meta-análisis en pacientes adultos con diagnóstico de AR y manejo con anti TNF (Certolizumab pegol, Adalimumab, Etanercept, Infliximab y Golimumab). Resultados: 37 estudios clínicos cumplieron los criterios de inclusión para el meta-análisis, con una población de 16567 pacientes. El análisis de heterogeneidad no fue significativo (p=1), no se encontró diferencia en el riesgo entre los grupos comparados DR -0.00 (IC 95% -0.001; -0.001). Un análisis adicional de los estudios en los que se reportó al menos 1 caso de melanoma (4222 pacientes) tampoco mostró diferencia en el riesgo DR -0.00 (IC 95% -0.004 ; -0.003). Conclusión: En la evidencia disponible a la fecha no encontramos asociación significativa entre el tratamiento con anti TNF en pacientes con diagnóstico de AR y el desarrollo de melanoma cutáneo.

Percentiles de grasa corporal por bioimpedancia eléctrica en niños y adolescentes de Bogotá, Colombia: Estudio FUPRECOL

Objetivo: Recientemente, se han propuesto varios dispositivos de impedancia bioeléctrica (BIA) para la estimación rápida de la grasa corporal. Sin embargo, no han sido publicadas referencias de grasa corporal para niños y adolescentes en población Colombiana. El objetivo de este estudio fue establecer percentiles de grasa corporal por BIA en niños y adolescentes de Bogotá, Colombia de entre 9 y 17.9 años, pertenecientes al estudio FUPRECOL. Métodos: Estudio descriptivo y transversal, realizado en 2.526 niños y 3.324 adolescentes de entre 9 y 17.9 años de edad, pertenecientes a instituciones educativas oficiales de Bogotá, Colombia. El porcentaje de grasa corporal fue medido con Tanita® Analizador de Composición Corporal (Modelo BF-689), según edad y sexo. Se tomaron medidas de peso, talla, circunferencia de cintura, circunferencia de cadera y estado de maduración sexual por auto-reporte. Se calcularon los percentiles (P3, P10, P25, P50, P75, P90 y P97) y curvas centiles por el método LMS según sexo y edad y se realizó una comparación entre los valores de la CC observados con estándares internacionales. Resultados: Se presentan valores de porcentaje de grasa corporal y las curvas de percentiles. En la mayoría de los grupos etáreos la grasa corporal de las chicas fue mayor a la de los chicos. Sujetos cuyo porcentaje de grasa corporal estaba por encima del percentil 90 de la distribución estándar normal se consideró que tenían un elevado riesgo cardiovascular (chicos desde 23,4-28,3 y chicas desde 31,0-34,1). En general, nuestros porcentajes de grasa corporal fueron inferiores a los valores de Turquía, Alemania, Grecia, España y Reino Unido. Conclusiones: Se presentan percentiles del porcentaje de grasa por BIA según edad y sexo que podrán ser usados de referencia en la evaluación del estado nutricional y en la predicción del riesgo cardiovascular desde edades tempranas.

Vozes d'África Transatlântica: trajetórias estudantis de Cabo Verde e da Guiné-Bissau - programa de estudantes - convénio de graduação

A presente investigação tem como centralidade a mobilidade internacional de estudantes no caso, a dos africanos oriundos de Cabo Verde e da Guiné-Bissau, participantes do Programa Estudantes-Convênio de Graduação na Universidade Federal do Rio Grande do Norte - UFRN, inserida no fenômeno da internacionalização universitária, acentuada na globalização. O objetivo principal foi analisar o processo de inserção social e acadêmica desses estudantes, com ênfase para os dos cursos de Arquitetura e Urbanismo, Ciências da Computação, Engenharia da Computação e Medicina, nessa Instituição de Ensino Superior - IES. A metodologia foi norteada pela conjugação dos aportes teóricos e metodológicos qualiquantitativa, em que, na primeira, utilizou-se da entrevista semiestrutura dirigida para dezesseis sujeitos; sendo, a metade estudantes e a outra docentes, cuja análise optou-se pela Análise de Discurso (AD) da linha francesa, resultando as formações discursivas: motivações da mobilidade, registro nacional de estrangeiro, identidade étnica, relações étnicoraciais e o PEC-G: seu funcionamento nas práticas sociais na UFRN. Já a pesquisa quantitativa, foi constituída pela aplicação do questionário para o universo de 40 estudantes dos dois grupos e de todas as áreas de conhecimento, cuja interpretação dos dados, recorreu-se ao Programa SPSS. Já, para o recorte dos cursos específicos, foi utilizado, o do Google Doc, os quais, estão expressos em tabelas e gráficos. Os resultados revelaram que essa mobilidade estudantil africana está imersa por um misto de semelhanças e diferenças entre o Brasil e dos Países Africanos de Língua Oficial Poruguesa - PALOP; e mais dos contextos das hierarquias entre os países centrais, semiperiféricos e periféricos, provocadas pelas políticas de reajustes estruturais sobre os serviços educacionais, Sousa (Santos 2008; 2010), que se refletem nas trajetórias acadêmicas temporária no país de acolhimento. Aqui, também, enfrenta as fragilidades e os avanços das políticas públicas do Sistema de Ensino Superior, implementadas pelo governo brasileiro nas IES. Em termos quantitativos para os quatros cursos analisados, em diferentes e curtos períodos, quanto a distribuição de vagas (acesso), formas de desligamentos e conclusão apontaram especificidades. E, grosso modo, o curso de Medicina, apresentou os melhores índices de conclusão, seguidos, pelos de Arquitetura e da Engenharia da Computação. A maioria dos estudantes são do sexo masculino, mais da metade está representada pelos oriundos de Cabo Verde, o restante, pelos da Guiné-Bissau. Enquanto, no curso de Ciências da Computação, foi nula a conclusão de curso, e em função deste histórico de baixo desempenho dos estudantes-convênio PEC-G, teria havido o fechamento de vagas. Mas, verificando-se, que os índices de conclusão nesses cursos, apresentou uma média abaixo dos cursos de graduação da UFRN, nos quais, esses estudantes são minoria ao lado dos afrobrasileiros nas universidades do Brasil.

Implications for early interventionists: Cross-cultural and low-income family differences

This study examined the existing literature on current early intervention processes for children who are deaf or hard of hearing who are from low-income or minority families. The review of literature includes a framework of understanding the dynamics of low-income households and cultural differences among African Americans, Latin Americans, and American Indians.

Motivaciones económicas en la manumisión de esclavas: una comparación entre ciudades de América Latina (Estudios)

La manumisión esclava fue una característica estructural de la sociedad colonial latinoamericana. Sin embargo, esto no quiere decir que todos, o que la mayoría,de los esclavos consiguieran salir del cautiverio. Solo un pequeño porcentaje logró terminar sus días como libre. En ese porcentaje la mayoría fueron mujeres. Desde las grandes regiones esclavistas hasta las periféricas, y desde el comienzo de la era colonial hasta la emancipación total, siempre las mujeres se manumitieron proporcionalmente más que los hombres. Este artículo propone como hipótesis parcial de tal fenómeno que las esclavas se manumitieron más porque contaban con una exención fiscal que no tenían los hombres. Para demostrar tal cosa, se enfatiza en que la familia esclava era la que tomaba la decisión de a quién manumitir y que la libertad era más una estrategia que un objetivo.

¿Eran cuidadanos los afrodescendientes libres en las sociedades esclavistas?: Cuba, Brasil y Estados Unidos en el siglo XIX (Estudios)

Se analiza el tema del estatus de los afrodescendientes libres en las sociedades esclavistas más pobladas de América, desde el punto de vista de los derechos políticos y sociales de súbditos y ciudadanos. Con la carta de libertad, los antiguos esclavos y sus descendientes libres adquirieron teóricamente los mismos derechos y obligaciones que la población blanca eurodescendiente. Sin embargo, por razones de “seguridad pública” y de “mantención del orden establecido”, en la práctica, se establecieron restricciones y privilegios para mantener la distancia social entre blancos y afrodescendientes. Desde una perspectiva comparada se estudian Brasil, Cuba y los Estados Unidos, las tres sociedades esclavistas más notorias en América durante el siglo XIX, y se examina este proceso tomando como objetos de análisis los derechos de libre movimiento, el acceso a la enseñanza superior, el sufragio y la propiedad.

African easterly wave variability and its relationship to Atlantic tropical cyclone activity

Automatic tracking of vorticity centers in European Centre for Medium-Range Weather Forecasts analyses has been used to develop a 20-yr climatology of African easterly wave activity. The tracking statistics at 600 and 850 mb confirm the complicated easterly wave structures present over the African continent. The rainy zone equatorward of 15 degreesN is dominated by 600-mb activity, and the much drier Saharan region poleward of 15 degreesN is more dominated by 850-mb activity. Over the Atlantic Ocean there is just one storm track with the 600- and 850-mb wave activity collocated. Based on growth/decay and genesis statistics, it appears that the 850-mb waves poleward of 15 degreesN over land generally do not get involved with the equatorward storm track over the ocean. Instead, there appears to be significant development of 850-mb activity at the West African coast in the rainy zone around (10 degreesN, 10 degreesW), which, it is proposed, is associated with latent heat release. Based on the tracking statistics, it has been shown that there is marked interannual variability in African easterly wave (AEW) activity. It is especially marked at the 850-mb level at the West African coast between about 10 degrees and 15 degreesN, where the coefficient of variation is 0.29. For the period between 1985 and 1998, a notable positive correlation is seen between this AEW activity and Atlantic tropical cyclone activity. This correlation is particularly strong for the postreanalysis period between 1994 and 1998. This result suggests that Atlantic tropical cyclone activity may be influenced by the number of AEWs leaving the West African coast, which have significant low-level amplitudes, and not simply by the total number of AEWs.

An evaluation of Bayesian designs for dose-escalation studies in healthy volunteers

In this paper, Bayesian decision procedures previously proposed for dose-escalation studies in healthy volunteers are reviewed and evaluated. Modifications are made to the expression of the prior distribution in order to make the procedure simpler to implement and a more relevant criterion for optimality is introduced. The results of an extensive simulation exercise to establish the proper-ties of the procedure and to aid choice between designs are summarized, and the way in which readers can use simulation to choose a design for their own trials is described. The influence of the value of the within-subject correlation on the procedure is investigated and the use of a simple prior to reflect uncertainty about the correlation is explored. Copyright (c) 2005 John Wiley & Sons, Ltd.

Including a time-of-year effect in the analysis of a matched case-control study

Motivated by a matched case-control study to investigate potential risk factors for meningococcal disease amongst adolescents, we consider the analysis of matched case-control studies where disease incidence, and possibly other risk factors, vary with time of year. For the cases, the time of infection may be recorded. For controls, however, the recorded time is simply the time of data collection, which is shortly after the time of infection for the matched case, and so depends on the latter. We show that the effect of risk factors and interactions may be adjusted for the time of year effect in a standard conditional logistic regression analysis without introducing any bias. We also show that, if the time delay between data collection for cases and controls is constant, provided this delay is not very short, estimates of the time of year effect are approximately unbiased. In the case that the length of the delay varies over time, the estimate of the time of year effect is biased. We obtain an approximate expression for the degree of bias in this case. Copyright © 2004 John Wiley & Sons, Ltd.

Sequential genome-wide association studies for monitoring adverse events in the clinical evaluation of new drugs

Pharmacovigilance, the monitoring of adverse events (AEs), is an integral part in the clinical evaluation of a new drug. Until recently, attempts to relate the incidence of AEs to putative causes have been restricted to the evaluation of simple demographic and environmental factors. The advent of large-scale genotyping, however, provides an opportunity to look for associations between AEs and genetic markers, such as single nucleotides polymorphisms (SNPs). It is envisaged that a very large number of SNPs, possibly over 500 000, will be used in pharmacovigilance in an attempt to identify any genetic difference between patients who have experienced an AE and those who have not. We propose a sequential genome-wide association test for analysing AEs as they arise, allowing evidence-based decision-making at the earliest opportunity. This gives us the capability of quickly establishing whether there is a group of patients at high-risk of an AE based upon their DNA. Our method provides a valid test which takes account of linkage disequilibrium and allows for the sequential nature of the procedure. The method is more powerful than using a correction, such as idák, that assumes that the tests are independent. Copyright © 2006 John Wiley & Sons, Ltd.

Sequentially testing for a gene-drug interaction in a genomewide analysis

Assaying a large number of genetic markers from patients in clinical trials is now possible in order to tailor drugs with respect to efficacy. The statistical methodology for analysing such massive data sets is challenging. The most popular type of statistical analysis is to use a univariate test for each genetic marker, once all the data from a clinical study have been collected. This paper presents a sequential method for conducting an omnibus test for detecting gene-drug interactions across the genome, thus allowing informed decisions at the earliest opportunity and overcoming the multiple testing problems from conducting many univariate tests. We first propose an omnibus test for a fixed sample size. This test is based on combining F-statistics that test for an interaction between treatment and the individual single nucleotide polymorphism (SNP). As SNPs tend to be correlated, we use permutations to calculate a global p-value. We extend our omnibus test to the sequential case. In order to control the type I error rate, we propose a sequential method that uses permutations to obtain the stopping boundaries. The results of a simulation study show that the sequential permutation method is more powerful than alternative sequential methods that control the type I error rate, such as the inverse-normal method. The proposed method is flexible as we do not need to assume a mode of inheritance and can also adjust for confounding factors. An application to real clinical data illustrates that the method is computationally feasible for a large number of SNPs. Copyright (c) 2007 John Wiley & Sons, Ltd.

A comparison of three different models for estimating relative risk in meta-analysis of clinical trials under unobserved heterogeneity

We focus on the comparison of three statistical models used to estimate the treatment effect in metaanalysis when individually pooled data are available. The models are two conventional models, namely a multi-level and a model based upon an approximate likelihood, and a newly developed model, the profile likelihood model which might be viewed as an extension of the Mantel-Haenszel approach. To exemplify these methods, we use results from a meta-analysis of 22 trials to prevent respiratory tract infections. We show that by using the multi-level approach, in the case of baseline heterogeneity, the number of clusters or components is considerably over-estimated. The approximate and profile likelihood method showed nearly the same pattern for the treatment effect distribution. To provide more evidence two simulation studies are accomplished. The profile likelihood can be considered as a clear alternative to the approximate likelihood model. In the case of strong baseline heterogeneity, the profile likelihood method shows superior behaviour when compared with the multi-level model. Copyright (C) 2006 John Wiley & Sons, Ltd.

A 25-year review of sequential methodology in clinical studies

This paper explores the theoretical developments and subsequent uptake of sequential methodology in clinical studies in the 25 years since Statistics in Medicine was launched. The review examines the contributions which have been made to all four phases into which clinical trials are traditionally classified and highlights major statistical advancements, together with assessing application of the techniques. The vast majority of work has been in the setting of phase III clinical trials and so emphasis will be placed here. Finally, comments are given indicating how the subject area may develop in the future.

Differences in perceived risks and benefits of herbal, over-the-counter conventional, and prescribed conventional, medicines, and the implications of this for the safe and effective use of herbal products

Objectives: To investigate people's views about the efficacy and specific risks of herbal, over-the-counter (OTC) conventional, and prescribed conventional medicines, and their likelihood of taking a second (herbal or OTC conventional) product in addition to a prescribed medicine. Methods: Experiment 1 (1 factor within-participant design); Experiment 2 (1 factor between-participant design). Convenience samples of general population were given a hypothetical scenario and required to make a number of judgements. Results: People believed herbal remedies to be less effective, but less risky than OTC and prescribed conventional medicines. Herbal medicines were not seen as being safer simply because of their easier availability. Participants indicated that they would be more likely to take a herbal medicine than a conventional OTC medicine in addition to a prescribed medicine, and less likely to consult their doctor in advance. Conclusion: People believe that herbal medicines are natural and relatively safe and can be used with less caution. People need to be given clear information about the risks and benefits of herbal medicines if they are to use such products safety and effectively. (c) 2006 Elsevier Ltd. All rights reserved.