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Introducción: El primer registro de la asociación causal entre el mosquito Aedes aegypti, y la transmisión de la fiebre amarilla, lo constituyó la comunicación presentada por Carlos J. Finlay a la Academia de Ciencias de La Habana en 1881. El científico cubano mostró los resultados de la inoculación, por picadura de mosquito infectado, en cinco sujetos de un conjunto de 20 personas sanas. Objetivo: Reanalizar la evidencia mediante la aplicación de técnicas estadísticas aún no desarrolladas en tiempo del científico cubano, y evaluar la fortaleza de la evidencia causal. Métodos: Los resultados se analizaron mediante el test exacto de Fisher, el factor de Bayes y la diferencia de riesgos, el riesgo relativo y el odds ratio de la asociación. Se valoró la fortaleza de la evidencia de la asociación causal mediante criterio estadístico sin desconocer los criterios de causalidad más actualizados. Resultados: El test exacto de Fisher fue altamente significativo (p= 0,009), y el factor de Bayes (24,9) resultó compatible con una evidencia fuerte a favor de la asociación entre la inoculación y el desarrollo de la enfermedad. También apoyaron la asociación, la diferencia de riesgos (0,55; IC 95 %: 0,15-0,96), el riesgo relativo (18,7; IC 95 %: 1,12-3-10,3) y el odds ratio (43,4; IC 95 %: 1,68-11-19,7). Conclusiones: Los resultados de Finlay resultaron robustos, y se ajustaron a los criterios de causalidad para explicar la transmisión de la fiebre amarilla por el mosquito.

Introduction: The first record of the causal association between the Aedes aegypti mosquito and the transmission of yellow fever was the communication submitted by Carlos J. Finlay to the Havana Academy of Sciences in 1881. The Cuban scientist showed the results of inoculation, by infected mosquito bite, in five subjects from a group of 20 healthy people. Objective: To revise the evidence through the use of statistical techniques not yet developed at the time of the Cuban scientist and to evaluate the strength of the causal evidence. Methods: Results were analyzed using Fisher's exact test, Bayes factor, and risk difference, relative risk, and odds ratio of association. The strength of the evidence of the causal association was assessed using statistical criteria minding the most up-to-date causality criteria. Results: Fisher's exact test was highly significant (p = 0.009), and the Bayes factor (24.9) was compatible with strong evidence in favor of the association between inoculation and disease development. The association was also supported by the risk difference (0.55; 95% CI: 0.15-0.96), the relative risk (18.7; 95% CI: 1.12-310.3), and the odds ratio (43.4; 95% CI: 1.68-1119.7). Conclusions: Finlay's results were robust, and adjusted to the causality criteria to explain the transmission of yellow fever by mosquitoes.

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BACKGROUND: Trace elements comprise both nutritionally essential and non-essential, and their presence in organisms plays important role in human health. OBJECTIVE: The aim of this study was to evaluate the levels of trace elements, together with cellular and molecular biomarkers, in adolescents from Tierrabomba Island, a Caribbean community located near an industrial area, comparing them with a group living in San Onofre, a reference community. METHODS: Hair and blood samples were obtained from 238 individuals aged 11-18 years old, 131 from Tierrabomba Island and 107 from San Onofre. Trace elements were quantified in hair using ICP-MS. The hematological evaluation was done by peripheral blood smears, and gene expression analysis was carried out through RT-PCR. RESULTS: Thirteen elements were analyzed; eight showed significant differences between sites. In Tierrabomba, arsenic (As) and tungsten (W) registered mean values greater than in San Onofre. In contrast, in the reference site, average values for boron (B), cobalt (Co), zinc (Zn), yttrium (Y), tin (Sn), and barium (Ba) were greater. The peripheral blood film showed differences between populations. Mean lymphocyte percentage was higher in the Island, while eosinophil and monocyte percentages displayed greater means in San Onofre. Some correlations between trace elements and hematological parameters were found, mainly with platelets in Tierrabomba. This trend remained even when partial correlation coefficients were adjusted for age. Levels of gene expression of metallothionein 1X (MT1X) and superoxide dismutase (SOD) registered significant differences between sites, being greater in Tierrabomba. Negative correlations between SOD and As were observed in both sampling sites. Discriminant analysis suggested sampling locations could be differentiated by Zn, Mo, Ba, and MT1X levels. SIGNIFICANCE: Trace elements and the relative gene expression associated with metal exposure are critical exposure biomarkers for coastal communities.

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BACKGROUND: Quality of Life Core Questionnaire of the European Organization for the Research and Treatment of Cancer (EORTC QLQ-C30) is one of the most used quality of life questionnaires in cancer studies. It provides scores for five functional scales, nine symptom scales, and two single items which assess overall health status and quality of life. However, high correlations among QLQ-C30 items suggest a reduced dimensionality for the scale. OBJECTIVE: To assess the dimensionality of the EORTC QLQ-C30 using item response theory (IRT) in a training sample and confirmatory factor analysis (CFA) in a test sample. METHODS: We analyzed responses to QLQ-C30 from 1,107 patients with advanced lung cancer who were included in five clinical trials of immunotherapy. We used non-parametric and parametric IRT models (Mokken, and Samejima's graded response) in a random training set (n = 332) for initial assessment of dimensions and item characteristics of the QLQ-C30. Finally, we used CFA in the test set (n = 775) to confirm the measurement domains. RESULTS: Mokken model showed that QLQ-C30 fits a unidimensional scale, whereas Samejima model showed that most QLQ-C30 items present adequate difficulty and discrimination. All items showed adequate scalability indexes with an overall scalability of 0.47 (medium scale). The QLQ-C30-reduced dimensionality was confirmed by CFA (comparative fit index = 0.98, root mean square error of approximation = 0.055) with all items presenting factorial loadings > 0.40. CONCLUSIONS: The EORTC QLQ-C30 fits a unidimensional latent construct identified with perceived quality of life in advanced lung cancer patients. TRIAL REGISTRATION: RPCEC00000161, RPCEC00000181 and RPCEC00000205.

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Five-nitroimidazole (5-NI) compounds are among the most commonly used medications in the treatment of giardiasis. However, after more than five decades of their initial indication for such treatment, there are some concerns about the efficacy of 5-NIs in giardiasis. This study sought to compare the efficacy of any 5-NI with any other antigiardial drug for the treatment of Cuban children with giardiasis. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). We searched CUMED, EBSCOhost and PubMed databases. Two reviewers independently assessed trial eligibility, trial quality and extracted appropriate data. The primary outcome was the parasitological cure. The effect estimate was the pooled relative risk (RR) with 95% confidence intervals (CI). We included seven RCTs in the systematic review, involving a total of 1046 children. When the effect of 5-NIs was compared with that of benzimidazole compounds, the pooled effect was significant and favored 5-NIs [the relative risk (RR) is 1.35, 95% CI =1.05 to 1.75], with high heterogeneity (4 studies, I2 =79%). Compared with chloroquine, the pooled effects of the 5-NIs were not significant [RR is 0.96, 95% CI=0.79 to 1.18, (2 studies, I2=68%)]. Our results support the use of 5-NIs (mainly tinidazole) as first-line therapy for Cuban pediatric patients infected with Giardia and may continue being used as reference drugs in future RCTs of giardiasis. These data could help inform policy decisions in Cuba. Caution is needed in extrapolating such data in other settings.

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Introducción: Frecuentemente la información médica sobre determinado aspecto clínico, es tan poco clara y contradictoria, que en ocasiones el profesional de la salud no tiene el tiempo o la orientación para poder analizarla en su totalidad, y poder así aprovecharla en su real magnitud. Objetivo: Revisar la metodología y los sistemas que existen para realizar meta-análisis de ensayos clínico. Métodos: Se ha revisado el proceso de análisis de esos conocimientos, llamado meta-análisis; éste es un estudio sistemático, cualitativo y cuantitativo de un grupo de informes o artículos de investigación, generalmente enfocado al análisis de un aspecto clínico. Resultados: En este artículo de revisión, se muestra cómo se diseña, se ejecuta y reporta el meta-análisis, así como los pasos para la realización del meta-análisis. Discusión: Se resumen y se comparan los sistemas que más se utilizan para realizar meta-análisis. Conclusiones: Con este trabajo se conocen que los análisis de sensibilidad, acumulado y de sesgo de publicación no pueden faltar para un meta-análisis, así los sistemas donde poder realizar cada uno de estos análisis(AU)

Introduction: Frequently the medical information on a certain clinical aspect is so unclear and contradictory, that health professional does not have the time or guidance to be able to analyze it in its entirety, and thus be able to take advantage of it in its real magnitude. Objective: To review the existing methodology and systems to perform meta-analysis of clinical trials. Methods: The process of analyzing this knowledge, called meta-analysis, has been reviewed; this is a systematic, qualitative and quantitative study of a group of reports or research articles, generally focused on the analysis of a clinical aspect. Results: In this review article, we show how the meta-analysis is designed, executed and reported, as well as the steps to carry out the meta-analysis. Discussion: The systems most used to perform meta-analysis are summarized and compared. Conclusions: With this work we know that the analysis of sensitivity, accumulated and publication bias cannot be missing for a meta-analysis, as well as the systems where each of these analyzes can be performed(AU)

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Introducción: Frecuentemente la información médica sobre determinado aspecto clínico, es tan poco clara y contradictoria, que en ocasiones el profesional de la salud no tiene el tiempo o la orientación para poder analizarla en su totalidad, y poder así aprovecharla en su real magnitud. Objetivo: Revisar la metodología y los sistemas que existen para realizar meta-análisis de ensayos clínico. Métodos: Se ha revisado el proceso de análisis de esos conocimientos, llamado meta-análisis; éste es un estudio sistemático, cualitativo y cuantitativo de un grupo de informes o artículos de investigación, generalmente enfocado al análisis de un aspecto clínico. Resultados: En este artículo de revisión, se muestra cómo se diseña, se ejecuta y reporta el meta-análisis, así como los pasos para la realización del meta-análisis. Discusión: Se resumen y se comparan los sistemas que más se utilizan para realizar meta-análisis. Conclusiones: Con este trabajo se conocen que los análisis de sensibilidad, acumulado y de sesgo de publicación no pueden faltar para un meta-análisis, así los sistemas donde poder realizar cada uno de estos análisis(AU)

Introduction: Frequently the medical information on a certain clinical aspect is so unclear and contradictory, that health professional does not have the time or guidance to be able to analyze it in its entirety, and thus be able to take advantage of it in its real magnitude. Objective: To review the existing methodology and systems to perform meta-analysis of clinical trials. Methods: The process of analyzing this knowledge, called meta-analysis, has been reviewed; this is a systematic, qualitative and quantitative study of a group of reports or research articles, generally focused on the analysis of a clinical aspect. Results: In this review article, we show how the meta-analysis is designed, executed and reported, as well as the steps to carry out the meta-analysis. Discussion: The systems most used to perform meta-analysis are summarized and compared. Conclusions: With this work we know that the analysis of sensitivity, accumulated and publication bias cannot be missing for a meta-analysis, as well as the systems where each of these analyzes can be performed(AU)

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BACKGROUND: Recently, with the access of low toxicity biological and targeted therapies, evidence of the existence of a long-term survival subpopulation of cancer patients is appearing. We have studied an unselected population with advanced lung cancer to look for evidence of multimodality in survival distribution, and estimate the proportion of long-term survivors. METHODS: We used survival data of 4944 patients with non-small-cell lung cancer (NSCLC) stages IIIb-IV at diagnostic, registered in the National Cancer Registry of Cuba (NCRC) between January 1998 and December 2006. We fitted one-component survival model and two-component mixture models to identify short- and long- term survivors. Bayesian information criterion was used for model selection. RESULTS: For all of the selected parametric distributions the two components model presented the best fit. The population with short-term survival (almost 4 months median survival) represented 64% of patients. The population of long-term survival included 35% of patients, and showed a median survival around 12 months. None of the patients of short-term survival was still alive at month 24, while 10% of the patients of long-term survival died afterwards. CONCLUSIONS: There is a subgroup showing long-term evolution among patients with advanced lung cancer. As survival rates continue to improve with the new generation of therapies, prognostic models considering short- and long-term survival subpopulations should be considered in clinical research.

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BACKGROUND: The prognosis of patients bearing high grade glioma remains dismal. Epidermal Growth Factor Receptor (EGFR) is well validated as a primary contributor of glioma initiation and progression. Nimotuzumab is a humanized monoclonal antibody that recognizes the EGFR extracellular domain and reaches Central Nervous System tumors, in nonclinical and clinical setting. While it has similar activity when compared to other anti-EGFR antibodies, it does not induce skin toxicity or hypomagnesemia. METHODS: A randomized, double blind, multicentric clinical trial was conducted in high grade glioma patients (41 anaplastic astrocytoma and 29 glioblastoma multiforme) that received radiotherapy plus nimotuzumab or placebo. Treatment and placebo groups were well-balanced for the most important prognostic variables. Patients received 6 weekly doses of 200 mg nimotuzumab or placebo together with irradiation as induction therapy. Maintenance treatment was given for 1 year with subsequent doses administered every 3 weeks. The objectives of this study were to assess the comparative overall survival, progression free survival, response rate, immunogenicity and safety. RESULTS: The median cumulative dose was 3200 mg of nimotuzumab given over a median number of 16 doses. The combination of nimotuzumab and RT was well-tolerated. The most prevalent related adverse reactions included nausea, fever, tremors, anorexia and hepatic test alteration. No anti-idiotypic response was detected, confirming the antibody low immunogenicity. The mean and median survival time for subjects treated with nimotuzumab was 31.06 and 17.76 vs. 21.07 and 12.63 months for the control group. CONCLUSIONS: In this randomized trial, nimotuzumab showed an excellent safety profile and significant survival benefit in combination with irradiation. TRIAL REGISTRATION: Cuban National Register for clinical trials (No. 1745) (http://registroclinico.sld.cu/ensayos).

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Se ha estudiado la utilización de preservativos en una muestra de 139 adictos a drogas por vía parenteral. Las categorías asociadas significativamente a la no utilización de preservativos son: el sexo femenino (OR=5.1;IC95%=2.0-13.2) y una historia de adicción de cinco o másaños (OR=3.0; IC95%=1.3-6.9). Menos del 25% de las mujeres incluidas en el estudio utilizan preservativos en sus relaciones sexuales. Por el contrario, un nivel educativo superior protege frente a la no utilización de preservativos (OR=0.3; IC95%=0.1-8.8) El modelo más parsimonioso ajustado a los datos incluye las variables sexo, nivel educativo, tipo y frecuencia de relaciones sexuales, y años de adicción. No son necesarias el tipo de convivencia, situación laboral, edad, ni antecedentes de enfermedades de transmisión sexual. Se sugiere la necesidad de implementar acciones con el fin de modificar las conductas de riesgo en las relaciones secuales establecidas por adictos a drogas por vía parenteral sin olvidar que la principal vía de transmisión del virus de la inmunodeficiencia humana en este colectivo se produce al compartir agujas y jeringuillas contamiandas (AU)

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Se ha estudiado la utilización de preservativos en una muestra de 139 adictos a drogas por vía parenteral. Las categorías asociadas significativamente a la no utilización de preservativos son: el sexo femenino (OR=5.1;IC95%=2.0-13.2) y una historia de adicción de cinco o másaños (OR=3.0; IC95%=1.3-6.9). Menos del 25% de las mujeres incluidas en el estudio utilizan preservativos en sus relaciones sexuales. Por el contrario, un nivel educativo superior protege frente a la no utilización de preservativos (OR=0.3; IC95%=0.1-8.8) El modelo más parsimonioso ajustado a los datos incluye las variables sexo, nivel educativo, tipo y frecuencia de relaciones sexuales, y años de adicción. No son necesarias el tipo de convivencia, situación laboral, edad, ni antecedentes de enfermedades de transmisión sexual. Se sugiere la necesidad de implementar acciones con el fin de modificar las conductas de riesgo en las relaciones secuales establecidas por adictos a drogas por vía parenteral sin olvidar que la principal vía de transmisión del virus de la inmunodeficiencia humana en este colectivo se produce al compartir agujas y jeringuillas contamiandas

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