An intensive model of care for hepatitis C virus screening and treatment with direct-acting antivirals in people who inject drugs in Nairobi, Kenya: a model-based cost-effectiveness analysis.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) treatment is essential for eliminating HCV in people who inject drugs (PWID), but has limited coverage in resource-limited settings. We measured the cost-effectiveness of a pilot HCV screening and treatment intervention using directly observed therapy among PWID attending harm reduction services in Nairobi, Kenya. DESIGN: We utilized an existing model of HIV and HCV transmission among current and former PWID in Nairobi to estimate the cost-effectiveness of screening and treatment for HCV, including prevention benefits versus no screening and treatment. The cure rate of treatment and costs for screening and treatment were estimated from intervention data, while other model parameters were derived from literature. Cost-effectiveness was evaluated over a life-time horizon from the health-care provider's perspective. One-way and probabilistic sensitivity analyses were performed. SETTING: Nairobi, Kenya. POPULATION: PWID. MEASUREMENTS: Treatment costs, incremental cost-effectiveness ratio (cost per disability-adjusted life year averted). FINDINGS: The cost per disability-adjusted life-year averted for the intervention was $975, with 92.1% of the probabilistic sensitivity analyses simulations falling below the per capita gross domestic product for Kenya ($1509; commonly used as a suitable threshold for determining whether an intervention is cost-effective). However, the intervention was not cost-effective at the opportunity cost-based cost-effectiveness threshold of $647 per disability-adjusted life-year averted. Sensitivity analyses showed that the intervention could provide more value for money by including modelled estimates for HCV disease care costs, assuming lower drug prices ($75 instead of $728 per course) and excluding directly-observed therapy costs. CONCLUSIONS: The current strategy of screening and treatment for hepatitis C virus (HCV) among people who inject drugs in Nairobi is likely to be highly cost-effective with currently available cheaper drug prices, if directly-observed therapy is not used and HCV disease care costs are accounted for.

A biosensor capable of identifying low quantities of breast cancer cells by electrical impedance spectroscopy.

Breast cancer (BC) is a malignant disease with a high prevalence worldwide. The main cause of death is not the primary tumor, but instead the spread of tumor cells to distant sites. The aim of the present study was to examine a new method for the detection of cancer cells in aqueous medium using bioimpedance spectroscopy assisted with magnetic nanoparticles (MNP's) exposure to a constant magnetic field. The spectroscopic patterns were identified for three breast cancer cell lines. Each BC cell line represents a different pathologic stage: the early stage (MCF-7), invasive phase (MDA-MB-231) and metastasis (SK-BR-3). For this purpose, bioimpedance measurements were carried out at a certain frequency range with the aid of nanoprobes, consisting of magnetic nanoparticles (MNPs) coupled to a monoclonal antibody. The antibody was specific for the predominant cell surface protein for each cell line, which was identified by using RT-qPCR and flow cytometry. Accordingly, EpCAM corresponds to MCF-7, MUC-1 to MDA-MB-231, and HER-2 to SK-BR-3. Despite their low concentrations, BC cells could be detected by impedance spectroscopy. Hence, this methodology should permit the monitoring of circulating tumor cells (CTC) and therefore help to prevent recurrences and metastatic processes during BC treatment.

Oral Immunotherapy With Egg and Milk: Changes in Peripheral Serum Cytokines Are Not Predictive Factors for Severe Adverse Reactions or for the Final Report.

BACKGROUND: Oral immunotherapy (OIT) is a new approach in patients with food allergy. Various immunological mechanisms underlie the reversal of food allergy. In this paper, we study possible changes in peripheral cytokine patterns during OIT. METHODS: Determinations of cytokines in peripheral blood were made in children who had milk or egg allergy and who received OIT. The determinations were made before and after OIT, and again following a final repeat oral challenge a month after a diet excluding the culprit food. RESULTS: No significant changes were registered in the cytokines studied (IL-2, IL-4, IL-6, IL-10, IL-12, IL-17, IFNγ, and TNF) at any of the 3 time points. Similarly, no differences in cytokine pattern were observed between children who had presented anaphylaxis during OIT and those who overcame or did not overcome the final oral challenge. DISCUSSION: Peripheral cytokines do not undergo significant changes during the OIT process. They are not predictors of serious adverse reactions or the final result of the OIT.

Oral immunotherapy with egg and milk: changes in peripheral serum cytokines are not predictive factors for severe adverse reactions or for the final report

Introduction: Oral immunotherapy (OIT) is a new approach in patients with food allergy. Various immunological mechanisms underlie the reversal of food allergy. In this paper, we study possible changes in peripheral cytokine patterns during OIT. Methods: Determinations of cytokines in peripheral blood were made in children who had milk or egg allergy and who received OIT. The determinations were made before and after OIT, and again following a final repeat oral challenge a month after a diet excluding the culprit food. Results: No significant changes were registered in the cytokines studied (IL-2, IL-4, IL-6, IL-10, IL-12, IL-17, IFNγ, and TNF) at any of the 3 time points. Similarly, no differences in cytokine pattern were observed between children who had presented anaphylaxis during OIT and those who overcame or did not overcome the final oral challenge. Discussion: Peripheral cytokines do not undergo significant changes during the OIT process. They are not predictors of serious adverse reactions or the final result of the OIT (AU)

Introducción: Se ha introducido la inmunoterapia oral frente a alimentos como una nueva terapia en pacientes con alergia alimentaria. Diferentes mecanismos inmunológicos han sido descritos en un intento de explicar la reversibilidad de esta situación de alergia alimentaria. En este artículo, estudiamos los posibles cambios en el patrón de citoquinas en sangre periférica a lo largo del proceso de la inmunoterapia oral. Métodos: Se realizó determinación de citokinas en sangre periférica en tantos niños con alergia a leche o huevo que realizaron inmunoterapia oral. Las determinaciones se realizaron tanto de forma previa como tras la finalización de la OIT, así como tras una reprovocación final, un mes después de seguir una dieta exenta del alimento implicado. Resultados: No se registraron cambios significativos en las citokinas estudiadas (IL-2, IL-4, IL-6, IL-10, IL-12, IL-17, IFNγ y TNF) entre ninguna de las tres determinaciones temporales. Tampoco existieron diferencias en el patrón de citokinas entre los niños que habían presentado anafilaxias durante la OIT ni entre los que superaron o no superaron la provocación final. Discusión: Las citokinas periféricas no sufren cambios significativos a lo largo del proceso de OIT. No son factores predictivos de reacciones adversas graves ni del resultado final de la OIT (AU)

Electrical bioimpedance spectroscopy as biosensor technique to identify cells lineages and cell differentiation process.

The identification and characterization of diverse cells types and cell differentiation process requires complex techniques as flow cytometry, immunocytochemistry and the exploration of molecular markers; such techniques require infrastructure and qualified personnel. The objective of this study was to analyze the use of Electrical Bioimpedance Spectroscopy (EBIS) measurements as a non-complex alternative technique to identify populations of undifferentiated mouse Pluripotent Stem Cells (mPSCs), Mouse Embryonic Fibroblasts (MEFs) and the differentiation process from preadipocytes (3T3-L1) to mature adipocytes. EBIS measurements were compared in populations of cells which were characterized previously using microscopy. The results indicate that EBIS technique has a potential sensitivity at certain frequency range to discriminate between both evaluated cell populations and some differentiation process. Additional studies with different concentrations to evaluate quantitatively the sensitivity and specificity of the proposed technique are recommended.

Componentes Principales mediante Espectroscopia FTIR como Técnica de Caracterización Innovadora durante la Diferenciación de Células Madre Pluripotentes a Células Pancreáticas / Principal Components by FTIR Spectroscopy as Innovative Characterization Technique during Differentiation of Pluripotent Stem Cells to Pancreatic Cells

Resumen: Dos de los grandes retos en la biología de las Células Madre (CM) y la Medicina Regenerativa, son el control en la diferenciación de estas células y asegurar la pureza de las células diferenciadas, por lo que es necesario contar con técnicas rápidas, eficientes y precisas para la caracterización de CM y su diferenciación a diferentes linajes celulares. El objetivo de este trabajo fue analizar Células Madre Pluripotentes (CMP) y Células Pancreáticas Diferenciadas (CPD) mediante espectroscopía Infrarroja por Transformada de Fourier (FTIR) y Análisis de Componentes Principales (ACP). Para ello se diferenciaron CMP a CPD, caracterizando el proceso de diferenciación a los días 0, 11, 17 y 21 mediante microscopía óptica y espectroscopia vibracional. Los espectros FTIR se analizaron con el método multivariado de ACP, utilizando su segunda derivada en las regiones de proteínas, carbohidratos y ribosas. Los resultados indican que el ACP permite caracterizar y discriminar CMP y CPD en sus diferentes etapas de diferenciación en las regiones espectrales analizadas. Con lo anterior concluimos que el ACP permite caracterizar química y estructuralmente CMP y diferentes etapas de su diferenciación en una forma rápida, precisa y no invasiva.

Abstract: Two of the greatest challenges in Stem Cells (SCs) biology and regenerative medicine, are differentiation control of SCs and ensuring the purity of differentiated cells. In this sense, fast, efficient and accurate techniques for SCs characterization and their differentiation into different cell lineages are needed. The aim of this study was to analyse Pluripotent Stem Cells (PSCs) and Differentiated Pancreatic Cells (DPCs) by Fourier Transform Infrared (FTIR) spectroscopy and Principal Component Analysis (PCA). For this purpose, we differentiated PSCs toward DPCs, characterizing the differentiation process at different stages (0, 11, 17 and 21 days) through light microscopy and vibrational spectroscopy. FTIR spectra were analysed with the multivariate method of PCA, using the second derivatives in the protein, carbohydrate and ribose regions. The results indicate that the PCA allows to characterize and discriminate PSCs and DPCs at different stages of differentiation in the analysed spectral regions. From these results, we concluded that the PCA allows the chemically and structural characterization of PSCs and the different stages of their differentiation in a fast, accurate and non-invasive way.

Evaluación de Termografía Tisular Diferenciada en Mama como Potencial Técnica para Asistir la Detección de Cáncer / Evaluation of Thermography Differentiated in Breast Tissue as Potential Technique to Assist Cancer Detection

Diversos grupos han propuesto el procesamiento de imágenes termográficas para detección de Cáncer de Mama (CaMa). Angiogénesis y vascularización dependientes del ciclo menstrual, edad e Índice de Masa Corporal (IMC) modifican la temperatura absoluta en la superficie tisular sin estar necesariamente asociadas a malignidad, en éste estudio proponemos la Termografía Tisular Diferenciada (TTD) en mama con respecto a su contralateral en espejo con el fin de observar diferencias térmicas características de malignidad. El presente trabajo evalúa la posibilidad de emplear la TTD como potencial técnica para asistir la detección de CaMa. Se muestrearon 110 mujeres voluntarias entre 40 y 60 años de edad segmentadas en dos grupos experimentales: grupo sanas (n=90) y grupo con CaMa (n=20) previamente diagnosticadas por mastografía e histopatología. Imágenes termográficas de ambas mamas fueron adquiridas con una cámara infrarroja y se estimó la TTD en relación a la mama contralateral de la misma paciente, se realizó un análisis de sensibilidad y especificidad y se comparó con el diagnóstico radiológico a través de curvas ROC tomando como referencia el diagnóstico histopatológico. La TTD en mama mostró rangos dinámicos diferenciables entre condiciones de malignidad respecto a benignidad. El análisis ROC mostró valores de sensibilidad y especificidad para el estimado TTD del 70% y 54% mientras que para el diagnóstico radiológico fue del 70% y 96%, respectivamente. La TTD muestra viabilidad técnica para asistir la detección de CaMa.

Several groups have proposed thermographic image processing for Breast Cancer (BC) detection. Angiogenesis and vascularization of menstrual cycle dependent, as well as age and Body Mass Index change the absolute temperature in the tissue surface without necessarily being associated with malignancy. We have proposed the Differentiated Tissue Thermography (DTT) in breast regarding its contralateral mirror in order to observe differences in temperature characteristics of malignancy. This study evaluates the possibility of using breast DTT as a potential technique to assist the detection of BC. We sampled 110 female volunteers between 40 and 60 years old segmented into two experimental groups: healthy group (n=90) and BC group (n=20), which were diagnosed by mammography and histopathology. Thermal images of both breasts were acquired with an infrared camera and the DTT was estimated relative to its contralateral breast in the same patient. A sensitivity and specificity analysis was developed and the DTT was compared with the radiological diagnosis by ROC curves with the histopathological report as reference. The DTT values showed distinguishable dynamic ranges between malignant and healthy conditions. ROC analysis showed sensitivity and specificity values for DTT of 70% and 54% while for the radiological diagnosis was 70% and 96% respectively. DTT showed technical viability to assist BC detection.

Unidad de Alergia Infantil: Asistencia especializada, docencia e investigación / Child Allergy Unit: Specialized care, teaching and research

La Alergología Pediátrica es un especialidad amplia y compleja que representa un área de capacitación específica que incluye habilidades de ambas especialidades: la pediatría y la alergología, y no es patrimonio específico de ninguna de ellas. La Sección de Alergología Infantil del Hospital Universitario Basurto es una Unidad Multidisciplinar que inicia su actividad en enero del 2008 cuya población de referencia es la población menor de 15 años de la comarca de Bilbao. La Alergología pediátrica ha adquirido un asombroso desarrollo en los últimos años, debido a los avances en diagnóstico molecular y el desarrollo de nuevas formas de inmunoterapia, especialmente a alimentos. En la Unidad realizamos aproximadamente 500 procedimientos de inmunoterapia a alimentos al año con una tasa de éxitos superior al 90%. En este artículo se refleja la actividad diaria de esta unidad en lo que respecta a la cartera de servicios, y actividad asistencial, docente e investigadora (AU)

Pediatric Allergy is a broad and complex specialty that represents a specific training area, which includes abilities of both specialties: Pediatrics and Allergy, and is not a specific patrimony of either of them. The Child Allergy unit of Hospital Universitario Basurto is a Multidisciplinary Unit that started its activity in January 2008, with its reference population being those under 15 years of age living in Bilbao. Pediatric Allergy has undergone an amazing development in the past few years due to the advances in molecular diagnosis and the development of new inmunotherapies specially to food. In our unit we conduct approximately 500 procedures of inmunotherapy to food a year, with a success rate above 90%. This article reflects the daily activity of the unit in respect to the service portfolio, the care, teaching and research activity (AU)

Diet and prevalence of atopic eczema in 6 to 7-year-old schoolchildren in Spain: ISAAC phase III.

BACKGROUND: The prevalence of atopic dermatitis (AD), a chronic skin disease, has increased substantially in recent decades, and different factors have been implicated in its etiology. Although dietary habits are being investigated, few conclusive findings have been reported. Nevertheless, increased consumption of polyunsaturated fatty acids (PUFA) and a diet poor in antioxidants have been related to AD. OBJECTIVES: The objectives of this study were to investigate the association between AD, the intake of different foods, and the effect of a Mediterranean diet among Spanish schoolchildren aged 6 to 7. METHODS: We performed a cross-sectional study with 20 106 schoolchildren aged 6-7 years from 10 different areas of Spain. The participation rate was 76.50%. The prevalence of AD was assessed using the International Study of Asthma and Allergies in Childhood questionnaire and the criteria of the Spanish Academy of Dermatology. To calculate the Mediterranean diet score, we classified food into 2 groups: Mediterranean food, including fruit, seafood, vegetables, pulses, cereals, pasta, rice, and potatoes; and non-Mediterranean food, including meat, milk, and fast food. RESULTS: Milk was negatively associated with AD. Butter and nuts also were negatively associated, although statistical significance was only reached when these foods were consumed 3 or more times a week. CONCLUSIONS: We found no association between the Mediterranean diet score and AD and a positive association between AD and obesity.

Parents’ smoking habit and prevalence of atopic eczema in 6-7 and 13-14 year-old schoolchildren in Spain. ISAAC Phase III

Background and aims: Atopic eczema (AE) is the most frequent inflammatory skin disease in childhood in the western world. Several studies have reported a significant increase of prevalence in recent decades and the environmental factors implicatedin its a etiology, including environmental tobacco smoke.This study aims to investigate the possible association of AE prevalence in Spanish school children aged 6-7 and 13-14 years in relation to their parents’smoking habits. Methods: We conducted a cross-sectional population-based study with 6-7 year-old (n = 27805) and 13-14 year-old (n = 31235) school children from10 Spanish centres. AE prevalence was assessed using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, and the Spanish Academy of Dermatology criteria, used in Spain to diagnose AE. Results: An association was found in school children aged 6-7 (adjusted for gender, presence of asthma, presence of rhinitis, siblings and mother’s level of education) between AE being clinically diagnosed with the mother’s smoking habit (RPRa 1.40,1.10-1.78) and there being more than 2 smokers at home (RPRa 1.34, 1.01-1.78). Regarding the presence of itchy rash, an association was observed with fathers who smoke (RPRa 1.40, 1.13-1.72). Among the 13-14 year-olds, no association was observed in relation to either clinically diagnosed AE or the appearance of itchy rash with parents’ smoking habit. Conclusions: Our results indicate the risk for children of being exposed to environmental tobacco smoke in terms of AE, especially when they are younger

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How the presence of rhinoconjunctivitis and the severity of asthma modify the relationship between obesity and asthma in children 6-7 years old.

BACKGROUND: The association between asthma and obesity in children, and the effect modification of allergy on this association have not been fully established. Aims The objective of the study was to know the effect modification of the severity of asthma and of the coexistence of rhinoconjunctivitis (RC) in the relationship between obesity and asthma. METHODS: A cross-sectional study of 17 145 schoolchildren 6-7 years old from eight Spanish cities who had completed information on height and weight of the ISAAC phase III questionnaire, which also included questions about asthma and RC symptoms and on various risk factors. Body mass index (BMI) was used to define obesity according to international standards. Two different logistic regressions, using current occasional asthma (COA) and current severe asthma (CSA) as dependent variables, were made stratifying for gender and for the coexistence of RC and controlling for age, older and younger siblings, exercise, mother's education, truck traffic, cat/dog during the first year of life and smoking father or mother. RESULTS: Obesity was a risk factor of CSA without RC, both for boys (1.92, CI 95% 1.13-3.25) and for girls (2.99, CI 95% 1.68-5.32). Every BMI unit increment increased by 6.7% the risk of CSA without RC in boys and by 12.4% in girls. Obesity was not a risk factor for CSA with RC. The association between COA and obesity was weaker and the coexistence of RC did not modify it greatly. CONCLUSIONS: Obese schoolchildren are more at risk of suffering from non-allergic asthma than the non-obese subjects.

Consensus Statement on the Management of Paediatric Asthma. Update 2007

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Parents' smoking habit and prevalence of atopic eczema in 6-7 and 13-14 year-old schoolchildren in Spain. ISAAC phase III.

BACKGROUND AND AIMS: Atopic eczema (AE) is the most frequent inflammatory skin disease in childhood in the western world. Several studies have reported a significant increase of prevalence in recent decades and the environmental factors implicated in its aetiology, including environmental tobacco smoke. This study aims to investigate the possible association of AE prevalence in Spanish schoolchildren aged 6-7 and 13-14 years in relation to their parents' smoking habits. METHODS: We conducted a cross-sectional population-based study with 6-7 year-old (n = 27805) and 13-14 year-old (n = 31235) schoolchildren from 10 Spanish centres. AE prevalence was assessed using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, and the Spanish Academy of Dermatology criteria, used in Spain to diagnose AE. RESULTS: An association was found in school-children aged 6-7 (adjusted for gender, presence of asthma, presence of rhinitis, siblings and mother's level of education) between AE being clinically diagnosed with the mother's smoking habit (RPRa 1.40, 1.10-1.78) and there being more than 2 smokers at home (RPRa 1.34, 1.01-1.78). Regarding the presence of itchy rash, an association was observed with fathers who smoke (RPRa 1.40, 1.13-1.72). Among the 13-14 year-olds, no association was observed in relation to either clinically diagnosed AE or the appearance of itchy rash with parents' smoking habit. CONCLUSIONS: Our results indicate the risk for children of being exposed to environmental tobacco smoke in terms of AE, especially when they are younger.

[Bronchodilators via metered-dose inhaler with spacer in the pediatric emergency department: what is the dosage?]. / Broncodilatadores inhalados mediante MDI con cámara espaciadora en urgencias pediátricas: cuál es la dosis?

INTRODUCTION: Bronchodilators administrated through a metered-dose inhaler (MDI) with spacer are as effective as nebulizers in the treatment of acute asthma exacerbations in childhood. However, consensus is lacking on the most suitable dosage. OBJECTIVE: To assess the effectiveness of distinct salbutamol and terbutaline doses delivered via an MDI with spacer for the treatment of acute asthma in the pediatric emergency department. METHODS: This was a prospective, double-blind randomized study. All consecutive children (n = 324) between 2 and 14 years of age with acute asthma exacerbations treated in the pediatric emergency department between October 1 and November 30, 2004, were included. Two treatment groups were established: one group received a number of puffs equivalent to half the child's weight (1 puff of salbutamol = 100 microg and 1 puff of terbutaline = 250 microg) and the other group received a number of puffs equivalent to one-third of the child's weight. RESULTS: Three hundred twenty-four episodes were studied; there were 164 children in the first group and 160 in the second. There were no significant differences between the two groups in the mean (6 SD) age (58.34 +/- 34.72 vs 66.04 +/- 36.45 months), arterial oxygen saturation (95.49 +/- 1.93 vs 95.56 +/- 1.97) or pulmonary score (4.04 +/- 1.55 vs 3.97 +/- 1.51) at recruitment and after treatment in the emergency department (arterial oxygen saturation [96.34 +/- 1.60 vs 96.18 +/- 1.77], pulmonary score [1.87 +/- 1.33 vs 1.64 +/- 1.31]). The number of doses administered (2.17 +/- 0.91 vs 2.24 +/- 1.00) and the hospitalization rate (8.56 % vs 6.87 %) were also similar in both groups. CONCLUSIONS: The distinct bronchodilator doses administered via an MDI with spacer showed similar effectiveness. These findings should contribute to a reevaluation of the use of high doses of bronchodilators, at least in most acute asthma exacerbations in children.