LAP+ Cells Modulate Protection Induced by Oral Vaccination with Rhesus Rotavirus in a Neonatal Mouse Model.

Transforming growth factor ß (TGF-ß) has been shown to play a role in immunity against different pathogens in vitro and against parasites in vivo However, its role in viral infections in vivo is incompletely understood. Using a neonatal mouse model of heterologous rhesus rotavirus (RV) vaccination, we show that the vaccine induced rotavirus-specific CD4 T cells, the majority of which lacked expression of KLRG1 or CD127, and a few regulatory rotavirus-specific CD4 T cells that expressed surface latency-associated peptide (LAP)-TGF-ß. In these mice, inhibiting TGF-ß, with both a neutralizing antibody and an inhibitor of TGF-ß receptor signaling (activin receptor-like kinase 5 inhibitor [ALK5i]), did not change the development or intensity of the mild diarrhea induced by the vaccine, the rotavirus-specific T cell response, or protection against a subsequent challenge with a murine EC-rotavirus. However, mice treated with anti-LAP antibodies had improved protection after a homologous EC-rotavirus challenge, compared with control rhesus rotavirus-immunized mice. Thus, oral vaccination with a heterologous rotavirus stimulates regulatory RV-specific CD4 LAP-positive (LAP+) T cells, and depletion of LAP+ cells increases vaccine-induced protection.IMPORTANCE Despite the introduction of several live attenuated animal and human rotaviruses as efficient oral vaccines, rotaviruses continue to be the leading etiological agent for diarrhea mortality among children under 5 years of age worldwide. Improvement of these vaccines has been partially delayed because immunity to rotaviruses is incompletely understood. In the intestine (where rotavirus replicates), regulatory T cells that express latency-associated peptide (LAP) play a prominent role, which has been explored for many diseases but not specifically for infectious agents. In this paper, we show that neonatal mice given a live oral rotavirus vaccine develop rotavirus-specific LAP+ T cells and that depletion of these cells improves the efficiency of the vaccine. These findings may prove useful for the design of strategies to improve rotavirus vaccines.

[Methodological Aspects of the Sampling Design for the 2015 National Mental Health Survey]. / Aspectos metodológicos del diseño de muestra para la Encuesta Nacional de Salud Mental 2015.

INTRODUCTION: The WHO has encouraged the development, implementation and evaluation of policies related to mental health all over the world. In Colombia, within this framework and promoted by the Ministry of Health and Social Protection, as well as being supported by Colciencias, the fourth National Mental Health Survey (NMHST) was conducted using a observational cross sectional study. According to the context and following the guidelines and sampling design, a summary of the methodology used for this sampling process is presented. The fourth NMHST used the Homes Master Sample for Studies in Health from the National System of Studies and Population Surveys for Health to calculate its sample. This Master Sample was developed and implemented in the year 2013 by the Ministry of Social Protection. METHODS: This study included non-institutionalised civilian population divided into four age groups: children 7-11 years, adolescent 12-17 years, 18-44 years and 44 years old or older. The sample size calculation was based on the reported prevalences in other studies for the outcomes of mental disorders, depression, suicide, associated morbidity, and alcohol use. A probabilistic, cluster, stratified and multistage selection process was used. Expansions factors to the total population were calculated. RESULTS: A total of 15,351 completed surveys were collected and were distributed according to the age groups: 2727, 7-11 years, 1754, 12-17 years, 5889, 18-44 years, and 4981, ≥45 years. All the surveys were distributed in five regions: Atlantic, Oriental, Bogotá, Central and Pacific. CONCLUSIONS: A sufficient number of surveys were collected in this study to obtain a more precise approximation of the mental problems and disorders at the regional and national level.

Alcohol consumption as an incremental factor in health care costs for traffic accident victims: evidence in a medium sized Colombian city.

OBJECTIVES: Identify the possibility that alcohol consumption represents an incremental factor in healthcare costs of patients involved in traffic accidents. METHODS: Data of people admitted into three major health institutions from an intermediate city in Colombia was collected. Socio-demographic characteristics, health care costs and alcohol consumption levels by breath alcohol concentration (BrAC) methodology were identified. Generalized linear models were applied to investigate whether alcohol consumption acts as an incremental factor for healthcare costs. RESULTS: The average cost of healthcare was 878 USD. In general, there are differences between health care costs for patients with positive blood alcohol level compared with those who had negative levels. Univariate analysis shows that the average cost of care can be 2.26 times higher (95% CI: 1.20-4.23), and after controlling for patient characteristics, alcohol consumption represents an incremental factor of almost 1.66 times (95% CI: 1.05-2.62). CONCLUSIONS: Alcohol is identified as a possible factor associated with the increased use of direct health care resources. The estimates show the need to implement and enhance prevention programs against alcohol consumption among citizens, in order to mitigate the impact that traffic accidents have on their health status. The law enforcement to help reduce driving under the influence of alcoholic beverages could help to diminish the economic and social impacts of this problem.

Regional variation on rates of bronchopulmonary dysplasia and associated risk factors.

Background. An abnormally high incidence (44%) of bronchopulmonary dysplasia with variations in rates among cities was observed in Colombia among premature infants. Objective. To identify risk factors that could explain the observed high incidence and regional variations of bronchopulmonary dysplasia. Study Design. A case-control study was designed for testing the hypothesis that differences in the disease rates were not explained by differences in city-of-birth specific population characteristics or by differences in respiratory management practices in the first 7 days of life, among cities. Results. Multivariate analysis showed that premature rupture of membranes, exposure to mechanical ventilation after received nasal CPAP, no surfactant exposure, use of rescue surfactant (instead of early surfactant), PDA, sepsis and the median daily FIO(2), were associated with a higher risk of dysplasia. Significant differences between cases and controls were found among cities. Models exploring for associations between city of birth and dysplasia showed that being born in the highest altitude city (Bogotá) was associated with a higher risk of dysplasia (OR 1.82 95% CI 1.31-2.53). Conclusions. Bronchopulmonary dysplasia was manly explained by traditional risk factors. Findings suggest that altitude may play an important role in the development of this disease. Prenatal steroids did not appear to be protective at high altitude.

Aspectos metodológicos del diseño de muestra para la Encuesta Nacional de Salud Mental 2015 / Methodological Aspects of the Sampling Design for the 2015 National Mental Health Survey

Resumen Introducción: La OMS ha incentivado la creación, implementación y evaluación de políticas relacionadas con la salud mental en todo el mundo. En Colombia, en ese marco e impulsada por el Ministerio de Salud y Protección Social y financiada por Colciencias, se realizó la cuarta Encuesta Nacional de Salud Mental (ENSM IV) usando un diseño observacional de corte transversal. En ese contexto, y de acuerdo con los lineamientos y el diseño demuestra proporcionado por el Ministerio de la Protección Social, se presenta a continuación un resumen de la metodología usada para el diseño muestral. La ENSM IV tuvo como base para su diseño muestral la Muestra Maestra de Hogares para Estudios en Salud del Sistema Nacional de Estudios y Encuestas Poblacionales para Salud, desarrollada e implementada en el año 2013 por el Ministerio de la Protección Social. Métodos: Para este estudio, se incluyó a la población civil no institucionalizada del país. Se consideraron cuatro grupos etarios de interés: niños de 7 a 11 años, adolescentes de 12 a 17 años, personas entre 18 y 44 años y mayores de 44 años. El cálculo del tamaño demuestra se basó en las prevalencias reportadas en otros estudios para los desenlaces de trastornos mentales, depresión, suicidio, morbilidad sentida y uso de alcohol. La selección fue de tipo probabilístico por conglomerados, estratificada y polietápica. Se calcularon los factores de expansión al total poblacional. Resultados: En este estudio se recolectaron 15.351 encuestas completas distribuidas según grupos de edad: 2.727 de 7-11 años; 1.754 de 12-17; 5.889 de 18-44 y 4.981 de = 45 años distribuidos en las 5 regiones: Atlántica, Oriental, Bogotá, Central y Pacífica. Conclusiones: En este estudio, se recolectó un número de encuestas completas suficiente para tener una aproximación bastante precisa a escalas nacional y regional de la salud mental y algunos trastornos y problemas mentales de la población colombiana.

Abstract Introduction: The WHO has encouraged the development, implementation and evaluation of policies related to mental health all over the world. In Colombia, within this framework and promoted by the Ministry of Health and Social Protection, as well as being supported by Colciencias, the fourth National Mental Health Survey (NMHST) was conducted using a observational cross sectional study. According to the context and following the guidelines and sampling design, a summary of the methodology used for this sampling process is presented. The fourth NMHST used the Homes Master Sample for Studies in Health from the National System of Studies and Population Surveys for Health to calculate its sample. This Master Sample was developed and implemented in the year 2013 by the Ministry of Social Protection. Methods: This study included non-institutionalised civilian population divided into four age groups: children 7-11 years, adolescent 12-17 years, 18-44 years and 44 years old or older. The sample size calculation was based on the reported prevalences in other studies for the outcomes of mental disorders, depression, suicide, associated morbidity, and alcohol use. A probabilistic, cluster, stratified and multistage selection process was used. Expansions factors to the total population were calculated. Results: A total of 15,351 completed surveys were collected and were distributed according to the age groups: 2727, 7-11 years, 1754, 12-17 years, 5889, 18-44 years, and 4981, ≥45 years. All the surveys were distributed in five regions: Atlantic, Oriental, Bogotá, Central and Pacific. Conclusions: A sufficient number of surveys were collected in this study to obtain a more precise approximation of the mental problems and disorders at the regional and national level.

Plasmaféresis terapéutica / Therapeutic plasmapheresis

Resumen Introducción: cada día hay más evidencia acerca de la utilidad de la plasmaféresis en diferentes entidades clínicas. Existen múltiples registros internacionales de plasmaféresis; sin embargo, la información en Colombia e incluso en Latinoamérica es limitada. Objetivo: realizar análisis descriptivo de la experiencia en plasmaféresis de una institución académica en Bogotá, Colombia. Analizar las características de la técnica, indicaciones, complicaciones y características demográficas de los pacientes. Material y métodos: se realiza un análisis descriptivo de las sesiones de plasmaféresis realizadas en el Hospital Universitario San Ignacio, en pacientes mayores de 18 años durante el periodo comprendido entre agosto de 2008 hasta agosto de 2011. Todas las sesiones se realizaron mediante la técnica de filtración transmembrana y no se usó anticoagulante en ninguna de ellas. Resultados: se analizaron 278 sesiones de plasmaféresis en 33 pacientes adultos durante un período de tres años. 69.7% de los pacientes eran mujeres, el promedio de edad era 42 años. 57% de las sesiones se realizaron en pacientes con diagnóstico de miastenia gravis y hemorragia alveolar. El volumen promedio de intercambios plasmáticos fue 1.28. El 9.3% de las sesiones presentaron al menosuna complicación. Se documentó frecuentemente hipotensión arterial en las sesiones realizadas con albúmina al 3.5%. 12% de los registros de electrolitos tenían hipocalcemia y 47% hipermagnesemia. No hubo muertes relacionadas con la terapia y pese al no uso de anticoagulante, no se presentó coagulación del circuito en ninguna de las sesiones. Conclusiones: dada nuestra experiencia consideramos que la plasmaféresis es una terapia segura. Es necesario evaluar la necesidad de la administración de anticoagulante al circuito de plasmaféresis, dado que no se documentó coagulación de éste en ninguna sesión y su uso podría estar asociado a eventos adversos. El monitoreo continuo de los electrolitos es fundamental y la reposición de los mismos debe ser individualizada. (Acta Med Colomb 2014; 39: 29-34).

Abstract Introduction: there is growing evidence for the usefulness of plasmapheresis in different clinical entities. There are many international records of plasmapheresis, but the information in Colombia and even in Latin America, is limited. Objective: to perform a descriptive analysis of the experience in plasmapheresis of an academic institution in Bogotá, Colombia. To analyze the characteristics of the technique, indications, complications and demographic characteristics of patients. Material and methods: descriptive analysis of plasmapheresis sessions performed in the Hospital Universitario San Ignacio in patients older than 18 years during the period from August 2008 to August 2011. All sessions were conducted by the technique of transmembrane filtration. No anticoagulation was used in any of them. Results: 278 sessions of plasmapheresis were analyzed in 33 adult patients over a period of three years. 69.7% of patients were female, with mean age of 42 years. 57% of the sessions were conducted in patients diagnosed with myasthenia gravis and alveolar hemorrhage. The average volume of plasma exchange was 1.28. 9.3% of the sessions presented at least one complication. Hypotension was frequently documented in the sessions performed with 3.5% albumin. 12% of electrolytes records had hypocalcemia and 47% hypermagnesemia. There were no therapy-related deaths and despite the non-use of anticoagulant, no clotting of the circuit in any of the sessions was presented. Conclusions: Given our experience, we believe that plasmapheresis is a safe therapy. It is necessary to assess the need for administration of anticoagulant to the plasmapheresis circuit since no clotting in it in any session was documented and its use could be associated with adverse events. Continuous monitoring of electrolytes is essential and its replacement should be individualized. (Acta Med Colomb 2014; 39: 29-34).

Very early surfactant without mandatory ventilation in premature infants treated with early continuous positive airway pressure: a randomized, controlled trial.

BACKGROUND: Chronic lung disease is one of the most frequent and serious complications of premature birth. Because mechanical ventilation is a major risk factor for chronic lung disease, the early application of nasal continuous positive airway pressure has been used as a strategy for avoiding mechanical ventilation in premature infants. Surfactant therapy improves the short-term respiratory status of premature infants, but its use is traditionally limited to infants being mechanically ventilated. Administration of very early surfactant during a brief period of intubation to infants treated with nasal continuous positive airway pressure may improve their outcome and further decrease the need for mechanical ventilation. OBJECTIVE: Our goal was to determine if very early surfactant therapy without mandatory ventilation improves outcome and decreases the need for mechanical ventilation when used in very premature infants treated with nasal continuous positive airway pressure soon after birth. DESIGN/METHODS: Eight centers in Colombia participated in this randomized, controlled trial. Infants born between 27 and 31 weeks' gestation with evidence of respiratory distress and treated with supplemental oxygen in the delivery room were randomly assigned within the first hour of life to intubation, very early surfactant, extubation, and nasal continuous positive airway pressure (treatment group) or nasal continuous airway pressure alone (control group). The primary outcome was the need for subsequent mechanical ventilation using predefined criteria. RESULTS: From January 1, 2004, to December 31, 2006, 279 infants were randomly assigned, 141 to the treatment group and 138 to the control group. The need for mechanical ventilation was lower in the treatment group (26%) compared with the control group (39%). Air-leak syndrome occurred less frequently in the treatment group (2%) compared with the control group (9%). The percentage of patients receiving surfactant after the first hour of life was also significantly less in the treatment group (12%) compared with the control group (26%). The incidence of chronic lung disease (oxygen treatment at 36 weeks' postmenstrual age) was 49% in the treatment group compared with 59% in the control group. All other outcomes, including mortality, intraventricular hemorrhage, and periventricular leukomalacia were similar between the groups. CONCLUSIONS: In premature infants treated with nasal continuous positive airway pressure early after birth, the addition of very early surfactant therapy without mandatory ventilation decreased the need for subsequent mechanical ventilation, decreased the incidence of air-leak syndrome, and seemed to be safe. Reduction in the need for mechanical ventilation is an important outcome when medical resources are limited and may result in less chronic lung disease in both developed and developing countries.

Factores asociados con el control glucémico óptimo en pacientes tratados con bomba de insulina y monitorización continua de glucosa en tiempo real / Factors associated with optimal glycemic control in patients with insulin pump therapy and continuous glucose monitoring in real time

OBJETIVO: Cuando se utiliza monitorización continua de glucosa (MCG) y algoritmos de estimación de bolos, muchos pacientes en terapia con bomba de insulina alcanzan euglucemia. Evaluamos patrones de uso en integración de tecnología de bomba/MCG asociados con niveles de HbA1c < 7%. MÉTODOS: Analizamos datos de 217 pacientes (edad > 11 años; 53,5% hombres; 91,7% con diabetes tipo 1; > 3 meses de experiencia en bomba) en manejo en un hospital universitario de Bogotá, Colombia, incluyendo aplicación de insulina, HbA1c, eventos hipoglucémicos severos, uso de MCG, culminación de cursos educativos en diabetes y frecuencia de glucometrías. Todos los pacientes recibieron entrenamiento para uso de bomba y la mayoría (73,7%) entrenamiento adicional en conteo de hidratos de carbono, ajustes de tasa basal y uso de datos de MCG. RESULTADOS: El inicio de terapia con bomba se asoció a disminución de HbA1c, uso de insulina y eventos hipoglucémicos severos (p < 0,001). Conductas específicas con bomba-MCG asociadas con menor A1c incluyeron uso de algoritmos de estimación de dosis en > 80% de los bolos y uso de sensor MCG > 80% del tiempo (p < 0,005). HbA1c menor se evidenció con culminación del entrenamiento adicional, edad > 18 años, uso de bomba Paradigm 722 con MCG integrado, uso de alarmas por MCG, HbA1c > 7% antes de terapia y controles de glucemia capilar más frecuentes (p < 0,05). Muchos pacientes (45,6%) alcanzaron HbA1c ≤ 7% con bomba. CONCLUSIONES: La educación, combinada con uso consistente de sensores-MCG y algoritmos de bolos confiere reducciones de HbA1c mayores a las alcanzadas con la terapia solamente con bomba

OBJECTIVE: When used with continuous glucose monitoring (CGM) and bolus estimation algorithms, many patients on insulin pump therapy achieve near-euglycemia. We evaluated the usage patterns of integrated pump/CGM technology that are associated with A1C levels < 7%. METHODS: Data from 217 patients (age > 11 years, 53.5% male, 91.7% with type 1 diabetes, all with > 3 months pump experience) receiving care at a teaching hospital in Bogotá, Colombia, were analyzed. Data included insulin delivery, A1C levels, severe hypoglycemic events, use of CGM, completion of diabetes education courses, and the frequency of blood glucose checks. All patients received training on the use of the pump, and most (73.7%) received additional training on carbohydrate counting, basal rate adjustments, and use of CGM data. RESULTS: Initiation of pump therapy was associated with decreases in A1C, insulin use, and severe hypoglycemic events (all P <0 .001). Pump and CGM-specific behaviors associated with lower A1C included the use of a dose estimation algorithm for > 80% of bolus doses and use of CGM sensors > 80% of the time (both P <0 .005). Lower A1C was also associated with the completion of additional training, age > 18, use of the Paradigm 722 pump with an integrated CGM device, use of CGM-based alarms, A1c >7% before pump therapy, and more frequent blood glucose checks (all P < 0.05). Many (45.6%) patients reached A1c ≤ 7% with pump therapy. CONCLUSIONS: Patient education, with an A1c below 7% before sensor-augmented pump therapy, when combined with consistent use of CGM sensors and bolus estimation algorithms, leads to favorable reductions in A1C beyond those achieved with pump therapy alone

Impacto de las facultades de medicina y de los estudiantes sobre los resultados en la prueba nacional de calidad de la educación superior (SABER PRO) / Impact of medical schools and students on the results of the national test on the quality of higher education (SABER PRO)

Introducción: Los resultados de las pruebas SABER PRO de medicina tienen un alto impacto en la comunidad académica a nivel de estudiante y de universidad, y son empleados como indicadores de fortalezas y debilidades de los procesos de formación. La amplia variabilidad de los resultados entre universidades y entre estudiantes dentro de las universidades hace necesario estudiar qué posibles variables están asociadas con el desempeño en estas pruebas. Objetivo: Analizarla relación entre las variables a nivel de las universidades y las variables a nivel de estudiante de medicina con el desempeño en las pruebas SABER PRO de estudiantes de medicina. Materiales y métodos: Se empleó la información de 4498 estudiantes de medicina evaluados en las pruebas SABER PRO 2009 y de las 40 facultades de medicina a las que pertenecían; mediante el uso de modelos jerárquicos de dos niveles se evaluó la asociación de las características de estudiantes y universidades con el puntaje obtenido en la prueba. Resultados: El puntaje promedio por universidades de la prueba SABER PRO 2009 para estudiantes de medicina fue 100,4, con un rango entre 84,3 y 110,8 puntos. La variabilidad de los puntajes en la prueba fue explicada en un 29% por las diferencias entre universidades. Conclusiones: Las universidades oficiales y las facultades de medicina que cuentan con hospitales universitarios propios tienen en promedio mejores desempeños. Sin embargo, la oferta de programas de especialización médica se asocia con menores puntajes.

Introduction: The results of the SABER PRO medical test have considerable impact on theaca-demic community. They are used as indicators of strengths and weaknesses of the education processes for both the student and the university. The wide variability of the results among different universities and students within the same university requires an analysis of the potential variables associated with the performance in these tests. Objective: To analyze the relationship of the inter-university variables and the inter-medical students variables against the performance on the SABER PRO tests. Materials and Methods: The information used was from 4498 medical students evaluated through the SABER PRO 2009 tests and of 40 schools of medicine the students belonged to. The association between the characteristics of the students and universities and the test scores obtained were evaluated using two-level hierarchical models. Results: The average score in the SABER PRO test per university for medical students was 100.4, with a range between 84.3 and 110.8 points. The variability of the test scores was accounted for in 29% of the cases by the inter-university differences. Conclusions: The public universities and the schools of medicine that have their own teaching hospital have better performance in average. However, the offer of medical specialization programs is associated with lower scores.

Algunos conceptos básicos para el cálculo del tamaño de la muestra / A few basic Concepts when estimating the Size of the Sample

Una de las etapas básicas en la planeación de cualquier tipo de investigación cuantitativa es la del cálculo del tamaño de la muestra; su importancia es tal que el simple hecho de no considerarla inicialmente o de realizarla inadecuadamente constituye una de las causas más comunes para estropear un estudio, o para no tener suficiente evidencia para rechazar una hipótesis de investigación o no hacerlo. Es por eso que se sugiere, antes de empezar a utilizar las fórmulas matemáticas para el cálculo del tamaño de la muestra, la lectura de este artículo y así lograr que el lector adquiera una idea básica de los requisitos generales para su correcta utilización.