Diagnostic performance of immunohistochemistry markers for malignant pleural mesothelioma diagnosis and subtypes. A systematic review and meta-analysis.

BACKGROUND: Malignant pleural mesothelioma (MPM) poses diagnostic challenges due to its resemblance to benign pleural pathologies and different histological subtypes. Several immunohistochemistry markers have been employed to aid in accurate diagnosis. METHODS: The present systematic review and meta-analysis aimed to assess the diagnostic performance of various immunohistochemistry markers in malignant pleural mesothelioma diagnosis and its histological subtypes. Following the PRISMA guidelines, we systematically searched the literature for articles on using different immunohistochemical markers in MPM and its histological subtypes. EMBASE, LILACS, MEDLINE, and Virtual Health Library were searched for studies published up to August 2023. We used the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) criteria to assess the quality of the included articles. Meta-analyses were performed to determine prevalence using a random-effects model. RESULTS: 103 studies met the inclusion criteria, comprising a diverse range of immunohistochemistry markers. EMA and desmin-loss exhibited high sensitivity (96% and 92%, respectively) in distinguishing malignant pleural mesothelioma from benign pleural pathologies. Specificity was notably high for both BAP1-loss and survivin expression at 100%. Subtype-specific analyses demonstrated that EMA and HEG1 were sensitive markers for epithelioid mesothelioma, while GLUT1 showed high sensitivity for sarcomatoid mesothelioma. In cases comparing epithelioid mesothelioma and lung adenocarcinoma, CAM5.2 and calretinin displayed high sensitivity, while WT1 and BAP1-loss demonstrated exceptional specificity for malignant epithelioid mesothelioma. In the case of sarcomatoid mesothelioma and sarcomatoid lung carcinoma, GATA3 exhibited the most heightened sensitivity, while GATA3 and D2-40 displayed the best specificity for sarcomatoid malignant mesothelioma diagnosis. CONCLUSION: Immunohistochemistry markers are essential in accurately diagnosing malignant pleural mesothelioma and its histological subtypes. This systematic review and meta-analysis provide a comprehensive insight into the diagnostic performance of these markers, facilitating their potential clinical utility in the discrimination of malignant pleural mesothelioma from other pleural pathologies and the differentiation of malignant pleural mesothelioma subtypes.

Effects of internet-based, psychosocial, and early medical interventions on professional burnout in health care workers: Systematic literature review and meta-analysis.

Background: The prevalence of professional burnout increased among healthcare workers during the coronavirus 2019 (COVID-19) pandemic, with negative effects on their mental health. Consequently, research interest in methods to decrease the prevalence of burnout and reduce the effects of burnout on healthcare workers has increased. Objective: This study was designed to evaluate the effects of Internet-based, psychosocial, and early medical interventions on professional burnout among healthcare workers. Methodology: This systematic review and meta-analysis involved 8004 articles identified from four databases: Cochrane, Web of Science, PubMed/Medline, and clinical trials. Results: Four articles were included in the systematic review, of which two could be meta-analyzed. The pooled effect of the group of interventions compared to control conditions was not statistically significant. Discussion: Evaluating therapeutic effectiveness requires more clinical trials that allow its evaluation. Although we did not find improvements in the three intervention categories, the methodological heterogeneity in each intervention and the need for a standardized intervention guide for managing and decreasing professional burnout, subject to the evaluation of its impact, are highlighted.

[Income inequality and early childhood caries in Colombia: a multilevel analysis]. / Inequidad en el ingreso y caries de la infancia temprana en Colombia: un análisis multinivel.

The association between income inequality and dental caries on early childhood in Colombia was evaluated using a multi-level analysis. We analyzed data from the latest national oral survey (2014) and information about income in absolute and relative terms on a state-level. The outcomes were caries experience, and untreated caries. A multilevel logistic regression model was used (2 levels) with children/households nested within states. Age, gender, area-level socioeconomic position (SEP), household income and health insurance regime were the level 1 explanatory variables. For level 2, variables were the Gini coefficient, Unsatisfied Basic Needs (UBN) and Gross Domestic Product (GDP). Data from 5.250 children, aged 1, 3 and 5 years were evaluated. Prevalence of caries experience and untreated caries was 36.9% and 33.0% respectively. Both outcomes showed significant associations with age, low SEP and belonging to the subsidized health insurance regime: untreated dental caries was associated with living in low and very low SEP (OR: 1.72; 95%CI 1.42, 2.07 and OR: 1.69; 95%CI 1.36, 2.09 respectively), and subsidized health insurance scheme (OR: 1.58; 95%CI 1.11, 2.24). When the Gini, GDP and UBN indicators were included in the models, no significant associations were found.

Evaluamos la asociación entre inequidad en los ingresos y caries de la infancia temprana en Colombia, utilizando un análisis multinivel. Analizamos datos del último estudio nacional de salud bucal (2014) e información sobre ingresos en términos absolutos y relativos a nivel departamental. Los desenlaces fueron experiencia de caries y caries no tratada. Se utilizó un modelo de regresión logística multinivel con dos niveles: niños/familias (nivel 1) anidados en departamentos (nivel 2). En el nivel 1 se consideraron variables de edad, sexo, posición socioeconómica (PSE) de la vivienda, ingresos del hogar y régimen de aseguramiento en salud. Para el nivel 2 las variables fueron coeficiente Gini, Necesidades Básicas Insatisfechas (NBI) y Producto Interno Bruto (PIB). Se evaluaron datos de 5.250 niños de 1, 3 y 5 años, 36.9% tenían experiencia de caries y 33.0% caries no tratada. Los desenlaces mostraron asociaciones significativas con edad, PSE baja del hogar y pertenecer al régimen subsidiado de salud. Para caries no tratada se encontraron asociaciones con PSE baja o muy baja (OR: 1.72; IC95% 1.42, 2.07 y OR: 1.69; IC95% 1.36, 2.09 respectivamente) y régimen subsidiado de salud (OR: 1.58; IC95% 1.11, 2.24). No se encontraron asociaciones significativas con indicadores de coeficiente Gini, PIB y NBI.

Inequidad en el ingreso y caries de la infancia temprana en Colombia: un análisis multinivel / Income inequality and early childhood caries in Colombia: a multilevel analysis

Resumen Evaluamos la asociación entre inequidad en los ingresos y caries de la infancia temprana en Colombia, utilizando un análisis multinivel. Analizamos datos del último estudio nacional de salud bucal (2014) e información sobre ingresos en términos absolutos y relativos a nivel departamental. Los desenlaces fueron experiencia de caries y caries no tratada. Se utilizó un modelo de regresión logística multinivel con dos niveles: niños/familias (nivel 1) anidados en departamentos (nivel 2). En el nivel 1 se consideraron variables de edad, sexo, posición socioeconómica (PSE) de la vivienda, ingresos del hogar y régimen de aseguramiento en salud. Para el nivel 2 las variables fueron coeficiente Gini, Necesidades Básicas Insatisfechas (NBI) y Producto Interno Bruto (PIB). Se evaluaron datos de 5.250 niños de 1, 3 y 5 años, 36.9% tenían experiencia de caries y 33.0% caries no tratada. Los desenlaces mostraron asociaciones significativas con edad, PSE baja del hogar y pertenecer al régimen subsidiado de salud. Para caries no tratada se encontraron asociaciones con PSE baja o muy baja (OR: 1.72; IC95% 1.42, 2.07 y OR: 1.69; IC95% 1.36, 2.09 respectivamente) y régimen subsidiado de salud (OR: 1.58; IC95% 1.11, 2.24). No se encontraron asociaciones significativas con indicadores de coeficiente Gini, PIB y NBI.

Abstract The association between income inequality and dental caries on early childhood in Colombia was evaluated using a multi-level analysis. We analyzed data from the latest national oral survey (2014) and information about income in absolute and relative terms on a state-level. The outcomes were caries experience, and untreated caries. A multilevel logistic regression model was used (2 levels) with children/households nested within states. Age, gender, area-level socioeconomic position (SEP), household income and health insurance regime were the level 1 explanatory variables. For level 2, variables were the Gini coefficient, Unsatisfied Basic Needs (UBN) and Gross Domestic Product (GDP). Data from 5.250 children, aged 1, 3 and 5 years were evaluated. Prevalence of caries experience and untreated caries was 36.9% and 33.0% respectively. Both outcomes showed significant associations with age, low SEP and belonging to the subsidized health insurance regime: untreated dental caries was associated with living in low and very low SEP (OR: 1.72; 95%CI 1.42, 2.07 and OR: 1.69; 95%CI 1.36, 2.09 respectively), and subsidized health insurance scheme (OR: 1.58; 95%CI 1.11, 2.24). When the Gini, GDP and UBN indicators were included in the models, no significant associations were found.

Manejo conservador de lesión aerodigestiva: reporte de un caso y revisión de la literatura / Conservative management of aerodigestive injury: A case report andreview of the literature

Introducción. El trauma penetrante de cuello representa un evento desafortunado de baja incidencia y alta complejidad diagnóstica y terapéutica, lo que supone un reto para el cirujano general.Caso clínico. Paciente femenina de 20 años de edad, quien sufrió una herida cervical por proyectil de arma de fuego, desarrollando de forma secundaria una lesión aerodigestiva. Se realizó un tratamiento expectante en un hospital de alta complejidad, con una evolución favorable. Discusión. En la literatura existe un claro debate en cuanto al manejo de las lesiones penetrantes en cuello y la sospecha de lesión orgánica oculta. En nuestro paciente la lesión aerodigestiva fue tratada mediante observación y seguimiento clínico. Conclusiones. El manejo de un paciente con lesión aerodigestiva se puede corroborar mediante las imágenes diagnósticas y se puede tratar de forma expectante con un resultado exitoso, sin agregar morbilidad y con un impacto adecuado en el buen uso de los recursos disponibles

Introduction. Penetrating neck trauma represents an unfortunate event with a low incidence and high diagnostic and therapeutic complexity, which represents a challenge for the general surgeon. Clinical case. A 20-year-old female patient, who suffered a cervical wound from a firearm projectile, secondarily developing an aerodigestive lesion. An expectant treatment was carried out in a high complexity hospital, with a favorable evolution.Discussion. In the literature there is a clear debate regarding the management of penetrating neck injuries and suspected occult organic injury. In our patient, the aerodigestive injury was treated by observation and clinical follow-up.Conclusions. The management of a patient with aerodigestive injury can be corroborated by diagnostic images and can be treated expectantly with a successful result, without adding morbidity and with an adequate impact on the proper use of available resources

Mortalidad por neumonía y por todas las causas en niños menores de 5 años en Colombia entre el 2005 y 2016 / Pneumonia and all causes mortality in children under 5 year old in Colombia between 2005 and 2016

RESUMEN Introducción: Las infecciones neumocócicas son una de las causas más importantes de enfermedades en niños menores de 5 años en Colombia. Objetivo: Calcular la mortalidad por neumonía y por todas las causas en niños menores de 5 años en Colombia. Métodos: Estudio ecológico, los principales desenlaces del estudio fue mortalidad por todas las causas y neumonía (CIE-10 J12-18). Resultados: Durante el año 2005 al 2016 se encontraron un total de 122.074 muertes por todas las causas, de las cuales 13359 (10.94%) correspondieron a muerte por neumonía, 750 a meningitis (0.61%) y 17.511 a muerte por otras causas respiratorias (14.34%). Conclusiones: Se ha observado una disminución de la mortalidad en las tasas de mortalidad por todas las causas, y las demás estudiadas en este artículo.

ABSTRACT Introduction: Pneumococcal infections are one of the most important causes of diseases in children under 5 years old in Colombia. Objective: Evaluate mortality from pneumonia and all causes in children under 5 years old in Colombia. Methods: Ecological study, the main outcomes of the study was all-cause mortality and pneumonia (ICD-10 J12-18). Results: During 2005 to 2016, a total of 122,074 deaths were found for all causes, of which 13,359 (10.94%) corresponded to death due to pneumonia, 750 to meningitis (0.61%) and 17,511 to death due to other respiratory causes (14.34% ). Conclusions: A decrease in mortality has been observed in all-cause mortality rates, and the others studied death causes in this article.

Effect of neural therapy on NGF and BDNF serum levels in patients with chronic pain. A pilot study / Efecto de la terapia neural sobre los niveles séricos del NGF y el BDNF en pacientes con dolor crónico. Estudio piloto

Abstract Introduction: Neurotrophins (NT) are a family of proteins consisting of the nerve growth factor (NGF), the brain-derived neurotrophic factor (BDNF) and NT-3 and NT-4/5. These proteins play an essential role in neuronal survival, differentiation, and proliferation. Objectives: To analyze the variations of NGF and BDNF serum levels in patients with chronic pain after undergoing neural therapy and to establish the effects of this type of intervention on their quality of life. Materials and methods: Prospective pilot study conducted in 10 patients with chronic pain treated with neural therapy between July 2017 and April 2018 in Bogotá D.C., Colombia. Three consultations were performed (one in which the intervention was initiated, and two follow-up visits every three weeks). During each consultation, the patients' quality of life was assessed using the SF-12 scale and their NGF and BDNF serum levels were measured. Data were analyzed by means of descriptive statistics, using medians and interquartile ranges for quantitative variables, and absolute frequencies and percentages for qualitative variables. Results: The median score on the SF-12 scale tended to improve in the first and second follow-up visits compared with the baseline score (pre-intervention), particularly during the first follow-up visit (consultation No. 1: 34.5; follow-up No. 1: 39.5, and follow-up No. 2: 38). Median NGF serum levels had a downward trend after the intervention, particularly in the first follow-up visit (157.6, 42.95, and 237.8, respectively), and in the case of BNDF, an overall downward trend was also found (29.96, 19.24 and 20.43, respectively). An improvement in quality of life related to the decrease in the serum levels of both neurotrophins was observed. Conclusion: Neural therapy intervention reduced NGF and BDNF serum levels and improved the quality of life of the participants. Therefore, the behavior of these neurotrophins could become a biomarker for the diagnosis, treatment, and follow-up of patients with chronic pain.

Resumen Introducción. Las neurotrofinas (NT) son una familia de proteínas conformada por el factor de crecimiento nervioso (NGF), el factor neurotrófico derivado del cerebro (BDNF) y las neurotrofinas NT-3 y NT-4/5; estas proteínas tienen un papel esencial en la supervivencia, diferenciación y proliferación neuronal. Objetivos. Analizar las variaciones de los niveles séricos del NGF y el BDNF en pacientes con dolor crónico luego de recibir terapia neural y establecer los efectos de este tipo de intervención en su calidad de vida. Materiales y métodos. Estudio piloto prospectivo realizado en 10 pacientes con dolor crónico tratados con terapia neural entre julio de 2017 y abril de 2018 en Bogotá D.C., Colombia. Se realizaron 3 consultas (una en la que se inició la intervención y dos de control cada tres semanas) y en cada una se evaluó la calidad de vida mediante el cuestionario de salud SF-12 y se midieron los niveles séricos del NGF y el BDNF. Los datos se analizaron mediante estadística descriptiva, utilizando medianas y rangos intercuartiles para las variables cuantitativas, y frecuencias absolutas y porcentajes para las cualitativas. Resultados. La mediana de puntaje del cuestionario SF-12 tendió a mejorar en el primer y segundo control comparada con la puntuación inicial (antes de la intervención), en particular en el primer control (consulta 1: 34.5; control 1: 39.5, y control 2: 38). La mediana de los niveles séricos del NGF tendió a disminuir luego de la intervención, en particular en el primer control (157.6, 42.95 y 62.2, respectivamente), y en el caso del BNDF, la tendencia global también fue hacia la disminución (29.96, 19.24 y 20.43, respectivamente). Se observó una mejora en la calidad de vida relacionada con la disminución de los niveles séricos de ambas neurotrofinas. Conclusión. La intervención de terapia neural produjo una reducción en los niveles séricos del NGF y el BDNF y mejoró la calidad de vida de los participantes; por tanto, el comportamiento de estas neurotro-finas podría convertirse en un biomarcador para el diagnóstico, tratamiento y seguimiento de pacientes con dolor crónico.

Disease modifying therapies in multiple sclerosis: cost-effectiveness systematic review.

OBJECTIVE: To identify and describe cost-effectiveness studies that  evaluate disease modifying therapies in the context of relapsing- remitting multiple sclerosis. METHOD: A systematic review of the literature was carried out by  searching MEDLINE, Embase, the Cochrane Library, LILACS, the Tufts  Medical Center Cost-Effectiveness Analysis Registry, the National Health  Service Economic Evaluation Database and Open Grey. The search was  performed in January 2018 and covered articles published between  January 2010 and December 2017. The studies reviewed were payer- perspective cost-effectiveness analyses for interferon beta-1a, interferon beta-1b, glatiramer acetate, teriflunomide, fingolimod, dimethyl  fumarate, natalizumab, alemtuzumab and rituximab. The Quality of  Health Economic Studies instrument was used to determine the quality  of the studies reviewed. Risk of bias was assessed without a  standardized tool. An analysis was made of direct costs, quality- adjusted life-years and the incremental cost-effectiveness ratio. Data  extraction and evaluation of information were conducted separately by  each author. RESULTS: Four hundred one references were found; nine studies were included. A great degree of variability was identified for several  methodological aspects. Two studies that applied the incremental cost- effectiveness ratio (cost) showed no first-line therapy to be cost- effective. A third study demonstrated dominance of interferon beta-1b  over placebo (USD -315,109.45) and a fourth paper showed dominance  of teriflunomide over interferons and glatiramer acetate (USD - 121,840.37). As regards second-line therapies, dimethyl fumarate was  cost-effective in a study that compared it to glatiramer acetate and  interferon beta-1a and it was dominant in another study that compared  it with glatiramer acetate (USD -158,897.93) and fingolimod (USD - 92,988.97). In the third line of treatment, one study showed  natalizumab to be cost-effective as compared with fingolimod, and  another study showed alemtuzumab to be dominant over fingolimod  (USD -49,221). A third trial demonstrated alemtuzumab to be dominant over natalizumab (USD -1,656,266.07). Many of the trials have  sponsorship bias. Eight of the trials received a high QHES score. CONCLUSIONS: The present paper shows that cost-effectiveness studies have high levels of methodological variability, some of them  reaching contradictory results. As a result, it is not possible to  determine which disease- modifying therapy is really cost-effective in  the context of relapsingremitting multiple sclerosis.

Objetivo: Identificar y describir los estudios de costo-efectividad que evalúan las terapias modificadoras de la enfermedad en esclerosis  múltiple recurrente-remitente.Método: Revisión sistemática de la literatura en MEDLINE, Embase,  Cochrane Library, LILACS, Tufts Medical Center cost-effectiveness  analysis registry, National Health Service economic evaluation database  y Open Grey; búsqueda limitada entre enero de 2010 y diciembre de  2017, se ejecutó en enero de 2018. Se incluyeron modelos de costo- efectividad con perspectiva de pagador para interferón beta-1a,  interferón beta-1b, acetato de glatiramero, teriflunomida, fingolimod,  dimetilfumarato, natalizumab, alemtuzumab y rituximab. La  herramienta Quality of Health Economic Studies fue usada para  determinar la calidad de los estudios, el sesgo se evaluó sin una  herramienta estandarizada, dada su no existencia. Se analizaron costos directos, años de vida ajustados por calidad y la razón de costo- efectividad incremental. La extracción de los datos y la evaluación de la  información se realizaron por cada autor de forma independiente.Resultados: Se encontraron 401 referencias, se incluyeron nueve  estudios; hubo variabilidad en múltiples aspectos metodológicos. Según  la razón de costo-efectividad incremental (costo), dos trabajos  mostraron que ninguna terapia de primera línea fue costo-efectiva, un  tercer estudio reporta al interferón beta-1b como dominante sobre  placebo (­315.109,45 dólar estadounidense [US$]) y un cuarto artículo  expone a teriflunomida como dominante sobre interferones y acetato de glatiramero (­121.840,37 US$). Respecto a las terapias de segunda  línea, dimetil fumarato fue costoefectivo en un estudio comparado con  acetato de glatiramero e interferón beta-1a y fue dominante en otro  trabajo frente a acetato de glatiramero (­158.897,93 US$) y fingolimod  (­92.988,97 US$). En la tercera línea de tratamiento, natalizumab fue  costo-efectivo sobre fingolimod en un artículo, y alemtuzumab fue  dominante contra fingolimod (­49.221 US$) en un segundo estudio. En  un tercer ensayo el alemtuzumab fue dominante sobre natalizumab (­ 1.656.266,07 US$). Muchos estudios tuvieron sesgo de patrocinador.  Ocho artículos obtuvieron alta puntuación de calidad con la herramienta  Quality of Health Economic Studies.Conclusiones: Este trabajo demuestra que existe una gran variabilidad metodológica entre los estudios de costo-efectividad, y  algunos de ellos tienen resultados contradictorios. No es posible  determinar qué terapia modificadora de la enfermedad en esclerosis  múltiple recurrente-remitente es costo-efectiva.

Terapias modificadoras de la enfermedad en esclerosis múltiple: revisión sistemática de costo-efectividad / Disease modifying therapies in multiple sclerosis: cost-effectiveness systematic review

OBJETIVO: Identificar y describir los estudios de costo-efectividad que evalúan las terapias modificadoras de la enfermedad en esclerosis múltiple recurrente-remitente. MÉTODO: Revisión sistemática de la literatura en MEDLINE, Embase, Cochrane Library, LILACS, Tufts Medical Center cost-effectiveness analysis registry, National Health Service economic evaluation database y Open Grey; búsqueda limitada entre enero de 2010 y diciembre de 2017, se ejecutó en enero de 2018. Se incluyeron modelos de costo-efectividad con perspectiva de pagador para interferón beta-1a, interferón beta-1b, acetato de glatiramero, teriflunomida, fingolimod, dimetilfumarato, natalizumab, alemtuzumab y rituximab. La herramienta Quality of Health Economic Studies fue usada para determinar la calidad de los estudios, el sesgo se evaluó sin una herramienta estandarizada, dada su no existencia. Se analizaron costos directos, años de vida ajustados por calidad y la razón de costo-efectividad incremental. La extracción de los datos y la evaluación de la información se realizaron por cada autor de forma independiente Resultados: Se encontraron 401 referencias, se incluyeron nueve estudios; hubo variabilidad en múltiples aspectos metodológicos. Según la razón de costo-efectividad incremental (costo), dos trabajos mostraron que ninguna terapia de primera línea fue costo-efectiva, un tercer estudio reporta al interferón beta-1b como dominante sobre placebo (-315.109,45 dólar estadounidense [US$]) y un cuarto artículo expone a teriflunomida como dominante sobre interferones y acetato de glatiramero (-121.840,37 US$). Respecto a las terapias de segunda línea, dimetil fumarato fue costo-efectivo en un estudio comparado con acetato de glatiramero e interferón beta-1a y fue dominante en otro trabajo frente a acetato de glatiramero (-158.897,93 US$) y fingolimod (-92.988,97 US$). En la tercera línea de tratamiento, natalizumab fue costo-efectivo sobre fingolimod en un artículo, y alemtuzumab fue dominante contra fingolimod (-49.221 US$) en un segundo estudio. En un tercer ensayo el alemtuzumab fue dominante sobre natalizumab (-1.656.266,07 US$). Muchos estudios tuvieron sesgo de patrocinador. Ocho artículos obtuvieron alta puntuación de calidad con la herramienta Quality of Health Economic Studies. CONCLUSIONES: Este trabajo demuestra que existe una gran variabilidad metodológica entre los estudios de costo-efectividad, y algunos de ellos tienen resultados contradictorios. No es posible determinar qué terapia modificadora de la enfermedad en esclerosis múltiple recurrente-remitente es costo-efectiva

OBJECTIVE: To identify and describe cost-effectiveness studies that eva-luate disease modifying therapies in the context of relapsing-remitting mul-tiple sclerosis. METHOD: A systematic review of the literature was carried out by searching MEDLINE, Embase, the Cochrane Library, LILACS, the Tufts Medical Center Cost-Effectiveness Analysis Registry, the National Health Service Economic Evaluation Database and Open Grey. The search was performed in January 2018 and covered articles published between January 2010 and December 2017. The studies reviewed were payer-perspective cost-effectiveness analy-ses for interferon beta-1a, interferon beta-1b, glatiramer acetate, teriflunomide, fingolimod, dimethyl fumarate, natalizumab, alemtuzumab and rituximab. The Quality of Health Economic Studies instrument was used to determine the quality of the studies reviewed. Risk of bias was assessed without a standardized tool. An analysis was made of direct costs, quality-adjusted life-years and the incremental cost-effectiveness ratio. Data extraction and evaluation of information were conducted separately by each author. RESULTS: Four hundred one references were found; nine studies were included. A great degree of variability was identified for several methodological aspects. Two studies that applied the incremental cost-effectiveness ratio (cost) showed no first-line therapy to be cost-effective. A third study demonstrated dominance of interferon beta-1b over placebo (USD -315,109.45) and a fourth paper showed dominance of teriflu-nomide over interferons and glatiramer acetate (USD -121,840.37). As regards second-line therapies, dimethyl fumarate was cost-effective in a study that compared it to glatiramer acetate and interferon beta-1a and it was dominant in another study that compared it with glatiramer acetate (USD -158,897.93) and fingolimod (USD -92,988.97). In the third line of treatment, one study showed natalizumab to be cost-effective as compared with fingolimod, and another study showed alemtuzumab to be dominant over fingolimod (USD -49,221). A third trial demonstrated alemtuzumab to be dominant over natalizumab (USD -1,656,266.07). Many of the trials have sponsorship bias. Eight of the trials received a high QHES score. CONCLUSIONS: The present paper shows that cost-effectiveness studies have high levels of methodological variability, some of them reaching contradictory results. As a result, it is not possible to determine which disease-modifying therapy is really cost-effective in the context of relapsing-remitting multiple sclerosis

The NTP Report on Carcinogens: A valuable resource for public health, a challenge for regulatory science.

The Report on Carcinogens (RoC), from the National Toxicology Program of the USA, is one of the world-leading programs for the identification and acknowledgment of substances that represent a hazard of cancer to humans. RoC covers several essential topics concerning environmental, occupational, and pharmaceutical agents that are known to be, or reasonably anticipated to be carcinogenic to humans. To promote the highest exploitation by its potential users, several RoC aspects and features were put together into one article. For doing so, a comprehensive description is provided regarding RoC history, scope, general features, listing criteria, contents, handbook, and website. Secondary and tertiary aims for this work were (a) to point out some improvement opportunities for the RoC, and (b) to discuss pending issues in regulatory science and cancer hazard assessments. In this regard, for agents classified as probably, likely, reasonably anticipated, possibly or suspected to be a human carcinogen, there is a lack of quantitative knowledge concerning the likelihood of those agents actually being carcinogenic to humans. Elucidating these probabilities is necessary, because the duration of current regulations and the arrival of new acts may depend on it. On the other hand, there is a dramatic imbalance in priorities toward carcinogens, compared with non-carcinogens, in current cancer hazard identification programs. That vision may ignore that the availability on the market of chemicals classified as probably not carcinogenic to humans can also be important for the employment, alimentation, economy, quality of life of consumers, and human health.

Levels of serum leptin in patients with primary hand osteoarthritis / Niveles de leptina sérica en pacientes con osteoartritis primaria de mano

ABSTRACT Introduction: Several studies have documented the statistical association between leptin and osteoarthritis (OA) especially in joints that support weight, such as hips and knees, demonstrating high concentrations of plasma leptin and synovial fluid. Few studies address the possible relationship between leptin and obesity/overweight with OA hand. Objectives: To determine the relationship between serum leptin levels and the severity of OA in hands. Establish the association between obesity/overweight with the severity of OA, using radiographic scales. Methods: Measurement of leptin levels by ELISA technique to 44 patients with primary OA of hand and 30 healthy controls. Analysis of hand radiographs using the classification system of Kellgren and Lawrence, and anthropometric measurements for the calculation of body mass index. Results: Serum leptin levels in the group of patients with primary hand OA were higher compared to healthy controls (P = 0.046). No significant associations were found between the different degrees of severity of the disease measured by radiological scale of de Kellgren and Lawrence with the average leptin levels (P = 0.94) as well as the obesity/overweight categorization according to the body mass index (P = 0.88). Conclusions: Serum leptin levels in the group of patients with primary hand OA in this study were higher compared to healthy controls, with a significant statistical difference. This difference was not maintained in relation to gender, as well as in the subgroup of patients with obesity or overweight.

RESUMEN Introducción: Varios estudios han documentado la asociación estadística entre leptina y osteoartritis (OA), en especial en las articulaciones que soportan peso, como caderas y rodillas, y han demostrado concentraciones elevadas de leptina en plasma y líquido sinovial. Pocos estudios abordan la posible relación entre leptina y obesidad/sobrepeso con la OA de mano. Objetivos: Determinar la relación entre el nivel sérico de leptina y la severidad de la OA en manos. Establecer la asociación entre obesidad/sobrepeso con la severidad de OA mediante escalas radiográficas. Métodos: Medición del nivel de leptina por técnica de ELISA en 44 pacientes con OA primaria de mano y 30 controles sanos. Análisis de radiografías de manos mediante el sistema de clasificación de Kellgren y Lawrence y toma de medidas antropométricas para el cálculo del índice de masa corporal. Resultados: El nivel sérico de leptina en el grupo de pacientes con OA primaria de manos fue mayor que el de los controles sanos (p = 0,046). No se encontraron asociaciones significativas entre los diferentes grados de severidad de la enfermedad medidos por escala radiológica de Kellgren y Lawrence y los niveles medios de leptina (p = 0,94), ni tampoco con la categorización de obesidad/sobrepeso de acuerdo con el índice de masa corporal (p = 0,88). Conclusiones: El nivel sérico de leptina en el grupo de pacientes con OA de manos primaria de este estudio fue mayor que el de los controles sanos, con una diferencia estadística significativa. Esta diferencia no se mantuvo con relación al género, como tampoco en el subgrupo de pacientes con obesidad o sobrepeso.

Intervención del riesgo químico mediante el sistema globalmente armonizado en el comercio de sustancias peligrosas / Chemical risk intervention through the Globally Harmonized System in the trade of hazardous substances

La constante exposición a sustancias químicas en diferentes espacios donde se desarrolla la vida humana, hace necesario conocer la naturaleza de éstas, para determinar la forma más adecuada de manipularlas disminuyendo su riesgo. Tomar a la ligera su uso en el trabajo o en el hogar, puede ser el origen para un accidente o una enfermedad. Los componentes químicos tienen unas características propias para ser clasificados, sea por sus propiedades fisicoquímicas o por sus efectos negativos sobre la salud de las personas y el medio ambiente. Por lo tanto, es necesario comprender la toxicología de los productos peligrosos, su potencial de envenenar y dañar, además de reconocer las vías de penetración al organismo: nariz, boca, piel u ojos; para tomar acciones de control que eviten la presencia de estos agentes en nuestro entorno. El riesgo químico se presenta cuando una sustancia peligrosa está en concentraciones por encima de sus valores límites permisibles en cualquiera que sea su presentación en el ambiente (sólido, líquido, gaseoso), y al entrar en contacto con el individuo amenaza su integridad y/o su bienestar mediante efectos adversos agudos o crónicos. Este riesgo no sólo afecta a las personas, sino también a los ecosistemas por medio de la contaminación del suelo y de las aguas, y del deterioro de la capa de ozono. Como los productos químicos hacen parte importante del desarrollo del ser humano, tener herramientas de información necesaria para su empleo es de gran ayuda para la gestión alrededor del riesgo químico, y es ahí donde el Sistema Globalmente Armonizado de Clasificación y Etiquetado de Sustancias Química se convierte es un aliado de la industria y la comercialización de estos productos, ofreciendo una serie de elementos de comunicación de peligros para mayor seguridad en el manejo, almacenamiento y transporte de sustancias peligrosas y prevención de la enfermedad.

The constant exposure to chemical substances in different spaces where human life develops, makes it necessary to know their nature, to determine the most appropriate way to handle them, reducing their risk. Take lightly its use at work or at home, It may be the source for an accident or illness. The chemical components have their own charac-teristics to be classified, either because of their physicochemical properties or because of their negative effects on people's health and the environment. Therefore, it is necessary to understand the toxicology of dangerous products, their potential to poison and damage, in addition to recognizing the penetration pathways to the organism: nose, mouth, skin or eyes; to take control actions that prevent the presence of these agents in our environ-ment. The chemical risk arises when a hazardous substance is in concentrations above its permissible limit values in whatever its presentation in the environment (solid, liquid, gas), and upon contact with the individual threatens its integrity and / or your well-be-ing through acute or chronic adverse effects. This risk not only affects people, but also ecosystems through soil and water pollution, and the deterioration of the ozone layer. As chemical products are an important part of the development of human beings, having the necessary information tools for their use is of great help for the management around chemical risk, and that is where the Globally Harmonized System of Classification and Labeling of Chemical Substances becomes It is an ally of the industry and the commer-cialization of these products, offering a series of danger communication elements for greater safety in the handling, storage and transport of dangerous substances and disease prevention.

Antibiotics for treating urogenital Chlamydia trachomatis infection in men and non-pregnant women.

BACKGROUND: The genital infection caused by Chlamydia trachomatis (CT) is a common sexually transmitted infection (STI) globally. The infection is mainly asymptomatic in women, thus it can produce infertility and chronic pelvic pain. In men infection is mainly symptomatic, but can evolve to prostatitis. Clinical practice guidelines for CT urogenital infections do not give any specific recommendation about which antibiotic use as first option OBJECTIVES: To assess the efficacy and safety of antibiotic treatment for CT genital infection in men and non-pregnant women. SEARCH METHODS: The Cochrane Sexually Transmitted Infections' (STI) Information Specialist developed the electronic searches in electronic databases (CENTRAL, MEDLINE, Embase and LILACS), and trials registers. We searched studies published from inception to June 2018. SELECTION CRITERIA: We included parallel, randomised controlled trials (RCTs) of men, and sexually-active, non-pregnant women with CT infection (urethritis or uterine cervicitis or asymptomatic), diagnosed by cell culture for CT, nucleic acid amplification tests (NAAT) or antigen-based detection methods, who had been treated with any of the antibiotic regimens recommended by any of the updated to 2013 CT Guidelines. DATA COLLECTION AND ANALYSIS: Four review authors screened evidence according to selection criteria and independently extracted data and assessed risk of bias. Two authors developed the 'Summary of findings' tables. We used a fixed-effect meta-analysis model for combining data where it was reasonable to assume that studies were estimating the same underlying treatment effect. We estimated the pooled risk ratio in order to establish the effects of the comparisons. Our primary outcomes were microbiological failure and adverse events, and our secondary outcomes were clinical failure, antimicrobial resistance and reinfection. MAIN RESULTS: We selected 14 studies ( 2715 participants: 2147 (79.08%) men and 568 (20.92%) women). The studies were conducted mainly at STD clinics. Sample sizes ranged from 71 to 606 participants; follow-up was 29.7 days on average.For the comparison: azithromycin single dose versus doxycycline once or twice daily for 7 days, in men treated for CT, the risk of microbiological failure was higher in the azithromycin group (RR 2.45, 95% CI 1.36 to 4.41; participants = 821; studies = 9; moderate-quality evidence), but regarding clinical failure, the results showed that the effect is uncertain (RR 0.94, 95% CI 0.43 to 2,05; I² = 55%; participants = 525; studies = 3; low-quality evidence). Regarding adverse events (AE) in men there could be little or no difference between the antibiotics (RR 0.83, 95% CI 0.67 to 1.02; participants = 1424; studies = 6; low-quality evidence). About women treated for CT, the effect on microbiological failure was uncertain (RR = 1.71, 95% CI 0.48 to 6.16; participants = 338; studies = 5; very low-quality evidence). There were no studies assessing clinical failure or adverse events in women, however, we found that azithromycin probably has fewer adverse events in both genders (RR 0.83, 95% CI 0.71 to 0.98; I² = 0%; participants = 2261; studies = 9; moderate-quality evidence).For the second comparison: doxycycline compared to ofloxacin, for men treated for CT the effect on microbiological failure was uncertain (RR 8.53, 95% CI 0.43 to 167.38, I² not applicable; participants = 80; studies = 2; very low-quality evidence), as also it was on clinical failure (RR 0.85, 95% CI 0.28 to 2.62; participants = 36; studies = 1; very low-quality evidence). The effect of in women on clinical failure was uncertain (RR 0.94, 95% CI 0.39 to 2.25; I² = 39%; participants = 127; studies = 2; very low-quality evidence).Regarding adverse events, the effect in both men and women was uncertain (RR 1.02 95% CI 0.66 to 1.55; participants = 339 studies = 3; very low-quality evidence). The effect on microbiological failure in women and in men and women together, the effect on microbiological failure was not estimable. The most frequently AE reported were not serious and of gastrointestinal origin.No studies assessed antimicrobial resistance or reinfection in either comparison. AUTHORS' CONCLUSIONS: In men, regimens with azithromycin are probably less effective than doxycycline for microbiological failure, however, there might be little or no difference for clinical failure. For women, we are uncertain whether azithromycin compared to doxycycline increases the risk of microbiological failure. Azithromycin probably slightly reduces adverse events compared to doxycycline in men and women together but may have little difference in men alone. We are uncertain whether doxycycline compared to ofloxacin reduces microbiological failure in men or women alone, or men and women together, nor if it reduces clinical failure or adverse events in men or women.Based on the fact that women suffer mainly asymptomatic infections, and in order to test the effectiveness and safety of the current recommendations (azithromycin, doxycycline and ofloxacin), for CT infection, especially in low and middle income countries, future RCTs should be designed and conducted to include a large enough sample size of women, and with low risk of bias. It is also important that future RCTs include adherence, CT resistance to antibiotic regimens, and risk of reinfection as outcomes to be measured. In addition, it is important to conduct a network meta-analysis in order to evaluate all those studies that included in one arm only the current antibiotic treatments for CT infection that are recommended by the updated clinical practice guidelines.

Bacteriuria is not associated with surgical site infection in patients undergoing cardiovascular surgery.

BACKGROUND: Despite absence of evidence, in practice, asymptomatic bacteriuria is perceived as a risk factor for surgical site infection (SSI) among patients with cardiac surgery. We aimed to identify whether an association exists between the preoperative presence of asymptomatic bacteriuria or urinary tract infection and SSI in patients undergoing cardiovascular surgery. METHODS: This is an analytical study with a retrospective cohort of patients undergoing coronary revascularization or valve replacement surgery. We identified cases of bacteriuria, urinary tract infection, and cardiovascular SSI and adjusted the results according to exposure to antibiotics and known risk factors for SSI using a multivariate logistic regression analysis. RESULTS: A total of 840 patients were included in the study, of whom 33 (3.9%) had asymptomatic bacteriuria and 13 (1.5%) had urinary tract infections. The incidence of SSI was 9.5% (80 patients), with 2.3% of cases having mediastinitis. In the multivariate analysis, asymptomatic bacteriuria (relative risk, 0.83; 95% confidence interval, 0.26-2.56; P = .74) and urinary tract infection (relative risk, 2.54; 95% confidence interval, 0.60-10.69; P = .20) were not risk factors for SSI. Traditional risk factors were found to increase the risk of SSI. CONCLUSIONS: The presence of bacteriuria is not a risk factor for presenting SSI in cardiovascular surgery. Screening with urinalysis or urine culture would not be recommended for patients undergoing cardiac surgery.

Considering health equity when moving from evidence-based guideline recommendations to implementation: a case study from an upper-middle income country on the GRADE approach.

The availability of evidence-based guidelines does not ensure their implementation and use in clinical practice or policy making. Inequities in health have been defined as those inequalities within or between populations that are avoidable, unnecessary and also unjust and unfair. Evidence-based clinical practice and public health guidelines ('guidelines') can be used to target health inequities experienced by disadvantaged populations, although guidelines may unintentionally increase health inequities. For this reason, there is a need for evidence-based clinical practice and public health guidelines to intentionally target health inequities experienced by disadvantaged populations. Current guideline development processes do not include steps for planned implementation of equity-focused guidelines. This article describes nine steps that provide guidance for consideration of equity during guideline implementation. A critical appraisal of the literature followed by a process to build expert consensus was undertaken to define how to include consideration of equity issues during the specific GRADE guideline development process. Using a case study from Colombia we describe nine steps that were used to implement equity-focused GRADE recommendations: (1) identification of disadvantaged groups, (2) quantification of current health inequities, (3) development of equity-sensitive recommendations, (4) identification of key actors for implementation of equity-focused recommendations, (5) identification of barriers and facilitators to the implementation of equity-focused recommendations, (6) development of an equity strategy to be included in the implementation plan, (7) assessment of resources and incentives, (8) development of a communication strategy to support an equity focus and (9) development of monitoring and evaluation strategies. This case study can be used as model for implementing clinical practice guidelines, taking into account equity issues during guideline development and implementation.

Construct and Criterion Validity of the PedsQL™ 4.0 Instrument (Pediatric Quality of Life Inventory) in Colombia.

BACKGROUND: This study aimed at determining the validity of the Pediatric Quality of Life Inventory 4.0 (PedsQL™ 4.0) for the measurement of health-related quality of life (HRQOL) in Colombian children. METHODS: Validation study of measurement instruments. The PedsQL™ 4.0 was applied by convenience sampling to 375 pairs of children and adolescents between the ages of 5 and 17 and to their parents-caregivers, as well as to 125 parents-caregivers of children between the ages of 2 and 4 in five cities of Colombia (Bogota, Medellin, Cali, Barranquilla and Bucaramanga). Construct validity was assessed through the use of exploratory and confirmatory factor analysis, and criterion validity was assessed by correlations between the PedsQL™ 4.0 and the KIDSCREEN-27. RESULTS: The instrument was applied to 375 children (ages 5-18) and 125 parents of children between the ages of 2 and 4. Factor analysis revealed four factors considered suitable for the sample in both the child and parent reports, whereas Bartlett's test of sphericity showed inter-correlation between variables. Scale and subscales showed proper indicators of internal consistency. It is recommended not to include or review some of the items in the Colombian version of the scale. CONCLUSIONS: The Spanish version for Colombia of the PedsQL™ 4.0 displays suitable indicators of criterion and construct validity, therefore becoming a valuable tool for measuring HRQOL in children in our country. Some modifications are recommended for the Colombian version of the scale.

Frequency of bullying perceived in clinical practices of last year interns of a medicine school: cross sectional study / Frecuencia de matoneo percibido en prácticas clínicas de estudiantes de internado en último año de una facultad de medicina. Estudio de corte transversal

Abstract Introduction: During the medical internship year, students attend several hospitals and are observed and influenced by postgraduate students, general practitioners and other interns, who provide them with fundamental support regarding professional training. Bullying is defined as an aggressive behavior that occurs between a perpetrator and a victim in different scenarios and authority relationships, such as clinical practices at Medicine programs. Objective: To describe the perceived frequency of bullying among a group of interns of the Faculty of Medicine from Universidad Nacional de Colombia during internship. Materials and methods: A transversal analytical study was performed through a questionnaire applied to 82 medical interns of the School of Medicine from Universidad Nacional de Colombia. Results: The perceived frequency of bullying was 90%. Statistically significant differences were not found in the stratified analysis by sex or place of practice. In most cases, bullying was perpetrated by other interns, while residents and specialists showed a lower frequency. Conclusion: Perceived frequency of bullying was higher than expected according to the existing literature. These results can be used as a basis for new studies.

Resumen Introducción. Durante el año de internado, los estudiantes acuden a diversos hospitales y se encuentran bajo la mirada e influencia de estudiantes de posgrado, médicos generales, otros médicos internos y especialistas que brindan un apoyo importante en su formación. El matoneo o bullying es un comportamiento agresivo que se da entre un atacante y una víctima y que puede ocurrir en múltiples escenarios con diferentes relaciones de poder como las prácticas clínicas en la carrera de Medicina. Objetivo. Describir la frecuencia de matoneo percibida en un grupo de médicos internos de la Universidad Nacional de Colombia. Materiales y métodos. Estudio de corte transversal analítico realizado a través de una encuesta aplicada a 82 médicos internos de la Universidad Nacional de Colombia. Resultados. Se encontró una percepción de matoneo del 90% sin diferencias estadísticamente significativas al realizar el análisis estratificado por género y lugar de rotación. Las conductas de matoneo son llevadas a cabo en su mayoría por pares académicos y en menor medida por residentes y especialistas. Conclusiones. La percepción de matoneo resultó ser mayor a la reportada en la literatura. Estos resultados pueden emplearse como información de base para nuevos estudios.

Análisis de impacto presupuestal del uso de inmunoglobulina humana normal para los pacientes con deficiencia inmune primaria en Colombia / Análisis de impacto presupuestal del uso de inmunoglobulina humana normal para los pacientes con deficiencia inmune primaria en Colombia

Tecnologías Evaluadas: Inmunoglobulina humana normal. Población: Pacientes con inmunodeficiencia primaria. Perspectiva: La perspectiva del presente AIP corresponde al tercero pagador, que en este caso es el Sistema General de Seguridad Social en Salud (SGSSS) en Colombia. Horizonte Temporal: El horizonte temporal de este AIP en el caso base corresponde a un año. Adicionalmente se reportan las estimaciones del impacto presupuestal para los años 2 y 3, bajo el supuesto de la inclusión en el POS en el año 1. Costos incluidos: El costo anual de la inmunoglobulina humana normal es de $41.883.552,73 pesos colombianos. Fuentes de costos: Dado que se estimó el costo de medicamentos, se utilizó la información de sistema deI nformación de Precios de Medicamentos y Dispositivos Médicos para el año 2014. Escenarios: Se plantearon los siguientes escenarios: adopción del 100% a su ingreso al plan de beneficios y un segundo escenario donde la adopción para el año uno es del 50%, hasta alcanzar el 100% al tercer año comparadora. Resultados: Debido a que no existe tecnología comparador dentro del análisis, se evidencia para el primer escenario donde la adopción es del 100%, se estima un impacto presupuestal por $185.125.303.066,60 pesos colombianos y para el escenario en el que comienza con el 50% y creciendo se evidencia un impacto de $92.562.651.533,3 pesos colombianos.(AU)