Design of a multiple criteria decision analysis framework for prioritizing high-impact health technologies in a regional health service.

OBJECTIVES: This study aims to develop a framework for establishing priorities in the regional health service of Murcia, Spain, to facilitate the creation of a comprehensive multiple criteria decision analysis (MCDA) framework. This framework will aid in decision-making processes related to the assessment, reimbursement, and utilization of high-impact health technologies. METHOD: Based on the results of a review of existing frameworks for MCDA of health technologies, a set of criteria was proposed to be used in the context of evaluating high-impact health technologies. Key stakeholders within regional healthcare services, including clinical leaders and management personnel, participated in a focus group (n = 11) to discuss the proposed criteria and select the final fifteen. To elicit the weights of the criteria, two surveys were administered, one to a small sample of healthcare professionals (n = 35) and another to a larger representative sample of the general population (n = 494). RESULTS: The responses obtained from health professionals in the weighting procedure exhibited greater consistency compared to those provided by the general public. The criteria more highly weighted were "Need for intervention" and "Intervention outcomes." The weights finally assigned to each item in the multicriteria framework were derived as the equal-weighted sum of the mean weights from the two samples. CONCLUSIONS: A multi-attribute function capable of generating a composite measure (multicriteria) to assess the value of high-impact health interventions has been developed. Furthermore, it is recommended to pilot this procedure in a specific decision context to evaluate the efficacy, feasibility, usefulness, and reliability of the proposed tool.

Predominantly Pro-Inflammatory Phenotype with Mixed M1/M2 Polarization of Peripheral Blood Classical Monocytes and Monocyte-Derived Macrophages among Patients with Excessive Ethanol Intake.

Excessive alcohol consumption impairs the immune system, induces oxidative stress, and triggers the activation of peripheral blood (PB) monocytes, thereby contributing to alcoholic liver disease (ALD). We analyzed the M1/M2 phenotypes of circulating classical monocytes and macrophage-derived monocytes (MDMs) in excessive alcohol drinkers (EADs). PB samples from 20 EADs and 22 healthy controls were collected for isolation of CD14+ monocytes and short-term culture with LPS/IFNγ, IL4/IL13, or without stimulation. These conditions were also used to polarize MDMs into M1, M2, or M0 phenotypes. Cytokine production was assessed in the blood and culture supernatants. M1/M2-related markers were analyzed using mRNA expression and surface marker detection. Additionally, the miRNA profile of CD14+ monocytes was analyzed. PB samples from EADs exhibited increased levels of pro-inflammatory cytokines. Following short-term culture, unstimulated blood samples from EADs showed higher levels of soluble TNF-α and IL-8, whereas monocytes expressed increased levels of surface TNF-α and elevated mRNA expression of pro-inflammatory cytokines and inducible nitric oxide synthase. MDMs from EADs showed higher levels of TNF-α and CD206 surface markers and increased IL-10 production. LPS/IFNγ induced higher mRNA expression of Nrf2 only in the controls. miRNA analysis revealed a distinctive miRNA profile that is potentially associated with liver carcinogenesis and ALD through inflammation and oxidative stress. This study confirms the predominantly pro-inflammatory profile of PB monocytes among EADs and suggests immune exhaustion features in MDMs.

Serum vitamin D levels and mortality in Mexicans: results from the Mexican Healthand Aging study / Niveles séricos de vitamina D y mortalidad en mexicanos: resultados del Estudio Nacional de Envejecimiento en México

Background: the population in Latin America is aging and elders face several obstacles for good health, including an elevated frequency of vitamin D deficiency. Thus, identification of patients at high risk to develop its negative consequences should be a priority. Objective: the objective of this analysis was to determine if levels of vitamin D lower than 15 ng/ml are associated with high mortality in Mexican elderly population, from the database of the Mexican Health and Aging Study (MHAS). Methods: prospective, population study in Mexico, that included Subjects of 50 years and older who were evaluated for Serum vitamin D levels during the year 2012 (third wave of the study). Serum 25(OH)D levels were categorized into four groups, based on cutoff points used in previous studies on vitamin D and frailty: < 15, 15-< 20, 20-< 30 and ≥ 30 ng/ml. Mortality was evaluated during 2015 (fourth wave of the study). Hazard ratio was calculated (for mortality) through Cox Regression Model, adjusted for covariates. Results: we included 1626 participants, and those with lower levels of vitamin D were older, more often women, required more aid for activities of daily living, reported higher number of chronic diseases, and lower scores on cognition. The relative risk of death was 5.421 (95 % CI 2.465-11.92, p < 0.001) for the participants with vitamin D levels < 15, which after adjusting for covariates, remained statistically significant. Conclusions: levels of vitamin D lower of 15, are associated with an increase in the rate of mortality in community-dwelling senior Mexicans.(AU)

Introducción: la población en América Latina está envejeciendo y los adultos mayores enfrentan varios obstáculos para gozar de buena salud,incluida una frecuencia elevada de deficiencia de vitamina D. Por lo tanto, la identificación de pacientes con alto riesgo de desarrollar susconsecuencias negativas debe ser una prioridad.Objetivo: el objetivo de este análisis fue determinar si los niveles de vitamina D inferiores a 15 ng/ml están asociados con una alta mortalidaden la población adulta mayor mexicana, a partir de la base de datos del Estudio de Salud y Envejecimiento en México.Métodos: estudio poblacional prospectivo en México, que incluyó Sujetos de 50 años y mayores que fueron evaluados para los niveles de vitaminaD en suero durante el año 2012 (tercera ola del estudio). Los niveles séricos de 25(OH)D se clasificaron en cuatro grupos, según los puntos decorte utilizados en estudios previos sobre vitamina D y fragilidad: < 15, 15-< 20, 20-< 30 y ≥ 30 ng/ml. La mortalidad se evaluó durante 2015(cuarta ola del estudio). Se calculó la razón de riesgo (para la mortalidad) a través del modelo de regresión de Cox, ajustado por covariables.Resultados: incluimos 1626 participantes, y aquellos con niveles más bajos de vitamina D eran mayores, más a menudo mujeres, requerían másayuda para las actividades de la vida diaria, informaron un mayor número de enfermedades crónicas y puntuaciones más bajas en cognición. Elriesgo relativo de muerte fue de 5,421 (IC 95 % 2,465-11,92, p < 0,001) para los participantes con niveles de vitamina D < 15, que despuésde ajustar por covariables, se mantuvo estadísticamente significativo.Conclusiones: niveles de vitamina D inferiores a 15, se asocian con un aumento en la tasa de mortalidad en adultos mayores mexicanosresidentes en la comunidad.(AU)

Serum vitamin D levels and mortality in Mexicans: results from the Mexican Health and Aging Study.

Introduction: Background: the population in Latin America is aging and elders face several obstacles for good health, including an elevated frequency of vitamin D deficiency. Thus, identification of patients at high risk to develop its negative consequences should be a priority. Objective: the objective of this analysis was to determine if levels of vitamin D lower than 15 ng/ml are associated with high mortality in Mexican elderly population, from the database of the Mexican Health and Aging Study (MHAS). Methods: prospective, population study in Mexico, that included Subjects of 50 years and older who were evaluated for Serum vitamin D levels during the year 2012 (third wave of the study). Serum 25(OH)D levels were categorized into four groups, based on cutoff points used in previous studies on vitamin D and frailty: < 15, 15-< 20, 20-< 30 and ≥ 30 ng/ml. Mortality was evaluated during 2015 (fourth wave of the study). Hazard ratio was calculated (for mortality) through Cox Regression Model, adjusted for covariates. Results: we included 1626 participants, and those with lower levels of vitamin D were older, more often women, required more aid for activities of daily living, reported higher number of chronic diseases, and lower scores on cognition. The relative risk of death was 5.421 (95 % CI 2.465-11.92, p < 0.001) for the participants with vitamin D levels < 15, which after adjusting for covariates, remained statistically significant. Conclusions: levels of vitamin D lower of 15, are associated with an increase in the rate of mortality in community-dwelling senior Mexicans.

Introducción: Introducción: la población en América Latina está envejeciendo y los adultos mayores enfrentan varios obstáculos para gozar de buena salud, incluida una frecuencia elevada de deficiencia de vitamina D. Por lo tanto, la identificación de pacientes con alto riesgo de desarrollar sus consecuencias negativas debe ser una prioridad. Objetivo: el objetivo de este análisis fue determinar si los niveles de vitamina D inferiores a 15 ng/ml están asociados con una alta mortalidad en la población adulta mayor mexicana, a partir de la base de datos del Estudio de Salud y Envejecimiento en México. Métodos: estudio poblacional prospectivo en México, que incluyó Sujetos de 50 años y mayores que fueron evaluados para los niveles de vitamina D en suero durante el año 2012 (tercera ola del estudio). Los niveles séricos de 25(OH)D se clasificaron en cuatro grupos, según los puntos de corte utilizados en estudios previos sobre vitamina D y fragilidad: < 15, 15-< 20, 20-< 30 y ≥ 30 ng/ml. La mortalidad se evaluó durante 2015 (cuarta ola del estudio). Se calculó la razón de riesgo (para la mortalidad) a través del modelo de regresión de Cox, ajustado por covariables. Resultados: incluimos 1626 participantes, y aquellos con niveles más bajos de vitamina D eran mayores, más a menudo mujeres, requerían más ayuda para las actividades de la vida diaria, informaron un mayor número de enfermedades crónicas y puntuaciones más bajas en cognición. El riesgo relativo de muerte fue de 5,421 (IC 95 % 2,465-11,92, p < 0,001) para los participantes con niveles de vitamina D < 15, que después de ajustar por covariables, se mantuvo estadísticamente significativo. Conclusiones: niveles de vitamina D inferiores a 15, se asocian con un aumento en la tasa de mortalidad en adultos mayores mexicanos residentes en la comunidad.

PPAR-γ Gene Expression in Human Adipose Tissue Is Associated with Weight Loss After Sleeve Gastrectomy.

BACKGROUND: The peroxisome proliferator-activated receptor (PPAR)-γ plays a key role in adipose tissue differentiation and fat metabolism. However, it is unclear which factors may regulate its expression and whether obese patients have changes in adipose tissue expression of PPAR-γor potential regulators such as miR-27. Thus, our aims were to analyze PPAR-γ and miR-27 expression in adipose tissue of obese patients, and to correlate their levels with clinical variables. SUBJECTS AND METHODS: We included 43 morbidly obese subjects who underwent sleeve gastrectomy (31 of them completed 1-year follow-up) and 19 non-obese subjects. mRNA expression of PPAR-γ1 and PPAR-γ2, miR-27a, and miR-27b was measured by qPCR in visceral and subcutaneous adipose tissue. Clinical variables and serum adipokine and hormone levels were correlated with PPAR-γ and miR-27 expression. In addition, a systematic review of the literature regarding PPAR-γ expression in adipose tissue of obese patients was performed. RESULTS: We found no differences in the expression of PPAR-γ and miR-27 in adipose tissue of obese patients vs. controls. The literature review revealed discrepant results regarding PPAR-γ expression in adipose tissue of obese patients. Of note, we described a significant negative correlation between pre-operative PPAR-γ1 expression in adipose tissue of obese patients and post-operative weight loss, potentially linked with insulin resistance markers. CONCLUSION: PPAR-γ1 expression in adipose tissue is associated with weight loss after sleeve gastrectomy and may be used as a biomarker for response to surgery.

Factores de riesgo materno asociados con macrosomía fetal en el Hospital de Clínicas / Maternal risk factors associated with fetal macrosomia in Hospital de Clínicas

Introducción: La incidencia de macrosomía está entre 4,7 a 16,4%. La Organización Mundial de la Salud (OMS) en el 2012 refiere que el 6.7% de los recién nacidos en el mundo presentaron sobrepeso u obesidad. En el 2014 reportó que en las regiones de Sudamérica el 7,6% de los recién nacidos nacieron con sobrepeso. Materiales y métodos: Estudio observacional, analítico de casos y controles. El método de muestreo no probabilístico de casos consecutivos. La población accesible son pacientes que dieron a luz a recién nacidos macrosómicos en la Cátedra y Servicio de Ginecología y Obstetricia del Hospital de Clínicas. Los casos son pacientes con ecografía obstétrica del tercer trimestre que dieron a luz a recién nacido único, vivo o muerto, mayor a 37 semanas por Capurro, con peso al nacer mayor o igual a 4000 gramos en la Cátedra y Servicio de Ginecología y Obstetricia del Hospital de Clínicas - San Lorenzo, del 1 de enero a 31 de diciembre de 2017. Resultados: Con diferencia significativa (p<0,05) el estudio manifiesta oportunidad a las cesáreas con 64 (84,21%) como vía de terminación del embarazo, siendo 5,77 veces mayor en las gestaciones con feto macrosómico. Las lesiones del canal del parto se reportaron 8 (10,53%) en los partos de recién nacidos macrosómico y 46 (30,26%) en los controles, representando diferencia significativa. Conclusión: los factores de riesgo materno asociados con macrosomía fetal son: la macrosomía anterior, la obesidad materna pregestacional, la hipertensión inducida por el embarazo, un aumento de ponderal > 15 kg durante la gestación. La mayoría de las mujeres estudiadas fueron de procedencia urbana, en unión libre, amas de casas y con escolaridad secundaria, pero no resultaron ser factores de riesgos de recién nacidos macrosómicos. No se encontró asociación entre macrosomía fetal y diabetes gestacional.

Introduction: The incidence of macrosomia is between 4.7 to 16.4%. The World Health Organization (WHO) in 2012 refers that 6.7% of newborns in the world were overweight or obese.9 In 2014 it reported that in the regions of South America 7.6% of newborns were born with overweight. Materials and methods: Observational, analytical study of cases and controls. The non-probability sampling method of consecutive cases. The accessible population are patients who gave birth to macrosomic newborns in the Department and Service of Gynecology and Obstetrics of the Hospital de Clínicas. The cases are patients with obstetric ultrasound of the third trimester who gave birth to a single newborn, alive or dead, greater than 37 weeks per Capurro, with a birth weight greater than or equal to 4000 grams in the Department and Service of Gynecology and Obstetrics of the Hospital de Clínicas - San Lorenzo, from January 1 to December 31, 2017. Results: With a significant difference (p <0.05), the study shows an opportunity for cesarean sections with 64 (84.21%) as the means of termination of pregnancy, being 5.77 times higher in pregnancies with a macrosomic fetus. Injuries to the birth canal were reported in 8 (10.53%) in macrosomic newborn deliveries and 46 (30.26%) in controls, representing a significant difference. Conclusion: maternal risk factors associated with fetal macrosomia are: anterior macrosomia, pre-pregnancy maternal obesity, pregnancy-induced hypertension, and a weight gain> 15 kg during pregnancy. Most of the women studied were of urban origin, in common union, housewives and with secondary schooling, but they did not turn out to be risk factors for macrosomic newborns. No association was found between fetal macrosomia and gestational diabetes.

Matrix metalloproteinases deregulation in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of upper and lower motor neurons that results in progressive paralysis and muscular atrophy. There are many molecules and genes involved in neuromuscular degeneration in ALS; among these, matrix metalloproteinases (MMPs). MMPs play an important role in the pathology of ALS, and MMP-1, 2, 3, and 9 might serve as disease progression markers. Tissue inhibitors of metalloproteinases (TIMPS) might also function as progression markers in ALS because they participate in regulating the proteolytic activity of MMPs. Moreover, a diversity of genes also plays a role in the pathogenesis of ALS; most MMPs-coding genes present variants related to the pathological proteolytic activity. This short review, however, will focus on the role of matrix metalloproteinases in ALS.

Circulating MicroRNAs in Extracellular Vesicles as Potential Biomarkers of Alcohol-Induced Neuroinflammation in Adolescence: Gender Differences.

Current studies evidence the role of miRNAs in extracellular vesicles (EVs) as key regulators of pathological processes, including neuroinflammation and neurodegeneration. As EVs can cross the blood-brain barrier, and EV miRNAs are very stable in peripheral circulation, we evaluated the potential gender differences in inflammatory-regulated miRNAs levels in human and murine plasma EVs derived from alcohol-intoxicated female and male adolescents, and whether these miRNAs could be used as biomarkers of neuroinflammation. We demonstrated that while alcohol intoxication lowers anti-inflammatory miRNA (mir-146a-5p, mir-21-5p, mir-182-5p) levels in plasma EVs from human and mice female adolescents, these EV miRNAs increased in males. In mice brain cortices, ethanol treatment lowers mir-146a-5p and mir-21-5p levels, while triggering a higher expression of inflammatory target genes (Traf6, Stat3, and Camk2a) in adolescent female mice. These results indicate, for the first time, that female and male adolescents differ as regards the ethanol effects associated with the inflammatory-related plasma miRNAs EVs profile, and suggest that female adolescents are more vulnerable than males to the inflammatory effects of binge alcohol drinking. These findings also support the view that circulating miRNAs in EVs could be useful biomarkers for screening ethanol-induced neuroinflammation and brain damage in adolescence.

Burden of rheumatoid arthritis on patients' work productivity and quality of life.

BACKGROUND: To determine the burden of Rheumatoid Arthritis (RA) on patients' work productivity and health related quality of life (HRQoL), and examine the influence of several exposure variables; to analyze the progression of RA over 1 year and its impact on work productivity and HRQoL. METHODS: International multicenter prospective survey including patients in 18 centers in Argentina, Brazil, Colombia and Mexico with diagnosis of RA and aged between 21-55 years. The following standard questionnaires were completed at baseline and throughout a 1-year follow-up: WPAI:RA, WALS, WLQ-25, EQ-5D-3 L and SF-36. Clinical and demographic variables were also collected through interview. RESULTS: The study enrolled 290 patients on baseline visit. Overall mean scores at baseline visit were: WPAI:RA (presenteeism) = 29.5% (SD = 28.8%); WPAI:RA (absenteeism) = 9.0% (SD = 23.2%); WPAI:RA (absenteeism and presenteeism) = 8.6% (SD = 22.6%); WALS = 9.0 (SD = 6.1); WLQ-25 = 7.0% (SD = 5.1%); SF-36 Physical Scale = 39.1 (SD = 10.3) and Mental Scale = 45.4 (SD = 11.3); EQ-5D-3 L VAS = 69.8 (SD = 20.4) and EQ-5D-3 L index = 0.67 (SD = 0.23). Higher educational levels were associated with better results in WLQ-25, while previous orthopedic surgeries reduced absenteeism results of WPAI:RA and work limitations in WLQ-25. Higher disease duration was associated with decreased HRQoL. Intensification of disease activity was associated with decreased work productivity and HRQoL, except in WLQ-25. In the longitudinal analysis, worsening in disease activity was associated with a decrease in both work productivity and HRQoL. CONCLUSIONS: RA patients are dealing with workplace disabilities and limitations and loss in HRQoL, and multiple factors seems to be associated with this. Worsening of disease activity further decreased work productivity and HRQoL, stressing the importance of disease tight control.

Burden of rheumatoid arthritis on patients' work productivity and quality of life

Abstract Background: To determine the burden of Rheumatoid Arthritis (RA) on patients' work productivity and health related quality of life (HRQoL), and examine the influence of several exposure variables; to analyze the progression of RA over 1 year and its impact on work productivity and HRQoL. Methods: International multicenter prospective survey including patients in 18 centers in Argentina, Brazil, Colombia and Mexico with diagnosis of RA and aged between 21-55 years. The following standard questionnaires were completed at baseline and throughout a 1-year follow-up: WPAI:RA, WALS, WLQ-25, EQ-5D-3 L and SF-36. Clinical and demographic variables were also collected through interview. Results: The study enrolled 290 patients on baseline visit. Overall mean scores at baseline visit were: WPAI:RA (presenteeism) = 29.5% (SD = 28.8%); WPAI:RA (absenteeism) = 9.0% (SD = 23.2%); WPAI:RA (absenteeism and presenteeism) = 8.6% (SD = 22.6%); WALS = 9.0 (SD = 6.1); WLQ-25 = 7.0% (SD = 5.1%); SF-36 Physical Scale = 39.1 (SD = 10.3) and Mental Scale = 45.4 (SD = 11.3); EQ-5D-3 L VAS = 69.8 (SD = 20.4) and EQ-5D-3 L index = 0.67 (SD = 0.23). Higher educational levels were associated with better results in WLQ-25, while previous orthopedic surgeries reduced absenteeism results of WPAI:RA and work limitations in WLQ-25. Higher disease duration was associated with decreased HRQoL. Intensification of disease activity was associated with decreased work productivity and HRQoL, except in WLQ-25. In the longitudinal analysis, worsening in disease activity was associated with a decrease in both work productivity and HRQoL. Conclusions: RA patients are dealing with workplace disabilities and limitations and loss in HRQoL, and multiple factors seems to be associated with this. Worsening of disease activity further decreased work productivity and HRQoL, stressing the importance of disease tight control.

Role of microRNAs in alcohol-induced liver disorders and non-alcoholic fatty liver disease.

MicroRNAs (miRNAs) are small non-coding RNAs that regulate multiple physiological and pathological functions through the modulation of gene expression at the post-transcriptional level. Accumulating evidence has established a role for miRNAs in the development and pathogenesis of liver disease. Specifically, a large number of studies have assessed the role of miRNAs in alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD), two diseases that share common underlying mechanisms and pathological characteristics. The purpose of the current review is to summarize and update the body of literature investigating the role of miRNAs in liver disease. In addition, the potential use of miRNAs as biomarkers and/or therapeutic targets is discussed. Among all miRNAs analyzed, miR-34a, miR-122 and miR-155 are most involved in the pathogenesis of NAFLD. Of note, these three miRNAs have also been implicated in ALD, reinforcing a common disease mechanism between these two entities and the pleiotropic effects of specific miRNAs. Currently, no single miRNA or panel of miRNAs has been identified for the detection of, or staging of ALD or NAFLD. While promising results have been shown in murine models, no therapeutic based-miRNA agents have been developed for use in humans with liver disease.

Influencia de la protocolización del tratamiento inicial con corticoides en la estancia y costo de las neumonías adquiridas en la comunidad. Estudio prospectivo 2015 / Influence of initial protocolized treatment with steroids in length of stay and costs of community acquired pneumonia

Objetivos. Valorar el impacto que la inclusión inicial de corticoides en el protocolo de tratamiento de un paciente con neumonía de la comunidad (NAC) puede tener en la estancia y costo de los procesos en enfermos ingresados con este diagnóstico en un hospital clínico universitario. Pacientes y métodos. Estudio prospectivo de los pacientes ingresados con el diagnóstico de NAC en los Servicios de Medicina Interna e Infecciosas durante los meses de enero a marzo de 2015; los pacientes se clasificaron en Grupo I, en caso de haber recibido esteroides desde el diagnóstico del proceso neumónico y hasta la finalización del tratamiento antibiótico y en Grupo II, si no habían recibido esteroides; la administración o no de esteroides fue realizada según la práctica clínica de cada médico responsable del paciente. Se valoró el costo según el GRD de NAC. Resultados. La edad < de 65 años es más frecuente en el grupo I que en el II, siendo el único factor diferencial entre ambas cohortes con significación estadística (p<0,05). En el análisis bivariado, las estancias medias del grupo I (5,37 vs 8,88 días) fueron significativamente menores (p<0,0005) y también lo fueron los costes (2.361 euros vs 3.907 euros) (p<0,0005). En el estudio multivariado se asociaron de forma independiente los costes altos (>3.520 euros) a los pacientes con EPOC (OR=2,602; IC95% 1,074-6,305) y al grupo II (pacientes que no habían recibido esteroides) (OR=6,2; p=0,007). Conclusiones. El no utilizar corticoides en el tratamiento de los pacientes con neumonías comunitarias se asoció, junto con el ser EPOC a un mayor coste del ingreso, valorado por el GRD/estancia diaria (AU)

Objective. The aim of the study was to analyze the impact of steroid treatment in patients with community acquired pneumonia (CAP), both in length of stay and economical cost of admission at a clinical university hospital. Patients and methods. Prospective study of admitted patients with the diagnosis of CAP, both in Internal Medicine and Infectious diseases department. The study was conducted from January to march 2015; patients receiving steroids from diagnosis to end of antibiotic treatment were classified as group I; otherwise, they were considered in group II. Administration of steroids was done according to the criteria of the responsible. Cost was stablished according to CAP Diagnostic Related Group (DRG). Results. Prevalence of patients younger than 65 year old was higher in group I (p<0.05). In bivariate analyses, mean admission time was lower in group I (5.37 vs 8.88 days) (p<0.0005) and also economical cost (2,361 euros vs 3,907 euros) (p<0.0005). In multivariate analysis, factors independently associated to higher cost (>3,520 euros) were COPD (OR=2.602; 95% CI 1.074-6.305) and group II (patients with no steroids) (OR=6.2; p=0,007). Conclusions. No administration of steroids in patients with CAP was associated, together with COPD, with higher economical cost (evaluated by DRG/length of stay) (AU)

Gender differences in the inflammatory cytokine and chemokine profiles induced by binge ethanol drinking in adolescence.

Heavy binge drinking in adolescence can cause long-term cognitive and behavioral dysfunctions. Recent experimental evidence indicates the participation of immune system activation in the effects of ethanol in the adolescent brain and suggests gender differences. The present study aims to assess plasma cytokine and chemokine levels in male and female adolescents and young adults during acute alcohol intoxication and to correlate these results with the toll-like receptor 4 (TLR4) response. The potential role of the TLR4 signaling response was also assessed in plasma and prefrontal cortex (PFC) of adolescent wild-type and TLR4-knockout male and female mice with binge ethanol treatment. The results showed that alcohol intoxication increased the plasma levels of several cytokine and chemokine [interferon-γ, interleukin (IL)-10, IL-17A, IL-1ß, IL-2, IL-4, IL-6, IL-8, fractalkine, monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein 1α (MIP-1α)] and the upregulation of TLR4 mRNA levels occurred in intoxicated females, while elevation of colony-stimulating factor was only observed in the plasma of males. In wild-type female adolescent mice, intermittent ethanol treatment increased the levels of several cytokines (IL-17A and IL-1ß) and chemokines (MCP-1, MIP-1α and fractalkine) in PFC and in serum (IL-17A, MCP-1 and MIP-1α), but significant differences in the fractalkine levels in PFC were observed only in male mice. No changes in serum or prefrontal cortex cytokine and chemokine levels were noted in ethanol-treated male or female TLR4-knockout mice. Our findings revealed that females are more vulnerable than males to inflammatory effects of binge ethanol drinking and suggested that TLR4 is an important target of ethanol-induced inflammation and neuroinflammation in adolescence.

Evaluation of a Mixing versus a Cycling Strategy of Antibiotic Use in Critically-Ill Medical Patients: Impact on Acquisition of Resistant Microorganisms and Clinical Outcomes.

OBJECTIVE: To compare the effect of two strategies of antibiotic use (mixing vs. cycling) on the acquisition of resistant microorganisms, infections and other clinical outcomes. METHODS: Prospective cohort study in an 8-bed intensive care unit during 35- months in which a mixing-cycling policy of antipseudomonal beta-lactams (meropenem, ceftazidime/piperacillin-tazobactam) and fluoroquinolones was operative. Nasopharyngeal and rectal swabs and respiratory secretions were obtained within 48h of admission and thrice weekly thereafter. Target microorganisms included methicillin-resistant S. aureus, vancomycin-resistant enterococci, third-generation cephalosporin-resistant Enterobacteriaceae and non-fermenters. RESULTS: A total of 409 (42%) patients were included in mixing and 560 (58%) in cycling. Exposure to ceftazidime/piperacillin-tazobactam and fluoroquinolones was significantly higher in mixing while exposure to meropenem was higher in cycling, although overall use of antipseudomonals was not significantly different (37.5/100 patient-days vs. 38.1/100 patient-days). There was a barely higher acquisition rate of microorganisms during mixing, but this difference lost its significance when the cases due to an exogenous Burkholderia cepacia outbreak were excluded (19.3% vs. 15.4%, OR 0.8, CI 0.5-1.1). Acquisition of Pseudomonas aeruginosa resistant to the intervention antibiotics or with multiple-drug resistance was similar. There were no significant differences between mixing and cycling in the proportion of patients acquiring any infection (16.6% vs. 14.5%, OR 0.9, CI 0.6-1.2), any infection due to target microorganisms (5.9% vs. 5.2%, OR 0.9, CI 0.5-1.5), length of stay (median 5 d for both groups) or mortality (13.9 vs. 14.3%, OR 1.03, CI 0.7-1.3). CONCLUSIONS: A cycling strategy of antibiotic use with a 6-week cycle duration is similar to mixing in terms of acquisition of resistant microorganisms, infections, length of stay and mortality.

Acquisition of Pseudomonas aeruginosa and its resistance phenotypes in critically ill medical patients: role of colonization pressure and antibiotic exposure.

INTRODUCTION: The objective of this work was to investigate the risk factors for the acquisition of Pseudomonas aeruginosa and its resistance phenotypes in critically ill patients, taking into account colonization pressure. METHODS: We conducted a prospective cohort study in an 8-bed medical intensive care unit during a 35-month period. Nasopharyngeal and rectal swabs and respiratory secretions were obtained within 48 hours of admission and thrice weekly thereafter. During the study, a policy of consecutive mixing and cycling periods of three classes of antipseudomonal antibiotics was followed in the unit. RESULTS: Of 850 patients admitted for ≥ 3 days, 751 (88.3%) received an antibiotic, 562 of which (66.1%) were antipseudomonal antibiotics. A total of 68 patients (8%) carried P. aeruginosa upon admission, and among the remaining 782, 104 (13%) acquired at least one strain of P. aeruginosa during their stay. Multivariate analysis selected shock (odds ratio (OR) = 2.1; 95% confidence interval (CI), 1.2 to 3.7), intubation (OR = 3.6; 95% CI, 1.7 to 7.5), enteral nutrition (OR = 3.6; 95% CI, 1.8 to 7.6), parenteral nutrition (OR = 3.9; 95% CI, 1.6 to 9.6), tracheostomy (OR = 4.4; 95% CI, 2.3 to 8.3) and colonization pressure >0.43 (OR = 4; 95% CI, 1.2 to 5) as independently associated with the acquisition of P. aeruginosa, whereas exposure to fluoroquinolones for >3 days (OR = 0.4; 95% CI, 0.2 to 0.8) was protective. In the whole series, prior exposure to carbapenems was independently associated with carbapenem resistance, and prior amikacin use predicted piperacillin-tazobactam, fluoroquinolone and multiple-drug resistance. CONCLUSIONS: In critical care settings with a high rate of antibiotic use, colonization pressure and non-antibiotic exposures may be the crucial factors for P. aeruginosa acquisition, whereas fluoroquinolones may actually decrease its likelihood. For the acquisition of strains resistant to piperacillin-tazobactam, fluoroquinolones and multiple drugs, exposure to amikacin may be more relevant than previously recognized.

Time to positivity and detection of growth in anaerobic blood culture vials predict the presence of Candida glabrata in candidemia: a two-center European cohort study.

This study shows the accuracy of exclusive or earlier growth in anaerobic vials to predict Candida glabrata in a large series of candidemic patients from two European hospitals using the Bactec 9240 system. Alternatively, C. glabrata can be predicted by a time to positivity cutoff value, which should be determined for each setting.

¿Por qué resulta útil una buena definición de medicina? / A suitable definition of medicine: Why is it useful?

Los autores explican el rol que desempeña la disciplina HISTORIA DE LA MEDICINA en el proceso de formación del invariante de habilidad, que unido al invariante de conocimiento permitirá que el futuro profesional de la salud pueda actuar. Se evalúan las preconcepciones que tienen los estudiantes sobre la medicina y se ofrecen recursos didácticos para aprender a definir el arte médico. Valorándose el significado que posee ese recurso para la proyección académica, investigativa y laboral de los mismos (AU)

The authors explain the role of the discipline HISTORY OF MEDICINE in the process of formation of the ability invariant that together to the knowledge invariant will allow the future health professional 's activity . The preconceptions that students have on medicine are evaluated and didactic resources to learn how to define medicine are offered. The impact this resource has in the academic, investigative and working areas of students' lives is also valued (AU)

Innovación educativa para el fortalecimiento del enfoque Ciencia-Tecnología-Sociedad en la educación postgraduada / Strengthening the Science-Technology-Society approach: an educative innovation for postgraduate courses

Los Estudios sociales de la ciencia y la tecnología también reconocidos bajo el nombre Estudios Ciencia- Tecnología- Sociedad (CTS), es un campo científico que a pesar de su relativa juventud es considerado un campo bien consolidado de investigación académica, en las áreas de la política científica y educación, Los Estudios CTS ponen énfasis en los aspectos sociales del fenómeno ciencia y tecnología en sus consecuencias sociales y ambientales, por eso su enfoque general es de carácter crítico respecto a las imágenes o visiones clásicas de la ciencia y la tecnología que aún resultan predominantes, y orienta hacia una actitud vigilante alrededor de la actividad científica. Sus valiosas estructuras teóricas y conceptuales son fundamentales para el análisis de las ciencias y tecnologías de la salud, lo que lo convierte en un instrumento de elevado significado para la educación médica superior y la práctica y la ciencia de la Salud Pública en general. La presente estrategia educativa permite actualizar los paradigmas desde los cuáles se piensa sobre las interrelaciones ciencia-tecnología-sociedad; como respuesta a las necesidades de satisfacer demandas cognoscitivas en ésta área. El objetivo esencial de la estrategia consiste en proporcionar visiones cada vez más desarrolladas y amplias sobre la actividad científico-tecnológica, de modo que promuevan una actitud ética y responsable de los profesionales de la salud. El Diplomado que se propone forma parte del Sistema de Educación Postgraduada del Centro de Humanidades y Ética en Ciencias de la Salud y ha sido aprobado por la Escuela Nacional de Salud Pública con carácter internacional (AU)

The social studies of science and technology, also known as Science - Technology - Society Studies (CTS), is a scientific field that in spite of its relative youth is considered a consolidated field of academic investigation, in the scientific politics and education areas. CTS Studies emphasize the social aspects of the science-technology phenomenon in its social and environmental consequences, for that reason it regards critically the images or classic approaches of science and technology that are still predominant. It also guides towards a careful attitude around the scientific activity. Their valuable theoretical and conceptual structures are fundamental for the analysis of health sciences and technologies, which turns it into a meaningful instrument of higher medical education and of the theory and practice of Public Health in general. This educational strategy allows upgrading the paradigms from which the interrelations science-technology-society is analyzed, as a way to answer the necessities of satisfying cognitive demands in this area. The essential objective of the strategy consists of providing better developed and vaster visions of the scientific-technological activity, so that this promotes an ethical and responsible attitude among health professionals. The post graduate course proposed is part of the Postgraduate System of Education of the Center of Humanities and Ethics in Health Sciences and it has been approved by the Public Health National School as an international course (AU)