Multizonal observational study conducted by clinical practitioners on Repatha® use in patients with hyperlipidemia (ZERBINI): Colombian results / Estudio Observacional Multizonal realizado por Médicos Clínicos sobre el Uso de Repatha® en Pacientes con Hiperlipidemia (ZERBINI): resultados colombianos

Background Cardiovascular disease (CVD) represents the primary cause of death and disability globally, with elevated cholesterol as one of the leading risk factors for CVD. We describe the clinical characteristics, treatment patterns, and effectiveness of evolocumab in treating hyperlipidemia. Methods Observational study conducted through a chart review of patients with hyperlipidemia receiving evolocumab as part of clinical management in Colombia. Results This study included 115 patients treated with evolocumab. A total of 101 patients (87.8%) had a history of CVD, 13 (11.3%) familial hypercholesterolemia (FH), and 23 (20%) type 2 diabetes. Thirty-nine patients reported intolerance to any statin (33.9%). The median value of LDL-C before initiation of evolocumab was 147mg/dL (IQR: 122.5–183.7mg/dL). Within the first 3 months of treatment, LDL-C value dropped to a median value of 53mg/dL (IQR: 34.0–95.5mg/dL), showing a reduction of 63.9%. The median LDL-C values remained below 45mg/dL until the end of follow-up. Among the patients with available data, up to 61% achieved an LDL-C level below 55mg/dL at the 10–12-month follow-up. A total of 72% of patients were persistent with treatment. Safety results showed a low frequency of hospitalizations (≤2%) and treatment-emergent adverse drug reactions (5.2%). No serious adverse events were reported. Conclusions Evolocumab was associated with reductions in LDL-C levels, with a relative decrease of 63.9% within the first 3 months of treatment. Low rates of interruptions due to adverse events and adequate medication persistence was reported. (AU)

Antecedentes Las enfermedades cardiovasculares (ECV) representan la principal causa de muerte y discapacidad en todo el mundo, siendo el colesterol elevado uno de los principales factores de riesgo de ECV. El presente estudio describe las características clínicas, patrones de tratamiento y la efectividad de evolocumab en el tratamiento de la hiperlipidemia. Métodos Estudio observacional de revisión de historias clínicas de pacientes con hiperlipidemia que reciben evolocumab como parte del manejo clínico en Colombia. Resultados Se incluyeron 115 pacientes tratados con evolocumab. Un total de 101 pacientes (87,8%) presentaron antecedentes de ECV, 13 (11,3%) de hipercolesterolemia familiar y 23 (20%) de diabetes tipo 2. De los pacientes estudiados, 39% declararon intolerancia a alguna estatina (33,9%). La mediana de C-LDL antes del inicio de evolocumab fue de 147mg/dL (IQR: 122,5-183,7mg/dL). En los primeros tres meses de tratamiento, el valor de C-LDL descendió a 53mg/dL (IQR: 34,0-95,5mg/dL), siendo una reducción de 63,9%. La mediana de C-LDL se mantuvo por debajo de 45mg/dL hasta el final del seguimiento. Entre los pacientes con datos disponibles, hasta 61% alcanzó un nivel de LDL-C inferior a 55mg/dL en el seguimiento de 10-12 meses. De los pacientes analizados, 72% fue persistente al tratamiento. Los resultados de seguridad mostraron una baja frecuencia de hospitalizaciones (≤2%) y de reacciones adversas relacionadas al tratamiento (5,2%). No se notificaron acontecimientos adversos graves. Conclusiones Evolocumab se asoció con reducciones en los niveles de C-LDL, con una disminución relativa de 63,9% en los primeros tres meses de tratamiento. Se reportaron bajas tasas de interrupciones por eventos adversos y adecuada persistencia a la medicación. (AU)

Multizonal observational study conducted by clinical practitioners on Repatha® use in patients with hyperlipidemia (ZERBINI): Colombian results.

BACKGROUND: Cardiovascular disease (CVD) represents the primary cause of death and disability globally, with elevated cholesterol as one of the leading risk factors for CVD. We describe the clinical characteristics, treatment patterns, and effectiveness of evolocumab in treating hyperlipidemia. METHODS: Observational study conducted through a chart review of patients with hyperlipidemia receiving evolocumab as part of clinical management in Colombia. RESULTS: This study included 115 patients treated with evolocumab. A total of 101 patients (87.8%) had a history of CVD, 13 (11.3%) familial hypercholesterolemia (FH), and 23 (20%) type 2 diabetes. Thirty-nine patients reported intolerance to any statin (33.9%). The median value of LDL-C before initiation of evolocumab was 147mg/dL (IQR: 122.5-183.7mg/dL). Within the first 3 months of treatment, LDL-C value dropped to a median value of 53mg/dL (IQR: 34.0-95.5mg/dL), showing a reduction of 63.9%. The median LDL-C values remained below 45mg/dL until the end of follow-up. Among the patients with available data, up to 61% achieved an LDL-C level below 55mg/dL at the 10-12-month follow-up. A total of 72% of patients were persistent with treatment. Safety results showed a low frequency of hospitalizations (≤2%) and treatment-emergent adverse drug reactions (5.2%). No serious adverse events were reported. CONCLUSIONS: Evolocumab was associated with reductions in LDL-C levels, with a relative decrease of 63.9% within the first 3 months of treatment. Low rates of interruptions due to adverse events and adequate medication persistence was reported.

Social media as source of information for Spanish-speaking patients with systemic lupus erythematosus.

INTRODUCTION: Although patients with systemic lupus erythematosus (SLE) may benefit from health-care information in social media (SoMe), they may also be prone to misleading information. An assessment of the reliability, comprehensiveness, and quality of information uploaded to SoMe for Spanish-speaking patients with SLE is lacking. METHODS: This analytical observational study evaluates the videos uploaded to YouTube® in Spanish about SLE. Information about video length, engagement (i.e., views and likes), time on the internet, popularity index, and source was retrieved, and an evaluation on reliability, comprehensiveness, and quality was performed using standardized scores. RESULTS: One hundred eighty-six videos were included in the analysis. Most videos were considered as useful (87%) or useful patient opinion (8.1%), whereas only 2.2% were considered misleading and 2.7% as misleading patient opinion. The number of views (Median 7207 vs 113,877, p = .012), popularity index (Median 13.8 vs 168.7, p < .001), number of likes (Median 155 vs 3400, p < .001), and number of dislikes (Median 3 vs 138, p = .004) were higher for misleading videos. The videos uploaded by independent users had a higher engagement than those from government or news agencies, professional organizations or academic channels. Misleading videos and those uploaded by independent users had lower rates of reliability, comprehensiveness and quality (p < .001). CONCLUSIONS: Most of the information shown in YouTube® videos on SLE tends to be useful. However, audience engagement parameters are larger for misleading videos. Exploring the qualitative features of the most popular videos is necessary to establish what features are more engaging for the audiences and to improve the content and popularity of reliable videos on chronic diseases.

Transcriptomics Reveals the Mevalonate and Cholesterol Pathways Blocking as Part of the Bacterial Cyclodipeptides Cytotoxic Effects in HeLa Cells of Human Cervix Adenocarcinoma.

The incidence of human cervix adenocarcinoma (CC) caused by papillomavirus genome integration into the host chromosome is the third most common cancer among women. Bacterial cyclodipeptides (CDPs) exert cytotoxic effects in human cervical cancer HeLa cells, primarily by blocking the PI3K/Akt/mTOR pathway, but downstream responses comprising gene expression remain unstudied. Seeking to understand the cytotoxic and anti-proliferative effects of CDPs in HeLa cells, a global RNA-Seq analysis was performed. This strategy permitted the identification of 151 differentially expressed genes (DEGs), which were either up- or down-regulated in response to CDPs exposure. Database analysis, including Gene Ontology (COG), and the Kyoto Encyclopedia of Genes and Genomes (KEGG), revealed differential gene expression on cancer transduction signals, and metabolic pathways, for which, expression profiles were modified by the CDPs exposure. Bioinformatics confirmed the impact of CDPs in the differential expression of genes from signal transduction pathways such as PI3K-Akt, mTOR, FoxO, Wnt, MAPK, P53, TGF-ß, Notch, apoptosis, EMT, and CSC. Additionally, the CDPs exposure modified the expression of cancer-related transcription factors involved in the regulation of processes such as epigenetics, DNA splicing, and damage response. Interestingly, transcriptomic analysis revealed the participation of genes of the mevalonate and cholesterol biosynthesis pathways; in agreement with this observation, total cholesterol diminished, confirming the blockage of the cholesterol synthesis by the exposure of HeLa cells to CDPs. Interestingly, the expression of some genes of the mevalonate and cholesterol synthesis such as HMGS1, HMGCR, IDI1, SQLE, MSMO1, SREBF1, and SOAT1 was up-regulated by CDPs exposure. Accordingly, metabolites of the mevalonate pathway were accumulated in cultures treated with CDPs. This finding further suggests that the metabolism of cholesterol is crucial for the occurrence of CC, and the blockade of the sterol synthesis as an anti-proliferative mechanism of the bacterial CDPs, represents a reasonable chemotherapeutic drug target to explore. Our transcriptomic study supports the anti-neoplastic effects of bacterial CDPs in HeLa cells shown previously, providing new insights into the transduction signals, transcription factors and metabolic pathways, such as mevalonate and cholesterol that are impacted by the CDPs and highlights its potential as anti-neoplastic drugs.

Effect of biostimulation and bioaugmentation on biodegradation of high concentrations of 1,4-dioxane.

1,4-Dioxane is a pervasive and persistent contaminant in numerous aquifers. Although the median concentration in most contaminant plumes is in the microgram per liter range, a subset of sites have contamination in the milligram per liter range. Most prior studies that have examined 1,4-dioxane concentrations in the hundreds of milligrams per liter range have been performed with industrial wastewater. The main objective of this study was to evaluate aerobic biodegradation of 1,4-dioxane in microcosms prepared with soil and groundwater from a site where concentrations range from ~ 1500 mg·L-1 in the source zone, to 450 mg·L-1 at a midpoint of the groundwater plume, and to 6 mg·L-1 at a down-gradient location. Treatments included biostimulation with propane, addition of propane and a propanotrophic enrichment culture (ENV487), and unamended. The highest rates of biodegradation for each location in the plume occurred in the bioaugmented treatments, although indigenous propanotrophs also biodegraded 1,4-dioxane to below 25 µg·L-1. Nutrient additions were required to sustain biodegradation of propane and cometabolism of 1,4-dioxane. Among the unamended treatments, biodegradation of 1,4-dioxane was detected in the mid-gradient microcosms. An isolate was obtained that grows on 1,4-dioxane as a sole source of carbon and energy and identified through whole-genome sequencing as Pseudonocardia dioxivorans BERK-1. In a prior study, the same strain was isolated from an aquifer in the southeastern United States. Monod kinetic parameters for BERK-1 are similar to those for strain CB1190.

Evaluation of natural attenuation of 1,4-dioxane in groundwater using a 14C assay.

Monitored Natural Attenuation (MNA) is a preferred remedy for sites contaminated with 1,4-dioxane due to its low cost and limited environmental impacts compared to active remediation. Having a robust estimate of the rate at which biodegradation occurs is an essential component of assessing MNA. In this study, an assay was developed using 14C-labeled 1,4-dioxane to measure rate constants for biodegradation based on accumulation of 14C products. Purification of the 14C-1,4-dioxane stock solution lowered the level of 14C impurities to below 1% of the total 14C activity. This enabled determination of rate constants in groundwater as low as 0.0021 yr-1, equating to a half-life greater than 300 years. Of the 54 groundwater samples collected from 10 sites in the US, statistically significant rate constants were determined with the 14C assay for 24. The median rate constant was 0.0138 yr-1 (half-life = 50 yr); the maximum rate constant was 0.367 yr-1 (half-life = 1.9 yr). The results confirmed that biodegradation of 1,4-dioxane is occurring at 9 of the 10 sites sampled, albeit with considerable variability in the level of activity. The specificity of the assay was confirmed using acetylene and the absence of oxygen to inhibit monooxygenases.

Comparison of Performance of the Pediatric Index of Mortality (PIM)-2 and PIM-3 Scores in the Pediatric Intensive Care Unit of a High Complexity Institution.

OBJECTIVE: To determine the performance of each of the available pediatric index of mortality (PIM) scores, by assessing the capability for discrimination and calibration in patients admitted to a pediatric intensive care unit in Bogotá. DESIGN AND SETTING: We designed a retrospective, observational cohort study, which included all patients aged between a month and 17 years and 364 days, admitted to the pediatric intensive care unit of a high complexity university hospital between April 1, 2016 and December 31, 2018. We analyzed the standardized mortality ratio, discrimination, calibration, and net reclassification index (NRI) for each model. RESULTS: A total of 722 patients were included, the mortality rate was 3.74%, and for PIM-3, the ratio between expected and observed mortality was 0.66 [confidence interval (CI) 0.40-1.05] for PIM-2 and 1.00 (CI 0.59-1.68) for PIM-3. The Hosmer-Lemeshow (HL) test suggests inadequate calibration for PIM-2 (HL = 13.18, p = 0.11) and adequate calibration for PIM-3 (HL = 28.08, p < 0.01). The area under the diagnostic performance curves for PIM-2 and PIM-3 were 0.87 (95% CI 0.80-0.94) and 0.89 (95% CI 0.82-0.95), respectively. The NRI was -27.1%. PIM-3 classified survivors better than PIM-2, but inadequately classified nonsurvivors. CONCLUSION: Although both models show adequate discrimination ability, PIM-3 shows a better correlation between predicted risk score and observed mortality. Thus, it may be a useful tool for measuring the internal processes of intensive care units in Colombia and for making comparisons between groups of similar characteristics. HOW TO CITE THIS ARTICLE: Quiñónez-López D, Patino-Hernandez D, Zuluaga CA, García ÁA, Muñoz-Velandia OM. Comparison of Performance of the Pediatric Index of Mortality (PIM)-2 and PIM-3 Scores in the Pediatric Intensive Care Unit of a High Complexity Institution. Indian J Crit Care Med 2020;24(11):1095-1102.

MEDIATOR18 influences Arabidopsis root architecture, represses auxin signaling and is a critical factor for cell viability in root meristems.

The Mediator (MED) complex plays a key role in the recruitment and assembly of the transcription machinery for the control of gene expression. Here, we report on the role of MEDIATOR18 (MED18) subunit in root development, auxin signaling and meristem cell viability in Arabidopsis thaliana seedlings. Loss-of-function mutations in MED18 reduce primary root growth, but increase lateral root formation and root hair development. This phenotype correlates with alterations in cell division and elongation likely caused by an increased auxin response and transport at the root tip, as evidenced by DR5:GFP, pPIN1::PIN1-GFP, pPIN2::PIN2-GFP and pPIN3::PIN3-GFP auxin-related gene expression. Noteworthy, med18 seedlings manifest cell death in the root meristem, which exacerbates with age and/or exposition to DNA-damaging agents, and display high expression of the cell regeneration factor ERF115. Cell death in the root tip was reduced in med18 seedlings grown in darkness, but remained when only the shoot was exposed to light, suggesting that MED18 acts to protect root meristem cells from local cell death, and/or in response to root-acting signal(s) emitted by the shoot in response to light stimuli. These data point to MED18 as an important component for auxin-regulated root development, cell death and cell regeneration in root meristems.

Draft Genome Sequence of the 1,4-Dioxane-Degrading Bacterium Pseudonocardia dioxanivorans BERK-1.

Pseudonocardia dioxanivorans strain BERK-1 grows aerobically with 1,4-dioxane as its sole substrate. Reported here is its draft genome sequence, with a size of 7.1 Mbp. Key genes are highlighted in this article. BERK-1 exhibits a reduced level of cell aggregation and adherence to surfaces compared to those of P. dioxanivorans CB1190, giving it an apparent advantage for movement through soil.

Insights on Structure and Function of a Late Embryogenesis Abundant Protein from Amaranthus cruentus: An Intrinsically Disordered Protein Involved in Protection against Desiccation, Oxidant Conditions, and Osmotic Stress.

Late embryogenesis abundant (LEA) proteins are part of a large protein family that protect other proteins from aggregation due to desiccation or osmotic stresses. Recently, the Amaranthus cruentus seed proteome was characterized by 2D-PAGE and one highly accumulated protein spot was identified as a LEA protein and was named AcLEA. In this work, AcLEA cDNA was cloned into an expression vector and the recombinant protein was purified and characterized. AcLEA encodes a 172 amino acid polypeptide with a predicted molecular mass of 18.34 kDa and estimated pI of 8.58. Phylogenetic analysis revealed that AcLEA is evolutionarily close to the LEA3 group. Structural characteristics were revealed by nuclear magnetic resonance and circular dichroism methods. We have shown that recombinant AcLEA is an intrinsically disordered protein in solution even at high salinity and osmotic pressures, but it has a strong tendency to take a secondary structure, mainly folded as α-helix, when an inductive additive is present. Recombinant AcLEA function was evaluated using Escherichia coli as in vivo model showing the important protection role against desiccation, oxidant conditions, and osmotic stress. AcLEA recombinant protein was localized in cytoplasm of Nicotiana benthamiana protoplasts and orthologs were detected in seeds of wild and domesticated amaranth species. Interestingly AcLEA was detected in leaves, stems, and roots but only in plants subjected to salt stress. This fact could indicate the important role of AcLEA protection during plant stress in all amaranth species studied.

Evaluación de los criterios apropiados para la indicación de ecocardiografía de estrés en un centro cardiovascular de referencia / Assessment of the appropriateness criteria for the indication of stress echocardiography in a cardiovascular reference center

Reseña: El propósito de este estudio es evaluar la aplicación clínica e indicación de los criterios apropiados para la ecocardiografía de estrés de acuerdo a la Fundación del Colegio Americano de Cardiología/Sociedad Americana de Ecocardiografía, en la práctica diaria de un centro cardiovascular de referencia. Materiales y métodos: Fueron incluidos los estudios consecutivos realizados entre enero de 2012 y julio de 2013. Los datos fueron revisados, analizados y clasificados por cuatro cardiólogos expertos teniendo en cuenta: la demografía, la especialidad que refiere, la indicación primaria y su clasificación final como apropiados, inapropiados o inciertos. Resultados: Un total de 1.556 estudios fueron incluidos inicialmente, 450 fueron excluidos por estar relacionados con programas de trasplante de órgano sólido y en 170 no se pudo determinar una indicación clara para el estudio. Los 936 estudios restantes (85%) fueron analizados para la determinación de criterios apropiados. De estos 679 (73%) tenían una indicación apropiada, 70 (7%) eran inciertos y 187 (20%) fueron inapropiados. Cuatrocientos veintiocho (46%) fueron referidos por medicina interna, 375 (40%) por cardiología, 51 (5%) por anestesiología y 82 (10%) por medicina general y otras especialidades. Un total de 159 (17%) estudios arrojaron un resultado anormal, todos ellos estaban apropiadamente indicados, ninguno fue anormal en los inapropiadamente indicados. Conclusiones: La revisión de la aplicación de los criterios apropiados para la ecocardiografía de estrés no solo permite una implementación clínica efectiva en un centro cardiovascular de referencia, sino que también estratifica razonablemente la posibilidad de tener un resultado anormal en aquellos con una indicación apropiada. Sin embargo, esto debería validarse extensamente en una cohorte multicéntrica.

Background: The purpose of this study is to evaluate the clinical application and assessment of appropriate criteria for the indication of stress echocardiograms according to the American College of Cardiology Foundation/American Society of Echocardiography in daily clinical practice at a cardiovascular reference center. Materials and methods: All consecutive studies carried out between January 2012 and July 2013 were included. The data was reviewed, analyzed and classified by four expert cardiologists regarding issues such as demography, referred specialty, primary indication and its final classification as appropriate, inappropriate or uncertain. Results: A total of 1,556 studies were initially included, 450 which were excluded as being related to program of solid organ transplantation and 170 as no clear indication of the study could be determined. Therefore, the remaining 936 were analyzed for the evaluation of appropriateness criteria. Of these 679 (73%) had appropriate indication, 70 (7%) were uncertain and 187 (20%) inappropriate. 428 (46%) were referred by internal medicine, 375 (40%) by cardiology, 51 (5%) by anesthesiology and 82 (10%) by general medicine and other specialties. A total of 159 (17%) studies rendered an abnormal result, all of them which were properly indicated, and no one was abnormal in the inappropriately indicated. Conclusions: Reviewing appropriateness criteria for SE not only allows an effective characterization and clinical performance in a single center, but also reasonably stratifies the possibility of having an abnormal result in those with an appropriate indication. However, this should be validated extensively in a multicenter cohort.

Efecto de las resinas secuestradoras de ácidos biliares en los desenlaces cardiovasculares y en los niveles séricos de lípidos: A systematic review / Effect of bile acid sequestrants on cardiovascular outcomes and seric lipids

Antecedentes: Las guías internacionales recientes proponen el uso de estatinas como piedra angular del manejo de la dislipidemia en adultos. Sin embargo, no se ha definido con claridad el tratamiento de los pacientes con intolerancia o efectos adversos asociados con estas. Las resinas secuestradoras de ácidos biliares son una alternativa interesante, pese a que la evidencia que avala su uso no ha sido evaluada cuidadosamente. Métodos: Se realizó una búsqueda de la literatura en MEDLINE, Embase y en la Biblioteca Cochrane hasta junio de 2013, acerca de artículos publicados en inglés y español, identificando experimentos clínicos aleatorizados y estudios de cohortes que evaluaran el impacto de las resinas secuestradoras de ácidos biliares en mortalidad, eventos cardiovasculares, niveles de lípidos séricos y efectos adversos. Se presenta la información de forma descriptiva. Resultados: Se identificaron cuatro experimentos clínicos aleatorizados y un estudio de cohortes, que incluían 6.833 pacientes. Solo uno de los estudios evaluó el impacto en la mortalidad cardiovascular, evidenciando que no hay diferencia estadísticamente significativa en comparación con placebo (RR de 0,76; IC 95% 0,5:1,15), aunque se observó una reducción del 16% en la incidencia de infarto agudo de miocardio (RR 0,84; IC 95% 0,67:1,00). Tres estudios evaluaron cambios en las fracciones lipídicas, los cuales mostraron disminución moderada en los niveles de colesterol LDL, sin percibir diferencias clínicamente significativas en los niveles de colesterol HDL y triglicéridos. Conclusión: La evidencia que respalda el uso de resinas secuestradoras de ácidos biliares es limitada y no avala su empleo como terapia de primera línea en pacientes con dislipidemia; no obstante, son una alternativa en pacientes con efectos adversos o intolerancia al manejo con estatinas.

Background: Recent international guidelines have proposed statins as the corner stone of dyslipidemia management in adults. However it is not clear if they are best option for patients with statin related intolerance or what their adverse effects are. The bile acid sequestrants are an interesting alternative, however its evidence has not been carefully evaluated. Methods: A search was conducted on MEDLINE, Embase and Cochrane library databases for articles published up to June 2013, limited to Spanish and English language. Randomized clinical trials (RCT) and cohort studies evaluating the impact of bile acid sequestrants on mortality, cardiovascular outcomes, seric lipids and adverse effects were selected. Information was presented in a descriptive way. Results: Four RCT and one cohort study with aggregate data on 6833 people were included. Just one study evaluated cardiovascular mortality showing no statistically significant difference when compared with placebo, (RR 0.76; 95% CI 0.5:1.15), however there was a 16% reduction on acute myocardial infarction incidence. (RR 0.84; 95% IC 0.67: 1.00). Three studies evaluated seric lipids changes showing a moderate reduction in LDL levels without clinical significant differences on HDL and triglyceride levels. Conclusions: The evidence supporting bile acid sequestrants use is lacking and not conclusive to recommend its use as first-line therapy in dyslipidemic patients; however, these are an alternative option for patients with statin-related intolerance or adverse effects.

Guía de práctica clínica para la prevención, detección temprana, diagnóstico, tratamiento y seguimiento de las dislipidemias: evaluación del riesgo cardiovascular / Clinical practice guidelines for the prevention, early detection, diagnosis, treatment and follow up of dyslipidemia: cardiovascular risk assessment

Objetivo: El tratamiento de la dislipidemia debe ser acorde con el riesgo individual de cada paciente. Existen múltiples ecuaciones de predicción de riesgo cardiovascular, sin embargo, es necesario determinar cuál es la más adecuada para ser utilizada en la población colombiana. Métodos: La alianza CINETS, comisionada por el Ministerio de la Protección Social y Colciencias, revisó la evidencia disponible con respecto a qué métodos de evaluación de riesgo cardiovascular son válidos en la población colombiana. Se generaron recomendaciones utilizando la metodología GRADE. Población: Población adulta con diagnóstico de dislipidemia o en riesgo de desarrollarla. Recomendaciones: En la población de prevención primaria o sin enfermedad cardiovascular clínicamente manifiesta se recomienda utilizar la escala de Framingham recalibrada para Colombia para clasificar el riesgo (Recomendación fuerte a favor de la intervención). Existen personas con condiciones que por sí mismas implican un riesgo mayor y ameritan manejo farmacológico directo.

Aim: The treatment of dyslipidemia must be related with patient's individual risk. There are multiple functions for predicting cardiovascular risk; however, it is necessary to determine the most appropriate for being used in Colombian population. Methods: The CINETS alliance, endorsed by the Colombian Social Protection Ministry and Colciencias, reviewed the evidence available about the validity of cardiovascular risk evaluation methods in Colombian Population. Recommendations were generated using GRADE methodology. Population: General adult population with or at risk of dyslipidemia. Recommendations In primary prevention population, or without clinically evident cardiovascular disease, Framingham risk function recalibrated for Colombia must be used to calculate cardiovascular risk (Strong recommendation). In patients with an especial condition increasing cardiovascular risk, direct pharmacologic treatment must be used.

Ensayo clínico aleatorizado de la comparación entre método de enseñanza tradicional y escenario simulado para la adquisición de competencias en el reconocimiento de signos de enfermedad respiratoria aguda en pacientes pediátricos / Randomized clinical trial to compare the traditional teaching method and the simulated-scenario teaching © 2015 FEM method in the acquisition of skills for the identification of acute respiratory disease signs in paediatric patients

INTRODUCCIÓN: La infección respiratoria aguda es un problema de salud pública en menores de 5 años; la detección e identificación tempranas de sus signos disminuye la mortalidad en este grupo de edad y es una meta de la formación médica. OBJETIVO: Comparar en estudiantes de medicina el método educativo tradicional y el escenario simulado para el reconocimiento de signos de enfermedad respiratoria aguda en niños de 2 meses a 5 años. SUJETOS Y MÉTODOS: Se realizó un ensayo clínico para estudiantes de medicina, aleatorizados en dos grupos: A (clase teórica y ayudas audiovisuales) y B (escenario simulado). El desenlace primario fue el desempeño en la evaluación global. Se realizó prueba de Mann-Withney Wilcoxon para comparación entre grupos y Mann-Withney Wilcoxon pareada para análisis intragrupo (antes y después de la intervención). RESULTADOS: Mediante prueba de Mann-Withney Wilcoxon pareada intragrupo pre y postintervención, el grupo A mostró mejor un desarrollo de competencias en el desenlace primario (p = 0,02) y en la evaluación global del escenario simulado (p = 0,04). El grupo B logró cambios significativos en el desenlace primario (p = 0,00), la anamnesis (p = 0,00) y la evaluación global del escenario simulado (p = 0,00). En la evaluación postintervención no se encontraron diferencias significativas en el desenlace primario ni secundario. CONCLUSIONES. La comparación postintervención entre los grupos A y B no mostró diferencias significativas en ninguna de las variables estudiadas entre ambos grupos

INTRODUCTION: The acute respiratory infection is a public health problem in children under 5 years of age. The early detection and identification of its signs reduces the mortality rates in these age groups and is an objective in medical education. AIM. To compare the traditional teaching method with the simulated-scenario teaching method in the acquisition of skills necessary to recognize respiratory distress in children between 2 months and 5 years of age by medical students. SUBJECTS AND METHODS: A clinical trial was done for medical students and they were divided into two randomized groups: group A which used the traditional teaching method and group B, which used the simulated-scenario method. The primary outcomes were seen in the global evaluation performances. A Mann-Withney Wilcoxon test was used for the comparison among groups and a paired Mann-Withney Wilcoxon test was used for the intra-group analysis (before and after the intervention). RESULTS: When using the paired Mann-Withney Wilcoxon intragroup test pre and post intervention, group A showed a better skill development in the primary outcome (p = 0.02) and the global evaluation in simulated scenario (p = 0.04). On the other hand, group B reached significant changes on the primary outcomes (p = 0.00), anamnesis (p = 0.00) and global evaluation with the simulated-scenario method (p = 0.00). It was observed that in the post-intervention evaluation there weren’t any significant differences between the primary and secondary outcomes. CONCLUSIONS: The post-intervention comparison between groups A and B didn’t show significant differences in the studied variables between both groups

Alternativas terapéuticas al manejo farmacológico con estatinas en adultos con dislipidemia. Revisión sistemática de la literatura y recomendaciones generales / Therapeutic alternatives to pharmacological management with statin drugs in adults with dyslipidemia. Systematic literature review and general recommendations

Objetivo: Evaluar el impacto sobre la incidencia y recurrencia de eventos cardiovasculares y cerebrovasculares (prevención primaria y secundaria), los niveles de las fracciones lipídicas y la incidencia de efectos secundarios en personas con hipercolesterolemia intolerantes al tratamiento con las estatinas. Métodos: Se elaboró una guía de práctica clínica siguiendo los lineamientos de la guía metodológica del Ministerio de Salud y Protección Social para recolectar de forma sistemática la evidencia científica y formular las recomendaciones utilizando la metodología GRADE. Población Población adulta, con diagnóstico de dislipidemia, o en riesgo de desarrollarla, intolerantes al manejo con las estatinas. Recomendaciones: Se formulan recomendaciones a favor del uso de diferentes medicamentos (los fibratos, la niacina, los ácidos omega 3, las resinas secuestradoras de ácidos biliares, el ezetimibe), según su efectividad hipolipemiante y reducción de eventos cardiovasculares, como propuesta adaptada al contexto social colombiano.

Objective To evaluate the impact on the incidence and recurrence of cardiovascular and cerebrovascular events (primary and secondary prevention), the levels of lipid fractions and the incidence of side effects in people with hypercholesterolemia intolerant to statin therapy. Methods: A clinical practice guideline was developed following the guidelines of the methodological guidance of the Ministry of Health and Social Protection to systematically collect the evidence and make recommendations using the GRADE methodology. Population: Adult population, diagnosed with dyslipidemia or at risk of developing, intolerant to management with statin drugs. Recommendations: Recommendations for the use of different medications (fibrates, niacin, omega 3 acids, bile acid binding resins, ezetimibe) are formulated according to their lipid-lowering effectiveness and reduction of cardiovascular events, a proposal adapted to the Colombian social context.

Validación de la escala CRUSADE para evaluar el riesgo de sangrado en pacientes con infarto agudo de miocardio sin elevación del ST / Validation of the CRUSADE scale to assess the risk of bleeding in patients with acute myocardial infarction without ST elevation

Objetivo: Evaluar si la escala CRUSADE es aplicable en la comunidad colombiana. Métodos:Se realizó un estudio de validación externa dentro de una cohorte histórica, en el que se incluyeron pacientes hospitalizados entre los años 2006 y 2012 en el Hospital Universitario San Ignacio, en Bogotá, Colombia. Se tomaron historias clínicas de pacientes mayores de 18 años, que tuvieran asignado el diagnóstico de infarto agudo de miocardio sin supradesnivel del ST. Se comparó el número de eventos (sangrado) predichos y observados durante la hospitalización (calibración). Finalmente, se estimó la capacidad para separar sujetos de alto y bajo riesgo (discriminación). Resultados: Se incluyeron 252 pacientes. El número de eventos mayores fue 30 (11,9%) y el de eventos menores 23 (9,12%); 12 pacientes (7,46%) fallecieron. En el grupo de muy alto riesgo (más de 50 puntos de la escala), se reportó el mayor número de eventos (respecto a la población estudiada). Al evaluar la escala se evidenció una buena capacidad de calibración (X² p = 0,84); sin embargo, la discriminación no fue adecuada (área bajo la curva 0,6128 {IC 95% 0,46-0,76}). Conclusiones: Se encontraron pocos eventos, si bien los datos sugieren que la escala subestima levemente los riesgos. La escala tiene buena calibración, pero no posee capacidad de discriminación adecuada, hecho que probablemente obedece a que se obtuvo un pequeño número de eventos, con desviaciones estándar altas. Por tanto, se requieren estudios adicionales, con mayor poder estadístico.

Objective: To assess whether CRUSADE scale is applicable in the Colombian community. Methods: A study of external validation in a historical cohort, which included patients hospitalized between 2006 and 2012 in the Hospital Universitario San Ignacio in Bogota Colombia, was performed. Medical records of patients older than 18 years, who had been diagnosed as acute myocardial infarction without ST segment elevation, were included. The number of events (bleeding) predicted and observed during hospitalization (calibration) were compared. Finally, the ability to separate subjects at high and low risk (discrimination) was estimated. Results:252 patients were included. The number of major events was 30 (11.9%) and that of minor events 23 (9.12%); 12 patients (7.46%) died. In the group of very high risk (more than 50 points on the scale), the largest number of events (regarding the study population) was reported. At assessing the scale, a good calibration capacity was evidenced (X² p = .84); however, discrimination was not adequate (0.6128 AUC {95% CI 0.46 to 0.76}). Conclusions Few events were found, although the data suggest that the scale slightly underestimates the risks. The scale has good calibration, but lacks adequate discriminatory capacity, probably due to the fact that a small number of events with high standard deviations were obtained. Therefore, further studies with greater statistical power are required.

Costo-efectividad de las estatinas para el tratamiento de dislipidemia en Colombia / Cost-effectiveness of statins for the treatment of dyslipidemia in Colombia

Objetivo: determinar la relación de costo-efectividad relativa de las estatinas entre sí en pacientes adultos con dislipidemia con predominio de hipercolesterolemia para la prevención de eventos cardiocerebrovasculares, en Colombia, desde la perspectiva del sistema de salud colombiano. Métodos: se construyó un modelo de Markov con años de vida ajustados por calidad (AVAC) ganados como desenlace principal, tasa de descuento de 3% tanto para costos como desenlaces, y cinco años de horizonte temporal. Probabilidades y costos se extrajeron de la literatura y de fuentes oficiales del país, respectivamente. El umbral de costo-efectividad fue tres veces el PIB per cápita de 2012. Se realizaron análisis de sensibilidad univariados, probabilísticos, umbral y curva de aceptabilidad. Resultados: el costo promedio del tratamiento con estatinas para un paciente con dislipidemia en cinco años es de $3 472 733. La ganancia en AVAC en rosuvastatina fue mayor con respecto a las otras estatinas; sin embargo, es la estrategia más costosa. La atorvastatina, que resultó segunda, es la más costo-efectiva. Conclusión: la intervención más costo-efectiva para pacientes con dislipidemia con predominio de hipercolesterolemia e indicación de manejo farmacológico con terapia moderada y alta con estatinas en Colombia es la atorvastatina. (Acta Med Colomb 2015; 40: 118-124).

Objective: to determine the relative cost-effectiveness among statins in adult patients with dyslipidemia with predominant hypercholesterolemia to prevent cardiocerebrovascular events in Colombia, from the perspective of Colombian health system. Methods: a Markov model with quality-adjusted life years (QALY) gained as the main outcome, discount rate of 3% for both costs and outcomes, and five-year time horizon was built. Probabilities and costs were extracted from the literature and from official sources in the country, respectively. The threshold for cost-effectiveness was three times the 2012 per capita GDP. Univariate probabilistic, sensitivity analysis, threshold and acceptability curve were performed. Results: the average cost of statin therapy for a patient with dyslipidemia in five years is $3 472 733. The QALY gain was higher in rosuvastatin compared to other statins, however, it is the most costly strategy. Atorvastatin, which was second, is the most cost-effective. Conclusion: the most cost-effective intervention for patients with dyslipidemia with predominant hypercholesterolemia and indication of pharmacological management with moderate and high statin therapy in Colombia is atorvastatin. (Acta Med Colomb 2015; 40: 118-124).

Urinary biomarkers of kidney diseases in HIV-infected children.

A significant number of children infected with the human immunodeficiency virus 1 (HIV-1) virus all over the world are at risk of developing renal diseases that could have a significant impact on their treatment and quality of life. It is necessary to identify children undergoing the early stages of these renal diseases, as well as the potential renal toxicity that could be caused by antiretroviral drugs, in order to prevent the development of cardiovascular complications and chronic renal failure. This article describes the most common renal diseases seen in HIV-infected children, as well as the value and limitations of the clinical markers that are currently being used to monitor their renal function and histological damage in a noninvasive manner. In addition, we discuss the progress made during the last 10 years in the discovery and validation of new renal biomarkers for HIV-infected children and young adults. Although significant progress has been made during the early phases of the biomarkers discovery, more work remains to be done to validate the new biomarkers in a large number of patients. The future looks promising, however, the new knowledge needs to be integrated and validated in the context of the clinical environment where these children are living.

Guía de práctica clínica para la prevención, detección temprana, diagnóstico, tratamiento y seguimiento de las dislipidemias: tratamiento farmacológico con estatinas / Clinical practice guidelines for prevention, early detection, diagnose, treatment and follow-up of dyslipidemias: farmacological treatment with statins

Objetivo: Evaluar el impacto del tratamiento con estatinas sobre la incidencia y la recurrencia de los eventos cardiovasculares y los cerebrovasculares (prevención primaria y secundaria), los niveles de las fracciones lipídicas y la incidencia de efectos secundarios (el cáncer y la diabetes mellitus) en personas con hipercolesterolemia. Métodos: Se elaboró una guía de práctica clínica siguiendo los lineamientos de la guía metodológica del Ministerio de Salud y Protección Social para recolectar de forma sistemática la evidencia científica y formular las recomendaciones utilizando la metodología GRADE. Resultados: Se evidenció un efecto benéfico del tratamiento farmacológico con estatinas tanto en población de prevención primaria como en prevención secundaria, logrando reducciones clínica y estadísticamente significativas en la mortalidad y en los eventos cardiovasculares y cerebrovasculares. Adicionalmente, el tratamiento intensivo con estatinas mostró mayor reducción en los eventos cardiovasculares y cerebrovasculares ateroscleróticos al compararlo con el tratamiento de intensidad moderada. No se encontraron diferencias significativas en el riesgo de desarrollar cáncer al comparar estatinas frente a placebo pero sí se encontró un incremento de nueve por ciento en el riesgo de presentar diabetes mellitus asociado al tratamiento con estatinas. Conclusiones: Se formulan recomendaciones a favor del uso de estatinas como primera línea de tratamiento de hipercolesterolemia, y se establecen criterios para definir la intensidad de la terapia (alta o moderada respuesta) según el riesgo cardiovascular a 10 años, el nivel de colesterol LDL (cLDL), la edad y los antecedentes personales y los familiares.

Objective: To evaluate the impact of statin therapy on the incidence and recurrence of cardiovascular and cerebrovascular events (primary and secondary prevention), the levels of lipid fractions and the incidence of side effects (cancer and diabetes mellitus) in people with hypercholesterolemia. Methods: A clinical practice guideline was developed following the guidelines of the methodological guidance of the Ministry of Health and Social Protection to systematically collect the evidence and make recommendations using the GRADE methodology. Results: A beneficial effect of pharmacological treatment with statins in both primary prevention and secondary prevention was evident, achieving clinically and statistically significant reductions in mortality and cardiovascular and cerebrovascular events. Additionally, intensive statin therapy showed greater reduction in atherosclerotic cardiovascular and cerebrovascular events as compared to the treatment of moderate intensity. No significant differences in the risk of developing cancer by comparing statins versus placebo were found, but a 9% increase in the risk of diabetes mellitus associated with statin therapy was found. Conclusions: Recommendations for the use of statins as first-line treatment of hypercholesterolemia are formulated, and criteria to define the intensity of therapy (high or moderate response) as cardiovascular risk at 10 years, level of LDL (LDLc), age and personal and family history were established.

Differentiation of Salmonella strains from the SARA, SARB and SARC reference collections by using three genes PCR-RFLP and the 2100 Agilent Bioanalyzer.

Rapid molecular typing methods are important tools in surveillance and outbreak investigations of human Salmonella infections. Here we described the development of a three-genes PCR-RFLP typing method for the differentiation of Salmonella species, subspecies and serovars using the Agilent 2100 Bioanalyzer. The fliC, gnd, and mutS genes were PCR-amplified in 160 Salmonella strains representing the two Salmonella species, six subspecies, and 41 different serovars of S. enterica subspecies enterica. PCR products were individually cut with two different restriction enzymes and the resulting 930 restriction patterns were collected using the Agilent 2100 Bioanalyzer followed by cluster analysis. Both species of Salmonella were differentiated by conventional PCR. All of S. bongori tested were gnd PCR negative due to a mismatch at the 3'-end in one the PCR primers. Salmonella subspecies were differentiated into third-teen homogeneous groups representing each of the six subspecies by cluster analysis of restriction patterns generated from the mutS gene cut with AciI. S. enterica subspecies enterica serovars were further differentiated by the combination of the three target genes and five out the six sets of restriction patterns with a discriminatory power of 0.9725 by cluster analysis. The combined RFLP results of five sets of restriction patterns allowed us to assign each of the 160 strains to one of 128 restriction types. During inoculation studies we were able to identify S. Saintpaul and Typhimurium from 24 h pre-enrichment samples using the described method. The use of fliC, gnd, and mutS PCR-RFLP with the Agilent 2100 Bioanalyzer can provide an accessible and automated alternative method for differentiation of Salmonella pathogens.