Resumen Las frutillas como zarzamoras, frambuesas, arándanos y fresas son ricas en compuestos fenólicos, metabolitos secundarios biosintetizados como resultado de la evolución de las plantas terrestres para hacer frente a los desafíos ambientales; en particular, las especies silvestres suelen tener características que les permiten adaptarse a ambientes adversos. El objetivo de este trabajo fue evaluar el potencial nutracéutico de genotipos silvestres del género Rubus, mediante la determinación de sus propiedades antioxidantes, para su posible inclusión en programas de mejoramiento genético. El contenido de fenoles, flavonoides y antocianinas totales, así como la capacidad antioxidante, por los ensayos ABTS y FRAP, fueron cuantificados en extractos polares de frutos correspondientes a seis zarzamoras: Rubus glaucus, la variedad Tupy, una muestra comercial y tres silvestres (Hidalgo 2.3, Hidalgo 2.4 y Chiapas 1) y una frambuesa (Rubus niveus). La concentración de compuestos fenólicos en las especies se encontró en el intervalo de 9.67 ± 0.47 a 17.81 ± 0.54 mg g-1 equivalentes de ácido gálico (EAG) en peso seco (PS), los flavonoides totales de 2.28 ± 0.20 a 10.27 ± 0.58 mg g-1 equivalentes de catequina (EC) en PS y antocianinas totales de 0.88 ± 0.05 a 19.19 ± 0.65 mg g-1 equivalentes de cianidina-3-glucósido EC3G en PS. Los valores de la capacidad antioxidante fueron de 715.09 ± 25.22 a 1357.29 ± 20.76 y de 19.67 ± 0.94 a 93.5 ± 6.03 µmol g-1 equivalentes de trolox (ET) en PS para los ensayos ABTS y FRAP, respectivamente. Se encontró que los genotipos silvestres, denominados Hidalgo 2.3 y Chiapas 1, presentaron las concentraciones más altas de compuestos fenólicos y, por lo tanto, una mayor capacidad antioxidante. Considerando que estos compuestos protegen a las plantas contra factores bióticos y abióticos adversos dentro de su ecosistema, los genotipos silvestres Hidalgo 2.3 y Chiapas 1 son candidatos para la selección en programas de mejoramiento genético.

Summary Berries such as blackberries, raspberries, blueberries and strawberries are rich in phenolic compounds, secondary metabolites biosynthesized as a result of the evolution of terrestrial plants to cope with environmental challenges. In particular, wild species often have characteristics that allow them to adapt to adverse environments. The objective of this study was to evaluate the nutraceutical potential of wild genotypes of the genus Rubus, by determining their antioxidant properties, for possible inclusion in breeding programs. The content of phenols, flavonoids and total anthocyanins, as well as the antioxidant capacity, by ABTS and FRAP assays, were quantified in polar extracts of fruits corresponding to six blackberries: Rubus glaucus, the Tupy variety, one commercial sample and three wild ones (Hidalgo 2.3, Hidalgo 2.4 and Chiapas 1) and one raspberry (Rubus niveus). The concentration of phenolic compounds in the especies was found in the range of 9.67 ± 0.47 to 17.81 ± 0.54 mg g-1 gallic acid (GAE) equivalents in dry weight (DW), total flavonoids from 2.28 ± 0.20 to 10.27 ± 0.58 mg g-1 mg catechin equivalents (CE) in DW, and total anthocyanins of 0.88 ± 0.05 to 19.19 ± 0.65 mg g-1 of cyanidin-3-glucoside (C3GE) equivalents in DW. The antioxidant capacity values were from 715.09 ± 25.22 to 1357.29 ± 20.76 and from 19.67 ± 0.94 to 93.5 ± 6.03 µmol g-1 of trolox equivalents (TE) in DW for ABTS and FRAP assays, respectively. Wild genotypes named Hidalgo 2.3 and Chiapas 1, were found to have the highest concentrations of phenolic compounds, and therefore, higher antioxidant capacity. Considering that these compounds protect plants against adverse biotic and abiotic factors within their ecosystem, the wild genotypes Hidalgo 2.3 and Chiapas 1 are candidates for selection in breeding programs.

Abstract For centuries, cannabis has been used with many different purposes, including medicinal use, usually bypassing any formal approval process. However, during the last decade, interest in cannabis in medicine has been increasing, and several countries, including the United States and Canada, have produced their own legislation about marihuana and cannabis-based medicines. Because of this, interest in research has been increasing and evidence about its medical effects is becoming necessary. We conducted a review examining the evidence of cannabis in pain. Cannabis had been shown to be useful in acute and chronic pain, however recently, these results have been controverted. Within the different types of chronic pain, it has a weak evidence for neuropathic, rheumatic pain, and headache, modest evidence for multiple sclerosis related pain, and as adjuvant therapy in cancer pain. There is no strong evidence to recommend cannabis in order to decrease opioids in patients with chronic use. Even though cannabis-based medications appear to be mostly safe, mild adverse effects are common; somnolence, sedation, amnesia, euphoric mood, hyperhidrosis, paranoia, and confusion may limit the use of cannabis in clinical practice. Risks have not been systematically analyzed. Special concern arises on how adverse effect might affect vulnerable population such as elderly patients. More research is needed in order to evaluate benefits and risks, as well as the ideal administration route and dosages. As cannabis use increases in several countries, answers to these questions might be coming soon.

RESUMEN INTRODUCCIÓN: Natalizumab es un anticuerpo monoclonal humanizado empleado en el tratamiento de esclerosis múltiple, la enfermedad crónica e inflamatoria más prevalente del sistema nervioso central. El estado de NEDA (sin evidencia de actividad de la enfermedad) es el objetivo del tratamiento de la esclerosis múltiple. METODOLOGÍA: Se analizaron las historias clínicas de 22 pacientes con esclerosis múltiple que fueron seguidos durante una media de 9,2 años (rango: 1,9-18,3 años) entre 2000 y 2018. Estos pacientes recibieron tratamiento con natalizumab en una clínica ambulatoria neurológica de alta complejidad en Bogotá, Colombia. RESULTADOS: Dieciocho pacientes (82)% alcanzaron el estado NEDA en un tiempo medio de seis meses. Siete pacientes (32%) dieron positivo para anticuerpos anti-virus JC. Sin embargo, ninguno desarrolló leucoencefalopatía multifocal progresiva. Durante el periodo de seguimiento cinco pacientes (23%) presentaron nuevas lesiones y 17 pacientes (77%) tuvieron recaídas antes de alcanzar el estado NEDA. CONCLUSIONES: Este estudio provee un análisis exploratorio de las características de una serie de pacientes colombianos con esclerosis múltiple.. En el análisis retrospectivo, se observó que más de 80% de ellos alcanzó el estado NEDA. A pesar de las limitaciones metodológicas inherentes al tipo de estudio y el tamaño de la muestra, este estudio sugiere que natalizumab podría ser un medicamento apropiado para el tratamiento de la esclerosis múltiple. en Colombia.

SUMMARY INTRODUCTION: Natalizumab is a humanized monoclonal antibody prescribed in the treatment of multiple sclerosis, the most prevalent chronic and inflammatory disease of the central nervous system (CNS). NEDA (no evidence of disease activity) status is the goal of multiple sclerosis treatment. METHODOLOGY: The clinical records of 22 patients with multiple sclerosis, followed for a mean of 9.2 years (range: 1.9 -18.3 years) between 2000 and 2018 were analyzed. These patients received treatment with natalizumab in a high-complexity neurological outpatient clinic in Bogotá, Colombia. RESULTS: Eighteen patients (82%) reached NEDA status within a median time of six months. Seven patients (32%) tested positive for anti-JC virus antibodies. However, none of them developed progressive multifocal leukoencephalopathy. During the evaluation period, five patients (23%) presented new lesions and 17 patients (77%) had relapses before reaching NEDA status. CONCLUSIONS: This study gave an exploratory analysis of the characteristics of a series of patients with MS in the Colombian context. In the retrospective analysis, it was observed that more than 80% of the studied sample that received treatment with natalizumab, reached NEDA status. Despite the methodological limitations inherent to this type of study and sample size, it suggests that natalizumab could be an appropriate medication for the management of multiple sclerosis in Colombia.

RESUMEN La epilepsia es un desorden neurológico común que afecta aproximadamente al 1% de la pobla-ción mundial. Alrededor de un tercio de los pacientes sufren de epilepsia resistente al tratamiento, que se define como la falla de parar las crisis epilépticas a pesar de haber recibido tratamiento con dos medicamentos a dosis terapéuticas. Se ha visto interés en el desarrollo de medicamentos antiepilépticos con dife-rentes mecanismos de acción. Esta revisión narrativa se basó en 42 referencias extraídas de Scopus y Medli-ne, que discuten hallazgos científicos sobre estudios en humanos y animales acerca de la eficacia del cannabis para el tratamiento de epilepsia. Los beneficios se des-cribieron en estudios preclínicos y clínicos en niños, sin embargo investigaciones en curso clarificarán el papel real de los cannabinoides para la epilepsia resistente al tratamiento.

SUMMARY Epilepsy is a common neurological disorder that affects approximately 1% of the world’s pop7u-lation. About one third of those patients suffer from treatment-resistant epilepsy (TRE8), defined as failure to stop seizures despite adequate trials of at least two medications at therapeutic dosa-ges. There has been a growing interest in the development of novel antiepileptic drugs with diffe-rent mechanisms of action. This narrative review, based on 42 references retrieved from Scopus and Medline, discusses the scientific data from human and animal studies regarding the efficacy of cannabis-based treatment for epilepsy. Benefits have been described in preclinical and cli-nical studies in children, but ongoing research will clarify the real role of cannabinoids in TRE.

Resumen Objetivo: Evaluar la costo-efectividad de ceftolozano/tazobactam + metronidazol (C/T + M) y ceftolozano/tazobactam (C/T) en comparación con 8 alternativas utilizadas en el tratamiento de las infecciones intraabdominales complicadas (IAAc) e infecciones del tracto urinario complicadas (ITUc) respectivamente. Métodos: Se usó un modelo de decisión de simulación de Monte Carlo para la estimación y comparación de los costos relacionados con el tratamiento y los años de vida ajustados por calidad para pacientes con IAAc tratados con C/T + M, en comparación con cefepima + metronidazol, ciprofloxacina + metronidazol, doripenem , levofloxacina + metronidazol, meropenem, piperacilina / tazobactam, ceftazidima + metronidazol o imipenem/cilastatina, y pacientes con ITUc tratados con C/T en comparación con cefepime, ciprofloxacina, doripenem, levofloxacina, meropenem, piperacilina / tazobactam, ceftazidima o imipenem/cilastatina . Los costos locales se estimaron por medio de casos base identificados por expertos y consultando bases de datos locales. Se utilizaron los valores de sensibilidad bacteriana del estudio PACTS (Programa para evaluar la susceptibilidad al ceftolozano/tazobactam) en América Latina para poblar el modelo. Resultados: C/T + M y C/T obtuvieron razones de costo-efectividad incrementales (RCEI) que estaban por debajo del umbral de costo-efectividad colombiano (3 PIB per cápita) en la mayoría de las comparaciones, y fueron dominados por meropenem, considerando solo microorganismos gran-negativos También se llevaron a cabo análisis de sensibilidad, en los que solo se consideró la población con infecciones por P. aeruginosa, mostrando resultados positivos para C/T + M y C/T (costo efectivo o dominante con respecto a todos los comparadores). Conclusiones: C/T + M y C/T podrían ser alternativas costo efectivas en el tratamiento de IAAc e ITUc en Colombia, cuando existe un uso adecuado y racional de antibióticos. Los resultados de los análisis de sensibilidad mostraron dominio y costo-efectividad en relación con todos los comparadores en pacientes infectados con P. aeruginosa.

Abstract Objective: To evaluate the cost-effectiveness of ceftolozane/tazobactam + metronidazole (C/T+M) and ceftolozane/tazobactam (C/T) compared with 8 alternatives used in the treatment of complicated intraabdominal infection (cIAI) and complicated urinary tract infection (cUTI) respectively. Methods: A Monte Carlo simulation decision model was used for the estimation and comparison of treatment-related costs, and quality adjusted life years for patients with cIAI treated with C/T+M in comparison with cefepime + metronidazole, ciprofloxacin + metronidazole, doripenem, levofloxacin + metronidazole, meropenem, piperacillin/tazobactam, ceftazidime + metronidazole or imipenem/cilastatin and patients with cUTI treated with C/T in comparison with cefepime, ciprofloxacin, doripenem, levofloxacin, meropenem, piperacillin/tazobactam, ceftazidime or imipenem/cilastatin. Local costs were estimated using base cases identified by experts and consulting local databases. Sensitivity values of the PACTS (Program to Assess Ceftolozane/Tazobactam Susceptibility) study in Latin America were used in the model. Results: C/T+M and C/T obtained incremental cost-effectiveness ratios (ICER) that were below the Colombian cost-effectiveness threshold (3 GDP per capita) in most comparisons, and were dominated by meropenem, considering only gram-negative microorganisms. Sensitivity assessments were also carried out, in which only the population with P. aeruginosa infections was considered, showing positive results for C/T+M and C/T (cost-effective or dominant with regards to all comparators). Conclusions: C/T+M and C/T could be cost-effective alternatives in the treatment of CIAI and CUTI in Colombia, when there is an adequate and rational use of antibiotics. The results of the sensitivity analyses showed dominance and cost-effectiveness with regards to every comparator in patients infected with P. aeruginosa

Resumen Introducción: si bien los cannabinoides se han utilizado durante varios años, apenas recientemente se han descrito los descubrimientos sobre sus mecanismos de acción y blancos terapéuticos, así como las alteraciones en el sistema endocannabinoide, observadas en diversas enfermedades y condiciones que se manifiestan con dolor, inflamación, patologías autoinmunes y distintos desórdenes específicos de los órganos. La enfermedad inflamatoria intestinal (EII) agrupa dos condiciones idiopáticas crónicas con patogénesis incierta, en las que se ha identificado que una desregulación del sistema inmune desempeña un papel importante. Así, pues se necesita desarrollar tratamientos alternativos para estos pacientes, ya que solo una minoría de ellos alcanza una remisión de la enfermedad. Nuestro objetivo es revisar las evidencias recientes relacionadas con el uso de cánnabis en la colitis ulcerativa (CU) y en la enfermedad de Crohn (EC). Métodos: se realizó una revisión narrativa focalizada, a partir de las bases de datos de búsqueda de Pubmed y Embase. Los artículos pertinentes fueron revisados y resumidos en forma narrativa. Resultados: los dos componentes principales del cannabis, el cannabidiol (CBD) y el tetrahidrocannabinol (THC), han sido estudiados extensivamente y han probado causar efectos antiinflamatorios y antinociceptivos. Se han descrito ampliamente las propiedades de estos componentes en el control sintomático de la CU y de la EC. No obstante, se sugieren estudios de alta calidad para seguir evaluando la eficacia y la seguridad del uso del cannabis en pacientes con la EII.

Abstract Introduction: Although cannabinoids have been used for several years, only recently have their mechanisms of action and therapeutic targets been described. Alterations in the endocannabinoid system have been observed in various diseases and conditions such as pain, inflammation, autoimmune diseases and various specific disorders. Inflammatory bowel disease groups two chronic idiopathic conditions with uncertain pathogeneses in which deregulation of the immune system plays an important role. Alternative treatments need to be developed for these patients since only a minority of patients achieve disease remission. Our goal is to review recent evidence related to the use of cannabis to treat ulcerative colitis and Crohn’s disease. Methods: This is a focused narrative review based on searches of Pubmed and Embase. Relevant articles have been reviewed and summarized in narrative form. Results: The two main components of cannabis, CBD and THC, have been extensively studied, and their anti-inflammatory and antinociceptive effects have been tested. The effects of these components for control of the symptoms of ulcerative colitis and Crohn’s disease have been widely described. However, high quality studies are needed to continue evaluating the efficacy and safety of cannabis use in patients with inflammatory bowel disease.

ABSTRACT The oil palm (Elaeis guineensis Jacq) plays an important role in the economy of some tropical countries; Colombia ranks first for production in Latin America and fifth in the world. The aim of this research was to characterize the genetic variability of 51 oil palm genotypes from the Congo with seven randomly amplified microsatellite markers RAM. As a result, 241 alleles were generated andthe number of polymorphic loci ranged from 46 to 14 for the ACA and CGA primers, respectively. High genetic diversity was found, with a total heterozygosity of 0.64, along with a high percentage of polymorphic loci, 89%. The coefficient of genetic differentiation (Fst) was 0.15, indicating that there was moderate genetic differentiation. The genetic diversity study differentiated the 51 genotypes into four groups with a similarity of 0.52. The RAM technique detected the genetic variability of the palm genotypes and showed a high degree of polymorphism and sensitivity for discrimination. These results provide information that can be used to develop conservation strategies for palm germplasm and breeding programs to obtain more productive palm genotypes with superior quality and tolerance to major diseases.

RESUMEN Objetivo: Evaluar la eficacia y seguridad de atosiban en gestantes con amenaza de parto pretérmino comparado con nifedipino, indometacina, terbutalina, fenoterol y placebo. Materiales y métodos: Se realizó una revisión sistemática de la literatura en ocho bases de datos electrónicas (Medline, Central, Embase, entre otras), mediante términos de búsqueda libres y estandarizados. Los desenlaces evaluados incluyeron tiempo de retardo del parto, mortalidad neonatal, proporción de eventos adversos maternos y proporción de complicaciones neonatales. Se evaluó la calidad de la evidencia por estudio y para el cuerpo de evidencia, y se sintetizó la información mediante metaanálisis, cuando fue posible; de lo contrario, se resumió de forma narrativa. Resultados: Se incluyeron once estudios. Atosiban no mostró diferencias estadísticamente significativas en retardo del parto contra otros uteroinhibidores. Mostró menor mortalidad neonatal que la indometacina (RR = 0,21; IC 95 %: 0,05 a 0,92), y menor proporción de eventos adversos maternos totales que el fenoterol (RR = 0,16; IC 95 %: 0,08 a 0,31), el nifedipino (RR = 0,48; IC 95 %: 0,3 a 0,78) y la terbutalina (RR = 0,44; IC 95 %: 0,28 a 0,71). Conclusiones: Atosiban tiene una eficacia similar para retardar el parto ante la amenaza de un parto pretérmino con otros comparadores (certeza moderada), con ventajas frente a indometacina en mortalidad neonatal (certeza baja) y frente a fenoterol, nifedipino y terbutalina en eventos adversos maternos (certeza moderada).

ABSTRACT Objective: To assess the efficacy and safety of atosiban in pregnant women with risk of preterm delivery as compared to nifedipine, indomethacin, terbutaline, fenoterol and placebo. Materials and methods: A systematic literature review was carried out in eight electronic databases, including Medline, Central, and Embase, using free and standardized search terms. Outcomes assessment included time delay until delivery, neonatal mortality, ratio of adverse maternal events, and ratio of neonatal complications. The quality of the evidence was evaluated per study and for the body of evidence and, whenever feasible, the information was synthesized into a meta-analysis. Alternatively, a narrative summary was presented. Results: Eleven studies were included. Atosiban did not show any statistically significant differences in terms of delaying delivery versus other uterine contraction inhibitors. The neonatal mortality was lower compared to indomethacin (RR = 0.21; 95% CI: 0.05 to 0.92), and the percentage of total maternal adverse events was lower compared to fenoterol (RR = 0.16; 95% CI: 0.08 to 0.31), nifedipine (RR = 0.48; 95% CI: 0.3 to 0.78), and terbutaline (RR = 0.44; 95% CI: 0.28 to 0.71). Conclusions: Atosiban has similar efficacy for delivery delay in patients with risk of preterm delivery as compared to other agents (moderate certainty), showing some advantages regarding neonatal mortality (low certainty) versus indomethacin, and compared to fenoterol, nifedipine and terbutaline in terms of maternal adverse events (moderate certainty).

Resumen Objetivo: Evaluar la costo-efectividad del acceso arterial radial comparado con el femoral en la realización tanto de arteriografía coronaria diagnóstica como de angioplastia coronaria transluminal percutánea. Métodos: Se construyó un modelo de árbol de decisión para determinar costos de las dos intervenciones en pacientes adultos con sospecha de enfermedad cardiovascular. Para el análisis de efectividad se evaluó la frecuencia de complicaciones mayores y menores en ambos abordajes. La perspectiva para los costos fue la del tercero pagador (sistema de salud colombiano); se incluyeron solo costos médicos directos asociados a los procedimientos y las complicaciones, expresados en pesos colombianos de 2016 (1 USD = COP 3.051). Resultados: El costo promedio estimado de la arteriografía coronaria con abordaje radial fue $1.384.945 y el femoral de $1.474.543. En angioplastia coronaria transluminal percutánea se estimó un costo ponderado de $8.037.743 en el abordaje radial y $8.319.178 en el femoral. El abordaje radial fue dominante para los eventos adversos cardiovasculares mayores respecto al femoral. Tanto en angiografía diagnóstica como en intervención el abordaje radial evita 0,9% de los eventos adversos cardiovasculares mayores y 1,6% de los sangrados mayores, pero presenta más complicaciones menores que el abordaje femoral. Conclusiones: El abordaje radial en arteriografía coronaria diagnóstica y en angioplastia coronaria transluminal percutánea mostró ser una estrategia dominante, al tener un menor costo y menos eventos adversos cardiovasculares mayores.

Abstract Objective: To evaluate the cost-effectiveness of radial artery access compared with that of femoral in the performing of diagnostic coronary angiography, as well as percutaneous transluminal coronary angioplasty. Methods: A decision tree model was constructed in order to determine the costs of two interventions in adult patients with a suspicion of cardiovascular disease. For the effectiveness analysis, an evaluation was made of the major and minor complications in both approaches. The perspective for the costs was the ``third party payer'' (Colombian health system), and included the medical costs associated with the procedure and the complications, expressed in Colombian pesos (2016, 1 US$ = COP 3.051) Results: The estimated mean cost of the coronary angiography using a radial approach was $1,384,945 and $1,474,543 by the femoral approach. In percutaneous transluminal coronary angioplasty the weighted cost was $8,037,743 in the radial approach and $8,319,178 in the femoral approach. The radial approach was dominant for major adverse cardiovascular events compared to the femoral one. In both diagnostic and interventionist angiography, the radial approach avoided 0.9% of the major cardiovascular events and 1.6% of major bleeds, but had more minor complications than the femoral approach. Conclusions: The radial artery approach in diagnostic coronary angiography and percutaneous transluminal coronary angioplasty is shown to be a dominant strategy, on being less costly and having less major cardiovascular adverse events.

RESUMEN INTRODUCCIÓN: La fibrilación auricular es la arritmia cardiaca más frecuente; su prevalencia aumenta con la edad y está asociada con un incremento en el riesgo de presentar accidentes cerebrovasculares e infarto agudo de miocardio. Los anticoagulantes son las alternativas de elección en la prevención de complicaciones tromboembólicas y disminución del riesgo de infarto en pacientes con fibrilación auricular no valvular (FANV). El uso de nuevos anticoagulantes orales como dabigatrán, rivaroxabán y apixabán ha aumentado debido a las diferencias en seguridad y facilidad de administración en comparación con los antagonistas de vitamina K. MÉTODOS: Se realizó un análisis presupuestal desde la perspectiva del tercero pagador, comparando dabigatrán, apixabán, rivaroxabán y warfarina en pacientes con FANV con indicación de anticoagulación. Se consideraron dos escenarios: el primero tenía una reducción relativa de uso de dabigatrán, comparado con apixabán y riva-roxabán; el segundo tenía un incremento de dabigatrán. En ambos, el uso de warfarina se mantenía estable. RESULTADOS: El escenario de disminución de uso de dabigatrán mostró aumento de presupuesto de $1.925.441.674 en el segundo año y $3.670.041.761 en el tercero. El escenario de aumento de uso de dabiga-trán mostró reducción global de costos de -$1.498.527.642 en el segundo año y -$2.119.252.605 en el tercero. CONCLUSIONES: Esta evaluación de impacto presupuestal mostró que el incremento en el uso de dabigatrán a lo largo del horizonte temporal de tres años representa un ahorro de hasta $2.119.252.605 en el tratamiento anticoagulante de FANV en Colombia. De acuerdo con el modelo utilizado en el presente estudio, es posible afirmar que la inclusión de dabigatrán en el presupuesto sanitario del sistema de salud colombiano para el tratamiento de FANV es económicamente viable, además de ser una opción que genera ahorro en el mediano plazo.

SUMMARY BACKGROUND: Atrial fibrillation is the most frequent cardiac arrhythmia; prevalence increases with age and is associated with an increase in the risk of stroke and acute myocardial infarction. Anticoagulants are the treatment of choice to prevent thromboembolic complications and reduce infarction risk in patients with non-valvular atrial fibrillation (NVAF). The utilization of new oral anticoagulants such as dabigatran, rivaroxaban and apixaban has increased, due to the safety profile of vitamin K antagonists. METHODOLOGY: A budget impact analysis comparing dabigatran, rivaroxaban, apixaban and warfarin in patients with NVAF was carried out from the third payer's perspective. Two scenarios were considered: In the first one, there is a relative decrease on dabigatran utilization compared with apixaban and rivaroxaban. In the other one, dabigatran utilization increased. In both scenarios, warfarin utilization remained constant. RESULTS: In the scenario in which dabigatran utilization decreased, there was a budget increase of $1,925,441,674 in the second year, and $3,670,041,761 in the third. In the increase of dabigatran utilization scenario, we find a global cost reduction of -$1,498,527,642 in the second year and -$2,119,252,605 in the third. CONCLUSIONS: Increase of dabigatran utilization throughout the time horizon is a cost saving decision on anticoagulant treatment of NVAF.

Resumen Introducción: este estudio busca estimar los costos de formar un médico en Colombia, tanto en una universidad pública como privada, desde la perspectiva de la sociedad. Materiales y métodos: se calcularon los costos directos e indirectos en pesos colombianos de 2016 (tasa de cambio promedio 3051 COP por USD), así como el retorno a la inversión, expresado en valor actual neto, retorno sobre la inversión, y tasa interna de retorno y, el periodo de recuperación de la inversión de estudiar medicina frente al contrafactual de estudiar otra carrera. Se empleó una tasa de descuento de 12 %. Se realizó un análisis de sensibilidad con varios escenarios. Resultados: en el escenario base, el costo total de la formación de un médico en Colombia es de $80971.80 USD en una universidad privada y de $54971.79 USD en una pública (de los cuales $14436.57 USD son aportados por el Estado). El tiempo de retorno de la inversión es de 3 años y 6 meses en una universidad pública y 7 años y 3 meses en una privada. Aplicando tasas de descuento de 5 %, 7,5 % y 12 %, estudiar medicina presenta mayor retorno que el obtenido con otra carrera. Conclusiones: el costo de formación de un médico en Colombia es un 70 % mayor al requerido para la formación de otro profesional; sin embargo, los retornos son mayores debido los mayores ingresos percibidos. Los retornos son mayores en los egresados de universidades públicas, debido a que la inversión es menor y los ingresos percibidos son similares.

Abstract Introduction: The aim of this project is to estimate the costs to society of training a doctor at either a public or a private university in Colombia. Materials and methods: Direct and indirect costs were estimated in 2016 Colombian pesos (average exchange rate 3051 COP per US dollar), as was the return on investment, expressed as net present value, return on investment, and internal rate of return. The time required to recover the investment in studying medicine was also determined, and this was contrasted with the counterfactual of studying in another academic program. A discount rate of 12 % was used. A sensitivity analysis was performed with several alternative scenarios. Results: In the baseline scenario, the total cost of training a physician in Colombia is US $80, 971.80 at a private university and US $54, 971.79 at a public university (of which $14, 436.57 is contributed by the State in the latter case). The time to return of investment is 3 years 6 months for study at a public university and 7 years 3 months for study at a public university. Applying discount rates of 5 %, 7.5 %, and 12 %, studying medicine presents a higher return than that obtained by studying in another academic program. Conclusions: The cost of training a medical doctor in Colombia is 70 % higher than the cost of training other professionals, but returns are greater due to subsequent higher income. Net returns are higher for graduates of public universities because their initial investment is smaller and their incomes are similar.

Resumo Introdução: o objetivo deste trabalho é estimar os custos de formar um médico na Colômbia, tanto em uma universidade pública quanto privada, desde a perspectiva da sociedade. Materiais e métodos: calcularam-se os custos diretos e indiretos em pesos colombianos de 2016 (taxa de câmbio médio 3051 COP por USD) assim como o retorno ao investimento, expressado em valor atual neto, retorno sobre o investimento, e taxa interna de retorno e, o período de recuperação do investimento de estudar medicina frente ao contrafactual de estudar outra carreira. Empregou-se uma taxa de desconto de 12 %. Se realizou uma análise de sensibilidade com vários cenários. Resultados: no cenário base, o custo total da formação de um médico na Colômbia é de $80971.80 USD em uma universidade privada e $54971.79 USD em uma pública (dos quais $14436.57 USD são aportados pelo Estado). O tempo de retorno do investimento é de 3 anos e 6 meses em uma universidade pública e 7 anos e 3 meses em uma privada. Aplicando taxas de desconto de 5 %, 7.5 % e 12 %, estudar medicina apresenta maior retorno que o obtido com outro curso. Conclusões: o custo de formação de um médico na Colômbia é um 70 % maior ao requerido para a formação de outro profissional, no entanto, os retornos são maiores devido aos maiores ingressos percebidos. Os retornos são maiores nos formados de universidades públicas, devido a que o investimento é menor e os ingressos percebidos são similares.

Resumen Las enfermedades de baja prevalencia requieren modelos de gestión diferentes a los de otras condiciones. Este trabajo buscó recoger las experiencias internacionales. Se realizaron búsquedas en numerosas bases de datos de literatura indexada y de documentos grises. Un panel de expertos de diferentes disciplinas revisó los resúmenes de la literatura y su posible adaptación al contexto colombiano. La búsqueda inicial arrojó 5604 referencias; la búsqueda manual adicionó 31 referencias, finalmente 78 artículos aportaron información útil para el análisis. Los resultados permiten afirmar que existen varios componentes de un modelo de gestión, estos son: políticas, legislación y aspectos administrativos; definición y codificación de enfermedades; investigación y educación; centros especializados, centros de excelencia y redes de atención; diagnóstico, tamizaje, prevención y promoción; inclusión de medicamentos huérfanos; rehabilitación y manejo paliativo; organizaciones de pacientes, grupos o redes de apoyo; y apoyo sociosanitario (inclusión laboral y educativa).

Abstract Low prevalence diseases require management models different from those used in other conditions. This work was intended to gather international experiences on this issue. Searches were made in many indexed literature databases as well as in those with gray literature. A panel of experts from different disciplines checked the abstracts and their potential adaptation into the Colombian context. The initial search retrieved 5604 references and the manual search added other 31 references. At the end, 78 articles provided useful information for the analysis. The results allow to state that a management model consists of several components, to wit: policies, legislation and administrative aspects; definition and coding of the diseases; research and education; specialized centers; excellence centers and service networks; diagnosis, screening, prevention, and promotion; orphan drug inclusion; rehabilitation and palliative care; organizations of patients and support groups or networks; and social-sanitary support (labor and educational inclusion).

Resumo As doenças de baixa prevalência requerem modelos de gestão diferentes aos de outras condições. Este trabalho visou coletar experiências internacionais. Realizaram-se pesquisas em numerosos bancos de dados de literatura indexada e documentos cinza. Um painel de expertos de diferentes disciplinas revisou os resumos da literatura e sua possível adaptação no contexto colombiano. A procura inicial resultou em 5604 referências; a procura manual adicionou 31 referências, por fim 78 artigos forneceram informações úteis para a análise. Os resultados permitem afirmar que existem vários componentes de um modelo de gestão, quais são: políticas, legislações e aspetos administrativos; definição e codificação de doenças; pesquisa e ensino; centros especializados, centros de excelência e redes de atendimento; diagnóstico, triagem, prevenção e promoção; inclusão de medicamentos órfãos; reabilitação e cuidados paliativos; organizações de pacientes, grupos ou redes de apoio; e apoio sócio-sanitário (inclusão laboral e educativa).

Resumo Objetivo Avaliar a relação custo-eficácia da carbetocina versus oxitocina para prevenção de hemorragia pós-parto (HPP) vaginal e cesariana devido à atonia uterina em mulheres com fatores de risco para desenvolver sangramento. Métodos Foram desenvolvidos protocolos de manejo para parto vaginal e outra para parto por cesárea e analisados resultados obtidos com carbetocina e oxitocina na prevenção de HPP, assim como, consequências relacionadas à ocorrência do evento hemorrágico. A perspectiva utilizada foi a do terceiro pagador, portanto, apenas os custos médicos diretos foram levados em consideração. Os custos incrementais e a eficácia em termos de anos de vida ajustados pela qualidade (QALY) foram avaliados para um horizonte de tempo de um ano. Os custos foram expressos em pesos colombianos de 2016 (1 USD = 3.051 Col$). Resultados No modelo de parto vaginal, o customédio de cuidados para um paciente que recebeu profilaxia com agentes uterotônicos foi de Col$ 347.750 com carbetocina e Col$ 262.491 com oxitocina, enquanto os QALYs foram 0,9980 e 0,9979, respectivamente. O índice incremental de custo-efetividade está acima do limite de custoefetividade adotado pela Colômbia. No modelo desenvolvido para parto por cesárea, o custo médio do paciente que recebeu profilaxia com terapia uterotônica foi de Col$ 461.750 com carbetocina e Col$ 481.866 com oxitocina e os QALYs foram 0,9959 e 0,9926, respectivamente. A carbetocina foi a alternativa com menor custo e maior efetividade com uma economia de $94.887 por evento hemorrágico evitado. Conclusão A carbetocina no parto eletivo por cesárea é uma alternativa dominante na prevenção da PPH em relação à oxitocina; porém representa custos mais altos com uma eficácia similar à da oxitocina no caso de parto vaginal.

Abstract Objective To assess the cost-effectiveness of carbetocin versus oxytocin for prevention of postpartum hemorrhage (PPH) due to uterine atony after vaginal delivery/ cesarean section in women with risk factors for bleeding. Methods A decision treewas developed for vaginal delivery andanother one for cesarean, in which a sequential analysis of the results was obtained with the use of carbetocin and oxytocin for prevention of PPH and related consequences. A third-party payer perspective was used; only directmedical costs were considered. Incremental costs and effectiveness in terms of quality-adjusted life years (QALYs) were evaluated for a one-year timehorizon. The costs were expressed in 2016 Colombian pesos (1 USD = 3,051 Col$). Results In the vaginal delivery model, the average cost of care for a patient receiving prophylaxis with uterotonic agents was Col$ 347,750 with carbetocin and Col$ 262,491 with oxytocin,while theQALYs were 0.9980 and 0.9979, respectively. The incremental costeffectiveness ratio is above the cost-effectiveness threshold adopted by Colombia. In the model developed for cesarean section, the average cost of a patient receiving prophylaxis with uterotonics was Col$ 461,750 with carbetocin, and Col$ 481,866 with oxytocin, and the QALYs were 0.9959 and 0.9926, respectively. Carbetocin has lower cost and is more effective, with a saving of Col$ 94,887 per avoided hemorrhagic event. Conclusion In case of elective cesarean delivery, carbetocin is a dominant alternative in the prevention of PPH compared with oxytocin; however, it presents higher costs than oxytocin, with similar effectiveness, in cases of vaginal delivery.

Resumen Introducción. El citomegalovirus es la causa más frecuente de infección en pacientes con trasplante renal. Existen dos estrategias de similar efectividad para prevenirlo: la profilaxis universal con valganciclovir durante 90 días o el tratamiento anticipado verificando la carga viral semanal y aplicándolo solo si esta es positiva. Objetivo. Determinar cuál de estas dos estrategias sería más costo-efectiva en pacientes de riesgo intermedio en Colombia. Materiales y métodos. Se diseñó un árbol de decisiones bajo la perspectiva del tercer pagador considerando únicamente los costos médicos directos en pesos colombianos (COP) del 2014 durante un periodo de un año en una población de pacientes con riesgo intermedio para citomegalovirus (donante positivo y receptor positivo, o donante negativo y receptor positivo). Las probabilidades de transición se extrajeron de los estudios clínicos y se validaron con expertos mediante el método Delphi. Los costos de los procedimientos se basaron en el manual tarifario ISS 2001, con un incremento del 33 % a partir del índice de precios al consumidor (IPC) en salud de 2014, en tanto que los de los medicamentos se extrajeron de las circulares del Ministerio de Salud y del Sistema de Información de Medicamentos (Sismed). Resultados. La profilaxis universal con valganciclovir resultó ser menos costosa y se asoció con una menor probabilidad de infección. El costo promedio del primer año de tratamiento anticipado sería de COP$ 30’961.290, mientras que el universal sería de COP$ 29’967.834, es decir, un costo ‘incremental’ de COP$ 993.456. Conclusiones. Para los pacientes de riesgo intermedio con trasplante renal en Colombia, la profilaxis universal es la mejor estrategia por ser menos costosa y reducir el riesgo de infección.

Abstract Introduction: Cytomegalovirus (CMV) is the most frequent opportunistic infection after renal transplantation. There are two strategies for its prevention: Universal prophylaxis, with valganciclovir for 90 days, and anticipated therapy, using weekly viral load surveillance, and therapy only if positive. Meta-analysis directly comparing both strategies have shown them to have similar effectiveness. Objective: To determine which strategy is more cost-effective in intermediate risk patients in Colombia. Materials and methods: We designed a third-party payer perspective decision tree, considering only direct medical costs in 2014 Colombian pesos (COP) (USD$ 1=COP$ 2,000) and a time horizon of one year. The target population was intermediate CMV risk patients (positive receptor). Transition probabilities were extracted from clinical studies, validated with a Delphi expert panel method; procedural costs were obtained from the ISS 2001 manual with a 33% increment based on the Consumer Price Index for 2014, while medication costs were obtained from the official Ministry of Health information system. Results: Universal prophylaxis with valganciclovir was dominant, with lower costs and less probability of infection. The average cost of the first year in anticipated therapy would be COP$ 30,961,290, whereas in the case of universal therapy the cost would be COP$ 29,967,834 (incremental cost of COP$ 993,456). Conclusions: For Colombian renal transplant patients at intermediate risk for CMV infection, universal prophylaxis strategy is the best option.