Modelo de costos asociados al ataque cerebrovascular y los eventos adversos en pacientes con fibrilación auricular no valvular tratados con warfarina / Model of costs associated with stroke and adverse events in patients with non-valvular atrial fibrillation treated with warfarin

Resumen Objetivo: estimar el número y el costo médico directo del accidente cerebrovascular y los eventos adversos en usuarios de warfarina por fibrilación auricular. Métodos: se utilizó la metodología del análisis de impacto presupuestario para estimar el número de casos y el costo de los eventos. Se calculó la población diana con base en información poblacional de Colombia, así como las tasas de uso de warfarina según el riesgo y la distribución del tiempo en rango terapéutico de la misma. Se estimaron los eventos con base en probabilidades reportadas, y los costos utilizados en el modelo fueron calculados con información de una cohorte de pacientes con accidente cerebrovascular que se lleva a cabo en la Fundación Cardiovascular de Colombia. Resultados: la población diana fue de 84 623 pacientes en 1 año. El costo total de los accidentes cerebrovasculares y los sangrados fue de $36 852 236 476 millones COP. El costo total de los accidentes cerebrovasculares fue $5 004 588 241 COP; el costo total de las hemorragias intracraneales fue $11 875 730 234 COP y el de las hemorragias gastrointestinales fue $19 246 023 614 COP. El sangrado retroperitoneal, la epistaxis y el sangrado del tracto urinario fueron $735 894 387COP. El análisis de sensibilidad mostró que un ajuste en 10% de los tiempos en rango terapéutico podría ahorrar $4 211 957 037 COP. Conclusiones: el costo del accidente cerebrovascular y de los eventos adversos por warfarina es grande. Sin embargo, un ajuste de los tiempos en rango terapéutico podría ahorrar costos, lo que significa vidas de pacientes.

Abstract Objective: The aim of this study is to estimate the number and direct medical cost of cerebrovascular accident (stroke) and the adverse events in patients on warfarin due to atrial fibrillation. Methods: A budget impact analysis methodology was used to estimate the number of cases and cost of the events. The target population was based on Colombian population information, as well as the rates of use of warfarin according to risk and the distribution of its therapeutic time range. The events were estimated base on reported probabilities, and the costs used in the model were calculated from a cohort of stroke patients that was performed in the Cardiovascular Foundation of Colombia. Results: The target population consisted of 84,623 patients in 1 year. The total cost the strokes and bleeding was €10,426,275.28 ($36 852 236 476 million COP (Note: 3,500 /3,000Colombian Pesos (COP) = 1 Euro approx). The total cost strokes was €1,415,903.61 ($5 004 588 241 COP). The total costs of intracranial and gastrointestinal bleeding was €3,359,894.66 ($11 875 730 234 COP) and €5,445,106.17 ($19 246 023 614 COP), respectively. Retroperitoneal bleeding, epistaxis (nosebleeds) and urinary tract bleeding was €208,200.05 ($735 894 387 COP). The sensitivity analysis showed that an adjustment of 10% in the therapeutic time ranges could save €1,191,651.52 ($4 211 957 037 COP). Conclusions: The cost of the cerebrovascular accident and the adverse effects due to warfarin is large. However, an adjustment in the therapeutic range times could save costs, which means patient lives.

Cost-effectiveness of new oral anticoagulants and warfarin in atrial fibrillation from adverse events perspective / Análisis de costo-efectividad de los nuevos anticoagulantes orales y la warfarina en fibrilación auricular desde la perspectiva de los eventos adversos

Abstract Objective: new oral anticoagulants (apixaban, dabigatran and rivaroxaban) are the newest advance for stroke's risk reduction in atrial fibrillation. These are as effective as warfarin in preventing stroke/systemic embolism, but exists heterogenic outcomes as gastrointestinal hemorrhage, mortality reduction, minor and major haemorrhage (adverse events). Despite of this, there is a lack of cost-effectiveness models focused on adverse events. Methods: a cost-effectiveness analysis with a third payer perspective, interventions included were apixaban, dabigatran, warfarin and rivaroxaban. Discount rate of 3%, and 10 years of temporal horizon. The Markov model is an international, validated, and modified to assess better adverse events. Major assumptions, patients with mild and moderate stroke returns to oral anticoagulation, patients with moderate and severe hemorrhage do not returns to oral anticoagulation. Probabilities and QALYs, taken from a cost-effectiveness analysis published. Costs, information from a cohort of stroke patients. Software, TreeAge pro( and Excel(. Results: overall results, 1.48 QALYs, $17 916 USD for apixaban, 1.49 QALYs, $18 122 USD for dabigatran, 1.32 QALYs, $21 966 USD for warfarin and 1.24 QALYs, $24 547 USD for rivaroxaban. The ICER for apixaban compared to dabigatran was $12 988 USD. Negative ICER for warfarin and rivaroxaban, shows that are dominated alternatives (less benefits and more costs). Apixaban is cost-effective at 70% and dabigatran at 30% of iterations in the probabilistic sensitivity analysis. Conclusions: apixaban and dabigatran are cost-effective alternatives, apixaban is the most cost-effective alternative from adverse events perspective. Warfarin shows better results than rivaroxaban to prevent stroke in atrial fibrillation from adverse events perspective.

Resumen Introducción: los nuevos anticoagulantes orales (apixabán, dabigatrán y rivaroxabán) son el avance más reciente para la reducción del riesgo de accidente cerebrovascular en la fibrilación auricular. Estos son tan efectivos como la warfarina en la prevención del accidente cerebrovascular/embolia sistémica, pero existen resultados heterogéneos como hemorragia gastrointestinal, reducción de la mortalidad y hemorragia menor y mayor (eventos adversos). Pese a ello, se carece de modelos de costo-efectividad enfocados en eventos adversos. Materiales y métodos: se hizo un análisis de costo-efectividad con una perspectiva de tercer pagador, en el que se incluyeron intervenciones como apixabán, dabigatrán, warfarina y rivaroxabán. La tasa de descuento fue del 3% y 10 años de horizonte temporal. El modelo de Markov es internacional, validado y modificado para evaluar mejor eventos adversos. Las principales suposiciones, los pacientes con accidente cerebrovascular leve y moderado vuelven a la anticoagulación oral, los pacientes con hemorragia moderada y grave no regresan a la anticoagulación oral. Probabilidades y AVAC, tomados de un análisis de costo-efectividad publicado. Los costos, información de una cohorte de pacientes con accidente cerebrovascular. Software, TreeAge pro y Excel. Resultados: resultados generales, 1.48 QALYs, $ 17 916 USD para apixabán, 1.49 QALYs, $ 18 122USD para dabigatrán, 1.32 QALYs, $ 21 966 USD para warfarina y 1.24 QALYs, $ 24 547 USD para rivaroxabán. El ICER para apixabán en comparación con dabigatrán fue de $ 12 988 USD. El ICER negativo para warfarina y rivaroxabán muestra que son alternativas dominadas (menos beneficios y más costos). Apixabán es rentable en 70% y dabigatrán en 30% de las iteraciones en el análisis de sensibilidad probabilístico. Conclusión: apixabán y dabigatrán son costo-efectivos; apixabán es la alternativa más costo-efectiva desde la perspectiva de los eventos adversos. Warfarina mostró mejores resultados que rivaroxabán para prevenir accidentes cerebrovasculares en fibrilación auricular desde la perspectiva de los eventos adversos.

Asociación entre niveles de proteína C-reactiva y óxido nítrico con el pronóstico de pacientes con infarto cerebral agudo / Association of C-reactive protein and nitric oxide levels with the prognosis of acute ischemic stroke

Introducción: La inflamación y alteraciones en la biodisponibilidad del óxido nítrico (NO) han sido involucradas en la fisiopatología de la enfermedad cerebrovascular. Objetivo: El objetivo del estudio fue determinar el valor pronóstico de la medición de metabolitos del NO y marcadores inflamatorios en pacientes con infarto cerebral agudo. Materiales y métodos: Se incluyeron 158 pacientes con diagnóstico de infarto cerebral agudo en un estudio observacional de cohorte. Entre 48 y 72 horas del inicio de los síntomas se tomó una muestra de sangre para determinación del perfil bioquímico, marcadores inflamatorios (PCR, IL1-β, IL6, TNF-α) y nitritos/nitratos plasmáticos. Se realizó seguimiento durante 2 años para determinar la aparición de un nuevo evento (infarto cerebral, infarto de miocardio, falla cardiaca) o muerte de origen vascular. Un análisis de regresión multivariada de Cox permitió determinar los factores asociados independientemente con el desenlace. Resultados: La edad promedio fue 70,5 ± 12,8 años. El 39,2% de los sujetos incluidos presentó el desenlace durante los primeros 24 meses de seguimiento. Los niveles de PCR > 12 mg/L (HR 2,22, IC 95% 1,07-4,59) y el puntaje > 13 en la escala NIHSS al ingreso (HR 2,81 IC 95% 1,46-5,41) se encontraron significativamente asociados con mayor riesgo de presentar un nuevo evento. La combinación de niveles de PCR < 12 mg/L y nitritos/nitratos < 35,5 µmol/L se identificó como un factor protector (HR 0,21, IC 95% 0,06-0,71). Conclusión: Este estudio sugiere que la determinación de nitritos/nitratos en conjunto con los niveles de PCR puede ser de utilidad para estratificar el riesgo de nuevos eventos en pacientes con infarto cerebral agudo.

Introduction: Inflammation and alterations in the bioavailability of nitric oxide (NO) have been involved in the pathophysiology of cerebrovascular disease. Objective: The aim of the study was to determine the prognostic value of measuring NO metabolites and inflammatory markers in patients with acute ischemic stroke. Materials and methods: A total of 158 patients with acute ischemic stroke were included in an observational cohort study. Between 48 and 72 hours post admission, a fasting blood sample was taken to determine the biochemical profile, inflammatory markers (CRP, IL1-β, IL6, TNF-α) and nitrites/nitrates plasma levels. The cohort's follow-up was conducted for two years to determine the occurrence of a new event (stroke, myocardial infarction, heart failure) or death of vascular origin. Comparisons between groups were made using the log-rank test. A Cox multivariate regression analysis permitted to determine factors independently associated with the outcome. Result: The mean age was 70.5 ± 12.8 years. 39.2% of the subjects presented the outcome during the first 24 months of follow-up. CRP levels > 12 mg/L (HR 2.22, 95% CI 1.07-4.59) and a score > 13 on the NIHSS scale at admission (HR 2.81 95% CI 1.46-5.41) were significantly associated with an increased risk of a new event. The combination of CRP levels < 12 mg/L and nitrites/nitrates levels < 35.5 mmol/L was identified as a protective factor (HR 0.21, 95% CI 0.06-0.71). Conclusion: This study demonstrates that the determination of CRP and NOx levels could be beneficial in clinical practice to stratify the risk of future events or death of vascular origin in acute ischemic stroke patients.

Complicaciones neurológicas de la endocarditis infecciosa: controversias / Neurological complications of infective endocarditis: controversies

En la endocarditis infecciosa aguda se describen complicaciones neurológicas entre 20% y 40% de los casos, lo cual representa un importante factor que predice morbimortalidad, secuelas y discapacidad. Esta entidad se caracteriza por un amplio espectro clínico debido a su compleja fisiopatología, que involucra entre otros, fenómenos inflamatorios, inmunes, infecciosos y embólicos. A pesar de la notable frecuencia de las complicaciones neurológicas en la endocarditis infecciosa, dadas especialmente por enfermedad cerebrovascular y neuroinfecciones, aun existen controversias acerca de algunos aspectos diagnósticos y terapéuticos, en parte por la poca evidencia disponible, las cuales se discuten a continuación, a partir de una serie de casos atendidos en la Fundación Cardiovascular de Colombia.

Neurological complications of acute infective endocarditis are described in 20%-40% of cases, representing an important predictive factor of morbidity, mortality, sequels and disability. Acute endocarditis is characterized by a wide clinical spectrum due to its complex physiopathology that involves inflammatory, immune, infectious and embolic phenomena. Despite the remarkable frequency of neurological complications in the infective endocarditis especially by cerebrovascular disease and neuroinfections, there are still some controversies about some diagnostic and therapeutic aspects, partly because of the little evidence available. This paper describes a number of cases seen in the Fundación Cardiovascular de Colombia and discusses some aspects related with the diagnosis and treatment of the neurological complications of acute endocarditis.

Double blind, randomized, placebo controlled clinical trial for the treatment of diabetic foot ulcers, using a nitric oxide releasing patch: PATHON.

BACKGROUND: Diabetes Mellitus constitutes one of the most important public health problems due to its high prevalence and enormous social and economic consequences. Diabetic foot ulcers are one of the chronic complications of diabetes mellitus and constitute the most important cause of non-traumatic amputation of inferior limbs. It is estimated that 15% of the diabetic population will develop an ulcer sometime in their lives. Although novel therapies have been proposed, there is no effective treatment for this pathology. Naturally produced nitric oxide participates in the wound healing process by stimulating the synthesis of collagen, triggering the release of chemotactic cytokines, increasing blood vessels permeability, promoting angiogenic activity, stimulating the release of epidermical growth factors, and by interfering with the bacterial mitochondrial respiratory chain. Topically administered nitric oxide has demonstrated to be effective and safe for the treatment of chronic ulcers secondary to cutaneous leishmaniasis. However, due to their unstable nitric oxide release, the topical donors needed to be applied frequently, diminishing the adherence to the treatment. This difficulty has led to the development of a multilayer polymeric transdermal patch produced by electrospinning technique that guarantees a constant nitric oxide release. The main objective of this study is to evaluate the effectiveness and safety of this novel nitric oxide releasing wound dressing for the treatment of diabetic foot ulcers. METHODS AND DESIGN: A double-blind, placebo-controlled clinical trial, including 100 diabetic patients was designed. At the time of enrollment, a complete medical evaluation and laboratory tests will be performed, and those patients who meet the inclusion criteria randomly assigned to one of two groups. Over the course of 90 days group 1 will receive active patches and group 2 placebo patches. The patients will be seen by the research group at least every two weeks until the healing of the ulcer or the end of the treatment. During each visit the healing process of the ulcer, the patient's health status and the presence of adverse events will be assessed. Should the effectiveness of the patches be demonstrated an alternative treatment would then be available to patients. TRIAL REGISTRATION: NCT00428727.

Endothelial function in patients with migraine during the interictal period.

OBJECTIVES: The aim of this study is to evaluate endothelial function in migraineurs subjects during the asymptomatic period. BACKGROUND: Migraine has been proposed as a risk factor for cerebrovascular events. The underlying mechanisms that relate these 2 pathologies are unknown. Nitric oxide (NO) has been proposed as the final causative molecule of migraine. Increased NO metabolites concentrations have been reported in migraineurs subjects during acute migraine attacks, but there is no evidence indicating alterations in endothelial NO release during the symptom free period in theses subjects. DESIGN AND METHODS: Fifty migraineurs subjects and 25 healthy subjects matched by gender and age were included. Every subject underwent a complete examination that included medical history, physical examination, resting electrocardiogram, forearm flow-mediated vasodilation (FMD), blood determinations of fasting nitrates and nitrites (NO(2) (-)+ NO(3) (-)), glucose, lipid profile, creatinine, C-reactive protein, and blood cell count. RESULTS: No differences in FMD or NO(2) (-)+ NO(3) (-) were detected among groups. The only difference between migraineurs and control subjects was a higher mean blood pressure 92.1 (8.8) mmHg versus 86.7 (8.2) mmHg P= .01. CONCLUSION: The endothelial function is not altered during the interictal period in migraineurs subjects.

Efectos de la terapia de reemplazo hormonal sobre la función autonómica en mujeres postmenopáusicas / Effects of estrogen replacement therapy on autonomic function of post-menopausal women

Antecedentes: el déficit de estrógenos propio de la etapa postmenopáusica, puede contribuir al desarrollo de un disbalance autonómico con la reducción del reflejo cardiovagal, lo que a su vez puede incrementar el riesgo cardiovascular. Aún no se han aclarado en su totalidad los mecanismos fisiopatológicos subyacentes de esta alteración. En este artículo se discute el efecto de la terapia hormonal de reemplazo sobre la función autonómica en mujeres sometidas a histerectomía.Métodos: en este ensayo clínico cruzado, placebo-controlado, doble ciego, se incluyeron mujeres con histerectomía y amenorrea al menos un año antes de la cirugía. De forma aleatoria, recibieron estrógenos conjugados 0,625 mg/dL o placebo durante doce semanas, con un período intermedio sin medicación de dos semanas. Se evaluó la función autonómica cardiovagal y vascular mediante técnicas convencionales y a tráves de pletismografía por oclusión venosa para calcular el flujo sanguíneo en el antebrazo y la resistencia vascular periférica en condiciones basales, durante la prueba de mesa basculante y en la prueba de presión negativa en miembros inferiores...

Background: estrogen deficit during menopause may be related to cardiac autonomic function imbalance, reducing the cardiovagal reflex response that could potentially increase cardiovascular risk. The physiological mechanisms that lead to this alteration in postmenopausal women remain unclear. In this article, the effect of hormonal replacement therapy on autonomic function in women submitted to hysterectomy is discussed.Methods: Fifty women with a previous hysterectomy and amenorrhea for 1 year prior to surgery were enrolled in a prospective randomized crossover double-blind placebo controlled trial. Either oral estrogen replacement therapy (ERT) conjugated estrogens 0.625 mg once a day or placebo, were randomly administered in a crossover design during 12 weeks with a 2 week washout period. Cardiovagal autonomic function was assessed by conventional techniques and through venous occlusion plethysmography in order to evaluate vascular autonomic function calculating forearm blood flow (FBF) and peripheral vascular resistance (PVR) at baseline, and during head-up tilt (HUT) and a non-hypotensive stimuli (-10mmHg) lower-body negative pressure (LBNP).Results: No differences were found in cardiovagal autonomic function comparing ERT vs. placebo at baseline resting conditions, nor during HUT and LBNP. A significant difference was identified in supine FBF [1.9(0.5) vs. 1.5(0.5), p=0.02] as well as in PVR [53.5(18.2) vs. 68.6(34), p=0.02] comparing ERT vs. placebo interventions.Conclusions: Short term ERT did not improve cardiovascular autonomic reflex responses in postmenopausal women, but increased vascular relaxation primarily by reducing peripheral vascular resistance. Hormone replacement therapy can be used under adequate supervision in order to improve menopausal symptoms during a short period of time, mainly in young non-hypertensive post-menopausal women.

Olive, soybean and palm oils intake have a similar acute detrimental effect over the endothelial function in healthy young subjects.

BACKGROUND AND AIM: Currently, more than 30% of the caloric intake in the Colombian population comes from vegetable oil consumption mainly by the ingestion of deep-fried foods. Recently, it has been reported that unsaturated fatty acid rich oils have a beneficial effect on the endothelial function. Nevertheless, it is well know that the deep-frying process alters the chemical composition of vegetable oils and can produce adverse effects in the endothelial function. OBJECTIVE: To evaluate the acute effect of the ingestion of large amounts of olive, soybean and palm oils, fresh and at two different deep-fry levels, on the glucose and lipid profiles and the endothelial function. METHODS AND RESULTS: Ten healthy young volunteers were included in the study. After performing a baseline evaluation of cardiovascular risk factors and drawing a fasting blood sample, subjects were exposed to a randomly assigned potato soup meal containing 60 mL of one of three different vegetable oils (olive, soybean and palm), either fresh or at one of two different deep-fry levels (10 and 20 fries, respectively). Flow-mediated vasodilation (FMD) was performed in fasting conditions and 3h after the intake of the oil rich meal. Furthermore, blood samples were taken at these stages for the lipid profiles and plasma glucose determinations. All the meals resulted in a similar acute endothelial impairment (FMD decrease of 32.1%, confidence interval [CI] 95%, 28.0-36.2) and postprandial increase in triglycerides (27.03%, CI 95%, 20.5-33.3), independently of the type of oil ingested (p=0.44) and regardless of its deep-fry level (p=0.62). No correlation was found between endothelial impairment and postprandial triglyceride increment (r=-0.22, p=0.09). CONCLUSIONS: No difference was found in the acute adverse effect of the ingestion of different vegetable oils on the endothelial function. All the vegetable oils, fresh and deep-fried, produced an increase in the triglyceride plasma levels in healthy subjects.

Características clínicas, electrocardiográficas y ecocardiográficas de la cardiomiopatía chagásica en la población santandereana / Clinical, electrocardiographic and echocardiographic characteristics of Chagas’ cardiomyopathy in Santander’s State (Colombia) population

Introducción: la enfermedad de Chagas es una infección parasitaria ocasionada por el Trypanosoma cruzi. En Latinoamérica esta enfermedad es endémica, y la cardiomiopatía chagásica es su manifestación más frecuente en Colombia. Este artículo describe las principales características clínicas, electrocardiográficas y ecocardiográficas de la cardiomiopatía chagásica en el Departamento de Santander, Colombia.Materiales y métodos: se realizó un estudio descriptivo, transversal, de sujetos provenientes de Santander, entre los 18 y 80 años, seropositivos para T. cruzi, con síntomas de falla cardiaca no terminal. A estos pacientes se les realizó examen físico, electrocardiograma y ecocardiograma bidimensional.Resultados: se evaluaron 119 pacientes, 62 mujeres y 57 hombres, con edad promedio de 58,5 +/- 10,7 años. Los antecedentes más frecuentes fueron: hipertensión arterial (49,6 porciento), implantación de marcapaso (8,4 porciento) y dislipidemia (7,6 porciento). En 34,3 porciento de los sujetos se encontró hipertrofia ventricular izquierda en asociación con trastornos de repolarización. De las anormalidades de conducción, el bloqueo de rama derecha fue el más frecuente (11,8 prociento). La valvulopatía más común fue la insuficiencia mitral (61,5 prociento). Ninguna de estas variables se asoció con un peor estado de clase funcional.Discusión: las características electrocardiográficas de la cardiomiopatía chagásica en Colombia, parecen tener un comportamiento diferencial por regiones, y para la zona del Departamento de Santander lo más usual es el hallazgo de hipertrofia ventricular izquierda, trastornos de repolarización y bloqueo de rama derecha. Las intervenciones tempranas en este grupo de pacientes son necesarias dado el alto costo social y económico que conlleva la cardiomiopatía chagásica.

Background: Chagas’ disease (CD) is a parasitic infection caused by the Trypanosoma cruzi. In Latin America the disease is endemic and Chagas’ cardiomyopathy(CCM) is the main clinical presentation of CD in Colombia. This article describes the main clinical, electrocardiographic and echocardiographic characteristics of the CCM in Santander, Colombia. Materials and methods: A cross-sectional study of patients of ages between 18 and 80 years, from the Department of Santander, Colombia, with positive serology for T. cruzi, and symptoms of non-terminal heart failure was performed. Physical examination, 12-lead electrocardiogram and 2D echocardiogram were carried out.Results: The study included 62 women and 57 men, mean age 58.5±10.7 years. Hypertension (49.6%), pacemaker implantation (8.4%) and dyslipidemia (7.6%) were the most frequent antecedents. Left ventricular hypertrophy was seen in 34.3% of the subjects and it was associated to abnormalities in re-polarization. Right bundle branch block was determined in 11.8% of the subjects. Mitral insufficiency was identified by echocardiogram in 61.5% of the participants. None of these variables were associated with a worse functional class state.Discussion: The electrocardiographic characteristics in patients with CCM in Colombia seem to have a different behaviour according to the regions, and for Santander the most frequent findings were left ventricular hypertrophy, abnormalities in repolarization and right bundle branch block. Early interventions on this group of patients are necessary in order to reduce the social and economic impact associated to the CCM.

Enfermedad cerebrovascular en Colombia / Cerebrovascular disease in Colombia

Introducción: la enfermedad cerebrovascular constituye un problema de salud pública mundial. En Colombia es la cuarta causa de muerte en la población adulta y genera una alta discapacidad en estos pacientes. Objetivo: describir algunos resultados obtenidos por el grupo de Ciencias Neurovasculares de la Fundación Cardiovascular de Colombia...

Introduction: cerebrovascular disease constitutes a worldwide public health problem. In Colombia, it is the fourth leading cause of death in the adult population and generates high disability in these patients. Objective: to describe some results obtained by the Neurovascular Sciences group from the Colombian Cardiovascular Foundation. Development and conclusions: cerebrovascular disease has a high prevalence in the Colombian population and generates mental, motor, and language disabilities. The implementation of neurovascular care units with trained personnel, defined protocols, adequate treatments and high technology, are necessary. This kind of units must be imposed in Colombia as a basic care for these patients in order to decrease morbidity, mortality and disability. The Colombian Cardiovascular Foundation is pioneer in the implementation of these care units.

CHARITY: Chagas cardiomyopathy bisoprolol intervention study: a randomized double-blind placebo force-titration controlled study with Bisoprolol in patients with chronic heart failure secondary to Chagas cardiomyopathy [NCT00323973].

BACKGROUND: Chagas' disease is the major cause of disability secondary to tropical diseases in young adults from Latin America, and around 20 million people are currently infected by T. cruzi. Heart failure due to Chagas cardiomyopathy is the main clinical presentation in Colombia. Heart failure due to Chagas' disease may respond to digoxin, diuretics and vasodilator therapy. Beta-adrenoreceptor antagonism seems to protect against the increased risk of cardiac arrhythmia and sudden death due to chronic sympathetic stimulation. The aim of this study is to evaluate the effects of the selective beta-adrenergic receptor blocker Bisoprolol on cardiovascular mortality, hospital readmission due to progressive heart failure and functional status in patients with heart failure secondary to Chagas' cardiomyopathy. METHODS/DESIGN: A cohort of 500 T. cruzi seropositive patients (250 per arm) will be selected from several institutions in Colombia. During the pretreatment period an initial evaluation visit will be scheduled in which participants will sign consent forms and baseline measurements and tests will be conducted including blood pressure measurements, twelve-lead ECG and left ventricular ejection fraction assessment by 2D echocardiography. Quality of life questionnaire will be performed two weeks apart during baseline examination using the "Minnesota living with heart failure" questionnaire. A minimum of two 6 minutes corridor walk test once a week over a two-week period will be performed to measure functional class. During the treatment period patients will be randomly assigned to receive Bisoprolol or placebo, initially taking a total daily dose of 2.5 mgrs qd. The dose will be increased every two weeks to 5, 7.5 and 10 mgrs qd (maximum maintenance dose). Follow-up assessment will include clinical check-up, and blood collection for future measurements of inflammatory reactants and markers. Quality of life measurements will be obtained at six months. This study will allow us to explore the effect of beta-blockers in chagas' cardiomyopathy.

Double blind, randomized controlled trial, to evaluate the effectiveness of a controlled nitric oxide releasing patch versus meglumine antimoniate in the treatment of cutaneous leishmaniasis [NCT00317629].

BACKGROUND: Cutaneous Leishmaniasis is a worldwide disease, endemic in 88 countries, that has shown an increasing incidence over the last two decades. So far, pentavalent antimony compounds have been considered the treatment of choice, with a percentage of cure of about 85%. However, the high efficacy of these drugs is counteracted by their many disadvantages and adverse events. Previous studies have shown nitric oxide to be a potential alternative treatment when administered topically with no serious adverse events. However, due to the unstable nitric oxide release, the topical donors needed to be applied frequently, making the adherence to the treatment difficult. The electrospinning technique has allowed the production of a multilayer transdermal patch that produces a continuous and stable nitric oxide release. The main objective of this study is to evaluate this novel nitric oxide topical donor for the treatment of cutaneous leishmaniasis. METHODS AND DESIGN: A double-blind, randomized, double-masked, placebo-controlled clinical trial, including 620 patients from endemic areas for Leishmaniasis in Colombia was designed to investigate whether this patch is as effective as meglumine antimoniate for the treatment of cutaneous leishmaniasis but with less adverse events. Subjects with ulcers characteristic of cutaneous leishmaniasis will be medically evaluated and laboratory tests and parasitological confirmation performed. After checking the inclusion/exclusion criteria, the patients will be randomly assigned to one of two groups. During 20 days Group 1 will receive simultaneously meglumine antimoniate and placebo of nitric oxide patches while Group 2 will receive placebo of meglumine antimoniate and active nitric oxide patches. During the treatment visits, the medications will be daily administered and the presence of adverse events assessed. During the follow-up, the research group will visit the patients at days 21, 45, 90 and 180. The healing process of the ulcer, the health of the participants, recidivisms and/or reinfection will also be assessed. The evolution of the ulcers will be photographically registered. In case that the effectiveness of the patches is demonstrated, a novel and safe therapeutic alternative for one of the most important public health problems in many countries will be available to patients.

[Extrapontine osmotic myelinolysis]. / Mielinólisis osmótica extrapóntica.

Extrapontine osmotic myelinolysis is a rare nervous system complication. Symptoms of this malady were presented during the clinical examination of a 49-year-old alcoholic male, who arrived at the hospital emergency room in a state of cardiorespiratory arrest. After resuscitation methods were applied, the patient was found in metabolic acidosis (pH 7.014) and was treated with sodium bicarbonate. Forty-eight hours later, sodium levels in the patient had risen from 142 to 174 mEq/l. During the period of clinical observation, the patient showed signs of cognitive impairment, disartria, bilateral amaurosis, hyporeflexia and right-half body hemiparesias. After 72 hours, computer tomography was applied; this showed a bilateral lenticular hypodensity with internal and external capsule compromise. One month later, when the patient was referred to another institution for rehabilitation, the patient showed cognitive impairment, bilateral optic atrophy, residual disartria, bradikynesia and double hemiparesia.

Mielinólisis osmótica extrapóntica / Extrapontine osmotic myelinolysis

La mielinólisis osmótica extrapóntica es una complicación rara del sistema nervioso central. Se presentan los hallazgos clínicos de un paciente de 49 años, alcohólico, que ingresó al servicio de urgencias en paro cardiorrespiratorio. Después de las maniobras de reanimación, el paciente se encontró en acidosis metabólica (pH 7,014) y fue tratado con bicarbonato de sodio. Cuarenta y ocho horas después, el sodio aumentó de 142 a 174 mEq/l. Durante el curso clínico, el paciente presentó signos de compromiso cognitivo, disartria, amaurosis bilateral, hiporreflexia y hemiparesia doble de predominio en el hemicuerpo derecho. La tomografía computarizada, tomada a las 72 horas de inicio del cuadro, evidenció hipodensidad lenticular bilateral con compromiso de las cápsulas internas y externas. Un mes después el paciente continuó con compromiso cognoscitivo, atrofia óptica bilateral, disartria residual, bradicinesia y hemiparesia doble

[Autonomic dysfunction syndromes associated with orthostatic intolerance]. / Síndromes de disfunción autonómica asociados con intolerancia ortostática.

In recent years increased interest has focused on the nature and pathophysiology of orthostatic intolerance and syndromes associated with autonomic disorders. Understanding the pathophysiology underlying these syndromes has led to the recognition of several distinct clinical entities with overlapping features and the associated need to reclassify many of the previously unrecognized syndromes. Among the clinical manifestations, syncope and near syncope are frequently associated with orthostatic intolerance. In addition, however, a wide spectrum of symptoms have been described ranging from chronic fatigue to recurrent neurally mediated vasodepressor reactions. The present review focuses on the pathophysiology and classification of syndromes of autonomic dysfunction associated with orthostatic intolerance. Primary and secondary causes of dysautonomia as well as therapeutic approach to these frequently unrecognized syndromes is presented.