Associations of Early Systolic Blood Pressure Control and Outcome After Thrombolysis-Eligible Acute Ischemic Stroke: Results From the ENCHANTED Study.

BACKGROUND AND PURPOSE: In thrombolysis-eligible patients with acute ischemic stroke, there is uncertainty over the most appropriate systolic blood pressure (SBP) lowering profile that provides an optimal balance of potential benefit (functional recovery) and harm (intracranial hemorrhage). We aimed to determine relationships of SBP parameters and outcomes in thrombolyzed acute ischemic stroke patients. METHODS: Post hoc analyzes of the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study), a partial-factorial trial of thrombolysis-eligible and treated acute ischemic stroke patients with high SBP (150-180 mm Hg) assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) alteplase and intensive (target SBP, 130-140 mm Hg) or guideline-recommended (target SBP <180 mm Hg) treatment. All patients were followed up for functional status and serious adverse events to 90 days. Logistic regression models were used to analyze 3 SBP summary measures postrandomization: attained (mean), variability (SD) in 1-24 hours, and magnitude of reduction in 1 hour. The primary outcome was a favorable shift on the modified Rankin Scale. The key safety outcome was any intracranial hemorrhage. RESULTS: Among 4511 included participants (mean age 67 years, 38% female, 65% Asian) lower attained SBP and smaller SBP variability were associated with favorable shift on the modified Rankin Scale (per 10 mm Hg increase: odds ratio, 0.76 [95% CI, 0.71-0.82]; P<0.001 and 0.86 [95% CI, 0.76-0.98]; P=0.025) respectively, but not for magnitude of SBP reduction (0.98, [0.93-1.04]; P=0.564). Odds of intracranial hemorrhage was associated with higher attained SBP and greater SBP variability (1.18 [1.06-1.31]; P=0.002 and 1.34 [1.11-1.62]; P=0.002) but not with magnitude of SBP reduction (1.05 [0.98-1.14]; P=0.184). CONCLUSIONS: Attaining early and consistent low levels in SBP <140 mm Hg, even as low as 110 to 120 mm Hg, over 24 hours is associated with better outcomes in thrombolyzed acute ischemic stroke patients. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01422616.

Efficacy and Safety of Text Messages Targeting Adherence to Cardiovascular Medications in Secondary Prevention: TXT2HEART Colombia Randomized Controlled Trial.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality worldwide, with a prevalence of approximately 100 million patients. There is evidence that antiplatelet agents and antihypertensive medications could reduce the risk of new vascular events in this population; however, treatment adherence is very low. An SMS text messaging intervention was recently developed based on behavior change techniques to increase adherence to pharmacological treatment among patients with a history of ASCVD. OBJECTIVE: This study aims to evaluate the efficacy and safety of an SMS text messaging intervention to improve adherence to cardiovascular medications in patients with ASCVD. METHODS: A randomized controlled clinical trial for patients with a prior diagnosis of cardiovascular events, such as acute myocardial infarction, unstable angina, cerebrovascular disease, or peripheral artery disease, in one center in Colombia was conducted. Patients randomized to the intervention arm were assigned to receive SMS text messages daily for the first 4 weeks, 5 SMS text messages on week 5, 3 SMS text messages each in weeks 6 and 7, and 1 SMS text message weekly from week 8 until week 52. In contrast, patients in the control arm received a monthly SMS text message reminding them of the next study appointment and the importance of the study, requesting information about changes in their phone number, and thanking them for participating in the study. The primary endpoint was the change in low-density lipoprotein cholesterol (LDL-C) levels, whereas the secondary endpoints were the changes in thromboxane B2 levels, heart rate, systolic and diastolic blood pressure, medication adherence, cardiac and noncardiac mortality, and hospitalization. Linear regression analyses and bivariate tests were performed. RESULTS: Of the 930 randomized patients, 805 (86.5%) completed follow-up and were analyzed for the primary endpoint. There was no evidence that the intervention changed the primary outcome (LDL-C levels; P=.41) or any of the secondary outcomes evaluated (all P>.05). There was also no evidence that the intervention was associated with adverse events. CONCLUSIONS: In this study, there was no evidence that a behavior modification intervention delivered by SMS text messaging improved LDL-C levels, blood pressure levels, or adherence at 12 months. More research is needed to evaluate whether different SMS text messaging strategies, including personalized messages and different timings, are effective; future studies should include mixed methods to better understand why, for whom, and in which context (eg, health system or social environment) SMS text messaging interventions work (or not) to improve adherence in patients with ASCVD. TRIAL REGISTRATION: ClinicalTrials.gov NCT03098186; https://clinicaltrials.gov/ct2/show/NCT03098186. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2018-028017.

Serie de Casos de Leishmaniasis Detectados en Centros Hospitalarios del Departamento de Caaguazú, Paraguay en 2019

Resumen La leishmaniasis es la tercera de las enfermedades de transmisión vectorial a humanos en importancia por el número de casos y la población en riesgo. En Paraguay la leishmaniasis cutánea es una enfermedad endémica atribuida en casi todos los casos a Leishmania (Viannia) braziliensis. El objetivo del artículo es describir las características demográficas y clínicas de una serie de casos de pacientes con leishmaniasis en el V departamento de Caaguazú y departamentos cercanos, epidemiológicamente endémicos. Se reportan casos diagnosticados en los meses enero a diciembre del año 2019. Los casos se presentaron en el departamento de Caaguazú, abarcando los diferentes distritos que componen y departamentos cercanos como Canindeyú, Alto Paraná y Guaira. De los casos registrados (9 casos) fueron hombres y (6 casos) tuvieron entre 50 a 70 años de edad. La lesión estuvo situada mayormente en el tabique nasal en 8 casos, con una evolución de menos de 10 años (6 casos) y en 4 casos dejo cicatriz. Solo 3 casos completaron su tratamiento. Se sugiere realizar el reporte de casos para tener un panorama de los casos de leishmaniasis en Paraguay como vigilancia sanitaria de la enfermedad y localizar focos de contagio.

Abstract Leishmaniasis is the third most important vector-borne diseases in humans due to the number of cases and the population at risk. In Paraguay, cutaneous leishmaniasis is an endemic disease attributed in almost all cases to Leishmania (Viannia) braziliensis. The objective of the article was to describe the demographic and clinical characteristics of a series of cases of patients with leishmaniasis in the V department of Caaguazú and nearby departments, epidemiologically endemic. Cases diagnosed in the months of January to December of the year 2019 are reported. The cases occurred in the department of Caaguazú, covering the different districts that make up and nearby departments such as Canindeyú, Alto Paraná and Guaira. Of the registered cases (9 cases) were men and (6 cases) were between 50 and 70 years of age. The lesion was located mainly in the nasal septum in 8 cases, with an evolution of less than 10 years (6 cases) and in 4 cases it left a scar. Only 3 cases completed their treatment. It is suggested to carry out the case report to have an overview of Leishmania cases in Paraguay as a health surveillance of the disease and to locate sources of contagion.

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.

Eficacia y seguridad de la estimulación magnética transcraneal en pacientes con afasia no fluente, posterior a ictus isquémico. Ensayo clínico controlado, aleatorizado y doble ciego / Efficacy and safety of transcranial magnetic stimulation in patients with non-fl uent aphasia, following an ischaemic stroke. A controlled, randomised and double-blind clinical trial

Introducción. La afasia no fluente es una complicación frecuente en pacientes postictus isquémico y la estimulación magnética transcraneal repetitiva (EMTr) representa una de las posibles alternativas de tratamiento. Objetivo. Evaluar la eficacia y la seguridad de la EMTr en pacientes con afasia no fluente postictus isquémico. Pacientes y métodos. Ensayo clínico controlado doble ciego, aleatorizado, en pacientes postictus isquémico que fueron asignados a recibir 10 sesiones (una diaria) de tratamiento activo o placebo de EMTr, sin adición de terapia del lenguaje. Las características basales fueron comparadas inicialmente, y la eficacia entre el grupo activo frente al grupo placebo el día 30 se evaluó a través de una prueba U de Mann-Whitney. Resultados. Se incluyó a 82 pacientes: grupo activo (n = 41) y grupo placebo (n = 41). Se encontraron diferencias basales estadísticamente significativas entre los grupos a favor del placebo en los dominios del test de Boston de compresión auditiva (p = 0,024), denominación (p = 0,014) y praxis (p = 0,026), e igualmente ocurrió el día 30 en los dominios de denominación (p = 0,037) y lectura (p = 0,001). Se presentaron 39 reacciones adversas, 23 en el grupo activo (26,83%) frente a 16 (21,96%) en el grupo placebo (p = 0,290), y la mayoría correspondía a episodios de cefalea leve. Conclusión. La EMTr es una terapia segura, pero dadas las condiciones de este estudio, no pudo demostrarse la eficacia de la EMTr frente al placebo en pacientes con afasia no fluente con afectación del área de Broca posterior a un ictus isquémico

Introduction. Non-fluent aphasia is a frequent complication in post-ischemic stroke patients, with repetitive transcranial magnetic stimulation (rTMS) being one of the possible treatment alternatives. Aim. To assess the efficacy and safety of rTMS in patients with non-flent after-ischemic stroke aphasia. Patients and methods. Double blind, randomized controlled clinical trial in post-stroke patients who were assigned to receive 10 sessions (one daily) of active treatment or placebo of rTMS, without the addition of language therapy. The baseline characteristics were compared initially and the efficacy between the active group versus the placebo group at day 30 was evaluated through a Mann-Whitney U test. Results. 82 patients were included: active group (n = 41) and placebo group (n = 41). At baseline, statistically significant differences were found between the groups in favor of the placebo in the domains of the Boston test of auditory compression (p = 0.024), denomination (p = 0.014) and praxis (p = 0.026), and also occurred on the 30th day in the naming domains (p = 0.037) and reading (p = 0.001). There were 39 adverse reactions: 23 (26.83%) in the active group vs 16 (21.96%) in the placebo group (p = 0.290); the majority corresponded to episodes of mild headache. Conclusion. rTMS is a safe therapy, however, given the conditions of this study, we could not demonstrate the efficacy of rTMS versus placebo in patients with non-fluent aphasia with involvement of Broca's area after an ischemic stroke

Intensive blood pressure reduction with intravenous thrombolysis therapy for acute ischaemic stroke (ENCHANTED): an international, randomised, open-label, blinded-endpoint, phase 3 trial.

BACKGROUND: Systolic blood pressure of more than 185 mm Hg is a contraindication to thrombolytic treatment with intravenous alteplase in patients with acute ischaemic stroke, but the target systolic blood pressure for optimal outcome is uncertain. We assessed intensive blood pressure lowering compared with guideline-recommended blood pressure lowering in patients treated with alteplase for acute ischaemic stroke. METHODS: We did an international, partial-factorial, open-label, blinded-endpoint trial of thrombolysis-eligible patients (age ≥18 years) with acute ischaemic stroke and systolic blood pressure 150 mm Hg or more, who were screened at 110 sites in 15 countries. Eligible patients were randomly assigned (1:1, by means of a central, web-based program) within 6 h of stroke onset to receive intensive (target systolic blood pressure 130-140 mm Hg within 1 h) or guideline (target systolic blood pressure <180 mm Hg) blood pressure lowering treatment over 72 h. The primary outcome was functional status at 90 days measured by shift in modified Rankin scale scores, analysed with unadjusted ordinal logistic regression. The key safety outcome was any intracranial haemorrhage. Primary and safety outcome assessments were done in a blinded manner. Analyses were done on intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01422616. FINDINGS: Between March 3, 2012, and April 30, 2018, 2227 patients were randomly allocated to treatment groups. After exclusion of 31 patients because of missing consent or mistaken or duplicate randomisation, 2196 alteplase-eligible patients with acute ischaemic stroke were included: 1081 in the intensive group and 1115 in the guideline group, with 1466 (67·4%) administered a standard dose among the 2175 actually given intravenous alteplase. Median time from stroke onset to randomisation was 3·3 h (IQR 2·6-4·1). Mean systolic blood pressure over 24 h was 144·3 mm Hg (SD 10·2) in the intensive group and 149·8 mm Hg (12·0) in the guideline group (p<0·0001). Primary outcome data were available for 1072 patients in the intensive group and 1108 in the guideline group. Functional status (mRS score distribution) at 90 days did not differ between groups (unadjusted odds ratio [OR] 1·01, 95% CI 0·87-1·17, p=0·8702). Fewer patients in the intensive group (160 [14·8%] of 1081) than in the guideline group (209 [18·7%] of 1115) had any intracranial haemorrhage (OR 0·75, 0·60-0·94, p=0·0137). The number of patients with any serious adverse event did not differ significantly between the intensive group (210 [19·4%] of 1081) and the guideline group (245 [22·0%] of 1115; OR 0·86, 0·70-1·05, p=0·1412). There was no evidence of an interaction of intensive blood pressure lowering with dose (low vs standard) of alteplase with regard to the primary outcome. INTERPRETATION: Although intensive blood pressure lowering is safe, the observed reduction in intracranial haemorrhage did not lead to improved clinical outcome compared with guideline treatment. These results might not support a major shift towards this treatment being applied in those receiving alteplase for mild-to-moderate acute ischaemic stroke. Further research is required to define the underlying mechanisms of benefit and harm resulting from early intensive blood pressure lowering in this patient group. FUNDING: National Health and Medical Research Council of Australia; UK Stroke Association; Ministry of Health and the National Council for Scientific and Technological Development of Brazil; Ministry for Health, Welfare, and Family Affairs of South Korea; Takeda.

Benefit, risk and cost of new oral anticoagulants and warfarin in atrial fibrillation; A multicriteria decision analysis.

INTRODUCTION: Warfarin and new oral anticoagulants are effective in reducing stroke in atrial fibrillation; however, the benefits and risks rates in clinical trials show heterogeneity for each anticoagulant, and is unknown the cost influence on a model considering most of the treatment consequences. We designed a benefit-risk and cost assessment of oral anticoagulants. DESIGN: We followed the roadmap proposed by IMI-PROTECT and the considerations of emerged good practice to perform Multi-Criteria Decision Analysis (MCDA). The roadmap defines the following steps: (1) planning, (2) evidence gathering and data preparation, (3) analyses, (4) explorations, and (5) conclusions. We defined two reference points (0-100) to allocate numerical values for scores and weights, and used an analogue numeric scale to assess physicians' preferences. As benefits of the anticoagulant therapy, we included reductions in stroke and all-cause mortality; intracranial haemorrhage, gastrointestinal haemorrhage, minor bleeding and myocardial infarction were considered risks. We also made an estimation of the annual drug cost per person. MAIN RESULTS: The scores were: Apixaban 33, Dabigatrán 25, warfarin 18 and Rivaroxaban 14 this score reveals the most preferred up to the less preferred option, considering the benefit-risk ratio and drug costs altogether. The relative model weights were: 51.1% for risks, 40.4% for benefits and 8.5% for cost. The sensitivity analysis confirms the model robustness. CONCLUSIONS: From this analysis, apixaban should be considered as the preferred anticoagulant option -due to a better benefit-risk balance and a minor cost influence- followed by dabigatran, warfarin and rivaroxaban.

Revisión sistemática de nuevos anticoagulantes orales frente a warfarina en fibrilación auricular no valvular / Systematic review of new oral anticoagulants versus warfarin in non valvular atrial fibrillation

RESUMEN INTRODUCCIÓN: Los nuevos anticoagulantes orales son el más reciente avance en anticoagulación oral. Existen suficientes estudios publicados, pero muy poca síntesis de la información. MÉTODOS: Se realizó una búsqueda sistemática de los estudios en Medline, Cochrane y Embase con los términos predefinidos. Se aplicaron los criterios de inclusión y exclusión definidos, se definieron las variables utilizadas en este estudio según el beneficio (reducción de la mortalidad y reducción del ACV) y el riesgo en la anticoagulación (sangrado intracraneal, sangrado gastrointestinal, sangrado mayor y otros sangrados). Se seleccionaron los artículos y se extrajo la información en una hoja de cálculo para análisis. RESULTADOS: Se incluyeron 24 meta-análisis y 62 subanálisis; 77 % de los meta-análisis mostraron reducción de ACV, 65 % mortalidad, 71 % reportó disminución de hemorragia intracraneal y 45 % de sangrado mayor, pero hubo aumento de sangrado gastrointestinal en el 5 4% de los estudios. En relación a los resultados de los subanálisis, 4 estudios mostraron algún dato estadísticamente significativo para apixabán, 5 para dabigatrán, 3 para edoxabán y 5 estudios para rivaroxabán. Existen diferencias en algunas variables como sexo, riesgo de ACV, resultados a 30 días, función renal; diferentes dosis (dabigatrán y edoxabán), según la edad, síntomas gastrointestinales, relación con el INR; niveles séricos del medicamento, uso de amiodarona, uso previo de warfarina; enfermedad arterial periférica, transición a warfarina; factores de riesgo de HGI y sangrado mayor para cada anticoagulante en particular. CONCLUSIONES: Los nuevos anticoagulantes orales muestran mejor perfil de seguridad y de eficacia frente a warfarina.

SUMMARY INTRODUCTION: New oral anticoagulants are the latest advancement in oral anticoagulation. Several studies are published, but a few studies of synthesis information. METHODS: A systematic review of the studies in MEDLINE, COCHRANE and EMBASE was performed with the predefined terms. The defined inclusion and exclusion criteria were applied; variables used in this study were defined according to benefits (reduction of mortality and reduction of stroke) and anticoagulation risks (intracranial bleeding, gastrointestinal bleeding, major bleeding and other bleeding). Articles were selected and information was extracted into a spreadsheet for analysis. RESULT: Were included 24 meta-analyzes and 62 sub-analyzes; 77% of meta-analyzes showed stroke reduction, 65% in mortality, 71% reported decreased of intracranial hemorrhage and 45% in major bleeding, but there was an increase in gastrointestinal bleeding in 54% of the studies. Regarding the results of the sub-analysis, 4 studies for apixaban, 5 for dabigatran, 3 for edoxaban and 5 studies for rivaroxaban showed some statistically significant data. There are differences in some variables such as sex, stroke risk, 30-day results, renal function; Different doses (dabigatran and Edoxaban), according to age, gastrointestinal symptoms, relation with INR; Serum levels of the drug, use of amiodarone, prior use of warfarin; Peripheral arterial disease, transition to warfarin; Risk factors for gastrointestinal bleeding and major bleeding for each particular anticoagulant. CONCLUSION: The new oral anticoagulants shows better safety and efficacy profile against Warfarin.

Repetitive Transcranial Magnetic Stimulation for Phantom Limb Pain in Land Mine Victims: A Double-Blinded, Randomized, Sham-Controlled Trial.

UNLABELLED: We evaluated the effects of repetitive transcranial magnetic stimulation (rTMS) in the treatment of phantom limb pain (PLP) in land mine victims. Fifty-four patients with PLP were enrolled in a randomized, double-blinded, placebo-controlled, parallel group single-center trial. The intervention consisted of real or sham rTMS of M1 contralateral to the amputated leg. rTMS was given in series of 20 trains of 6-second duration (54-second intertrain, intensity 90% of motor threshold) at a stimulation rate of 10 Hz (1,200 pulses), 20 minutes per day, during 10 days. For the control group, a sham coil was used. The administration of active rTMS induced a significantly greater reduction in pain intensity (visual analogue scale scores) 15 days after treatment compared with sham stimulation (-53.38 ± 53.12% vs -22.93 ± 57.16%; mean between-group difference = 30.44%, 95% confidence interval, .30-60.58; P = .03). This effect was not significant 30 days after treatment. In addition, 19 subjects (70.3%) attained a clinically significant pain reduction (>30%) in the active group compared with 11 in the sham group (40.7%) 15 days after treatment (P = .03). The administration of 10 Hz rTMS on the contralateral primary motor cortex for 2 weeks in traumatic amputees with PLP induced significant clinical improvement in pain. PERSPECTIVE: High-frequency rTMS on the contralateral primary motor cortex of traumatic amputees induced a clinically significant pain reduction up to 15 days after treatment without any major secondary effect. These results indicate that rTMS is a safe and effective therapy in patients with PLP caused by land mine explosions.