Chronic pelvic pain is a debilitating disease that directly impacts on quality of life and generates costs for health services. Nutcracker Syndrome is an important cause of pelvic pain and consists of a set of signs secondary to compression of the left renal vein, most commonly between the superior mesenteric artery and the aorta. Treatment remains controversial and varies depending on the patient's clinical severity. However, endovascular treatment with renal vein stenting has achieved excellent results. We report the case of a 59 year-old female treated by endovascular repair with a self-expanding nitinol stent. Clinical data, details of the procedure, and follow-up results are presented. Technical success was achieved and there patient reported no postoperative complications. Short-term, there was relief from symptoms and follow-up imaging tests showed improvement. Chronic pelvic pain is a debilitating disease with considerable impact on quality of life and productivity. It is defined as non-menstrual or non-cyclic pelvic pain, with duration of at least 6 months, sufficiently intense to interfere in daily activities and requiring clinical or surgical treatment. One of the main causes of chronic pelvic pain is pelvic congestion syndrome (PCS), which has clinical status characterized by varying degrees of pain, dysuria, dysmenorrhea, dyspareunia, and vulvar congestion, very often associated with vulvar varicose veins.Laboratory tests often reveal signs of microhematuria, which is possibly associated with nutcracker syndrome (NCS), an anatomic variant in which the superior mesenteric artery (SMA) and the aorta clamp the left renal vein (LRV), causing reflux from this vein and the LGV. According to Robertson & McCuaig,-Nutcracker syndrome generally affects women aged from 20 to 40 years, especially multiparous women. The venous reflux provokes varicose veins in the deep and superficial venous pelvic plexus and is responsible for a typical clinical status comprising left flank pain and chronic abdominal pain. In men, the syndrome can manifest in a similar manner and has been described as one of the causes of varicocele.This article describes a case of NCS, diagnosed and treated with endovascular techniques in a private clinic in the city of Salvador, state of Bahia, Brazil.The patient was a 59-year-old female with a history of pain in the left iliac fossa and flank after prolonged standing and dyspareunia with onset 3 years previously. She was free from lower limb edema and other comorbidities. Physical examination was normal other than lower limb telangiectasias. During this period, she consulted with a rheumatologist and gynecologist, who referred her to the vascular surgery service.Transvaginal ultrasonography found adnexal varicose veins on the left. Duplex scan findings of the aorta and renal arteries were normal. Finally, angiotomography revealed a significant reduction of the LRV in the mid third, in the topography of the passage between the SMA and the aorta, associated with ipsilateral adnexal varicose veins, providing evidence of NCS .After 6 months of conservative treatment, with phlebotonics and analgesics, without resolution, the decision was taken to perform surgical treatment. Repair was performed via endovascular access, after local anesthesia and sedation. The right common femoral vein was punctured and a 6F introducer sheath inserted. The LRV was catheterized with a Cobra 2 5F diagnostic catheter and phlebography was performed. This confirmed critical stenosis of the LRV and pelvic varicose veins on the left, with a discretely dilated gonadal vein -4. The Control phlebography demonstrated complete resolution of the LRV stenosis .There were no complications during the surgical procedure or the immediate postoperative period. The patient recovered satisfactorily and was discharged 24 h after the procedure, with immediate relief from pain. She took clopidogrel and acetylsalicylic acid (ASA) for 30 days and then ASA only thereafter.The patient agreed to publication of this case report and signed an informed consent form.Five months after the endovascular treatment, the patient remained asymptomatic and was in outpatients follow-up at the clinic. During this period, control tomography showed the stent was patent and free from thrombi, with satisfactory correction of the renal compression  and 8. ,The nutcracker phenomenon (NCP) consists of compression of the LRV, most often between the aorta and the SMA, with debilitation of blood flow that is frequently accompanied by distension of the hilar portion of the vein. The NCS is the clinical equivalent of the NCP, characterized by a complex of symptoms with substantial variations. The more common examples include hematuria and proteinuria, flank pain, pelvic congestion in female patients, and varicocele in male patients.,The exact prevalence of NCS is unknown, partly because of an absence of definitive diagnostic criteria and the variability of symptomatic presentation. Patients can exhibit the condition at any age from infancy to the seventh decade of life, with peaks in youth  and middle-age.Depending on the specific manifestations, NCS may be identified by a number of different medical specialties and, although it is associated with considerable morbidity, diagnosis tends to be difficult and is generally late.,,Treatment for NCS varies depending on the patient’s clinical severity and is reserved for symptomatic patients only. According to Macedo et al.,,Transposition of the renal vein has been the gold standard for treatment and proven effective. It was employed for the first time in 1982, and appears to be the most common surgical intervention. The procedure is performed using a mid-line transperitoneal approach (mini laparotomy).The Wallstent was the first stent to be used and, according to Macedo et al.,The ideal stent should have high radial strength, to eliminate the stenosis, good conformability to adapt to the epithelium of the vessel, and should suffer little length shrinkage, to enable adequate positioning. With our patient, we chose to use a Luminex self-expanding nitinol stent, which offers more precise placement, without risk of shortening like the Wallstent, and we achieved a good result. Embolization of the LGV was unnecessary.It is important to emphasize that protrusion of the stent into the inferior vena cava should not be considered a complication, since, similar to the technique used by Raju et al.With relation to anticoagulation and antiplatelet drugs, it should be noted that complications such as thrombosis and stent restenosis can occur, but are rare.A high degree of clinical suspicion is needed to diagnose NCS. There are a wide range of treatment possibilities, depending on clinical status and the anatomic characteristics of each case. In this study, the endovascular technique proved safe and effective. The LGV was not embolized, since this conduct does not yet enjoy consensus in the literature. A dor pélvica crônica é uma doença debilitante, com grande impacto na qualidade de vida e na produtividade. Ela é definida como dor pélvica não menstrual ou não cíclica, com duração de pelo menos 6 meses, suficientemente intensa para interferir em atividades habituais e que necessita de tratamento clínico ou cirúrgico. Entre as causas de dor pélvica crônica, destaca-se a síndrome de congestão pélvica (SCP), com quadro clínico caracterizado por graus variados de dor, disúria, dismenorreia, dispareunia e congestão vulvar, muitas vezes acompanhada de varizes vulvaresExames laboratoriais para esses casos frequentemente mostram sinais de microhematúria, possivelmente associada à síndrome do quebra-nozes (SQN), uma variação anatômica na qual a artéria mesentérica superior (AMS) e a aorta realizam um clampeamento da veia renal esquerda (VRE), com consequente refluxo dessa veia e da VGE. Segundo Robertson & McCuaig-A SQN geralmente afeta as mulheres de idade entre 20 e 40 anos, especialmente mulheres multíparas. O refluxo venoso provoca varizes do plexo venoso pélvico profundo e superficial e é responsável por um quadro clínico típico dor em flanco esquerdo e dor abdominal crônica. Nos homens, essa síndrome pode se manifestar de forma semelhante, sendo uma das causas descritas de varicoceleEste trabalho relata um caso de SQN, diagnosticado e tratado por meio da técnica endovascular em uma clínica particular na cidade de Salvador (BA).Paciente do sexo feminino, 59 anos, com história de dor em fossa ilíaca e flanco esquerdos após ortostatismo prolongado e dispareunia há 3 anos. Negava edema de membros inferiores e comorbidades. O exame físico revelou-se normal, apenas com telangiectasias em membros inferiores. Durante esse tempo, se consultou com reumatologista e ginecologista, que a encaminhou para o Serviço de Cirurgia Vascular.duplex scan de aorta e artérias renais mostrou-se sem alterações. Por fim, a angiotomografia revelou uma redução significativa da VRE no terço médio, na topografia da sua passagem entre a AMS e a aorta, associada a varizes anexiais homolaterais evidenciando a SQN  durante 30 dias e manteve apenas o AAS após o término desse período.A paciente concordou em participar do relato de caso mediante assinatura do termo de consentimento livre e esclarecido.Após 5 meses do tratamento endovascular, a paciente mantinha-se assintomática em acompanhamento ambulatorial no serviço. Nesse período, foi realizada uma tomografia de controle, que evidenciou stent pérvio e sem trombos, com correção satisfatória da compressão renal  e 8. Nã,O fenômeno do quebra-nozes (FQN) refere-se à compressão da VRE, mais comumente entre a aorta e a AMS, com fluxo sanguíneo debilitado frequentemente acompanhado por distensão da porção hilar da veia. A SQN é o equivalente clínico do FQN, caracterizada por um complexo de sintomas com variações substanciais. Exemplos mais comuns incluem hematúria e proteinúria, dor no flanco, congestão pélvica em pacientes do sexo feminino e varicocele em pacientes do sexo masculino,A prevalência exata da SQN é desconhecida, em parte devido à ausência de critérios diagnósticos definitivos e à variabilidade na apresentação sintomática. Os pacientes podem apresentar o quadro em qualquer idade desde a infância até a sétima década de vida, com picos culminando em jovens  e em adultos de meia-idadeDependendo de manifestações específicas, a SQN pode ser encontrada por diferentes especialidades médicas e, embora seja associada a considerável morbidade, seu diagnóstico costuma ser difícil e geralmente atrasado,,O tratamento da SQN varia de acordo com a gravidade clínica do paciente e está reservado apenas para pacientes sintomáticos. Segundo Macedo et al.,A transposição de veia renal tem sido o padrão-ouro para tratamento, e se mostrou eficaz. Foi aplicada pela primeira vez em 1982, e parece ser a intervenção cirúrgica mais frequente. O procedimento é executado utilizando uma abordagem transperitoneal na linha média (mini laparotomia)O Wallstent foi o primeiro stent utilizado e, segundo Macedo et al.O stent ideal deve ter alta força radial para abolir a estenose, boa conformabilidade para se adaptar ao epitélio do vaso, e pouco encolhimento no comprimento para permitir um posicionamento adequado. Na nossa paciente, optamos por usar o stent autoexpansível de nitinol Luminex, que é mais preciso na sua colocação, sem risco de encurtamento como o Wallstent, e obtivemos um bom resultado. Não foi necessária a embolização da VGE.É importante destacar que não se deve considerar a protrusão do stent na veia cava inferior como uma complicação, pois, de forma semelhante à técnica usada por Raju et al.Com relação à anticoagulação e à antiagregação, vale ressaltar que complicações como trombose e reestenose do stent podem acontecer, mas são rarasA SQN requer um alto índice de suspeição para seu diagnóstico. O tratamento passa por uma ampla gama de possibilidades, dependendo do quadro clínico e das características anatômicas de cada caso. Neste estudo, a técnica endovascular se mostrou segura e eficaz. A embolização da VGE não foi realizada, já que essa conduta ainda não é consenso na literatura


Nature Communications8:14267; 10.1038/ncomms14267; published online 24 Jan 2017Correction to: The original version of this Article omitted the fourth author, Sara Ducci from Matériaux et Phénomènes Quantiques, Université Paris Diderot, CNRS UMR 7162, Sorbonne Paris-Cité, 10 rue Alice Domon et Léonie Duquet, Paris 75013, France. This mistake has been corrected in both the HTML and PDF versions of the Article.


A strategy for reducing the number of cesarean sections is to allow vaginal delivery after cesarean section. To validate two predictive models, Metz and Grobman, for successful vaginal delivery after a cesarean section. Retrospective cohort study involving women with previous history of a previous segmental cesarean section, single pregnancy ≥37 weeks and cephalic presentation. The proportion of vaginal delivery in all pregnant women was determined, and it was compared with those (women) with successful delivery after cesarean section. Then, there were elaborated the models, and their predictive capacity was determined by curve-receiver-operator. The proportion of successful delivery in pregnant women with a previous cesarean section and indication of vaginal delivery was 85.64%. The observed proportion of birth for each decile predicted in the Grobman model was less than 15%, except for the 91-100% decile, where it was 64.09%; the area under the curve was 0.95. For the Metz model, the actual successful delivery rate was lower than predicted in scores between 4 and 14, and within expected for a score between 15 and 23; the area under the curve was 0.94. The vaginal delivery rate after cesarean was lower than expected according to the predictive models of Grobman and Metz. The implementation of these models in a prospective way can lead to a higher rate of successful birth. Hospital Universitario del Valle, the proportion of C-sections in the last five years ranged between 27% and 29%.Cesarean section (C-section) is one of the most common surgical procedures performed in women, especially in developed countries. In 1985, the World Health Organization (WHO) recommended that the rate for cesarean rate should not exceed 10-15% of total births The most common indications in the world for a primary cesarean include: stationary labor, altered or indeterminate fetal monitoring, anomalous fetal presentation and multiple gestation; corresponding the first two ones to more than half At the beginning of the 20th century, there prevailed the concept of "once a cesarean, always a cesarean" ,Between 1996 and 2010, VBAC was reduced from 28% to 8% In 2007, Grobman In 2009, Grobman et al. et al. Recently, Metz Hospital Universitario del Valle is an institution that provides services for a population of high obstetric risk; an average of 7,500 births are attended every year, of which, 28-30% are by C-section. Currently, it is considered that the route of termination of a pregnancy, after cesarean delivery, is by vaginal delivery, but no predictive model is applied, and the decision depends mainly on the pelvic assessment and the Bishop index upon admission. For those reasons, the main objective of this study was to validate two predictive models, those by Metz and Grobman, for successful vaginal delivery after C-section (VBAC) in a pregnant population with previous C-section that enter to the Hospital for delivery; and to describe the maternal and fetal morbidity associated with vaginal delivery after C-section.Retrospective cohort study, in women who were pregnant for 37 weeks or longer, with a previous C-section and who were admitted to HUV during the study period (January-2009 to December-2013); there were included all pregnant women with a only previous cesarean procedure, pregnancy of 37 weeks or longer, and fetus in cephalic presentation at the time of defining the end of pregnancy; there were excluded patients with previous corporal C-section documented in the clinical history, previous uterine surgery  or fetal death before the moment of defining the route of termination of pregnancy, as well as patients with inadequate pelvis.Antepartum Variables: maternal age (years), body mass index (Kg/m2), ethnicity, prior vaginal delivery, the occurrence of VBAC and recurring indication for C-section; Variables determined at admission to labor: gestational age (complete weeks from the last reliable menstruation date or from the first available ultrasound), cervical dilatation, effacement, station, position and cervical consistency, induction of labor, cervical ripening, state of the membranes upon admission; and Maternal-fetal complications: uterine rupture, vaginal tear, uterine hypotonia, postpartum hemorrhage, bladder injury, pelvic or abdominal organ injury, maternal infection , weight of the newborn, Apgar score at minute and at 5 minutes, vitality at birth, neonatal complications . In addition, the outcome variable was the mode of delivery: vaginal (spontaneous or instrumented) or C-section.The evaluated clinical variables were those included in the Grobman and Metz models, that is: ® program for analysis. For quality control, 20% of the medical records were reviewed and double typing was done. In case of discrepancies, the database was confronted with the data collection formats. The study was approved by the ethics committee of Universidad del Valle and HUV.The information was collected in a Data Collection Format designed for that purpose and then exported to the Stata 10The sample size was determined according to the recommendation of Harrel The cumulative incidence of vaginal delivery after C-section was determined by the equation: patients with successful vaginal delivery (VBAC)/total patients with a previous C-section during the observation period. The proportion of deliveries in patients allowed TOLAC was calculated with the equation: patients with successful vaginal delivery (VBAC)/patients with previous C-section in whom labor was attempted. 2 ) or the Fisher's exact test for categorical data, according to the expected values in each one of the cells. Subsequently, a multivariate analysis was carried out using logistic regression, including in the model those variables that in the univariate analysis obtained a value of p <0.2 or those that theoretically are considered predictive potentials, that is, those included in the models to be validated.For clinical characteristics at entering (the study), it was carried out a univariate analysis of the different independent variables according to the level of measurement of the variables; for continuous variables, there were used the Student's t-test and the Wilcoxon rank-sum test according to the distribution of the variables; and the Chi-squared test /[1 + exp (w)] where w = 7.059 - 0.037 (age) - 0.44 (BMI) -0.46 (Afro-Americans) - 0.761 (Hispanic population) + 0.955  + 0.851  - 0.655 (recurrent indication for C-section) - 0.109  - 0.499 (hypertensive disease of pregnancy) + 0.044 (effacement) + 0.109 (dilatation ) + 0.082 (station) - 0.452 (induction of labor).This prediction probability was divided into 10 deciles ; in each category, it was determined the actual (95%) proportion of success (that was) found. The predictive capacity of the model was established by calculating the area under the curve (AUC) of the operator receiver curve (ROC). The area under the curve was determined non-parametrically (in a non-parametric way), using the trapezoidal rule. Finally, a graphical comparison was made of the observed values in the midpoints of each decile, in relation to the predicted values.+ and RV-) were determined.For the Metz model, the predicted probabilities were calculated using the points assigned to each variable of the model, (which were) previously published by the author During the years 2009 to 2013, there were 29,866 births in the HUV, of which 8,572 were via C-section, for a proportion of C-sections of 28.7%. In the same period, there were 483 pregnant women who met the inclusion criteria of the study and who did not present exclusion criteria, of which 203 (42.0%) were offered TOLAC, and 280 were scheduled for C-section from admission . The chaThe number of deliveries was 174 (171 spontaneous and 3 instrumented), for a proportion of deliveries in pregnant women with a previous C-section of 36.0%. The majority of patients who had a delivery (86.2%) entered with Bishop's index ≥7, while only 13.9% of the pregnant women who underwent C-section were admitted with a favorable index of Bishop for induction. The median of the Bishop index (RIQ) at admission was 8 (0-4) for pregnant women with C-section and 10 (8-11) for those who completed delivery.Of the 203 pregnant women subjected to TOLAC, 174 (85.7%) had a delivery. The characteristics of admission are presented in The main cause of an iterative C-section was a Bishop’s index unfavorable to admission in 179 (58.1%) pregnant women, followed by cephalic-pelvic disproportion in 30 (9.7%) patients and suspicion of fetal macrosomia in 20 (6.5%) patients. 9 (2.9%) C-sections were performed due to unsatisfactory fetal status, with two newborns with Apgar less than 7 at 5 minutes. Nine C-sections were performed due to imminence of uterine rupture; however, the uterus did not present solution of continuity in any of them.The real probability of VBAC for each decile of success probability of the Grobman model was lower than expected, being less than 20% in all deciles; except in the 91-100% decile, where the proportion of VBAC was 64.1% . The numFor a score lower than 14 in the Metz model, the real probability of VBAC was lower than predicted; in contrast, for scores ≥14, the real probabilities were higher than 65%, without significant differences in relation to the predicted ones . The nump= 0.38).The sensitivity, specificity and likelihood ratios of the Grobman and Metz model are presented in p= 0.09 for both models); however, with a difference between them (p= 0.009): a better performance for the Grobman model.In After selecting from the Grobman model only the variables that contribute to the logistic regression model for the pregnant women of the study, there persisted for our population the antecedent of delivery after C-section, effacement, station, dilatation at admission to the delivery service, and the presence of a hypertensive disorder. The association between these variables and the opportunity of delivery is presented in p= 0.00); however, when discarding vaginal tears, which are an exclusive complication of labor, these differences disappear (p= 0.07).It was found in the present study that for both models, the observed probability of successful vaginal delivery after C-section was lower than predicted. In the case of the Grobman model for predicted probabilities lower than 90%, the observed ones were less than 20%; and for the Metz model for predicted probabilities lower than 70% (score lower than 13), the observed probabilities were less than 40%. This is possibly due to the fact that these models are not applied at HUV, and the delivery decision is based exclusively on medical criteria, depending on the Bishop’s index on admission, which was reflected in the fact that the delivery attempt (TOLAC) was made in only 42.0% of pregnant women.p= 0.38).Despite the above, the performance of both models was adequate, with areas under the curve higher than 0.90, a sensitivity of around 80%, and a false positive rate close to 10%, without significant differences between the two models , the antecedent of a birth after C-section and the presence of hypertensive disorder, which decreased the chance of VBAC; while for the Metz model, the only variable that persisted was Bishop's index at admission, which may be explained for being the cervical changes at the moment of pregnant woman's admission, a characteristic that determines the attempt of TOLAC.In pregnant women undergoing TOLAC, there were found a delivery rate of 85.7% and a C-section of 14.3%, lower than the proportion of C-sections recorded in the HUV and in the same period, which was between 25-30%. This shows the adequate selection of pregnant women with a previous C-section undergoing TOLAC, based on cervical changes. However, we believe that the application of a predictive model in clinical practice can potentially increase the overall success rate, which in our case was only 36.0%. If TOLAC had been attempted in those pregnant women with a predicted probability equal to or greater than 50%, according to the Grobman model, TOLAC should have been attempted in 77.6% of the pregnant women and not only in 42.0%; while for the Metz model, the attempt of TOLAC should have occurred in 54.2% of the cases. ,,,,The high rate of C-sections worldwide and nationally ,One of the most important concerns for medical personnel is the risk of maternal complications such as uterine rupture and neonatal complications such as fetal death or neonatal asphyxia in patients undergoing delivery after C-section. In the present study, there were found no significant differences for 5 years between the pregnant women taken to C-section or delivery; however, there were more cases of postpartum hemorrhage in cases of vaginal delivery (5.75 vs. 1.29%), but in no case was there a need for hysterectomy within the management, or maternal death. With regard to newborns, no differences were found in the Apgar score at 5 minutes, or in the need for mechanical ventilation. Currently, there is no universally accepted discriminatory point regarding the predicted probability of success that is related to lower morbidity; however, apparently a probability of minimum success of 60-70% has equal or less probability of maternal complications for pregnant women subjected to TOLAC in relation to pregnant women taken to a repeated C-section The limitations of this study are those of the retrospective studies, based solely on the collection of information in the clinical history; however, there occurred missing data in less than 1% of the variables. Because of the retrospective nature, the decisions of delivery attempt depended on the criterion of the attending physician, and not on a previously standardized protocol, which may explain the low proportion of births (36.0%) in the population studied.Most of the variables included in the Grobman and Metz models do not contribute to the final model of HUV, which may also be due to the retrospective nature of the study, since neither race, maternal age or antecedent of childbirth are considered as potential characteristics that modify the probability of delivery; currently, in pregnant women with unfavorable Bishop’s index, cervical ripening is not attempted with potentially useful alternatives such as the use of cervical balloon or dilatation through the use of trans-cervical Foley catheter; therefore, a prospective study with the application of a predictive model and with the implementation of cervical non-pharmacological ripening techniques, would allow a better validation of the models. Taking into account the similar performance between both models and the ease of application of the Metz model, we consider this one to be the most likely to be implemented in most obstetrical services, without the requirement of access to software or programs for determining the probability of successful vaginal delivery after C-section. La cesárea es uno de los procedimientos quirúrgicos más comunes que se realiza en mujeres, especialmente en países desarrollados. En 1985, la Organización Mundial de la Salud (OMS) recomendó que la tasa de cesárea no debía exceder el 10-15% del total de nacimientos Las indicaciones más comunes en el mundo para una cesárea primaria incluyen: trabajo de parto estacionario, monitorias fetales alteradas o indeterminadas, presentación fetal anómala y gestación múltiple, las dos primeras corresponden a más de la mitad A principios del siglo XX, se tuvo el concepto “una vez cesárea, siempre cesárea” ,Entre 1996 y 2010 se encontró que la VBAC se redujo del 28% al 8% En 2007, Grobman et al. Recientemente Metz El Hospital Universitario del Valle es una institución que maneja una población de alto riesgo obstétrico, atiende un promedio 7,500 nacimientos al año, de los cuales, el 28-30% son por vía cesárea. Actualmente se considera que la vía de finalización del embarazo después de una cesárea es el parto vaginal pero no se aplica ningún modelo predictivo y la decisión depende fundamentalmente de la valoración pélvica y del índice de Bishop al ingreso, por lo cual el objetivo principal del estudio fue validar dos modelos predictivos, Metz y Grobman, para parto vaginal exitoso después de cesárea VBAC en la población gestante con cesárea previa que ingresan para parto al Hospital y describir la morbilidad materna y fetal asociada al parto vaginal después de cesárea. Estudio de cohorte retrospectivo, en gestantes de 37 o más semanas con una cesárea previa que ingresaron para atención al Hospital Universitario del Valle (HUV) durante el periodo de estudio (Enero-2009 a Diciembre-2013), se incluyeron todas las gestantes con una sola cesárea previa, embarazo de 37 semanas o más y feto en presentación cefálica al momento de definir la finalización del embarazo, se excluyeron pacientes con cesárea previa corporal documentada en la historia clínica, antecedente de cirugía uterina previa  o muerte fetal antes del momento de definición de la vía de finalización del embarazo y pacientes con pelvis inadecuada. variables anteparto; edad materna (años), Índice de masa corporal (Kg/m2), etnia, antecedente de parto vaginal previo a la cesárea y de parto vaginal después de cesárea, gravidez, causa de cesárea previa; variables determinadas a la admisión al trabajo de parto ; edad gestacional (semanas completas a partir de fecha de ultima menstruación confiable o partir de primera ecografía disponible), dilatación cervical, borramiento, estación, posición y consistencia cervical, inducción del trabajo de parto, maduración cervical, estado de las membranas al ingreso y adicionalmente complicaciones maternofetales como ruptura uterina, desgarro vaginal, hipotonía uterina, hemorragia posparto, lesión vesical, lesión de órganos pélvico o abdominales, infección materna , peso del recién nacido, apgar al minuto y a los 5 minutos, vitalidad al nacimiento, complicaciones neonatales . Adicionalmente la variable resultado fue modo de parto, vaginal (espontáneo o instrumentado) o cesárea.Las variables clínicas evaluadas fueron las incluidas en los modelos de Grobman y Metz asi: La información se recolectó en un Formato de Recolección de Datos diseñado para tal fin y se exportó al programa Stata 10 ® para su análisis. Para control de calidad se realizó la revisión del 20% de las historias clínicas y se hizo doble digitación. En caso de discrepancias se confrontó la base de datos con los formatos de recolección de datos. el estudio fue aprobado por el comité de ética de la Universidad del Valle y del Hospital Universitario del Valle.El tamaño de muestra se determinó según la recomendación de Harrel Se determinó la Incidencia acumulada de parto vaginal después de cesárea mediante la ecuación: pacientes con parto vaginal exitoso (VBAC)/total pacientes con una cesárea previa en periodo de observación, la proporción de partos en pacientes que se permitió TOLAC se calculó con la ecuación: pacientes con parto vaginal exitoso (VBAC)/pacientes con cesárea previa en quienes se intentó parto.2 o la prueba exacta de Fisher de acuerdo a los valores esperados en cada una de las celdas. Posteriormente se realizó un análisis multivariado mediante la regresión logística incluyendo en el modelo aquellas variables que en el análisis univariado obtuvieron un valor de p <0.2 o las que teóricamente se consideran potenciales predictores, es decir las incluidas en los modelos a validar. Para las características de ingreso se realizó un análisis univariado de las diferentes variables independientes de acuerdo al nivel de medición de las variables; para las variables continuas se utilizó la prueba T de student y rango de suma de wilconxon de acuerdo a la distribución de las variable y para las categóricas chi2 o prueba exacta de Fisher de acuerdo a los valores esperados en cada una de las celdas.La morbilidad materna y fetal se presenta como frecuencias absolutas y relativas. Se realizó la comparación de las complicaciones mediante chiPara determinar la capacidad predictiva del modelo de Grobman en la población del Hospital Universitario del Valle, se determinó la probabilidad predicha mediante el uso de la ecuación previamente publicada por Grobman Predicción de parto = exp(w)/[1+exp(w)] donde w= 7.059 - 0.037(edad) - 0.44(IMC) -0.46(raza negra-raza americana) - 0.761(raza hispana) + 0.955 + 0.851 - 0.655(indicación recurrente de cesárea) - 0.109 - 0.499(enfermedad hipertensiva del embarazo) + 0.044(borramiento) + 0.109(dilatación) + 0.082(estación) - 0.452(inducción del parto).Esta probabilidad de predicción se fraccionó en 10 deciles , en cada categoría se determinó la proporción (IC 95%) real de éxito encontrada. La capacidad predictiva del modelo se estableció mediante el cálculo del área bajo la curva (AUC) de la curva receptor operador (ROC). El área bajo la curva se determinó de forma no paramétrica, utilizando la regla trapezoidal. Finalmente se realizó una comparación grafica de los valores observados en los puntos medios de cada decil en relación a los valores predichos. + y RV-).Para el modelo de Metz se calculó las probabilidades predichas utilizando los puntos asignados a cada variable del modelo, previamente publicados por el autor Durante los años 2009 a 2013 se presentaron en el HUV 29,866 nacimientos de los cuales 8,572 fueron vía cesárea, para una proporción de cesáreas del 28.7%. En el mismo periodo se presentaron 483 gestantes que cumplieron con los criterios de inclusión del estudio y sin criterios de exclusión, de las cuales a 203 (42.0%) se les ofreció TOLAC y a 280 se las programo para cesárea desde el ingreso . Las carEl número de partos fue de 174 (171 espontáneos y 3 instrumentados), para una proporción de partos en gestantes con una cesárea previa de 36.0%. La mayor parte de pacientes que tuvieron parto (86.2%) ingresaron con índice de Bishop ≥7, mientras solo 13.9% de las gestantes a quienes se les realizó cesárea, ingresaron con índice de Bishop favorable para inducción. La mediana del índice de Bishop (RIQ) al ingreso fue 8 (0-4) para las gestantes con cesárea y 10 (8-11) para las que finalizaron por parto. De las 203 gestantes sometidas a TOLAC, 174 (85.7%) tuvieron parto. Las características de ingreso se presentan en la La principal causa de cesárea iterativa fue un índice de Bishop desfavorable al ingreso en 179 (58.1%) gestantes, seguida por desproporción cefalopélvica en 30 (9.7%) pacientes y sospecha de macrosomía fetal en 20 (6.5%) pacientes. Se realizaron 9 (2.9%) cesáreas por estado fetal no satisfactorio, con dos recién nacidos con apgar menor de 7 a los 5 minutos. Nueve cesáreas se realizaron por inminencia de ruptura uterina, sin embargo, en todas ellas el útero no presento solución de continuidad.La probabilidad real de VBAC para cada decil de probabilidad de éxito del modelo de Grobman fue menor a lo esperado, siendo inferior al 20% en todos los deciles, excepto en el decil 91-100%, donde la proporción de VBAC fue 64.1% . El númePara el modelo de Metz en puntaje inferior a 14 la probabilidad real de VBAC fue menor a las predicha y para puntaje ≥14, las probabilidades reales fueron superiores a 65%, sin diferencias significativas en relación a las predichas . El númep= 0.38). La sensibilidad, especificidad y razones de verosimilitud del modelo de Grobman y de Metz se presentan en la p= 0.09 para ambos modelos), sin embargo, con diferencia entre ellos (p= 0.009) con un mejor rendimiento para el modelo de Grobman. La sensibilidad, especificidad y razones de verosimilitud de los modelos de Grobman y Metz con solo las variables que aportaron a la predicción del estudio se presentan en la Después de seleccionar del modelo de Grobman solo las variables que aportan al modelo de regresión logística para las gestantes del estudio, persistieron para nuestra población el antecedente de parto después de cesárea, el borramiento, estación, dilatación al ingreso al servicio de partos y la presencia de un trastorno hipertensivo. La asociación entre estas variables y la oportunidad de parto se presenta en la p= 0.00), sin embargo, al descartar los desgarros vaginales los cuales son una complicación exclusiva del parto, estas diferencias desaparecen (p= 0.07). En la En el presente estudio se encontró que para ambos modelos la probabilidad observada de parto vaginal exitoso después de cesárea fue menor a la predicha. En el caso del modelo de Grobman para probabilidades predichas inferiores al 90%, las observadas fueron menores al 20% y para el modelo de Metz para probabilidades predichas inferiores al 70% (puntaje inferior a 13), las probabilidades observadas fueron inferiores a 40%, esto se debe posiblemente a que en la institución no se aplican estos modelos y la decisión de parto se basa exclusivamente en el criterio médico, dependiendo del índice de Bishop al ingreso, lo cual se reflejó en que solo se realizó el intento de parto (TOLAC) en el 42.0% de las gestantes.p= 0.38). A pesar de lo anterior el rendimiento de ambos modelos fue adecuado con áreas bajo la curva superiores al 0.90, una sensibilidades alrededor del 80% y una tasa de falsos positivos cercana al 10%, sin diferencias significativas entre ambos modelos , el antecedente de un parto después de cesárea y la presencia de trastorno hipertensivo el cual disminuyó la oportunidad de VBAC, mientras para el modelo de Metz la única variable que persistió fue el índice de Bishop al ingreso, lo anterior posiblemente explicado por ser los cambios cervicales al ingreso de la gestante la característica que determina el intento de TOLAC.En gestantes sometidas a TOLAC se encontró una proporción de parto del 85.7% y una proporción de cesárea del 14.3%, inferior a la proporción de cesárea registradas en el HUV y en el mismo periodo, la cual estuvo entre 25-30%. Esto muestra la adecuada selección de las gestantes con cesárea previa sometidas a TOLAC, basada en los cambios cervicales. Sin embargo consideramos que la aplicación de un modelo predictivo en la práctica clínica, potencialmente puede aumentar la proporción de éxito global que en nuestro caso fue de solo 36.0%. Si se hubiera intentado TOLAC en aquellas gestantes con una probabilidad predicha igual o superior al 50% según el modelo de Grobman se debió haber intentado TOLAC en el 77.6% de las gestantes y no solo en el 42.0%, mientras que para el modelo de Metz el intento de TOLAC debió ser en 54.2% de los casos.,,,,La alta tasa de cesárea a nivel mundial y nacional ,Una de las preocupaciones más importantes en el personal médico es el riesgo de complicaciones maternas como la ruptura uterina y, neonatales como muerte fetal o asfixia neonatal, en pacientes sometidas a parto después de cesárea. En el presente estudio durante 5 años no se encontró diferencias significativas entre las gestantes llevadas a cesárea o a parto, no obstante, hubo más casos de hemorragia postparto en casos de parto vaginal (5.75 vs 1.29%), pero en ningún caso hubo necesidad de histerectomía dentro del manejo o muerte materna. Con respecto a los recién nacidos no se encontró diferencias en el apgar a los 5 minutos o en la necesidad de ventilación mecánica. No existe en la actualidad ningún punto discriminatorio universalmente aceptado respecto a la probabilidad predicha de éxito que se relaciona con menor morbilidad, sin embargo, aparentemente una probabilidad de éxito mínima del 60 -70%, tiene igual o menor probabilidad de complicaciones maternas para gestantes sometidas a TOLAC en relación a gestantes llevadas a una cesárea a repetición Las limitaciones del estudio son las propias de los estudios retrospectivos, basado únicamente en la recolección de información en la historia clínica, sin embargo, se presentaron datos faltantes en menos del 1% de las variables. Por la naturaleza retrospectiva, las decisiones de intento de parto dependieron del criterio del médico tratante y no de un protocolo previamente estandarizado, lo cual puede explicar la baja proporción de partos (36.0%) en la población estudiada. La mayoría de variables incluidas en los modelos de Grobman y de Metz, no aportan al modelo final del Hospital Universitario del Valle, lo cual puede ser debido también a la característica retrospectiva del estudio, puesto que ni la raza, ni la edad materna o el antecedente de parto se consideran como características potenciales que modifiquen la probabilidad de parto y en la actualidad en gestantes con índice de Bishop desfavorable no se intenta maduración cervical con alternativas potencialmente útiles como el uso de balón cervical o dilatación mediante el uso de sonda Foley transcervical, por lo cual un estudio prospectivo con la aplicación de un modelo predictivo y con la implementación de técnicas de maduración cervical no farmacológicas, permitirían una mejor validación de los modelos.Teniendo en cuenta el rendimiento similar entre ambos modelos y la facilidad de aplicación del modelo de Metz consideramos este es el de mayor posibilidad de implementación en la mayoría de servicios de obstetricia, sin el requerimiento de acceso a software o programas para la determinación de la probabilidad de éxito de parto vaginal después de cesárea.


The following information is missing from the Funding section: This study was supported in part by Fundación Séneca Region de Murcia, Grant# 19409/PI/14 (SCG).


Dear Editors:et alSánchez, In their article, power twomeans command). In this manner, the detectable effect size would be 3.5; which is higher than the ACT effect size estimated in the Sánchez, Sánchez and Cardona’s article (i.e.: 3.0), leading to an underpowered study, at least for the cross-sectional estimates. In this manner, what was the appropriate sample size calculation?1) The sample size calculation is not clear. The authors mentioned the prevalence of asthma and rhinitis in the urban areas and their corresponding error, but they did not use these parameters in the sample size calculation. On the other hand, the authors argued that the main outcome was comparing the treatment of asthma and rhinitis between urban and rural areas; thus readers could assume that the measure of effect was the difference of the Asthma Control Test (ACT) score between both areas; but the authors did not clearly explain it. Furthermore, it is not clear why the ratio of urban/rural subjects is 1.57; is the ratio observed in the study health centers? In this line, it seems that the appropriate sample size calculation must have been the difference of means between two independent populations, although the authors did not report any ACT effect size based on previous studies. Thus, I have estimated the means difference (as the effect size) given the power (80%) and the study sample size  provided by the authors; using Stata® 14.2  The research was designed as a follow-up study with four assessments, at 3, 6, 9 and 12 months, but the statistical analyses were done using a cross-sectional approach at each measurement without taking into account the multilevel nature of the repeated  measures of each patient and without the baseline adjustments of the outcome scores. The cross-sectional analyses are not appropriate for determining within-subject’s longitudinal patterns; for example, 3) When the design of a research is a longitudinal study with repeated measures, and its data are appropriately analyzed with up-to-date statistical methods, this situation allows dealing with smaller sample size given the efficiency of the longitudinal data analysis methods, which improves when adding more measurements per subject ,4) Neither the location nor the health care level of the study centers are clear; nor are the criteria to select them. For example, if children of rural areas with the worst symptoms levels are referred to higher complexity health centers different to those in the study, it could be a selection bias which could affect the study findings  Dear Editors:We greatly appreciate the interest shown in the article "Clinical differences between children with asthma and rhinitis in rural and urban areas", which we hope will be one of several future articles that we intend to carry out in the study cohort. To the questions generated by the reader, one is focused on the calculation of the sample size, while the other two questions are focus in the method of analysis, and the reader suggests, it could be more robust.… the appropriate sample size calculation must have been the difference of means between two independent populations, although the authors did not report any ACT effect size based on previous studies." First, we fully agree with the reader that for this type of design, the study lost power by the form of sample size calculation. We did not find studies with the urban and rural ACT tests in the studied population, which made it impossible to obtain these parameters to perform the sample size calculation by the technique "power two means" (difference of means of two independent groups). ). As we noted in the article, we do not have previous data in the rural population that allow us to infer the precise prevalence of asthma in this area; as we also noted in the article the prevalence in Colombia of asthma in the general urban population is 11%, there are also data that indicate that in the child population (less than 12 years) it is around 23%; if we work with these two prevalence where we assume that the highest in children is for the urban population and that possibly the lowest corresponds to what happens in the rural population Regarding the sample size, we describe that infant asthma in urban areas of Medellin was 11% and rhinitis 23%, according to previous studies. There is no data available for the rural area. We note that with a confidence level of 95%, a power of 80% and a sample size error of 0.5%, the sample size was calculated; estimating 201 children for the urban area and 128 for the rural area. Finally, we recruited and were able to continue for a year, a total of 248 children from the urban area and 134 from the rural area. The complaint of the reader, is focus that the more appropriated technique would be "Regarding the following two questions of the reader that are focus in the design of the study and the analysis of the data; it is important to clarify that although a follow-up was carried out over time, for this study we wanted to focus in compared two groups  specially after 12 months of clinical treatment. We agree with the reader that a longitudinal analysis of repetitive measures would be appropriate and would provide additional interesting information for the effect of changes in the tests over time (e.g. ACT), however, for this study, we wanted to focus the results and the discussion, in compare these measures in two moments clinically relevant for the doctor; In the first consultation, the doctor sends a treatment and in the follow-up can make adjustments according to the clinical response; usually after one year if patient have a good clinical control, begins the process of dismantling the therapies. That’s why we preferred to highlight the final moment versus the initial moment. We recognized that the information in the intermediate times (3 months and 6 months) could be analyze in a longitudinal way, and in this form, we could evaluate the effect, but it contributes less for the objective that we planted, that was to compare if there were differences in the groups studied, especially at the end of the study, presumably due to the medical interventions carried out.Again, we thank the reader for their pertinent suggestions that put in their real dimension the results of our research and that will serve us for the next analyzes that we will carry out with this population. Estimados Editores:et al.En el artículo de Sánchez, power twomeans). De esta forma, el tamaño del efecto mínimamente detectable debería ser 3.5; el cual es mayor que la medida del efecto sobre el puntaje del ACT, estimada en eeste estudio 1) El cálculo del tamaño de la muestra no es claro. Los autores mencionaron las prevalencias de asma y rinitis en las áreas urbanas, con su error correspondiente, pero ellos no utilizaron esos parámetros para el cálculo del tamaño de la muestra. Por otro lado, los autores argumentaron que el desenlace (o variable resultado) principal del estudio fue comparar el tratamiento de asma y rinitis entre los niños de las áreas urbanas y rurales; entonces, los lectores pueden asumir que la medida de efecto utilizada fue la diferencia en el puntaje de la Prueba de Control del Asma  entre las dos áreas; pero los autores no explicaron este punto claramente. Adicionalmente, no es claro por qué el cociente entre los sujetos de las áreas urbanas/rurales es 1.57: ¿Es éste el cociente encontrado en las instituciones de salud del estudio? En consecuencia, parece que el cálculo para el tamaño de la muestra apropiado debe haber sido la diferencia de medias (o promedios) entre dos poblaciones independientes, aunque los autores no reportaron ningún tamaño de efecto de la prueba ACT basado en estudios previos. De esta forma, recalculé la diferencia de medias (como medida de efecto), utilizando el poder (80%) y el tamaño de muestra  reportado por los autores; usando Stata® 14.2  La investigación se diseñó como un estudio de seguimiento con cuatro mediciones  después de transcurridos 3, 6, 9 y 12 meses; pero los análisis estadísticos fueron realizados siguiendo un abordaje transversal en el momento de cada medición, sin tener en cuenta la naturaleza longitudinal (o multinivel) de las medidas repetidas de cada paciente y sin ajustar tampoco por los puntajes de línea de base de cada paciente. Los análisis transversales no son apropiados para determinar los patrones longitudinales intra-sujetos; por ejemplo, la 3) Cuando el diseño de una investigación es un estudio longitudinal con medidas repetidas y los datos son analizados adecuadamente utilizando los métodos estadísticos actualizados, esta situación permite utilizar tamaños de muestra más pequeños, dada la eficiencia de los métodos de análisis de datos longitudinales. La eficiencia mejora cuando se agregan más mediciones para cada sujeto de investigación ,4) En el artículo no se especifica ni la ubicación ni el nivel de atención de las instituciones de salud del estudio; ni tampoco se explican los criterios para haber elegido esas instituciones. Esta situación tiene varias implicaciones: Por ejemplo si los niños del área rural con los peores niveles de síntomas fueron referidos a centros de atención diferentes a los centros elegidos en esta investigación, entonces pudo haber ocurrido un sesgo de selección, el cual afecta la validez de los hallazgos del estudio  Estimados editores: Apreciamos enormemente el interés mostrado por el artículo "Diferencias clínicas entre niños con asma y rinitis en áreas rurales y urbanas", el cual esperamos sea uno de los futuros artículos que pretendemos llevar a cabo en la cohorte del estudio. A las preguntas generadas por el lector, una se enfoca en el cálculo del tamaño de la muestra, mientras que las otras dos preguntas se enfocan en el método de análisis. El lector sugiere que podría ser más sólido.Con respecto al tamaño de la muestra, describimos que el asma infantil en las áreas urbanas de Medellín fue del 11% y la rinitis del 23%, según estudios anteriores. No hay datos disponibles para el área rural. Notamos que con un nivel de confianza del 95%, una potencia del 80% y un error de tamaño de muestra del 0.5%, se calculó el tamaño de la muestra; estimando 201 niños para el área urbana y 128 para el área rural. Finalmente, reclutamos y pudimos seguir por un año, un total de 248 niños del área urbana y 134 del área rural. La solicitud del lector, se centró en que la técnica más apropiada sería "... el cálculo del tamaño de muestra apropiado debe haber sido la diferencia de medias entre dos poblaciones independientes, aunque los autores no informaron ningún tamaño de efecto de ACT basado en estudios anteriores". Primero, estamos totalmente de acuerdo con el lector en que para este tipo de diseño, el estudio perdió potencia por la forma de cálculo del tamaño de la muestra. No se encontraron estudios con las pruebas ACT urbanas y rurales en la población estudiada, lo que hizo imposible obtener estos parámetros para realizar el cálculo del tamaño de la muestra mediante la técnica "potencia de dos medias" (diferencia de medias de dos grupos independientes). Como señalamos en el artículo, no tenemos datos previos en la población rural que nos permitan inferir la prevalencia precisa del asma en esta área; Como también señalamos en el artículo, la prevalencia de asma en Colombia en la población urbana en general es del 11%, también hay datos que indican que en la población infantil (menos de 12 años) es de alrededor del 23%; si trabajamos con estas dos prevalencias donde asumimos que la más alta se encuentra en niños de la población urbana y que posiblemente la más baja corresponda a lo que sucede en la población rural Con respecto a las siguientes dos preguntas del lector que se centran en el diseño del estudio y el análisis de los datos; es importante aclarar que aunque se realizó un seguimiento a lo largo del tiempo, para este estudio quisimos centrarnos en comparar los dos grupos , especialmente después de 12 meses del tratamiento clínico. Estamos de acuerdo con el lector en que un análisis longitudinal de medidas repetitivas sería apropiado y proporcionaría información adicional interesante para el efecto de los cambios en las pruebas a lo largo del tiempo ; sin embargo, para este estudio, quisimos enfocar los resultados y la discusión en comparar estas medidas en dos momentos clínicamente relevantes para el médico; en la primera consulta, el médico envía un tratamiento y en el seguimiento puede realizar ajustes de acuerdo con la respuesta clínica. Generalmente después de un año, si el paciente tiene un buen control clínico, comienza el proceso de desmantelamiento de las terapias. Es por eso que preferimos resaltar el momento final frente al momento inicial. Reconocimos que el análisis de la información en los tiempos intermedios (3 meses y 6 meses) fue de forma longitudinal y, que de esta forma, podíamos evaluar el efecto, pero contribuye menos al objetivo que planteamos, que fue comparar si hubo diferencias en los grupos estudiados, especialmente al final del estudio, probablemente debido a las intervenciones médicas realizadas.Nuevamente, agradecemos al lector sus sugerencias pertinentes que ponen en su dimensión real los resultados de nuestra investigación y que nos servirán para los próximos análisis que realizaremos con esta población


A number of limitations of standard therapy with warfarin for deep vein thrombosis (DVT) have been established. This overview of systematic reviews presents the baseline results for efficacy and safety of the new direct oral anticoagulants (DOACs) thrombin inhibitors, and activated factor X (Xa) inhibitors in patients with DVT. Searches were run on PubMed and the Cochrane Database of Systematic Reviews. Twenty-three studies were retrieved, and one systematic review was judged eligible. This review scored maximum according to AMSTAR criteria and included 7,596 patients for analysis of thrombin inhibitors and 16,356 patients for analysis of factor Xa inhibitors. The results of the meta-analysis indicate that DOACs are similar for DVT treatment when compared to standard treatment with warfarin. The incidence of major bleeding is somewhat lower in patients treated with factor Xa inhibitors and similar to standard therapy when treated with direct thrombin inhibitors.  Deep venous thrombosis (DVT) in the lower limbs is a serious and potentially fatal disease. Incidence in the general population is five cases per 10,000 inhabitants annually. ,, Standard treatment is initially based on parenteral administration of unfractionated heparin or low molecular weight heparin for 5 to 7 days, followed by long-term treatment with oral vitamin K antagonists (VKAs).  According to the American College of Chest Physicians (ACCP) guidelines,  Direct thrombin inhibitors, such as dabigatran, bond directly to thrombin with no need for a cofactor, such as antithrombin. Unlike VKAs and heparins, direct thrombin inhibitors can inhibit both soluble thrombin and thrombin bound to fibrin.  Factor Xa inhibitors bond directly to the active site of factor Xa, blocking this coagulation factor’s activity. In contrast to the pentasaccharides (indirect factor Xa inhibitors), these medications inactivate free factor Xa and factor Xa that is has been incorporated into complex prothrombinase, and do not interact with antithrombin inhibitor.  Safe and effective clinical use of direct oral anticoagulants (DOACs) demands monitoring of evidence of their clinical efficacy. Studies of their adverse effects, primarily bleeding, are also an essential part of understanding the balance between benefits and harmful effects in comparison with the anticoagulants currently used in clinical practice. Our objective was therefore to review the scientific evidence on the benefits and adverse effects of new anticoagulants for treatment of DVT compared with standard treatment (low molecular weight heparin or unfractionated heparin followed by VKAs).  This is an overview of systematic reviews of the efficacy and adverse effects of treating patients with DVT using DOACs, selecting studies that systematically review controlled and randomized clinical trials comparing the standard treatment with DOACs in patients diagnosed with DVT. No publication date or language restrictions were imposed. Narrative reviews, guidelines, and specialist opinions were not included. novel oral anticoagulant* and deep vein thrombosis .  Searches were run on PubMed and the Cochrane Database of Systematic Reviews. The search run on the PubMed database employed a high-sensitivity search filter to return systematic reviews.  The studies retrieved were selected independently by two authors. Initial screening consisted of reading all titles and abstracts and then the full texts of articles considered potentially eligible in the first stage were analyzed. Disagreements during the selection process were resolved by participation of a third author.  Two outcomes were considered essential for assessment of efficacy and adverse effects of DOACs in relation to VKAs: (i) recurrence of DVT or VTE; and (ii) bleeding. Data on these outcomes and a general description of studies were extracted by one author and reviewed by a second author. Data were extracted using a data collection form, describing studies according to the update date of the systematic search, the patient population studied, the type of oral anticoagulant studied, and the number of clinical trials included. , The internal validity  of systematic reviews was assessed using the AMSTAR tool.  The systematic reviews included were described in terms of their general characteristics , results of outcomes of interest, and methodological quality. Statistical analysis  was not possible because of the limited number of studies included.  A total of 23 articles were retrieved by the searches. After exclusion of duplicates, 21 articles were assessed against the inclusion criteria. Of these, 19 articles were excluded after reading titles and abstracts, and the full texts of two articles that were considered potentially eligible were analyzed. At the end of the selection process, one systematic review was considered eligible and included in our review   .  A systematic review conducted by Robertson et al.  This review scored maximum points on AMSTAR    and cov The accumulated evidence indicates that DOACs, both direct thrombin inhibitors and direct factor Xa inhibitors, offer a balance between efficacy and adverse effects similar to standard treatment. This means that these medications do not offer a different balance between risk and benefit than the combination of heparins and VKAs for treatment of DVT. - The evidence found is limited to a single systematic review. The systematic review available for this evaluation was considered of high methodological quality. However, the likelihood of its results being modified by future research depends on the methodological quality of the clinical trials included and analyzed by the systematic review. Unfortunately, the systematic review in question did not conduct an assessment of evidence quality using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology,  One limitation of these results is the fact that analysis of efficacy and adverse effects was only conducted taking medications in each of the two DOAC categories, direct thrombin inhibitors and direct factor Xa inhibitors, together as a group. While it is probable that individual medications that share the same mechanism of action will exhibit similar effects, it is useful to confirm the clinical effects of each medication empirically.  The DOACs offer simpler management of anticoagulant treatment; they are administered in fixed doses with no need for adjustment by body weight. These medications have rapid onset of action, do not need to be controlled using laboratory test results, and have a short half-life . The drug-drug, drug-alcohol, and drug-food interactions described to date are few and permit use in ambulatory level treatment.  One practical problem with use of DOACs, however, is related to these medications’ different treatments, doses and, primarily, posologies.  This is because, while some are used in monotherapy , others  are used as an adjuvant therapy with low molecular weight heparin. Additionally, even medications used as monotherapy have different doses and posologies, which may vary during the initial phase and maintenance phase of anticoagulation . The standard treatment, which is established clinical practice for more than 50 years, offers a therapeutic regimen that is more effective, safe, and compatible with care at the ambulatory level, despite the need for dosage adjustments. Another relevant practical problem is access to these new medications, especially in countries with low levels of socioeconomic development, since they are expensive. , One determinant factor for routine clinical use of DOACs is availability of a reversal agent for the entire class of medications. The anticoagulant effect of VKAs can be reversed by administration of vitamin K, fresh frozen plasma, or prothrombin complex.  Below, we present a summarized review of the status of available phase III studies of the different DOACs.  Dabigatran etexilate (Pradaxa®) is a pro-drug that is rapidly metabolized by the liver, transforming it into an active compound that binds competitively and reversibly to the thrombin site of activity, blocking its procoagulatory activity. Dabigatran is absorbed by the gastrointestinal tract, has a half-life of 12 to 17 hours, and renal and fecal excretion. The RE-COVER study compared treatment with warfarin to dabigatran, after initial treatment with a parenteral anticoagulant, in 2,539 patients diagnosed with acute VTE over a 6-month period.  Rivaroxaban (Xarelto®) is an oral factor Xa inhibitor that binds reversibly to the site of activity of factor Xa. This medication has hepatic metabolization, an estimated half-life of 8 to 10 hours, and renal and fecal excretion. The EINSTEIN-DVT study compared standard treatment  of 1,718 patients with treatment of 1,731 patients with rivaroxaban  over a 15-week period. The results demonstrated that administration of 15 mg of rivaroxaban, twice a day, for a period of 3 weeks, followed by administration of 20 mg for 12 weeks is not inferior to standard treatment for reduction of recurrent VTE. The incidence of recurrent VTE was 2.1% in the group treated with rivaroxaban compared with an incidence of 3.0% in the group given standard treatment. The principal outcome related to adverse effects — major and clinically relevant bleeding — was no more frequent, occurring in 139 patients (8.1%) in the group treated with rivaroxaban and 138 patients (8.1%) in the group treated with standard treatment.  Apixaban (Eliquis®) is a oral factor Xa inhibitor that impedes activity of factor Xa when free or bound to platelets, in a selective and reversible manner, and blocks activity of the prothrombinase complex. This medication has hepatic metabolization, plasma half-life from 8 to 15 hours, and renal and fecal excretion. The AMPLIFY study compared treatment of 2,704 patients with enoxaparin followed by warfarin with 2,691 patients treated with apixaban  with symptomatic proximal DVT or PE (with or without DVT) for a 6-month period. The results demonstrate that treatment with 10 mg apixaban, twice a day, for 7 days, followed by 6 months of 5 mg apixaban, twice a day, is not inferior to treatment with enoxaparin followed by warfarin in terms of frequency of recurrent VTE and VTE-related mortality. However, the frequency of major bleeding was significantly lower in the group given apixaban (0.6%) than in the standard treatment group (1.8%).  Edoxaban (Lixiana®) is an oral factor Xa inhibitor that bonds reversibly to the activity site of factor Xa. It has hepatic metabolization, plasma half-life of 9 to 11 hours, and 1/3 of excretion is renal and the remainder fecal. The phase III trial Hokusai-VTE compared treatment of 2,453 patients with heparin followed by VKAs (standard treatment) with treatment of 2,468 patients using edoxaban  over a 12-month period. The patients eligible for this study had symptomatic acute DVT involving iliac, femoral, and popliteal veins or acute symptomatic PE (with or without DVT). The results showed that administration of 60 mg of edoxaban, once a day  is not inferior to standard treatment in terms of recurrent VTE. The frequency of recurrent VTE was 3.2% (130 patients) in the group treated with edoxaban and 3.5% in the group treated with warfarin (146 patients). However, frequencies of major bleeding and clinically significant non-major bleeding were considerably lower in the group given edoxaban than in the group given warfarin: 8.5% (345 patients) and 10.3% (423 patients) respectively.  The available evidence suggests that treatment of DVT with DOACs, irrespective of the class, appears not to be inferior to standard treatment in terms of efficacy and safety. However, these medications are subject to certain restrictions, since the profile of adverse effects in children and patients with renal failure is unknown, and they are not yet indicated for treatment of cancer patients.  It is undeniable that DOACs offer greater comfort for management of patients with VTE, both for physicians and their patients. This review reaffirms the robust evidence of the imminent capacity of DOACs to substitute medications used in conventional treatment. This enables us to reflect that we are close to a paradigm shift in anticoagulant treatment. Nevertheless, there is still a need for long-term studies that confirm that these new medications have safety profile that are not inferior to medications used in a standard treatment. There is still a long way to go before DOACs are consolidated as the definitive treatment for VTE. Currently, it is therefore necessary to take care when tailoring medical prescriptions to the peculiarities of the thromboembolic disease of each patient.   A trombose venosa profunda (TVP) dos membros inferiores é uma doença grave e potencialmente fatal. Sua incidência na população geral é de cinco casos por 10.000 habitantes por ano ,, O tratamento padrão se baseia, inicialmente, na administração parenteral de heparina não fracionada ou heparinas de baixo peso molecular durante 5 a 7 dias, seguida de terapia em longo prazo com antagonistas orais de vitamina K (AVKs) American College of Chest Physician De acordo com as diretrizes do  Os inibidores diretos da trombina, como a dabigatrana, ligam-se diretamente à trombina sem a necessidade de um cofator, como a antitrombina. Diferentemente dos AVKs e das heparinas, os inibidores diretos da trombina podem inibir tanto a trombina solúvel quanto a trombina ligada à fibrina  Os inibidores do fator Xa se ligam diretamente ao sítio ativo do fator Xa, bloqueando a atividade desse fator de coagulação. Diferentemente dos pentassacarídeos (inibidores indiretos do fator Xa), esses medicamentos inativam o fator Xa livre e o fator Xa incorporado ao complexo protrombinase, além de não interagirem com o inibidor antitrombínico  A utilização clínica efetiva e segura dos anticoagulantes orais diretos (DOACs) requer o acompanhamento das evidências sobre a eficácia clínica desses medicamentos. O estudo dos efeitos adversos, principalmente sangramento, também é essencial para compreender o balanço de benefícios e efeitos nocivos em comparação aos anticoagulantes atualmente utilizados na prática clínica. Portanto, nosso objetivo foi revisar as evidências científicas sobre os benefícios e efeitos adversos dos novos anticoagulantes no tratamento da TVP em comparação com a terapia padrão (heparina de baixo peso molecular ou heparina não fracionada seguida por AVKs). overview of systematic reviews) sobre a eficácia e os efeitos adversos do tratamento de pacientes com TVP com os DOACs, de modo que foram incluídos estudos de revisão sistemática de ensaios clínicos controlados e randomizados comparando a terapia padrão com DOACs em pacientes diagnosticados com TVP. Não foram aplicados limites de ano nem de idioma da publicação. Revisões narrativas, guidelines e opiniões de especialistas não foram consideradas.  Revisão de revisões sistemáticas  recorrência de TVP ou TEV; e (ii) sangramento. Dados sobre esses desfechos e de descrição geral dos estudos foram extraídos por um autor e revisados por um segundo autor. Os dados foram extraídos de acordo com um formulário de extração de dados, descrevendo os estudos de acordo com a data da atualização da busca sistemática, população de pacientes estudada, o tipo de anticoagulante oral estudado e a quantidade de ensaios clínicos incluídos. , A validade interna  das revisões sistemáticas foi avaliada com o uso da ferramenta AMSTAR  As revisões sistemáticas incluídas foram descritas em termos de suas características gerais , resultados sobre os desfechos de interesse e sua qualidade metodológica. Uma análise estatística (metanálise) não pôde ser realizada devido ao limitado número de estudos incluídos.  No total, 23 artigos foram recuperados. Após a exclusão de duplicados, 21 artigos foram avaliados de acordo com os critérios de inclusão. Desses, 19 artigos foram excluídos com base na leitura do título e resumo, e dois artigos que foram considerados potencialmente elegíveis tiveram o artigo completamente analisados. Ao final do processo de seleção, uma revisão sistemática foi considerada elegível e incluída em nossa revisão   .  A revisão sistemática conduzida por Robertson e colaboradores  A revisão atingiu escore máximo no AMSTAR   , e incl As evidências acumuladas indicam que os DOACs, tanto inibidores diretos de trombina quanto do fator Xa, apresentam um balanço de eficácia e efeitos adversos semelhantes ao da terapia padrão. Isso significa que esses medicamentos não apresentam balanço entre risco e benefício diferente do apresentado pela combinação de heparinas com AVKs no tratamento da TVP. Grading of Recommendations, Assessment, Development and Evaluations ) - As evidências encontradas são limitadas a uma revisão sistemática. A revisão sistemática disponível para essa avaliação foi considerada de alta qualidade metodológica. No entanto, a probabilidade de seus resultados serem alterados por novas pesquisas depende da qualidade metodológica dos ensaios clínicos incluídos e analisados na revisão sistemática. Infelizmente, a revisão sistemática em questão não realizou uma avaliação da qualidade das evidências segundo a metodologia GRADE . As interações fármaco-fármaco, fármaco-álcool e fármaco-alimentos descritas até o momento são poucas e permitem o tratamento ambulatorial.  Um problema prático da utilização dos DOACs, no entanto, está relacionado às diferentes terapias, doses e, principalmente, posologias desses medicamentos.  Isso porque, enquanto alguns são utilizados como monoterapia , outros  são utilizados como terapia adjuvante a heparina de baixo peso molecular. Além disso, mesmo os medicamentos utilizados como monoterapia apresentam diferentes doses e posologias, as quais podem variar durante a fase inicial e a fase de manutenção da anticoagulação . A terapia padrão, estabelecida como prática clínica há mais de 50 anos, apresenta um esquema terapêutico mais eficaz, seguro e compatível com o atendimento em nível ambulatorial, apesar dos ajustes de doses necessários. Outro problema prático relevante é o acesso a esses novos medicamentos, especialmente em países com baixo nível de desenvolvimento socioeconômico, uma vez que apresentam custo elevado. , Um fator determinante para a utilização clínica rotineira dos DOACs é a disponibilidade de um agente reversor disponível para toda essa nova classe de medicamentos. O efeito anticoagulante dos AVKs pode ser revertido pela administração de vitamina k, plasma fresco congelado ou complexo protrombínico status dos estudos de fase III disponíveis sobre os diferentes DOACs.  A seguir, apresentamos uma revisão sumarizada do  O etexilato de dabigatrana (Pradaxa®) é um pró-fármaco rapidamente metabolizado pelo fígado, transformando-se em um composto ativo que se liga de forma competitiva e reversível ao sítio de atividade da trombina, bloqueando sua atividade pró-coagulante. A dabigatrana é absorvida pelo trato gastrointestinal, apresenta uma meia-vida de 12 a 17 horas, e excreção renal e fecal. O estudo RE-COVER comparou o tratamento da varfarina com a dabigratrana, após o tratamento inicial com um anticoagulante parenteral, em 2.539 pacientes diagnosticados com TEV agudo pelo período de 6 meses  A rivaroxabana (Xarelto®) é um inibidor oral do fator Xa que se liga de forma reversível ao sítio de atividade do fator Xa. O medicamento apresenta metabolização hepática, meia-vida estimada entre 8 e 10 horas e excreção renal e fecal. O estudo EINSTEIN-DVT comparou o tratamento padrão  realizado em 1.718 pacientes com o tratamento realizado em 1.731 pacientes com rivaroxabana  pelo período de 15 semanas. Os resultados demostraram que a administração de 15 mg de rivaroxabana, duas vezes ao dia, pelo período de 3 semanas, seguida da administração de 20 mg por 12 semanas não é inferior à terapia padrão para a redução de TEV recorrente. A incidência de TEV recorrente foi de 2,1% no grupo tratado com rivaroxabana em comparação a uma incidência de 3,0% do grupo que recebeu a terapia padrão. O principal desfecho relacionado aos efeitos adversos — sangramento maior e clinicamente relevante não maior — ocorreu em 139 pacientes  do grupo tratado com rivaroxabana e 138 pacientes  do grupo tratado com terapia padrão  A apixabana (Eliquis®) é um inibidor oral do fator Xa que impede a atividade do fator Xa livre ou ligado a plaqueta, de forma seletiva e reversível, e bloqueia a atividade do complexo protrombinase. O medicamento apresenta metabolização hepática, meia-vida plasmática de 8 a 15 horas e excreção renal e fecal. O estudo AMPLIFY comparou o tratamento de 2.704 pacientes usando enoxaparina seguida por varfarina com 2.691 pacientes usando apixabana  com TVP sintomática proximal ou EP (com ou sem TVP) pelo período de 6 meses. Os resultados demostraram que o tratamento com apixabana 10 mg, duas vezes ao dia, por 7 dias, seguido de 6 meses de apixabana 5 mg, duas vezes ao dia, não é inferior ao tratamento com enoxaparina seguido pela varfarina em relação à frequência de TEV recorrente e de mortalidade relacionada ao TEV. No entanto, a frequência de sangramento maior foi significativamente menor no grupo que recebeu apixabana  em comparação ao grupo tratado com a terapia padrão  clearence de creatinina entre 30-50 mL/min, peso corporal menor que 60 kg ou recebendo inibidor da glicoproteína-P) não é inferior ao tratamento padrão em relação ao TEV recorrente. A frequência de TEV recorrente foi igual a 3,2% (130 pacientes) no grupo tratado com edoxabana e igual a 3,5% no grupo tratado com varfarina (146 pacientes). No entanto, as frequências de sangramento maior e sangramento clinicamente significante não maior foram expressivamente menores no grupo que recebeu edoxabana em relação ao grupo que recebeu varfarina: 8,5% (345 pacientes) e 10,3% (423 pacientes) respectivamente  A edoxabana (Lixiana®) é um inibidor oral do fator Xa que se liga de forma reversível ao sítio de atividade do fator Xa. Apresenta metabolização hepática, meia-vida plasmática de 9 a 11 horas, 1/3 de excreção renal e o restante fecal. O estudo de fase III Hokusai-VTE comparou o tratamento de 2.453 pacientes usando heparina seguida por AVKs (tratamento padrão) com o tratamento de 2.468 pacientes usando edoxabana  pelo período de 12 meses. Os pacientes elegíveis para esse estudo apresentavam TVP aguda sintomática envolvendo as veias ilíaca, femoral e poplítea ou EP aguda sintomática (com ou sem TVP). Os resultados mostraram que a administração de 60 mg de edoxabana, uma vez ao dia , acreditando-se que em breve possa estar liberado pela Agência Nacional de Vigilância Sanitária (ANVISA). Espera-se, para o começo da próxima década, o ciraparantag  As evidências disponíveis sugerem que o tratamento da TVP com os DOACs, independentemente da classe, parece ser não inferior à terapia padrão em termos de eficácia e segurança. No entanto, esses medicamentos apresentam algumas importantes restrições, pois não se conhece o perfil de efeitos adversos em crianças e em pacientes com insuficiência renal, além de ainda não serem indicados para o tratamento de pacientes oncológicos  É inegável que os DOACs trouxeram conforto no manejo dos pacientes com TEV, tanto para os médicos quanto para os pacientes. Esta revisão reforça as robustas evidências da iminente capacidade dos DOACs em substituir os medicamentos usados no tratamento convencional. Isso permite refletir que estamos próximos a uma mudança de paradigma na terapia anticoagulante. Contudo, ainda são necessários estudos de longo prazo que confirmem a não inferioridade do perfil de segurança desses novos medicamentos em relação aos medicamentos usados na terapia padrão. Há, portanto, um longo caminho a ser percorrido antes dos DOACs se firmarem como terapia definitiva do TEV. Assim, nesse momento, é necessário haver cautela e individualizar a prescrição médica conforme as peculiaridades da doença tromboembólica de cada paciente.