Actividad biológica in vitro de los extractos acuosos y alcohólicos de tubérculos andinos

Introducción: La medicina ancestral ha utilizado plantas con cualidades medicinales para prevenir y tratar enfermedades; aun cuando este tipo de investigaciones se han incrementado, son escasos los estudios con tubérculos andinos. Objetivo: Determinar la actividad biológica de extractos acuosos y etanólicos de los tubérculos andinos Tropaeolum tuberosum (mashua) y Ullucus tuberosus (melloco). Métodos: La investigación fue experimental y se desarrolló in vitro. La muestra estuvo constituida por 2 tubérculos andinos utilizados en la medicina ancestral. Se aplicaron técnicas de extracción en medio acuoso y etanólico. Los extractos fueron evaluados para determinar la actividad hemoaglutinante, anticoagulante y antimicrobiana con cepas ATCC. Resultados: Se demostró actividad hemoaglutinante en el extracto acuoso de T. tuberosum sobre eritrocitos A. Todos los extractos acuosos mostraron actividad anticoagulante, Tropaeolum tuberosum inhibió la actividad de la coagulación sanguínea (vía intrínseca) con un TTPa> 300 seg. Tanto los extractos acuosos y etanólicos exhibieron actividad antimicrobiana contra cepas ATCC, Tropaeolum tuberosum inhibió el crecimiento de Staphylococcus aureus 25923 con halos de 17 y 22 mm y Ullucus tuberosus (blanco) con halos de 10 y 30 mm, respectivamente. Los extractos acuosos de Tropaeolum tuberosum y Ullucus tuberosus (rojo) inhibieron el crecimiento de Candida tropicalis 66029 con halos de 27 y 12 mm y respectivamente. Conclusiones: Determinada la actividad biológica, se evidencia que los tubérculos andinos estudiados aglutinan eritrocitos humanos, específicamente eritrocitos del grupo A, así mismo, capacidad de inhibir las proteínas plasmáticas de la coagulación y de inhibir el crecimiento bacteriano y micótico de cepas ATTC.

Introduction: Ancestral medicine has used plants with medicinal qualities to prevent and treat diseases, even though this type of research has increased, studies with Andean tubers are scarce. Objective: To determine the biological activity of aqueous and ethanolic extracts of the Andean tubers Tropaeolum tuberosum (mashua) and Ullucus tuberosus (melloco). Methods: The research was experimental and was developed in vitro. The sample consisted of 2 Andean tubers used in ancestral medicine. Extraction techniques were applied in aqueous and ethanolic medium. The extracts were evaluated for hemagglutinating, anticoagulant and antimicrobial activity with ATCC strains. Results: Hemagglutinating activity was demonstrated in the aqueous extract of T. tuberosum on A erythrocyte. All aqueous extracts showed anticoagulant activity, Tropaeolum tuberosum inhibited blood coagulation activity (intrinsic pathway) with an aPTT>300 sec. Both aqueous and ethanolic extracts exhibited antimicrobial activity against ATCC strains, Tropaeolum tuberosum inhibited the growth of Staphylococcus aureus 25923 with halos of 17 and 22 mm and Ullucus tuberosus (white) with halos of 10 and 30 mm, respectively. The aqueous extracts of Tropaeolum tuberosum and Ullucus tuberosus (red) inhibited the growth of Candida tropicalis 66029 with halos of 27 and 12 mm, respectively. Conclusions: Once the biological activity was determined, it was evident that the Andean tubers studied agglutinated human erythrocytes, specifically group A erythrocytes, as well as the ability to inhibit plasma coagulation proteins and inhibit the bacterial and fungal growth of ATTC strains.

Desenho de Estudo de um Estudo Observacional Brasileiro sobre o uso de Edoxabana em Pacientes com Fibrilação Atrial (EdoBRA) / Study Design of a Brazilian Observational Study of Edoxaban in Patients with Atrial Fibrillation (EdoBRA)

Resumo Fundamento: Os ensaios clínicos demonstraram a segurança da Edoxabana, um anticoagulante oral não dependente de vitamina K (NOAC), e a sua eficácia na prevenção de acidente vascular cerebral e embolia sistémica em pacientes com fibrilação atrial não valvar (FANV) e também na prevenção e tratamento de tromboembolismo venoso. No entanto, pesquisas adicionais são necessárias para avaliar a segurança e a eficácia da Edoxabana em um cenário real na população brasileira. Objetivo: A fim de compreender os riscos e benefícios do uso da Edoxabana em cenários clínicos de rotina, o estudo EdoBRA está sendo conduzido para obter informações sobre a segurança e eficácia do uso da Edoxabana em pacientes não pré-selecionados com FANV no Brasil. Métodos: O estudo EdoBRA é um estudo multicêntrico, prospectivo e observacional, realizado em 36 centros no Brasil. São elegíveis para este estudo pacientes com FANV, ≥ 18 anos de idade, tratados com Edoxabana disponível comercialmente, que iniciaram o tratamento por pelo menos 14 dias e não mais do que 90 dias antes da data de inclusão no estudo, e que não estão participando de nenhum outro estudo de intervenção. Ao todo, 700 pacientes devem ser inscritos e acompanhados por um ano, com coletas de dados programadas para o período basal e 3, 6 e 12 meses após a inscrição no estudo. O objetivo primário de segurança é o sangramento clinicamente relevante (de acordo com critérios da Sociedade Internacional de Trombose e Hemostasia - ISTH), e o objetivo secundário de eficácia são desfechos cardiovasculares relevantes relacionados à FANV. Conclusão: O estudo observacional EdoBRA gerará informações adicionais relevantes sobre a Edoxabana enquanto NOAC em diversos aspectos do manejo de pacientes no atendimento clínico de rotina, como perfil de segurança e efetividade em pacientes com FANV no Brasil.

Abstract Background: Clinical trials showed the safety of Edoxaban, a non-vitamin K-dependent oral anticoagulant (NOAC), and its efficacy to prevent stroke and systemic embolism in non-valvular atrial fibrillation (NVAF) patients and also to prevent and treat venous thromboembolism. However, additional research is needed to evaluate the safety and effectiveness of Edoxaban in a real-world scenario in the Brazilian population. Objective: In order to understand the risks and benefits of Edoxaban use in routine clinical settings, the EdoBRA study is being conducted to gain insight into the safety and effectiveness of Edoxaban use in non-preselected patients with NVAF in Brazil. Methods: The EdoBRA study is a multicenter, prospective, observational study conducted in 36 sites in Brazil. NVAF patients ≥ 18 years treated with commercially available Edoxaban who initiated treatment for at least 14 days and no longer than 90 days prior to enrollment, and who are not simultaneously participating in any interventional study are eligible for this study. Seven hundred patients are planned to be enrolled and one-year of follow up, with data collections expected at baseline and 3, 6, and 12 months after the study enrollment. The primary safety objective is ISTH Clinically Relevant Bleeding, and the secondary effectiveness objective focuses on relevant cardiovascular outcomes related to NVAF. Conclusion: EdoBRA observational study will generate relevant additional information about NOAC Edoxaban on various aspects of patient management in routine care, such as its safety and effectiveness profile in patients with NVAF in Brazil.

Anticoagulação Crônica em Pacientes com Fibrilação Atrial e COVID-19: Uma Revisão Sistemática e Metanálise / Chronic Anticoagulation in Patients with Atrial Fibrillation and COVID-19: A Systematic Review and Meta-Analysis

Resumo Fundamento: A doença por coronavírus 2019 (COVID-19) está associada à hipercoagulabilidade. Permanece incerto se a anticoagulação contínua para fibrilação atrial (FA) em pacientes que posteriormente contraem COVID-19 melhora os desfechos clínicos. Objetivos: Comparar a anticoagulação oral crônica com ausência de anticoagulação prévia em pacientes com FA que contraíram uma infecção por COVID-19 em relação aos desfechos de mortalidade por todas as causas, mortalidade por COVID-19, admissão em unidade de terapia intensiva (UTI) e hospitalização. Métodos: Buscamos sistematicamente no PubMed, Embase e Cochrane Library estudos elegíveis desde o início até dezembro de 2022. Incluímos estudos que compararam desfechos de COVID-19 em pacientes com e sem anticoagulação crônica prévia para FA. Foram agrupadas razões de risco (RR) com intervalos de confiança (IC) de 95% por meio de um modelo de efeitos aleatórios. O nível de significância foi estabelecido em p < 0,05. As avaliações da qualidade e do risco de viés foram realizadas de acordo com as recomendações da Cochrane. Resultados: Foram identificados 10 estudos abrangendo 1.177.858 pacientes com COVID-19 e FA, dos quais 893.772 (75,9%) estavam em anticoagulação crônica prévia para FA. Em pacientes com COVID-19, a anticoagulação crônica para FA reduziu significativamente a mortalidade por todas as causas (RR 0,75; IC 95% 0,57 a 0,99; p = 0,048; I2 = 89%) e a mortalidade relacionada à COVID-19 (RR 0,76; IC 95% 0,72 a 0,79; p < 0,001; I2 = 0%) quando comparada com a ausência de anticoagulação prévia. Em contrapartida, não houve diferença entre os grupos em relação à hospitalização (RR 1,08; IC 95% 0,82 a 1,41; p = 0,587; I2 = 95%) ou internação em UTI (RR 0,86; IC 95% 0,68 a 1,09; p = 0,216; I2 = 69%). Conclusões: Nesta metanálise, a anticoagulação crônica para pacientes com FA que contraíram COVID-19 foi associada a taxas significativamente mais baixas de mortalidade por todas as causas e mortalidade relacionada à COVID-19 em comparação com a ausência de anticoagulação anterior.

Abstract Background: Coronavirus disease 2019 (COVID-19) is associated with hypercoagulability. It remains uncertain whether ongoing anticoagulation for atrial fibrillation (AF) in patients who later contract COVID-19 improves clinical outcomes. Objectives: To compare chronic oral anticoagulation with no previous anticoagulation in patients with AF who contracted a COVID-19 infection concerning the outcomes of all-cause mortality, COVID-19 mortality, intensive care unit (ICU) admission, and hospitalization. Methods: We systematically searched PubMed, Embase, and Cochrane Library for eligible studies from inception to December 2022. We included studies comparing COVID-19 outcomes in patients with versus without prior chronic anticoagulation for AF. Risk ratios (RR) with 95% confidence intervals (CI) were pooled with a random-effects model. The level of significance was set at p < 0.05. Quality assessment and risk of bias were performed according to Cochrane recommendations. Results: Ten studies comprising 1,177,858 patients with COVID-19 and AF were identified, of whom 893,772 (75.9%) were on prior chronic anticoagulation for AF. In patients with COVID-19, being on chronic anticoagulation for AF significantly reduced all-cause mortality (RR 0.75; 95% CI 0.57 to 0.99; p = 0.048; I2 = 89%) and COVID-19-related mortality (RR 0.76; 95% CI 0.72 to 0.79; p < 0.001; I2 = 0%) when compared with no prior anticoagulation. In contrast, there was no difference between groups regarding hospitalization (RR 1.08; 95% CI 0.82 to 1.41; p = 0.587; I2 = 95%) or ICU admission (RR 0.86; 95% CI 0.68 to 1.09; p = 0.216; I2 = 69%). Conclusions: In this meta-analysis, chronic anticoagulation for patients with AF who contracted COVID-19 was associated with significantly lower rates of all-cause mortality and COVID-19-related mortality as compared with no previous anticoagulation.

ABCG2 polymorphism and rivaroxaban pharmacokinetics in healthy individuals after a single dose

Rivaroxaban is a direct factor Xa inhibitor. Its interindividual variability is large and may be connected to the occurrence of adverse drug reactions or drug inefficacy. Pharmacogenetics studies concentrating on the reasons underlying rivaroxaban's inadequate response could help explain the differences in treatment results and medication safety profiles. Against this background, this study evaluated whether polymorphisms in the gene encoding the ABCG2 transporter modify the pharmacokinetic characteristics of rivaroxaban. A total of 117 healthy volunteers participated in two bioequivalence experiments with a single oral dose of 20 mg rivaroxaban, with one group fasting and the other being fed. Ultra-high-performance liquid chromatography coupled with mass spectrometry was employed to determine the plasma concentrations of rivaroxaban, and the WinNonlin program was used to calculate the pharmacokinetics parameters. In the fasting group, the rivaroxaban pharmacokinetic parameters of Vd (508.27 vs 334.45 vs 275.59 L) and t1/2 (41.04 vs 16.43 vs 15.47 h) were significantly higher in ABCG2 421 A/A genotype carriers than in ABCG2 421 C/C and 421 C/A genotype carriers (P<0.05). The mean values of Cmax (145.81 vs 176.27 vs 190.19 ng/mL), AUC0-t (1193.81 vs 1374.69 vs 1570.77 ng/mL·h), and Cl (11.82 vs 14.50 vs 13.01 mL/h) for these groups were lower, but this difference was not statistically significant (P>0.05). These findings suggested that the ABCG2 421 A/A genotype may impact rivaroxaban parameters after a single dose in healthy subjects. This finding must be validated before it is applied in clinical practice.

Vertebral fractures combined with prolonged activated partial prothrombin time:A case report / 北京大学学报(医学版)

With the development of modern medical standards,autoimmune diseases and their associ-ated successive osteoporosis have received increasing attention in recent years.Patients with autoimmune diseases,due to the characteristics of the disease and the prolonged use of glucocorticoid hormone thera-py,may affect the bone formation and bone absorption of the patient,followed by severe successive osteo-porosis,thereby increasing the risk of osteoporotic vertebral fractures.Vertebral compression fractures of the spine are common fracture types in patients with osteoporotic fractures.Osteoporosis is a common complication after glucocorticoid therapy in patients with autoimmune diseases.Percutaneous vertebro-plasty(PVP)and percutaneous kyphoplasty(PKP)are minimally invasive operation and are commonly used surgical methods for the treatment of osteoporotic vertebral compression fractures.However,due to the operation of spinal puncture during the operation,there are serious surgical risks such as bone cement leakage,spinal epidural hemorrhage,subdural hemorrhage,and subarachnoid hemorrhage in both PVP and PKP.As a result,it is necessary to evaluate the patient's body before surgery carefully,especially in the case of blood coagulation.This article reports a case of autoimmune disease patient admitted to Peking University People's Hospital due to lumbar 4 vertebral compression fracture combined with Sj?gren's syn-drome.The patient's preoperative examination showed that the activated partial thromboplastin time(APTT)was significantly prolonged.After completing the APTT extended screening experiment and lu-pus anticoagulant factor testing,the multi-disciplinary team(MDT)of Peking University People's Hospi-tal jointly discussed the conclusion that the patient's test results were caused by an abnormal self-immuni-ty anti-copulant lupus(LAC).Based on the results of the laboratory examination,the patient was con-sidered to be diagnosed with combined antiphospholipid syndrome(APS).For such patients,compared with the patient's tendency to bleed,we should pay more attention to the risk of high blood clotting in the lower limbs of the patient,pulmonary clots and so on.With timely anti-coagulation treatment,the patient safely passed the peripheral period and was successfully discharged from the hospital.Therefore,for pa-tients with autoimmune diseases with prolonged APTT in the perioperative period,doctors need to careful-ly identify the actual cause and carry out targeted treatment in order to minimize the risk of surgical and perioperative complications and bring satisfactory treatment results to the patients.

Aspirin for thromboprophylaxis in orthopedic surgery: advancements in clinical evidence and guidelines / 中华创伤骨科杂志

As patients undergoing orthopedic surgery are a high-risk group for venous thromboembolism (VTE), clinical guidelines suggest anticoagulant drugs for VTE prophylaxis during perioperative period. Global antithrombotic guidelines vary in recommendations for anticoagulant drugs, but there is a general consensus in favor of using low-molecular-weight heparin (LMWH) as the first choice for prophylaxis, followed by unfractionated heparin, fondaparinux, warfarin, aspirin, and other direct oral anticoagulants (DOACs). Of them, aspirin is an inexpensive, widely used antiplatelet drug with limited complications and clear efficacy in prevention of myocardial infarction, stroke, and certain specific cancers. It was also used early for venous thromboembolism prophylaxis in orthopedic patients after surgery. Clinical experience of orthopedic physicians in North America has shown the effectiveness of aspirin in VTE prevention over several decades so that aspirin continues to be used to this day, but its use for VTE prophylaxis is less common in Europe and Asia. Historically, the role and efficacy of aspirin in VTE prevention have been the subjects of considerable controversy, for the early and recent research findings contradict each other, and recommendations conflict in different guidelines. This review focuses on the advancements in clinical evidence and guideline recommendations regarding the use of aspirin for VTE prophylaxis in major orthopedic surgeries.

Embolic stroke of undetermined source: knowledge validated and refuted in the past 10 years / 中华神经科杂志

Embolic stroke of undetermined source (ESUS) is a concept proposed by an international working group in 2014 to define a class of stroke patients and explore the rationality of secondary prevention by anticoagulation in them. During the decade since the concept was proposed, numerous studies have been conducted on the pathogenesis and prevention strategies of ESUS. However, the research results are not quite consistent with the speculations and assumptions when the concept was proposed. Based on the review of the findings of related studies over the past decade, this article discusses the inherent defects in the ESUS concept, the new idea derived from the research results, the future role of ESUS, and trends in etiological diagnosis of ischemic stroke.

Research Progress on the Effect of Abnormal Thyroid Function on the Coagulation System and the Interaction of Therapeutic Drugs / 医药导报

For patients with abnormal thyroid function,the detection of peripheral blood coagulation indicators may be irregular,and there is a potential risk of thrombosis or bleeding.Patients with hyperthyroidism have significant endothelial dysfunction and risk of thrombosis.However,the reports on the effect of hypothyroidism on coagulation function are still controversial.The potential risk of abnormal thyroid function to the coagulation system may interfere with the safety of anticoagulant therapy,and the interaction between thyroid disease treatment drugs and anticoagulant drugs also affects the safety of the patient's medication.Therefore,this article is based on previous research literature,analyzes the correlation between abnormal thyroid function and coagulation function,and evaluates and discusses the impact of abnormal thyroid function on the coagulation system and related therapeutic drug interactions.It is expected to provide a reference for diagnosing and treating patients with thyroid dysfunction and abnormal coagulation function.

Clinical Comprehensive Evaluation of Oral Anticoagulants Based on A Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions(the Second Edition) / 医药导报

Objective A comprehensive evaluation of oral anticoagulants(OACs)was conducted using the A Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions(the Second Edition),to provide a reference for drug selection and clinical medication decisions in medical institutions.Methods Evaluation evidence was collected,and the drugs included in the evaluation were quantified on four dimensions of clinical properties(efficiency and safety),pharmaceutical properties,economy and others.Results All oral anticoagulants included in the evaluation had a score of 70 or higher in the comprehensive evaluation,while warfarin had the highest overall score.Clinical properties and pharmacologic properties were identified as the core attributes for drug selection evaluation.When considering only these factors,edoxaban received the highest score.Conclusion OACs are the preferred option for patients requiring long-term anticoagulation therapy.Various OACs offer distinct clinical advantages.Utilizing the Guidelines(Second Edition)for oral anticoagulant selection and evaluation can offer visual evidence for drug selection and promote the scientific,rational,and safe use of drugs in clinical management.

Meta-analysis of efficacy and safety of aspirin versus other anticoagulants in the prevention of thromboembolism after orthopedic surgery / 中国药房

OBJECTIVE To evaluate the clinical efficacy and safety of aspirin versus other anticoagulants in the prevention of thromboembolism after orthopedic surgery. METHODS Retrieved from PubMed， Embase， the Cochrane Library， CNKI， Wanfang data and VIP， randomized controlled trials （RCTs） and cohort studies about aspirin （trial group） versus other anticoagulants （control group） were collected during the inception and June 1st， 2023. After literature screening， data extraction and quality evaluation， the meta-analysis was conducted by using RevMan 5.4 software. RESULTS A total of 22 studies were included， involving 9 RCTs and 13 cohort studies. RCT results showed that the incidences of deep vein thrombosis （DVT） [RR＝1.81， 95%CI（1.36， 2.40）， P＜0.000 1] and postoperative pulmonary embolism （PE） [RR＝1.55， 95%CI（1.01， 2.40）， P＝0.05] in trial group were significantly higher than control group. There was no statistically significant difference in the incidences of postoperative massive bleeding， postoperative surgical site infection， all-cause death， or any bleeding after surgery between 2 groups. In the cohort study， the incidence of any bleeding in trial group was significantly lower than control group [RR＝0.71，95%CI （0.64， 0.79）， P＜0.000 1]， while the differences in other indicators were not statistically significant （P＞0.05）. The results of subgroup analysis based on different anticoagulants showed that in RCT， the incidences of DVT and PE after surgery in patients using low-molecular-weight heparin （LMWH） were significantly lower than using aspirin （P＜0.05）； in the cohort study， the incidences of DVT and PE after surgery were significantly lower in patients using direct oral anticoagulants （DOAC） than using aspirin （P＜0.05）. There was no statistically significant difference in the incidence of major bleeding between patients using aspirin and using DOAC and LWMH （P＞0.05） in both RCT and cohort study. CONCLUSIONS Aspirin is equally safe as other anticoagulants for the prevention of thromboembolism after orthopedic surgery， but its efficacy may not be as good as other anticoagulants. After orthopedic surgery， other anticoagulants should be preferred to prevent venous thromboembolism， and aspirin should be carefully considered.

Características clínicas de pacientes con accidente cerebrovascular isquémico y fibrilación auricular internados en hospital de referencia durante el periodo 2021 a 2022

Introducción: se ha demostrado que uno de cada tres accidentes cerebrovasculares (ACV) isquémicos es consecuencia de una fibrilación auricular (FA) no conocida y, por ende, no tratada. Por eso es de vital importancia el diagnóstico y tratamiento oportuno de la FA, ya que el ACV isquémico es un motivo frecuente de ingreso hospitalario. Objetivos: determinar las características clínicas de pacientes con ACV isquémico y FA internados en el Hospital XX, durante los años 2021 y 2022. Metodología: se realizó un estudio observacional, descriptivo, de corte transversal, retrospectivo. Se incluyeron pacientes de ambos sexos, mayores de edad, con FA y ACV isquémico confirmados por electrocardiograma y tomografía. Las variables se obtuvieron de los expedientes clínicos. La investigación fue aprobada por el comité de ética de la Universidad Nacional de Itapúa. Resultados: se estudiaron 113 pacientes. La edad media fue 69 ± 10 años, el 54,87% (62) fueron varones. Entre los factores de riesgo, 96,46% eran conocidos con hipertensión arterial y 61,06% con diabetes mellitus. En 24 (21%) pacientes se realizó ecocardiograma y 14 tenían dilatación auricular, con una media de 44 ± 8 mm, y 11 de éstos tenían estenosis mitral. La media de frecuencia cardiaca era 92 ± 18 latidos/min. El ictus isquémico se presentó como debut en 52,21% y de éstos solo 7,08% se conocían portadores de FA. Entre los portadores conocidos de FA 7,08% recibían anticoagulación con acenocumarol. No se encontraron pacientes en tratamiento con otros anticoagulantes. Conclusión: el 22,12% de los pacientes con ACV isquémico estaban diagnosticados con FA. Aproximadamente, un tercio de los pacientes con FA bajo el régimen de anticoagulación no alcanzaron rangos terapéuticos ni una frecuencia cardiaca controlada.

Introduction: It has been shown that one in three ischemic cerebrovascular accidents (CVA) is a consequence of unknown and, therefore, untreated atrial fibrillation (AF). That is why timely diagnosis and treatment of AF is of vital importance since ischemic stroke is a frequent reason for hospital admission. Objectives: To determine the clinical characteristics of patients with ischemic stroke and AF hospitalized at Hospital XX, during 2021 and 2022. Methodology: An observational, descriptive, cross-sectional, retrospective study was carried out. Male and female adult patients, with AF and ischemic stroke confirmed by electrocardiogram and tomography were included. The variables were obtained from the clinical records. The research study was approved by the ethics committee of the National University of Itapúa. Results: One hundred thirteen patients were studied. The mean age was 69 ± 10 years, and 54.87% (62) were men. Among the risk factors, 96.46% were known to have arterial hypertension, and 61.06% were known to have diabetes mellitus. An echocardiogram was performed in 24 (21%) patients, 14 had atrial dilation, with a mean of 44 ± 8 mm, and 11 of these had mitral stenosis. The mean heart rate was 92 ± 18 beats/min. Ischemic stroke occurred as a debut in 52.21% and of these, only 7.08% were known to have AF. Among known AF carriers, 7.08% received anticoagulation with acenocoumarol. No patients were found being treated with other anticoagulants. Conclusion: AF was diagnosed in 22.12% of patients with ischemic stroke. Approximately one-third of AF patients on anticoagulation regimens did not achieve therapeutic ranges or a controlled heart rate.

Factores asociados a la adherencia al tratamiento en pacientes con anticoagulación oral

Introducción: El tratamiento con anticoagulantes ha demostrado su eficacia en la prevención de complicaciones cardioembólicas; sin embargo, la adherencia probablemente tiene el mayor impacto en la calidad de la anticoagulación. Objetivo: Determinar los factores que influyen en la adherencia al tratamiento anticoagulante y en la estabilidad del índice de estandarización internacional (INR). Métodos: Se realizó un estudio analítico, observacional y prospectivo que se corresponde con un estudio farmacoepidemiológico de utilización de medicamentos (Esquema Terapéutico), en pacientes con diagnóstico de trastornos de la coagulación, en el área de salud del municipio Manzanillo, entre el 1ro de septiembre de 2018 al 1ro de diciembre de 2020. Los datos de la investigación se obtuvieron de una entrevista y su historia clínica. Fueron utilizados el test del Xi-cuadrado (X2), t de Student, ANOVA y Kruskall Wallis, con un valor de p=0,05 durante el procesamiento estadístico. Resultados: Se constató un grado bajo de adherencia farmacoterapéutica en la población estudiada. Las variables sociodemográficas relacionadas con la adherencia terapéutica fueron el sexo, la escolaridad y la ocupación. Existe relación entre los recursos económicos, el conocimiento que tiene el paciente sobre su enfermedad, el cumplimiento del tratamiento no farmacológico y el cumplimiento del tratamiento farmacológico con la adherencia. Las reacciones adversas y la disponibilidad de los medicamentos fueron los factores dependientes del tratamiento relacionados con la adherencia. Las orientaciones del médico al paciente, el seguimiento del paciente y la relación médico-paciente, fueron los factores dependientes del médico. Conclusiones: Las cinco dimensiones de la adherencia terapéutica que plantea la OMS (factores socioeconómicos, relacionados con el paciente, relacionados con la enfermedad, relacionados con el tratamiento y relacionados con el sistema de salud) se asociaron con la adherencia al tratamiento y la estabilidad del índice de estandarización internacional.

Introduction: Anticoagulant therapy has demonstrated efficacy in preventing cardioembolic complications. However, adherence is probably the most important determinant of the quality of anticoagulation. Objective: The aim of this research wasto determine the factors that influence adherence to anticoagulation therapy and the stability of the international normalized ratio (INR). Methods: Between September 1, 2018 and December 1, 2020was conducted an analytical, observational andprospective study, corresponding to a pharmacoepidemiological study of drug utilization (Therapeutic Scheme). The object of this study were patients with a diagnosis of coagulation disorders, in the health area of the municipality of Manzanillo. The research data were obtained through an interview and their clinical history. The Xi-squared test (X2), Student's t-test, ANOVA and Kruskall Wallis were used, with a value of p = 0.05 in statistical processing. Results: As a result, a low level of pharmacotherapeutic adherence was observed in the studied population. The sociodemographic variables associated with adherence were sex, education and occupation. There was an association between economic resources, patients' knowledge of their disease, compliance with nonpharmacological treatment, and compliance with pharmacological treatment and adherence. Also, adverse drug reactions and drug availability were the treatment-related factors associated with adherence. And, physician orientation to the patient, patient follow-up, and physician-patient relationship were the physician-dependent factors. Conclusions: To sump up, the five dimensions of adherence proposedbyWHO (socioeconomic, patient-related, disease-related, treatment-related and health system-related factors) were associated with adherence and stability of the international standardization index.

Introdução: A terapêutica anticoagulante tem-se revelado eficaz na prevenção de complicações cardioembólicas. Objetivo: O objetivo desta investigação foi determinar os factores que influenciam a adesão à terapêutica anticoagulante e a estabilidade do rácio normalizado internacional (INR). Métodos: Um estudo analítico, observacional e prospetivo, correspondente a um estudo farmacoepidemiológico de utilização de medicamentos (Esquema Terapêutico) foi realizado entre 1 de setembro de 2018 e 1 de dezembro de 2020.O objeto deste estudo foram pacientes com diagnóstico de distúrbios de coagulação, da área de saúde do município de Manzanillo. Os dados da pesquisa foram obtidos através de uma entrevista e sua história clínica. Utilizou-se o teste do Xi-quadrado (X2), teste t de Student, ANOVA e Kruskall Wallis, com um valor de p = 0,05 no processamento estatístico. Resultados: Como resultado, observou-se um baixo nível de adesão à farmacoterapia na população estudada. As variáveis sociodemográficas associadas à adesão foram sexo, escolaridade e ocupação. Observou-se associação entre recursos financeiros, conhecimento da doença pelo paciente, adesão ao tratamento não farmacológico e adesão ao tratamento farmacológico e adesão. Além disso, as reacções adversas a medicamentos e a disponibilidade de medicamentos foram os factores relacionados com o tratamento associados à adesão. E a orientação médico-paciente, o acompanhamento do paciente e a relação médico-paciente foram os factores dependentes do médico. Conclusões: Concluindo, as cinco dimensões da adesão propostas pela OMS (factores socioeconómicos, relacionados com o doente, relacionados com a doença, relacionados com o tratamento e relacionados com o sistema de saúde) estiveram associadas à adesão e à estabilidade do índice de normalização internacional.

Informe de un caso clínico con síndrome de Paget-Schroetter / Report of a clinical case with Paget-Schroetter Syndrome

Introducción: El síndrome de Paget-Schroetter (SPS) es una trombosis venosa profunda primaria del complejo venoso subclavio-axilar que ocurre después del uso repetitivo y extenuante de los hombros y los brazos. Muestra una incidencia de 1 por 100 000 personas al año. Se informa con mayor frecuencia en atletas jóvenes. Objetivo: Presentar un caso inusual de síndrome de Paget-Schroetter en un individuo joven no deportista. Caso clínico: Varón militar activo de 24 años de edad, sin antecedentes patológicos personales, que ingresó con inflamación del miembro superior izquierdo de 24 horas de evolución. Presentó una trombosis de la vena cefálica izquierda después de un esfuerzo físico de carga y descarga. Tras descartar trastornos secundarios de hipercoagulabilidad se le diagnosticó un SPS. Se le informó de la opción de intervención quirúrgica, pero la rechazó. El diagnóstico fue confirmado con ecografía Doppler y tratado con anticoagulación endovenosa al inicio y luego por vía oral durante 6 meses. Durante el seguimiento no se evidenció trombosis crónica de la vena cefálica izquierda ni formación de intervalo de colaterales vasculares. Conclusiones: El SPS es una condición clínica que necesita un alto índice de sospecha y un diagnóstico oportuno, por tanto, los médicos deben estar atentos a esta rara entidad para su reconocimiento temprano y derivación oportuna a cirugía vascular(AU)

Introduction: Paget-Schroetter syndrome (PSS) is a primary deep vein thrombosis of the subclavian-axillary venous complex that occurs after repetitive and strenuous use of the shoulders and arms. It shows an incidence of 1 per 100,000 people per year. It is reported more frequently in young athletes. Objective: To present an unusual case of Paget-Schroetter syndrome in a young non-athlete individual. Clinical case: 24-year-old active military man with no personal pathological history is presented, who was admitted with inflammation of the left upper limb of 24 hours of evolution. He presented a thrombosis of the left cephalic vein after a physical effort of loading and unloading. After ruling out secondary hypercoagulability disorders, he was diagnosed with SPS. He was informed of the option of surgical intervention, but he declined it. The diagnosis was confirmed with Doppler ultrasound and treated with intravenous anticoagulation at the beginning, and then orally for 6 months. During the follow-up of the patient, there was no evidence of chronic thrombosis of the left cephalic vein or interval formation of vascular collaterals. Conclusions: SPS is a clinical condition that requires a high index of suspicion and prompt diagnosis, therefore, physicians must be attentive to this rare entity for early recognition and timely referral to vascular surgery(AU)

Risk of bias assessment of clinical trials referenced in the technical notes on direct-acting oral anticoagulants available on e-NatJus / Avaliação do risco de viés dos ensaios clínicos referenciados nas notas técnicas sobre os anticoagulantes orais diretos disponíveis no e-NatJus

Objective: Assess and classify the risks of bias in the clinical trials (CTs) that make up the technical notes (TNs) referring to direct-acting oral anticoagulants (DOAC) requests. Methods: The TNs related to the DOAC requests of apixaban, dabigatran, edoxaban, and rivaroxaban were selected on the e-NatJus website and, after excluding duplicate references, an analysis of the CT used for their writing was carried out. The CT risk of bias (low, high, or uncertain bias) was assessed using the Cochrane Risk of Bias tool, and the results were added to Review Manager 5.4. Results: 181 TNs were selected, 236 articles were analyzed and after applying the inclusion criteria, 28 CTs were analyzed in full. None of the CTs were free of bias. Most CTs, 71% (20/28), had a low risk of bias regarding attrition bias and reporting bias. In contrast, 61% (17/28) of the studies did not control for selection, performance, and detection bias, as they present uncertainties and a high risk of bias. In addition, it was observed that 21% (6/28) of the CTs had a high risk of bias for conflict of interest. Conclusion: The biases present in the CT cited as a reference for the TN referring to the DOAC request are significant and compromise their quality (AU).

Objetivo: Avaliar e classificar os riscos de vieses dos ensaios clínicos (EC) que compõem as NTs referentes à solicitação dos DOAC. Métodos: As NTs relacionadas à solicitação dos DOAC apixabana, dabigatrana, edoxabana e rivaroxabana foram selecionadas no website e-NatJus e, após exclusão das referências duplicadas, foi realizada uma análise dos EC utilizados para a redação das mesmas. O risco de viés dos EC (baixo, alto ou viés incerto) foi avaliado utilizando a ferramenta Cochrane Risk of Bias e os resultados foram adicionados no Review Manager 5.4. Resultados: Foram selecionadas 181 NTs, analisados 236 artigos e após aplicação dos critérios de inclusão, resultou em 28 EC analisados na íntegra. Nenhum dos EC ficou isento de viés. A maioria dos EC, 71% (20/28), apresentou baixo risco de viés em relação ao viés de atrito e viés de relato. Por outro lado, 61% (17/28) dos estudos não controlaram o viés de seleção, performance e detecção, uma vez que apresentam incertezas e alto risco de viés. Além disso, foi observado que 21% (6/28) dos EC apresentaram alto risco de viés para conflito de interesses. Conclusão: Os vieses presentes nos EC citados como referência das NT referentes a solicitação dos DOAC são significativos e comprometem a sua qualidade (AU).

Manejo odontológico del paciente en tratamiento de anticoagulante oral sometido a cirugía oral: una revisión narrativa / Stomatological management of anticoagulated patients undergoing oral surgery: a narrative review

Resumen Los pacientes que se encuentran bajo tratamiento de anticoagulantes orales, presentan alteraciones en distintas etapas de la hemostasia, lo que conlleva a tener implicancias y consideraciones médico/quirúrgicas durante su atención. En la actualidad, no existe un consenso en relación con el manejo odontológico de estos pacientes que serán sometidos a procedimientos quirúrgicos, llevando a protocolos clínicos que siguen diversas posturas, como la de disminuir la ingesta farmacológica del anticoagulante, sustituir con heparina y la de mantener el tratamiento bajo control. Objetivo Establecer el manejo estomatológico del paciente que se encuentra en tratamiento de anticoagulante oral mediante una revisión profunda de la literatura Materiales y método Se realizó una búsqueda de revisión bibliográfica manualmente de artículos indexados a las bases de datos de PUBMED y EBSCO que correspondiesen a las palabras "cirugía bucal", "anticoagulantes", "atención dental" y "hemorragia oral". En cuanto a los criterios de inclusión, se consideraron revisiones bibliográficas, estudios observacionales, ensayos clínicos, guías, revisiones sistemáticas y metaanálisis publicados entre noviembre de 2005 y 2022, en idiomas inglés o español. Conclusiones Existen múltiples protocolos para la atención del paciente anticoagulado que será sometido bajo procedimiento de cirugía oral menor. Es importante considerar el anticoagulante utilizado, motivo, control de este, el procedimiento a realizar en el paciente y medidas hemostáticas tanto intra como postoperatorias por realizar, tras analizar lo anterior, se advierte que disminuir la ingesta del fármaco para realizar el procedimiento, puede ser más perjudicial al paciente como al clínico, por lo tanto se sugiere mantener el tratamiento antitrombótico y realizar un correcto manejo médico/quirúrgico.

Abstract Patients undertaking oral anticoagulant treatment may experience alterations in different stages of hemostasis, which lead to medical/surgical implications and considerations during their care. Currently, there is no consensus regarding the dental management of these patients, as they go through surgical procedures. This leads to clinical protocols that follow numerous approaches, such as reducing the pharmacological intake of the anticoagulant, replacing it with heparin, and maintaining the controlled treatment. Objective: To establish the stomatological management of the patient undergoing oral anticoagulant treatment through an in depth review of the literature. Materials and Method: A manual bibliographic review search of articles indexed to the PUBMED and EBSCO databases corresponding to the words "oral surgery", "oral bleeding", "anticoagulants" and "dental management" was performed. Regarding the inclusion criteria: bibliographic reviews, observational studies, clinical trials, guidelines, systematic reviews, and meta-analyses published between November 2005 and 2022, in English or Spanish, were considered. Conclusion: There are multiple protocols for the care of the anticoagulated patient who will undergo a minor oral surgery procedure. It is important to reflect on the anticoagulant used, the reason for it, its supervision, the surgical procedure that will be undertaken by the patient, and both intraoperative and postoperative hemostatic measures to be implemented. After analyzing the above, it is noted that reducing the intake of the drug to perform the surgical procedure may be harmful to the patient and to the clinician, therefore it is suggested to maintain the antithrombotic treatment and carry out a correct medical/surgical management.

Comparing follow-up of patients with vitamin K antagonists in a health center: pre- and post-COVID-19 pandemic / Comparação do seguimento de doentes hipocoagulados com antagonistas da vitamina K numa unidade de saúde: pré e pós pandemia COVID-19

Introduction and objectives: During the COVID-19 pandemic, the follow-up of patients treated with vitamin K antagonists (VKAs) may have been affected. This study aims to compare how these patients were monitored pre- and post-COVID-19 pandemic and understand the impact of non-face-to-face appointments on their follow-up. Methods: We conducted a retrospective cohort study in a Portuguese Health Center. The study included patients treated with VKAs and followed at the Health Center for international normalized ratio (INR) monitoring between March 2019 and March 2021. Data collected: sex, age, type of VKA; INR; date of INR assessment, type of appointment (face-to-face or phone/e-mail). Rosendaal's method was used to calculate pre-COVID-19 and post-COVID-19 time in therapeutic range (TTR). Good TTR control was defined if values ≥ 70%. Results: 44 patients were included. The mean TTR in the pre-COVID-19 period was 64.55% (95% CI: 58.10 - 71.00%). The post-COVID-19 mean was slightly higher (+ 2.26%), 66.81% (95% CI: 59.66 - 73.97%), but the difference was not statistically significant (p = 0.576). The use of non-face-to-face appointments did not contribute to worsening post-pandemic TTR, show-ing no lower follow-up than during pre-pandemic period in which all contacts were face-to-face [CI (95%) -0.397 - 0.196 for a reference range -0.489 - 0.693]. Conclusions: The TTR value in both periods was similar and lower than the value defined for effective hypocoagulation. The use of non-face-to-face consultation in the post-COVID-19 period does not seem to have influenced the quality of hypocoagulation (AU).

Introdução e objetivos: Durante a pandemia COVID-19 o acompanhamento de doentes medicados com antagonistas da vitamina K (AVKs) pode ter sido afetado. Este estudo pretende comparar a forma como estes doentes foram monitorizados antes e depois da pandemia COVID-19 e compreender o impacto da consulta não presencial no seu seguimento. Métodos: Estudo de coorte retrospetivo num Centro de Saúde em Portugal. O estudo incluiu doentes tratados com AVKs e seguidos no Centro de Saúde para monitorização do International Normalized Ratio(INR) entre março de 2019 e março de 2021. Dados recolhidos: sexo, idade, tipo de AVK; INR; data da avaliação do INR, tipo de consulta (presencial ou por telefone/e-mail). Foi utilizado o método de interpolação linear de Rosendaal para calcular o tempo em intervalo terapêutico (TTR) pré- e pós-COVID-19. Foi definido um bom controle se valores de TTR ≥ 70%. Resultados: Foram incluídos 44 doentes. A média de TTR no período pré-COVID-19 foi de 64,55% (95% IC: 58,10 - 71,00%). A média pós-COVID-19 foi ligeiramente superior (+ 2,26%), 66,81% (95% IC: 59,66 - 73,97%), mas a diferença não foi estatisticamente significativa (p = 0,576). A utilização da consulta não presencial não contribuiu para o agravamento do TTR no período pós-pandemia, não mostrando um seguimento inferior ao do período pré-pandemia em que todos os contatos foram presenciais [IC (95%) -0,397 - 0,196 para um intervalo de referência -0,489 - 0,693]. Conclusões: O valor de TTR em ambos os períodos foi semelhante e inferior ao valor definido para hipocoagulação eficaz. A utilização da consulta não presencial no período pós-COVID-19 não parece ter influenciado a qualidade da hipocoagulação (AU).

Manejo perioperatorio de medicación anticoagulante y antiagregante antiplaquetaria en radiología intervencionista / Perioperative management of anticoagulants and antiplatelets agents in interventional radiology

Resumen El número de personas en tratamiento con fármacos anticoagulantes o antiplaquetarios está en crecimiento constante debido al aumento de la supervivencia de los pacientes con fibrilación auricular, válvulas cardiacas mecánicas o que han sufrido un evento isquémico o trombótico agudo. Cuando estos pacientes necesitan un procedimiento radiológico intervencionista que acarrea riesgo de sangrado, es necesario analizar el riesgo trombótico del paciente al interrumpir la medicación frente al riesgo hemorrágico del procedimiento para tomar la decisión más adecuada en cada caso. Por tanto, es una decisión individualizada y supone un desafío para los/as radiólogos/as que realicen estas técnicas. Nuestro objetivo en esta revisión es mostrar las recomendaciones actuales sobre el manejo perioperatorio de la medicación anticoagulante y antiplaquetaria, adaptada al intervencionismo radiológico.

Abstract The number of people treated with anticoagulant or antiplatelet agents is constantly growing due to the increased survival of patients with atrial fibrillation, mechanical cardiac valves or who have suffered an acute thrombotic or ischemic event. When these patients need an interventional radiological procedure that carries a risk of bleeding, it is necessary to analyze the thrombotic risk of the patient when interrupting the medication against the hemorrhagic risk of the procedure, to make the most appropriate decision in each case. Therefore, it is an individualized decision, and it is a challenge for radiologists who perform these techniques. Our goal in this review is to update the current recommendations on the perioperative management of anticoagulant and antiplatelet agents, adapted to the radiological interventionism.

Outcomes of recurrent stroke in patients with atrial fibrillation according to presumed etiology / Desfecho de AVC recorrente em pacientes com fibrilação atrial de acordo com etiologia presumida

Abstract Background Atrial fibrillation (AF) is a potent risk factor for stroke. The presence of competing etiologies can modify disease outcomes and demand different treatment strategies. Objective The primary purpose of the study was to examine the differences in outcomes for patients with AF admitted with a recurrent stroke, stratified according to the presumed etiology of the stroke. Methods We analyzed AF patients admitted for a recurrent ischemic stroke in an academic comprehensive stroke center. Recurrent strokes were categorized as "Cardioembolic", meaning AF without any competing mechanism, versus "Undetermined" etiology due to competing mechanisms. We used logistic regression to test the association between recurrent stroke etiology and favorable outcome (discharge home), after accounting for important covariates. Results We included 230 patients, with a mean age 76.9 (SD ± 11.3), 52.2% male, median National Institute of Health Stroke Scale (NIHSS) score of 7 (IQR 2-16). Patients with cardioembolic stroke (65.2%) had higher median NIHSS 8.5 (3-18) versus 3 (1-8) and were more likely to be treated with reperfusion therapies. The favorable outcome was reached by 64 patients (27.8%), and in-hospital mortality was 15.2% overall. After adjustment, there was no difference in outcome between patients with cardioembolic versus undetermined stroke etiology (odds ratio for discharge home: 1.41; 95% CI: 0.65-3.15). Conclusions In this single-center sample of AF patients with history of stroke, there was no difference in discharge outcomes between those with cardioembolic and those with undetermined stroke etiology. This question warrants examination in larger samples to better understand the importance of the stroke mechanism and secondary prophylaxis.

Resumo Antecedentes Fibrilação atrial (FA) é um fator de risco importante para AVC. A presença de mecanismos concorrentes para o AVC pode modificar o desfecho e demandar estratégias de tratamento diferentes. Objetivo O objetivo primário do estudo foi examinar diferenças no desfecho de pacientes com FA admitidos por um AVC recorrente, sendo estratificados de acordo com a etiologia presumida do AVC. Métodos Nós analisamos pacientes com FA admitidos por conta de AVC recorrente em um centro acadêmico terciário de AVC. Os casos de AVC recorrentes foram classificados como "Cardioembólicos", sendo FA sem outros mecanismos alternativos, versus aqueles de etiologia "Indeterminada" por conta de mecanismos concorrentes. Foi usada regressão logística para testar a associação entre a etiologia do AVC recorrente e desfecho favorável (alta direto para casa) após controle para covariáveis importantes. Resultados Nós incluímos 230 pacientes, com uma idade média 76,9 anos (DP ± 11.3), 52.2% homens, com um escore mediano do National Institute of Health Stroke Scale (NIHSS) de 7 (IIQ 2-16). Pacientes com AVC cardioembólicos (65,2%) tiveram um escore de NIHSS mediano mais alto 8,5 (3-18) versus 3 (1-8), e com maior chance de tratamento com terapias de reperfusão. O desfecho favorável ocorreu em 64 pacientes (27,8%) e a mortalidade institucional foi de 15,2% no total. Após ajustes, não encontramos diferença no desfecho entre pacientes com AVC cardioembólico versus AVC de etiologia indeterminada (odds ratio para alta para casa: 1,41; 95% IC: 0,65-3,15). Conclusões Nessa amostra de pacientes com FA e história de AVC recorrente de centro único, não houve diferença no desfecho de alta entre aqueles com AVC cardioembólico e aqueles com etiologia indeterminada. Essa questão deve ser examinada em amostras maiores para melhor compreender a importância do mecanismo do AVC e a profilaxia secundária.