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1.
Data Recorded in Real Life Support the Safety of Nattokinase in Patients with Vascular Diseases.
Gallelli, G, Di Mizio, G, Palleria, C, Siniscalchi, A, Rubino, P, Muraca, L, Cione, E, Salerno, M, De Sarro, G, Gallelli, L
Nutrients. 2021;(6)
Abstract
Nattokinase (NK) is a serine protease enzyme with fibrinolytic activity. Even if it could be used for the treatment of several diseases, no data have been published supporting its use patients who underwent vascular surgery. In this study, we evaluated both the efficacy and the safety of nattokinase (100 mg/day per os) in patients admitted to vascular surgery. Patients were of both sexes, >18 years of age, with vascular diseases (i.e., deep vein thrombosis, superficial vein thrombosis, venous insufficiency), and naïve to specific pharmacological treatments (anticoagulants or anti-platelets). Patients were divided into three groups. Group 1: patients with deep vein thrombosis, treated with fondaparinux plus nattokinase. Group 2: patients with phlebitis, treated with enoxaparin plus nattokinase. Group 3: patients with venous insufficiency after classical surgery, treated with nattokinase one day later. During the study, we enrolled 153 patients (age 22-92 years), 92 females (60.1%) and 61 males (39.9%;), and documented that nattokinase was able to improve the clinical symptoms (p < 0.01) without the development of adverse drug reactions or drug interactions. Among the enrolled patients, during follow-up, we did not record new cases of vascular diseases. Attention to patients' clinical evolution, monitoring of the INR, and timely and frequent adjustment of dosages represent the cornerstones of the safety of care for patients administered fibrinolytic drugs as a single treatment or in pharmacological combination. Therefore, we can conclude that the use of nattokinase represents an efficient and safe treatment able to both prevent and treat patients with vascular diseases.
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2.
Early prophylaxis of central venous catheter-related thrombosis using 1% chlorhexidine gluconate and chlorhexidine-gel-impregnated dressings: a retrospective cohort study.
Yamashita, T, Takamori, A, Nakagawachi, A, Tanigawa, Y, Hamada, Y, Aoki, Y, Sakaguchi, Y
Scientific reports. 2020;(1):15952
Abstract
To determine the prophylactic effect of using combined 1% alcoholic chlorhexidine gluconate and chlorhexidine gel-impregnated dressings (CGCD) on catheter-related thrombosis (CRT) in critically ill patients. This retrospective cohort study was performed in an intensive care unit from November 2009 to August 2014. The CRT incidence diagnosed with ultrasound examination was compared between patients applying CGCD and combined 10% aqueous povidone-iodine and standard transparent dressings (PITD) after central venous catheter insertion into the internal jugular vein for ≥ 48 h. CRT was stratified into early (within 7 days) and late (days 8-14) thromboses. Multivariate analyses using logistic regression models clarified the relationships between early- and late-CRT risks and skin antiseptic and catheter site dressing combinations. CRT occurred in 74 of 134 patients (55%), including 52 with early CRT and 22 with late CRT. Patients receiving CGCD had a significantly lower incidence of early CRT than those receiving PITD (odds ratio = 0.18; 95% confidence interval = 0.07-0.45, p < .001). No significant association was evident between using CGCD and late CRT (p = .514). Compared to PITD, CGCD reduced the CRT risk over 7 days in critically ill patients.UMIN Clinical Trials Registry: UMIN000037492.
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Phase II Study of Sorafenib Combined with Concurrent Hepatic Arterial Infusion of Oxaliplatin, 5-Fluorouracil and Leucovorin for Unresectable Hepatocellular Carcinoma with Major Portal Vein Thrombosis.
He, MK, Zou, RH, Li, QJ, Zhou, ZG, Shen, JX, Zhang, YF, Yu, ZS, Xu, L, Shi, M
Cardiovascular and interventional radiology. 2018;(5):734-743
Abstract
BACKGROUND Sorafenib is recommended for the first-line treatment of advanced hepatocellular carcinoma (HCC). However, the median progression-free survival (PFS) of patients with HCC and major portal vein tumor thrombosis treated with sorafenib monotherapy is no more than 3 months. A prospective single-arm phase II study was conducted to determine whether adding hepatic arterial infusion chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin to sorafenib could improve on these results. METHODS Thirty five patients were treated with sorafenib 400 mg orally twice a day, oxaliplatin 85 mg/m2 HAI on day 1, leucovorin 400 mg/m2 HAI on days 1, and 5-fluorouracil 2800 mg/m2 on days 1 and 2, repeated every 21 days. The primary end point was the 3-month PFS rate. RESULTS The 3-, 6-, and 12-month PFS rates were 82.9, 51.4, and 22.9%, respectively. The median PFS and overall survival was 6.7 and 13.2 months, respectively. The objective response rate was 40%, and the disease control rate was 77.1% by RECIST criteria. Five (14.3%) patients achieved conversion to complete resection after the study treatment, and one of them experienced a pathological complete response. Treatment-related deaths did not occur. Grade 3-4 toxicities consisted of increases in aspartate aminotransferase (31.4%), hand-foot syndrome (17.1%), thrombocytopenia (14.3%), and neutropenia (8.6%). CONCLUSIONS The combination treatment met the pre-specified end point of a 3-month progression free survival rate exceeding 65% and was clinical tolerable. The merits of this approach need to be established with a phase III trial. Clinical trial number http://ClinicalTrials.gov (No. NCT02981498).
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4.
Genetic polymorphisms in the FVII gene is associated with lower extremity deep venous thrombosis: A case-control study.
Liu, JW, Chen, DQ
Journal of cellular biochemistry. 2018;(8):6715-6722
Abstract
This study aims to explore the associations between FVII gene polymorphisms (R353Q, 5'F7, and -402G/A) and lower extremity deep venous thrombosis (LEDVT) in a Chinese Han population. LEDVT patients (153) and healthy people (174) were, respectively, as case and control groups and evaluated related biochemical indicators. Gene polymorphisms of R353Q, 5'F7, and -402G/A of FVII, serum FVII level, antithrombin activity, plasma fibrinogen content, and plasma D-dimer (D-D) level were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), ELISA, chromogenic substrate assay, coagulating assay, and Immunoturbidimetry assay, respectively. Compared with the control group, the case group had a higher level of body mass index (BMI), glucose, and fibrinogen, and lower level of total cholesterol (TC). Notable differences were found in GG genotype, G and A alleles, as well as distribution of recessive model of -402G/A. The serum FVII level of GG genotype was higher than that of GA and AA genotypes. FIB and D-D had a higher level had a lower level in GG genotype when compared with GA and AA genotypes. Smoking, drinking, serum FVII level, and -402G/A-GG were the independent risk factors for LEDVT. This study demonstrates that -402G/A of FVII may be a risk factor for LEDVT patients in a Chinese Han population.
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Analysis of patients with deep vein thrombosis switched from standard therapy to rivaroxaban in the non-interventional XALIA study.
Turpie, AGG, Mantovani, LG, Haas, S, Kreutz, R, Monje, D, Schneider, J, van Eickels, M, Gebel, M, Ageno, W
Thrombosis research. 2017;:23-27
Abstract
INTRODUCTION XALIA assessed the safety and effectiveness of rivaroxaban for deep vein thrombosis (DVT) treatment in routine clinical practice. This substudy describes the clinical characteristics and outcomes of 'early switchers' - patients who received heparin or fondaparinux for >2-14days and/or a vitamin K antagonist (VKA) for 1-14days before switching to rivaroxaban. MATERIALS AND METHODS Patients with DVT (latterly with concomitant pulmonary embolism) received rivaroxaban or standard anticoagulation (initial treatment with heparin or fondaparinux, usually overlapping with and followed by a VKA). Patients administered rivaroxaban alone, or heparin or fondaparinux for ≤48h pre-enrollment were included in the rivaroxaban cohort. Therapy type, dose, and duration were at the physician's discretion. Primary outcomes were major bleeding, recurrent venous thromboembolism (VTE), and all-cause mortality. RESULTS In 368 early switchers, recurrence or bleeding risk factors were more prevalent versus the rivaroxaban cohort, including creatinine clearance<50mL/min (6.5% vs. 3.9%), previous major bleeding (4.6% vs. 1.4%), active cancer (8.2% vs. 5.6%), and concomitant pulmonary embolism (20.9% vs. 8.4%). Crude incidence rates were numerically higher versus the rivaroxaban cohort for major bleeding (1.4% vs. 0.7%), recurrent VTE (2.2% vs. 1.4%), and all-cause mortality (0.8% vs. 0.5%). CONCLUSIONS Patients who switched to rivaroxaban early in the treatment process had a higher frequency of risk factors for bleeding and recurrent VTE than patients treated with rivaroxaban; reflected by the higher risk of adverse events in that group during follow-up.
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Indirect comparison and cost-utility of dabigatran etexilate and rivaroxaban in the treatment and extended anticoagulation of venous thromboembolism in a UK setting.
Jugrin, AV, Hösel, V, Ustyugova, A, De Francesco, M, Lamotte, M, Sunderland, T
Journal of medical economics. 2016;(1):1-10
Abstract
BACKGROUND Acute venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is traditionally managed with a short course of parenteral anticoagulation followed by 3-6 months of a vitamin-K antagonist. Non-vitamin K oral anticoagulants (NOACs) do not require routine monitoring and dose adjustment, thus potentially provide an alternative treatment option. METHODS AND RESULTS Because of the lack of head-to-head clinical studies, an indirect comparison was conducted of dabigatran etexilate and rivaroxaban based on the respective phase III clinical trial. The derived relative safety and efficacy estimates were used to evaluate the cost-utility of dabigatran compared with rivaroxaban in the treatment and secondary prevention of VTE. The results of the indirect comparison showed no significant difference between dabigatran and rivaroxaban in avoiding recurrent VTE following index PE, index DVT, or DVT/PE combined, in treatment and extended anticoagulation. Dabigatran has significantly less major or clinically relevant bleeds (MCRBE) compared to rivaroxaban in treatment after index DVT and treatment after DVT or PE combined, but was not significantly different from rivaroxaban after index PE or in extended anticoagulation. In cost-utility deterministic analyses, dabigatran was projected dominant in all analyzed settings, given its marginally lower total cost and marginally higher QALYs gained compared to rivaroxaban. Probabilistic analyses results showed a high likelihood of dabigatran being considered good value for money in the UK, in treatment and in secondary prevention of VTE. CONCLUSION The cost-effectiveness evaluations showed that dabigatran can be considered the dominant treatment strategy compared to rivaroxaban in the patients' sub-groups considered, given the projected marginally higher clinical benefits and lower treatment costs.
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Reduction in the length of stay with rivaroxaban as a single-drug regimen for the treatment of deep vein thrombosis and pulmonary embolism.
van Bellen, B, Bamber, L, Correa de Carvalho, F, Prins, M, Wang, M, Lensing, AW
Current medical research and opinion. 2014;(5):829-37
Abstract
OBJECTIVE The phase III EINSTEIN DVT and EINSTEIN PE trials demonstrated the potential of oral rivaroxaban for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). The length of initial hospitalization in patients presenting with either symptomatic DVT or PE was assessed using hospitalization records from these trials. METHODS Analyses were carried out in the intention-to-treat population, using non-parametric and parametric statistical methods. RESULTS Overall, 52% (1781/3434) of EINSTEIN DVT patients and 90% (4328/4821) of EINSTEIN PE patients were admitted to hospital. The proportion of hospitalized patients with a length of stay of five or fewer days receiving rivaroxaban was 54% compared with 31% for enoxaparin/vitamin K antagonist (VKA) in patients with DVT. For patients with PE, the corresponding values were 45% and 33%. Stays of 6-10 days were observed in 29% of rivaroxaban-treated patients compared with 45% of enoxaparin/VKA-treated patients for DVT. For patients with PE, these values were 39% and 46% in the rivaroxaban and enoxaparin/VKA groups, respectively. Overall, length of stay was significantly shorter in the rivaroxaban group, compared with the enoxaparin/VKA group across all analyses performed (p < 0.0001). Across regions, the observed admission rates and length of stay duration varied greatly: Asia had the longest overall hospitalization rates, whereas the lowest rates were reported in North America, Australia and New Zealand. Nevertheless, a consistent trend was observed: length of hospital stay in patients with DVT or PE receiving rivaroxaban was shorter than, or at least similar to, patients receiving enoxaparin/VKA. CONCLUSION A single-drug regimen with rivaroxaban may reduce the burden on healthcare systems and patients, and provides effective and well tolerated treatment. The studies shared an open-label design that allowed comparison of initial hospitalization, but limitations include the well monitored clinical trial setting in which decisions on admission and discharge could vary from real-world management.
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Safety of deep venous thrombosis prophylaxis with low-molecular-weight heparin in brain surgery. Prospective study on 746 patients.
Chibbaro, S, Tacconi, L
Surgical neurology. 2008;(2):117-21; discussion 121
Abstract
BACKGROUND Pharmacologic prophylaxis of deep vein thrombosis for intracranial surgery is still a controversial matter due to the concern of possible increased risk of postoperative hemorrhage. The objective of this prospective study was to assess the safety of the deep vein thrombosis prophylaxis protocol applied in our neurosurgical unit. METHODS This is a prospective clinical trial on 746 consecutive patients undergoing intracranial surgery during a 30-month period managed by our deep vein thrombosis prophylaxis protocol. All patients were managed with elastic stockings, perioperative mechanical pneumatic sequential compression leg device, and 3500 units (daily) of sodium Tinzaparin starting from the first postoperative day. In those patients who were considered to be at higher risk to develop deep vein thrombosis, the dose of heparin was doubled and was started in the preoperative period. RESULTS Eight (1.07%) significant postoperative hemorrhages were recorded among 746 procedures, 6 (0.8%) of those occurred among patients undergoing major cranial procedures. Clinical evidence of deep vein thrombosis was present in 3 patients (0.4%). One patient (0.13%) died of fatal PE 2 months after surgery. CONCLUSION The results of this study show the safety of our deep vein thrombosis prevention protocol in patients undergoing intracranial neurosurgical operation.
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Activation of coagulation system during air travel: a crossover study.
Schreijer, AJ, Cannegieter, SC, Meijers, JC, Middeldorp, S, Büller, HR, Rosendaal, FR
Lancet (London, England). 2006;(9513):832-8
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Abstract
BACKGROUND There is an increased risk of venous thrombosis after air travel, but the underlying mechanism is unclear. Our aim was to ascertain whether flying leads to a hypercoagulable state. METHODS We did a crossover study in 71 healthy volunteers (15 men, 56 women), in whom we measured markers of activation of coagulation and fibrinolysis before, during, and after an 8-h flight. The same individuals participated in two control exposure situations (8-h movie marathon and daily life) to separate the effect of air travel on the coagulation system from those of immobilisation and circadian rhythm. To study the effect of risk factors for thrombosis, we included participants with the factor V Leiden mutation (n=11), those who took oral contraceptives (n=15), or both (n=15), as well as 30 individuals with no specific risk factors. FINDINGS After the flight, median concentrations of thrombin-antithrombin (TAT) complex increased by 30.1% (95% CI 11.2-63.2), but decreased by 2.1% (-11.2 to 14) after the cinema and by 7.9% (-16.2 to -1.2) after the daily life situation. We recorded a high response in TAT levels in 17% (11 of 66) of individuals after air travel (3% [2 of 68] for movie marathon; 1% [1 of 70] in daily life). These findings were most evident in the group with the factor V Leiden mutation who used oral contraceptives. We noted a high response in all variables (prothrombin fragment 1 and 2, TAT, and D-dimer) in four of 63 (6.3%) volunteers after the flight, but in no-one after either of the control situations. INTERPRETATION Activation of coagulation occurs in some individuals after an 8-h flight, indicating an additional mechanism to immobilisation underlying air travel related thrombosis.
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A randomized trial comparing 2 low-molecular-weight heparins for the outpatient treatment of deep vein thrombosis and pulmonary embolism.
Wells, PS, Anderson, DR, Rodger, MA, Forgie, MA, Florack, P, Touchie, D, Morrow, B, Gray, L, O'Rourke, K, Wells, G, et al
Archives of internal medicine. 2005;(7):733-8
Abstract
BACKGROUND Low-molecular-weight heparins (LMWHs) are now standard therapy for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). No published trials have compared LMWHs, and few studies have examined outpatient therapy for PE. Only tinzaparin sodium has demonstrated superiority to unfractionated heparin in a clinical trial. METHODS We compared 2 LMWH products, tinzaparin and dalteparin sodium, for the treatment of acute DVT and PE in a randomized, controlled clinical trial of consecutive outpatients presenting to a venous thromboembolism service at 4 tertiary-care hospitals. Patients were treated with subcutaneous tinzaparin sodium, 175 IU/kg every 24 hours, or subcutaneous dalteparin sodium, 200 IU/kg every 24 hours, for at least 5 days. Warfarin sodium therapy was started simultaneously and continued for 90 days. The primary end point was efficacy (recurrence of venous thromboembolism); safety (bleeding) was a composite end point. RESULTS Two hundred fifty-four patients received tinzaparin (39 with PE and 215 with DVT) and 251 received dalteparin (51 with PE and 200 with DVT). Most patients had an active malignancy or idiopathic DVT/PE. The outcome events occurred in 11 (4.4%; 95% confidence interval [CI], 2.2%-7.7%) and 15 patients (5.9%; 95% CI, 3.3%-9.5%) in the dalteparin and tinzaparin groups, respectively, including 9 and 10 recurrences, respectively, and 2 and 5 major hemorrhages, respectively (P = .44). The 95% CI on the difference of -1.5% was -5.3% to 2.4%. CONCLUSIONS Tinzaparin and dalteparin are safe and effective for the outpatient treatment of DVT or PE. Our finding of no differences between the LMWHs based on major clinical end points means that practical issues can be the deciding factor on which drug to use.