Effect of Direct Oral Anticoagulant, Patient, and Surgery Characteristics on Clinical Outcomes in the Perioperative Anticoagulation Use for Surgery Evaluation Study.

Introduction  The Perioperative Anticoagulation Use for Surgery Evaluation (PAUSE) Study assessed a standardized perioperative management strategy in patients with atrial fibrillation who were taking a direct oral anticoagulant (DOAC) and required an elective surgery or procedure. The aim of this substudy is to analyze the safety of this management strategy across different patient subgroups, according to four presurgical variables: (1) DOAC type and dose, (2) surgery/procedure bleed risk, (3) patient renal function, and (4) age. Methods  Clinical outcomes analyzed included major bleeding (MB), arterial thromboembolism, any bleeding, and any thromboembolism. We used descriptive statistics to summarize clinical outcomes, where the frequency, proportion, and 95% confidence interval were reported. Fisher\u27s exact tests were used for testing the hypothesis of independence between the clinical outcome and patient characteristic, where the test p -values were reported. Results  There were 3,007 patients with atrial fibrillation requiring perioperative DOAC management. There was no significant difference in bleeding or thromboembolic outcomes according to DOAC type/dose regimen, renal function, or patient age. The rate of MB was significantly higher with high bleed risk procedures than low bleed risk procedures in apixaban-treated patients (2.9 vs. 0.59%; p  \u3c 0.01), but not in dabigatran-treated patients (0.88 vs. 0.91%; p  = 1.0) or rivaroxaban-treated patients (2.9 vs. 1.3%; p  = 0.06). The risk for thromboembolism did not differ according to surgery/procedure-related bleed risk. Conclusion  Our results suggest that in DOAC-treated patients who received standardized perioperative management, surgical bleed risk is an important determinant of bleeding but not thromboembolic outcomes, although this finding was not consistent across all DOACs. There were no differences in bleeding and thromboembolism according to DOAC type and dose, renal function, or age

The normal field instability under side-wall effects: comparison of experiments and computations

We consider a single spike of ferrofluid, arising in a small cylindrical container, when a vertically oriented magnetic field is applied. The height of the spike as well as the surface topography is measured experimentally by two different technologies and calculated numerically using the finite element method. As a consequence of the finite size of the container, the numerics uncovers an imperfect bifurcation to a single spike solution, which is forward. This is in contrast to the standard transcritical bifurcation to hexagons, common for rotational symmetric systems with broken up-down symmetry. The numerical findings are corroborated in the experiments. The small hysteresis observed is explained in terms of a hysteretic wetting of the side wall.Comment: accepted to New Journal of Physic

Multicenter randomized controlled trial on Duration of Therapy for Thrombosis in Children and Young Adults (the Kids-DOTT trial): pilot/feasibility phase findings

BACKGROUND: Randomized controlled trials (RCTs) on pediatric venous thromboembolism (VTE) treatment have been challenged by unsubstantiated design assumptions and/or poor accrual. Pilot/feasibility (P/F) studies are critical to future RCT success. METHODS: The Kids-DOTT trial is a multicenter RCT investigating non-inferiority of a 6-week (shortened) versus 3-month (conventional) duration of anticoagulation in patients aged \u3c 21 years with provoked venous thrombosis. Primary efficacy and safety endpoints are symptomatic recurrent VTE at 1 year and anticoagulant-related, clinically relevant bleeding. In the P/F phase, 100 participants were enrolled in an open, blinded-endpoint, parallel-cohort RCT design. RESULTS: No eligibility violations or randomization errors occurred. Of the enrolled patients, 69% were randomized, 3% missed the randomization window, and 28% were followed in prespecified observational cohorts for completely occlusive thrombosis or persistent antiphospholipid antibodies. Retention at 1 year was 82%. Interobserver agreement between local and blinded central determination of venous occlusion by imaging at 6 weeks after diagnosis was strong (k-statistic = 0.75; 95% confidence interval [CI] 0.48-1.0). The primary efficacy and safety event rates were 3.3% (95% CI 0.3-11.5%) and 1.4% (95% CI 0.03-7.4%). CONCLUSIONS: The P/F phase of the Kids-DOTT trial has demonstrated the validity of vascular imaging findings of occlusion as a randomization criterion, and defined randomization, retention and endpoint rates to inform the fully powered RCT

Management and 1-year outcomes of patients with newly diagnosed atrial fibrillation and chronic kidney disease: Results from the prospective garfield-af registry

© 2019 The Authors. Background-—Using data from the GARFIELD-AF (Global Anticoagulant Registry in the FIELD–Atrial Fibrillation), we evaluated the impact of chronic kidney disease (CKD) stage on clinical outcomes in patients with newly diagnosed atrial fibrillation (AF). Methods and Results-—GARFIELD-AF is a prospective registry of patients from 35 countries, including patients from Asia (China, India, Japan, Singapore, South Korea, and Thailand). Consecutive patients enrolled (2013–2016) were classified with no, mild, or moderate-to-severe CKD, based on the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative guidelines. Data on CKD status and outcomes were available for 33 024 of 34 854 patients (including 9491 patients from Asia); 10.9% (n=3613) had moderate-to-severe CKD, 16.9% (n=5595) mild CKD, and 72.1% (n=23 816) no CKD. The use of oral anticoagulants was influenced by stroke risk (ie, post hoc assessment of CHA2DS2-VASc score), but not by CKD stage. The quality of anticoagulant control with vitamin K antagonists did not differ with CKD stage. After adjusting for baseline characteristics and antithrombotic use, both mild and moderate-to-severe CKD were independent risk factors for all-cause mortality. Moderate-to-severe CKD was independently associated with a higher risk of stroke/systemic embolism, major bleeding, new-onset acute coronary syndrome, and new or worsening heart failure. The impact of moderate-to-severe CKD on mortality was significantly greater in patients from Asia than the rest of the world (P=0.001). Conclusions-—In GARFIELD-AF, moderate-to-severe CKD was independently associated with stroke/systemic embolism, major bleeding, and mortality. The effect of moderate-to-severe CKD on mortality was even greater in patients from Asia than the rest of the world

Venous thromboembolism following hematopoietic stem cell transplantation-a systematic review and meta-analysis

Venous thromboembolism (VTE) is a common complication of hematopoietic stem cell transplantation (HSCT). Graft-versus-host disease (GVHD) is another complication of HSCT that may modify the risk of VTE. Our objective was to explore the incidence of VTE (deep venous thrombosis and pulmonary embolism) following HSCT and to evaluate its association with GVHD. A comprehensive search of Medline In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus was conducted to search for both retrospective and prospective HSCT studies which had reported VTE. Random-effects meta-analysis was used to pool incidence rates. We included 17 studies reporting on allogeneic- and 10 on autologous-HSCT; enrolling 6693 patients; of which 5 were randomized. The overall incidence of VTE after HSCT was 5%(4-7%). Incidence in allogeneic-HSCT was 4%(2-6%) and in autologous-HSCT was 4%(1-15%). Eleven and nine studies reported data on acute and chronic GVHD, respectively. The incidence of VTE in chronic GVHD was 35%(20-54%), whereas in acute GVHD it was 47%(32-62%). Based on the results of this meta-analysis, VTE is a fairly common complication after HSCT, emphasizing the importance of assimilating guidelines for both treatment and prophylaxis in this patient population

Rationale and design for the study of rivaroxaban to reduce thrombotic events, hospitalization and death in outpatients with COVID-19: The PREVENT-HD study

© 2021 Elsevier Inc. Background: COVID-19 is associated with both venous and arterial thrombotic complications. While prophylactic anticoagulation is now widely recommended for hospitalized patients with COVID-19, the effectiveness and safety of thromboprophylaxis in outpatients with COVID-19 has not been established. Study Design: PREVENT-HD is a double-blind, placebo-controlled, pragmatic, event-driven phase 3 trial to evaluate the efficacy and safety of rivaroxaban in symptomatic outpatients with laboratory-confirmed COVID-19 at risk for thrombotic events, hospitalization, and death. Several challenges posed by the pandemic have necessitated innovative approaches to clinical trial design, start-up, and conduct. Participants are randomized in a 1:1 ratio, stratified by time from COVID-19 confirmation, to either rivaroxaban 10 mg once daily or placebo for 35 days. The primary efficacy end point is a composite of symptomatic venous thromboembolism, myocardial infarction, ischemic stroke, acute limb ischemia, non-central nervous system systemic embolization, all-cause hospitalization, and all-cause mortality. The primary safety end point is fatal and critical site bleeding according to the International Society on Thrombosis and Haemostasis definition. Enrollment began in August 2020 and is expected to enroll approximately 4,000 participants to yield the required number of end point events. Conclusions: PREVENT-HD is a pragmatic trial evaluating the efficacy and safety of the direct oral anticoagulant rivaroxaban in the outpatient setting to reduce major venous and arterial thrombotic events, hospitalization, and mortality associated with COVID-19