Pharmacokinetics, Pharmacodynamics, and Safety of Edoxaban in Pediatric Subjects: A Phase I Single-Dose Study.

This was an open-label, single-dose, phase I study to characterize the pharmacokinetics (PKs), pharmacodynamics (PDs), and safety of edoxaban in pediatric subjects from birth to 18 years at risk for venous thromboembolism (VTE). Children requiring anticoagulant therapy were enrolled into 5 age cohorts (0 to < 6 months (N = 12), 0.5 to < 2 years (N = 13), 2 to < 6 years (N = 13), 6 to < 12 years (N = 13), and 12 to < 18 years (N = 15)) receiving tablet or oral suspension of edoxaban at doses expected to be equivalent to 30 or 60 mg once daily (q.

Impact of mild thrombocytopenia on bleeding and recurrent thrombosis in cancer.

Thrombocytopenia occurs frequently in patients with cancer-associated thrombosis (CAT), however prospective evaluation of clinical outcomes following randomization to anticoagulants is limited. The HOKUSAI VTE Cancer study was a randomized, open-label, non-inferiority, phase III trial comparing dalteparin with edoxaban in CAT patients. This post hoc analysis of Hokusai VTE Cancer Study was performed to compare outcomes in patients with platelet count ≤100x109/L at one or more specified time points (baseline, 1-month, or 3-month) versus those without thrombocytopenia.

Sex Differences Among Patients Receiving Edoxaban vs Vitamin K Antagonist for Atrial Fibrillation After TAVR.

Background: In the ENVISAGE-TAVI AF (Edoxaban vs Standard of Care and Their Effects on Clinical Outcomes in Patients Having Undergone Transcatheter Aortic Valve Implantation-Atrial Fibrillation) trial, edoxaban was noninferior to vitamin K antagonists (VKA) for a composite outcome of ischemic and bleeding complications but increased major bleeding in patients with atrial fibrillation after successful transcatheter aortic valve replacement. Women are at higher risk of bleeding and stroke than men after transcatheter aortic valve replacement. It is unclear whether the effect of edoxaban on these complications varies in relation to sex.

Edoxaban for Thromboembolism Prevention in Pediatric Patients With Cardiac Disease.

Background: Standard of care (SOC) anticoagulation for thromboembolism (TE) prevention in children with cardiac disease includes low molecular weight heparins or vitamin K antagonists. Limited data exists for alternate use of direct oral anticoagulants in children.

Objectives: The investigators aimed to obtain safety and efficacy data for edoxaban in children.

Edoxaban Exposure in Patients With Atrial Fibrillation and Estimated Creatinine Clearance Exceeding 100 mL/min.

Edoxaban 60 mg is approved for stroke prevention in patients with atrial fibrillation (AF) not fulfilling any dose-reduction criteria. As edoxaban is partially renally cleared (≈50%), this study compared pharmacokinetics (PK) and pharmacodynamics of edoxaban 60 mg once daily with edoxaban 75 mg once daily in patients with AF with high renal clearance (creatinine clearance > 100 mL/min) over 12 months. Primary PK and pharmacodynamics end points were plasma edoxaban exposure and anti-factor Xa (FXa) concentration.

Risk factors for gastrointestinal bleeding in patients with gastrointestinal cancer using edoxaban.

Background: In the Hokusai VTE Cancer study, the risk of major bleeding was 2.9% higher in the edoxaban group compared with the dalteparin group, mainly due to more gastrointestinal bleedings in patients with gastrointestinal cancer. The identification of risk factors for gastrointestinal bleeding may help to guide the use of DOACs in these patients.

Edoxaban versus Vitamin K Antagonist for Atrial Fibrillation after TAVR.

Background: The role of direct oral anticoagulants as compared with vitamin K antagonists for atrial fibrillation after successful transcatheter aortic-valve replacement (TAVR) has not been well studied.

Methods: We conducted a multicenter, prospective, randomized, open-label, adjudicator-masked trial comparing edoxaban with vitamin K antagonists in patients with prevalent or incident atrial fibrillation as the indication for oral anticoagulation after successful TAVR. The primary efficacy outcome was a composite of adverse events consisting of death from any cause, myocardial infarction, ischemic stroke, systemic thromboembolism, valve thrombosis, or major bleeding.

ENNOBLE-ATE trial: an open-label, randomised, multi-centre, observational study of edoxaban for children with cardiac diseases at risk of thromboembolism.

Children with cardiac diseases suffer from significant morbidity and mortality secondary to thromboembolic complications. Anticoagulant agents currently used for thromboprophylaxis have many limitations, including subcutaneous administration (low molecular weight heparins) and requirement for frequent monitoring via venipuncture (vitamin K antagonists). Edoxaban is an oral direct factor Xa inhibitor without need of monitoring.

The Edoxaban Hokusai VTE PEDIATRICS Study: An open-label, multicenter, randomized study of edoxaban for pediatric venous thromboembolic disease.

Background: Little evidence is available for treatment of pediatric venous thromboembolism (VTE). Large randomized controlled trials are challenging in children. Current antithrombotic agents have many limitations, including nonoral administration and frequent monitoring.

Efficacy and Safety of Edoxaban in Patients With Active Malignancy and Atrial Fibrillation: Analysis of the ENGAGE AF - TIMI 48 Trial.

Background Anticoagulation in patients with malignancy and atrial fibrillation is challenging because of enhanced risks for thrombosis and bleeding and the frequent need for invasive procedures. Data on direct oral antagonists in such patients are sparse. Methods and Results The ENGAGE AF - TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction Study 48) trial randomized 21 105 patients with atrial fibrillation to edoxaban or warfarin.

An Open-Label Crossover Study of the Pharmacokinetics of the 60-mg Edoxaban Tablet Crushed and Administered Either by a Nasogastric Tube or in Apple Puree in Healthy Adults.

Background: Edoxaban is an orally active, direct factor Xa inhibitor indicated to reduce the risk of stroke and systemic embolism in non-valvular atrial fibrillation and for the treatment of venous thromboembolism.

Objectives: This study assessed the pharmacokinetics, safety, and tolerability of the edoxaban 60-mg tablet crushed and administered via a nasogastric tube in a water suspension or orally mixed in apple puree.

Methods: This phase 1, open-label, crossover study randomized 30 healthy adults to receive three edoxaban treatment regimens (oral 60-mg edoxaban tablet, or 60-mg edoxaban tablet crushed and administered via a nasogastric tube or orally in apple puree) in one of six treatment sequences.

Complementary feeding at 4 versus 6 months of age for preterm infants born at less than 34 weeks of gestation: a randomised, open-label, multicentre trial.

Background: Evidence on the optimal time to initiation of complementary feeding in preterm infants is scarce. We examined the effect of initiation of complementary feeding at 4 months versus 6 months of corrected age on weight for age at 12 months corrected age in preterm infants less than 34 weeks of gestation.

Methods: In this open-label, randomised trial, we enrolled infants born at less than 34 weeks of gestation with no major malformation from three public health facilities in India.

Translational Science for Energy and Beyond.

A clear challenge for the coming decades is decreasing the carbon intensity of the global energy supply while simultaneously accommodating a rapid worldwide increase in power demand. Meeting this challenge of providing abundant, clean energy undoubtedly requires synergistic efforts between basic and applied researchers in the chemical sciences to develop and deploy new technologies. Among the available options, solar energy is one of the promising targets because of the high abundance of solar photons over much of the globe.

A review of antithrombotic therapy and the rationale and design of the randomized edoxaban in patients with peripheral artery disease (ePAD) trial adding edoxaban or clopidogrel to aspirin after femoropopliteal endovascular intervention.

Compared with the coronary setting, knowledge about antithrombotic therapies after endovascular treatment (EVT) is inadequate in patients with peripheral artery disease (PAD). Based on a review of trials and guidelines, which is summarized in this article, there is scant evidence that antithrombotic drugs improve outcome after peripheral EVT. To address this knowledge gap, the randomized, open-label, multinational edoxaban in patients with Peripheral Artery Disease (ePAD) study (ClinicalTrials.

Cerebrovascular events in 21 105 patients with atrial fibrillation randomized to edoxaban versus warfarin: Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48.

Background And Purpose: The once-daily oral factor Xa inhibitor, edoxaban, is as effective as warfarin in preventing stroke and systemic embolism while decreasing bleeding in a phase III trial of patients with atrial fibrillation at moderate-high stroke risk. Limited data regarding cerebrovascular events with edoxaban were reported previously.

Methods: We analyzed the subtypes of cerebrovascular events in 21 105 patients participating in Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) comparing outcomes among patients randomized to warfarin versus 2 edoxaban regimens (high dose, low dose).

Surgical aspects of donor hand recovery for transplantation.

The purpose of this article is to share our institution's experience in optimizing the suitability of composite donor tissue for use in hand transplantation. The centerpiece of this process includes procurement techniques, preservation and timing issues, and anatomical matching. Recovery of the donor hand must proceed in an efficient, organized, and expedient manner.

Utility scores for facial disfigurement requiring facial transplantation [outcomes article].

Background: Controversy exists as to whether the benefits of facial transplantation outweigh the risk of continuous immunosuppression. Utility scores [range, 0 (death) to 1 (perfect health)] are a standardized tool with which to objectify health states or diseases and can help answer such controversy.

Methods: An Internet-based utility assessment study using visual analogue scale, time trade-off, and standard gamble was used to obtain utilities for facial disfigurement requiring facial transplantation from a sample of the general population and medical students at McGill University.

International interdisciplinary rhytidectomy survey.

Facial rhytidectomy is a complex and multi-faceted operation performed by different methodologies between practitioners. This study elucidates current international trends in facelift surgery, including patient selection, operative technique, and postoperative care. A 43-item questionnaire was sent electronically to 7247 members of the following societies: ASPS, ISAPS, CSPS, IFFPS, and the AAFPRS.

Prevention of diabetes and cardiovascular disease in patients with impaired glucose tolerance: rationale and design of the Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) Trial.

Patients with impaired glucose tolerance (IGT) have increased risk for developing type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Lifestyle modification and medication can prevent or delay progression to diabetes (PD), but whether such interventions also reduce the risk of CVD has not been rigorously tested. The Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial is a multinational, randomized, double-blind, 2 x 2 factorial trial in subjects with IGT (on a screening oral glucose tolerance test [OGTT]) aged > or = 50 years with known CVD or aged > or = 55 years with > or = 1 CVD risk factor.

Pathological reporting of colorectal cancer specimens: a retrospective survey in an academic Canadian pathology department.

Objective: To survey and improve the pathological reporting of colorectal cancer (CRC) specimens in a tertiary care pathology department.

Methods: We identified CRC specimens reported in a 6-month period before and after educational sessions and the introduction of a standardized CRC synoptic reporting protocol. Gross and microscopic descriptions were analyzed according to published guidelines for important staging and prognostic features.

A Phase II study of intravenous exatecan mesylate (DX-8951f) administered daily for 5 days every 3 weeks to patients with metastatic breast carcinoma.

Background: The objective of the current study was to determine the antitumor activity, safety, and pharmacokinetic (PK) profile of exatecan mesylate in patients with anthracycline-resistant and taxane-resistant, metastatic breast carcinoma.

Methods: All patients had clinical evidence of metastatic breast carcinoma; disease resistance or progression after chemotherapy that included anthracyclines and taxanes; no prior chemotherapy with camptothecin derivatives; and bidimensionally measurable disease. The starting dose of exatecan mesylate was either 0.