Very Elderly Patients With Atrial Fibrillation Treated With Edoxaban: Impact of Frailty on Outcomes.

Background: Age and frailty are associated with underuse of anticoagulation in elderly patients with atrial fibrillation (AF).

Objectives: This study aimed at assessing major clinical outcomes in very elderly patients with AF treated with recommended dose edoxaban and look for a possible relation with frailty measured by a validated score.

Methods: This prospective multicenter cohort study enrolled consecutive very elderly (age ≥80 years) anticoagulation-naïve patients starting recommended doses of edoxaban.

Cardiac and Cerebral Arterial Complications of Lemierre Syndrome: Results from a Systematic Review and Individual Patient Data Meta-analysis.

Background:  Lemierre syndrome is a potentially life-threatening disease, which affects otherwise healthy young adults and adolescents. It is characterized by acute neck vein thrombosis and septic embolism, usually complicating a bacterial infection. Data on the syndrome are sparse, particularly concerning arterial complications.

Free fatty acid receptor 4 inhibitory signaling in delta cells regulates islet hormone secretion in mice.

Objective: Maintenance of glucose homeostasis requires the precise regulation of hormone secretion from the endocrine pancreas. Free fatty acid receptor 4 (FFAR4/GPR120) is a G protein-coupled receptor whose activation in islets of Langerhans promotes insulin and glucagon secretion and inhibits somatostatin secretion. However, the contribution of individual islet cell types (α, β, and δ cells) to the insulinotropic and glucagonotropic effects of GPR120 remains unclear.

Nordic Walking and Walking in Parkinson's disease: a randomized single-blind controlled trial.

Introduction: Non-pharmacological interventions are increasingly being acknowledged as valuable options to overcome or reduce functional problems in patients with Parkinson's disease. In the last decades, Nordic Walking was employed and investigated by rehabilitation specialists. Clinical trials on the effect of Nordic Walking on motor and non-motor Parkinson's disease symptoms are few, small, and heterogeneous for inclusion criteria and intervention protocols.

Patients with Lemierre syndrome have a high risk of new thromboembolic complications, clinical sequelae and death: an analysis of 712 cases.

Background: Lemierre syndrome is characterized by head/neck vein thrombosis and septic embolism usually complicating an acute oropharyngeal bacterial infection in adolescents and young adults. We described the course of Lemierre syndrome in the contemporary era.

Methods: In our individual-level analysis of 712 patients (2000-2017), we included cases described as Lemierre syndrome if these criteria were met: (i) primary site of bacterial infection in the head/neck; (ii) objectively confirmed local thrombotic complications or septic embolism.

Palmitate and oleate modify membrane fluidity and kinase activities of INS-1E β-cells alongside altered metabolism-secretion coupling.

Chronic exposure to elevated levels of glucose and free fatty acids impairs beta-cell function, leading to insulin secretion defects and eventually beta-cell failure. Using a semi-high throughput approach applied to INS-1E beta-cells, we tested multiple conditions of chronic exposure to basal, intermediate and high glucose, combined with saturated versus mono- and polyunsaturated fatty acids in order to assess cell integrity, lipid metabolism, mitochondrial function, glucose-stimulated calcium rise and secretory kinetics. INS-1E beta-cells were cultured for 3 days at different glucose concentrations (5.

Determinants of the Quality of Warfarin Control after Venous Thromboembolism and Validation of the SAMe-TT2-R2 Score: An Analysis of Hokusai-VTE.

Background:  Time in therapeutic range (TTR) measures the quality of vitamin K antagonist (VKA) anticoagulation. In patients with atrial fibrillation, the dichotomized SAMe-TT2-R2 score (≥2 vs. < 2 points) can predict if adequate TTR is unlikely to be achieved.

Primary thromboembolic prevention in multiple myeloma patients: An exploratory meta-analysis on aspirin use.

Background: Multiple myeloma (MM) is a common hematological disorder, often complicated by venous thromboembolism, especially during treatment with immunomodulatory drugs. Acetylsalicylic acid (ASA) has been extensively used as thromboprophylaxis but its rationale is unclear and the efficacy versus low-molecular weight heparins (LMWH) is still matter of debate. European and American guidelines suggest different approaches and the optimal antithrombotic strategy is yet to be established.

Lemierre Syndrome: Clinical Update and Protocol for a Systematic Review and Individual Patient Data Meta-analysis.

Lemierre syndrome usually affects otherwise healthy adolescents or young adults and occurs at an overall rate of 1 to 10 cases per million person-years with an estimated fatality rate of 4 to 9%. Diagnostic criteria remain debated and include acute neck/head bacterial infection (often tonsillitis caused by anaerobes at high potential for sepsis and vascular invasion, notably ) complicated by local vein thrombosis, usually involving the internal jugular vein, and systemic septic embolism. Medical treatment is based on antibiotic therapy with anaerobic coverage, anticoagulant drugs and supportive care in case of sepsis.

The Novel Oral Anticoagulants for Acute Venous Thromboembolism: Is Warfarin Dead?

The direct oral anticoagulants (DOACs) have been compared with parenteral anticoagulants and vitamin K antagonists (VKAs) for the treatment of venous thromboembolism (VTE) in several robust studies. DOACs have shown similar efficacy in preventing recurrent VTE and significant reductions in critical site (intracranial) bleeding, fatal bleeding, major and nonmajor bleeding. Warfarin and other VKAs are not dead as treatment modalities for VTE.

Reasons for and consequences of vitamin K antagonist discontinuation in very elderly patients with non-valvular atrial fibrillation.

Unlabelled: Essentials Anticoagulation in the elderly is still a challenge and suspension of warfarin is common. This is an observational study reporting reasons and consequences of warfarin suspension. Vascular disease, age, time in therapeutic range, and bleedings are associated with suspension.

Donepezil plasma concentrations, CYP2D6 and CYP3A4 phenotypes, and cognitive outcome in Alzheimer's disease.

Purpose: The purpose of the study is to evaluate whether donepezil (D) plasma concentrations and activity of CYP2D6 and CYP3A4 are associated with the therapeutic response of patients with mild to moderate Alzheimer's disease (AD).

Methods: This study comprised 54 patients affected by probable AD in therapy with D 10 mg/daily for at least 3 months. Plasma concentrations of D and its three main metabolites (6DD, 5DD, DNox) were assayed with a novel high performance liquid chromatography (HPLC) technique.

Monitoring Plasma Levels of Donepezil, 5-O-Desmethyl-Donepezil, 6-O-Desmethyl-Donepezil, and Donepezil-N-Oxide by a Novel HPLC Method in Patients With Alzheimer Disease.

Background: In humans, donepezil (D) is metabolized to 5-O-desmethyl-donepezil (5DD), 6-O-desmethyl-donepezil (6DD), and donepezil-N-oxide (DNox). Although 6DD and DNox are pharmacologically active, the activity of 5DD is unknown. At present, no routine methods are available to detect D and its 3 metabolites simultaneously.

Direct Oral Anticoagulants and Their Use in Treatment and Secondary Prevention of Acute Symptomatic Venous Thromboembolism.

Direct oral anticoagulants (DOACs) have been compared with standard therapy in large phase III studies to assess their safety and efficacy in the treatment of deep vein thrombosis and/or pulmonary embolism and in the secondary prevention of recurrent venous thromboembolism. Although the mean population age and the gross inclusion and exclusion criteria were similar across these studies, they differed in other aspects such as overall study design and acute treatment strategies. The 4 DOACs examined in phase III trials (apixaban, edoxaban, rivaroxaban, and dabigatran) showed noninferiority compared with standard therapy for the treatment of deep vein thrombosis and/or pulmonary embolism and for the prevention of recurrent venous thromboembolism.

Increasing incidence of non-valvular atrial fibrillation in the UK from 2001 to 2013.

Objective: To determine whether the incidence of atrial fibrillation (AF) is static or rising in the UK.

Design: Among the cohort of all individuals aged ≥45 years in the UK Clinical Practice Research Datalink (CPRD) (linked to hospital discharges) we identified incident non-valvular AF cases between 2001 and 2013. Overall and annual AF incidence rates were calculated and standardised to the UK population.

Vitamin K antagonists' use and fracture risk: results from a systematic review and meta-analysis.

Background: Although vitamin K antagonists (VKAs) lower serum values of bone deposition markers, the link with osteoporosis and fractures remains controversial.

Objectives: To assess whether the use of VKAs is associated with an increased prevalence and/or incidence of osteoporosis, fractures, or lower bone mineral density (BMD) values.

Methods: We conducted a systematic PubMed and EMBASE literature search until August 31, 2014, and a meta-analysis of cross-sectional and longitudinal studies investigating fractures and BMD, comparing patients treated with VKAs and healthy controls (HCs) or with patients with medical illness (medical controls, MCs).

To treat or not to treat very elderly naïve patients with atrial fibrillation with vitamin K antagonists (VKA): results from the VENPAF cohort.

Despite the recommendations in the guidelines, physicians still underuse warfarin in very elderly patients with non-valvular atrial fibrillation (NVAF). The risks of stroke and major bleeding both increase with age, but it is still not clear whether the beneficial effects of vitamin K antagonists (VKA) in preventing stroke outweigh the related bleeding risks in fragile, very elderly patients. The bleeding rates reported in real-world observational studies differ considerably.

VTE primary prevention, including hospitalised medical and orthopaedic surgical patients.

Primary prevention is the key to managing a significant proportion of the burden of venous thromboembolism (VTE), defined as deep venous thrombosis (DVT) or pulmonary embolism (PE). This is because VTE may lead to sudden death or are often misdiagnosed and therefore treatment is not feasible. Primary prevention usually commences in hospital as VTE following hospitalisation adds to the significant disease burden worldwide.

Minimizing the risk of hemorrhagic stroke during anticoagulant therapy for atrial fibrillation.

Introduction: Oral anticoagulation (OAC) is given for ischemic stroke prevention in patients with nonvalvular atrial fibrillation. OAC's most serious complications are major bleeding and, in particular, hemorrhagic stroke. Together with vitamin K antagonists (VKAs), direct oral anticoagulants (DOAC) are now available which have a more rapid onset/offset of action and more predictable anticoagulant effect.

Thromboembolic prevention in frail elderly patients with atrial fibrillation: a practical algorithm.

Atrial fibrillation is a common condition in the elderly, and the incidence of thromboembolic events secondary to atrial fibrillation increases with age. Antithrombotic therapy effectively prevents stroke and systemic embolism but also exposes patients to the risk of bleeding. Because the risk of bleeding also increases with age, clinicians tend to withhold anticoagulation in the elderly.

The use of aspirin for primary and secondary prevention in venous thromboembolism and other cardiovascular disorders.

Cardiovascular disease (CVD) includes a number of conditions such as myocardial infarction, coronary heart disease, stroke, and venous thromboembolism. CVD is a leading health problem worldwide and a major cause of mortality, morbidity, and disability; it is also associated with high healthcare costs. The incidence of CVD is predicted to increase in the forthcoming years, and thus it is crucial that physicians are aware of the benefits and limitations of the available therapies to ensure patients receive optimized treatment.