Ischemic Stroke and Transient Ischemic Attack Risk Following Vitamin K Antagonist Cessation in Newly Diagnosed Atrial Fibrillation: A Cohort Study.

Background In nonvalvular atrial fibrillation (AF), oral anticoagulants prevent ischemic strokes and transient ischemic attacks (TIAs), but nonpersistence with vitamin K antagonist (VKA) oral anticoagulant therapy (20-50% at 1 year) is problematic. The precise risk of stroke/TIA after VKA cessation and its time course during extended follow-up is unknown. Methods and Results The study cohort of incident AF in patients receiving initial VKA between 2001 and 2013 was identified from the UK Clinical Practice Research Datalink (linked hospitalizations and causes of death).

Incidence of Lyme disease in the UK: a population-based cohort study.

Objectives: The purpose of this study was to estimate the annual incidence of Lyme disease (LD) in the UK.

Design: This was a retrospective descriptive cohort study.

Setting: Study data were extracted from the Clinical Practice Research Datalink (CPRD), a primary care database covering about 8% of the population in the UK in 658 primary care practices.

Thirteen-year trend in the persistence with vitamin K antagonists for venous thromboembolism in the UK: a cohort study.

Background: Venous thromboembolism (VTE) comprises deep vein thrombosis (DVT) and pulmonary embolism (PE) and is associated with significant recurrence and mortality risk. Standard VTE treatment includes at least 3 months anticoagulation. The objective was to describe time trends in the duration of oral anticoagulation in patients initially treated with vitamin K antagonists (VKAs).

Testosterone treatment and risk of venous thromboembolism: population based case-control study.

Objective:  To determine the risk of venous thromboembolism associated with use of testosterone treatment in men, focusing particularly on the timing of the risk.

Design:  Population based case-control study SETTING:  370 general practices in UK primary care with linked hospital discharge diagnoses and in-hospital procedures and information on all cause mortality.

Participants:  19 215 patients with confirmed venous thromboembolism (comprising deep venous thrombosis and pulmonary embolism) and 909 530 age matched controls from source population including more than 2.

Epidemiology of first and recurrent venous thromboembolism in patients with active cancer. A population-based cohort study.

Population studies on the incidence of venous thromboembolism (VTE) in patients with active cancer are limited. An observational cohort study was undertaken to estimate the incidence of first and recurrent VTE. The source population consisted of all patients in the UK Clinical Practice Research Datalink, with additional information on hospitalisation and cause of death, between 2001 and 2011.

Trends in the prevalence of antipsychotic drug use among patients with Alzheimer's disease and other dementias including those treated with antidementia drugs in the community in the UK: a cohort study.

Objective: To investigate the pattern and trends of use of antipsychotics, antidepressants, hypnotics and anxiolytics in Alzheimer's disease and other dementias and in patients treated with antidementia medications.

Design: Cohort study with dementia patients formed in the UK Clinical Practice Research Datalink. Participants Patients with incident dementia, between 1995 and 2011 and a reference non-dementia cohort matched on age, gender and date of dementia diagnosis.

How effective are dose-adjusted warfarin and aspirin for the prevention of stroke in patients with chronic atrial fibrillation? An analysis of the UK General Practice Research Database.

The objective of this study was to evaluate the rate of stroke associated with aspirin and warfarin in routine clinical practice. The study included patients aged 40+ with chronic atrial fibrillation (cAF) registered in the UK General Practice Research Database. The outcome was the rate of stroke during current, past and no use of aspirin and warfarin.

Chronic atrial fibrillation: Incidence, prevalence, and prediction of stroke using the Congestive heart failure, Hypertension, Age >75, Diabetes mellitus, and prior Stroke or transient ischemic attack (CHADS2) risk stratification scheme.

Background: The aim of the study is to estimate the incidence and prevalence of chronic AF (cAF) in the United Kingdom and test the accuracy of the CHADS2 score for stroke prediction.

Methods: The General Practice Research Database was used to identify patients aged 40+ years diagnosed with cAF and control patients. Harrell's C-statistic was used to test possible improvements in CHADS2.

Fracture outcomes related to persistence and compliance with oral bisphosphonates.

The effects of low persistence on fracture risk have not been fully addressed. The objectives of this study were to describe the persistence and compliance with bisphosphonates and to evaluate the association with fracture risk. The General Practice Research database was used to identify patients >or=18 yr of age prescribed alendronate or risedronate.

Patterns of treatment for restless legs syndrome in primary care in the United Kingdom.

Background: The dopamine agonists pramipexole and ropinirole are licensed for the treatment of moderate to severe idiopathic restless legs syndrome (RLS) in Europe and the United States. In addition, various drugs that are not approved for this indication have been used for symptomatic treatment of RLS, including analgesics, quinine, and anxiolytics.

Objective: The purpose of this analysis was to describe patterns of treatment of newly diagnosed RLS, including treatment effectiveness and resource utilization, in primary care in the United Kingdom.

Population pharmacokinetics of the BEACOPP polychemotherapy regimen in Hodgkin's lymphoma and its effect on myelotoxicity.

Background And Objective: The BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone) chemotherapy regimen for the treatment of advanced Hodgkin's lymphoma has a superior outcome, but its toxicity (mainly haematotoxicity) is pronounced and highly variable. The present study was conducted to address the role of pharmacokinetics in individual toxicity.

Study Design: Three plasma samples and a 24-hour urine collection for day 1 of the first three cycles of chemotherapy were analysed in 30 patients, and the pharmacokinetic parameters of the respective drugs were estimated by population pharmacokinetic methods (nonlinear mixed-effects model [NONMEM] software).

Aceclofenac spares cyclooxygenase 1 as a result of limited but sustained biotransformation to diclofenac.

Objective: The mechanism of action of aceclofenac is currently unclear. This study investigated whether biotransformation to metabolites (4'-hydroxy-aceclofenac, diclofenac, 4'-hydroxy-diclofenac) contributes to inhibitory effects on the cyclooxygenase (COX) isozymes in vitro and ex vivo.

Methods: In vitro investigations were performed with human whole blood and human blood monocytes.

Simultaneous determination of aceclofenac and three of its metabolites in human plasma by high-performance liquid chromatography.

Aceclofenac [[2-(2',6'-dichlorophenyl)amino]phenylacetoxyacetic acid] is a phenylacetic acid derivative with potent analgesic and anti-inflammatory properties and an improved gastro-intestinal tolerance. In the present study, a liquid-liquid extraction-based reversed-phase HPLC method with UV detection was validated and applied for the analysis of aceclofenac and three of its metabolites (4'-hydroxy-aceclofenac, diclofenac, 4'-hydroxy-diclofenac) in human plasma. The analytes were separated using an acetonitrile-phosphate buffer gradient at a flow rate of 1 mL/min, and UV detection at 282 nm.

Modulation of steady-state kinetics of digoxin by haplotypes of the P-glycoprotein MDR1 gene.

Objective: We investigated the effect of polymorphisms in the P-glycoprotein (P-gp) MDR1 gene on steady-state pharmacokinetics of digoxin in Caucasians. According to earlier data, homozygous TT of the exon 26 complementary deoxyribonucleic acid (cDNA) 3435C>T polymorphism was associated with low P-gp expression in the human intestine.

Methods: Eight healthy male homozygous carriers of the wild-type exon-26 3435C>T (CC), 8 heterozygous subjects (CT), and 8 homozygous mutant (TT) subjects were selected.