Uninterrupted edoxaban vs. vitamin K antagonists for ablation of atrial fibrillation: the ELIMINATE-AF trial.

AIMS: Edoxaban is a direct factor Xa inhibitor approved for stroke prevention in atrial fibrillation (AF). Uninterrupted edoxaban therapy in patients undergoing AF ablation has not been tested. METHODS AND RESULTS: The ELIMINATE-AF trial, a multinational, multicentre, randomized, open-label, parallel-group study, was conducted to assess the safety and efficacy of once-daily edoxaban 60 mg (30 mg in patients indicated for dose reduction) vs. vitamin K antagonists (VKAs) in AF patients undergoing catheter ablation. Patients were randomized 2:1 to edoxaban vs. VKA. The primary endpoint (per-protocol population) was time to first occurrence of all-cause death, stroke, or International Society of Thrombosis and Haemostasis-defined major bleeding during the period from the end of the ablation procedure to end of treatment (90 days). Overall, 632 patients were enrolled, 614 randomized, and 553 received study drug and underwent ablation; 177 subjects underwent brain magnetic resonance imaging to assess silent cerebral infarcts. The primary endpoint (only major bleeds occurred) was observed in 0.3% (1 patient) on edoxaban and 2.0% (2 patients) on VKA [hazard ratio (95% confidence interval): 0.16 (0.02-1.73)]. In the ablation population (modified intent-to-treat population including patients with ablation), the primary endpoint was observed in 2.7% of edoxaban (N = 10) and 1.7% of VKA patients (N = 3) between start of ablation and end of treatment. There were one ischaemic and one haemorrhagic stroke, both in patients on edoxaban. Cerebral microemboli were detected in 13.8% (16) patients who received edoxaban and 9.6% (5) patients in the VKA group (nominal P = 0.62). CONCLUSION: Uninterrupted edoxaban therapy represents an alternative to uninterrupted VKA treatment in patients undergoing AF ablation

Periprocedural anticoagulation in the uninterrupted edoxaban vs. vitamin K antagonists for ablation of atrial fibrillation (ELIMINATE-AF) trial.

AIMS : This post hoc analysis of ELIMINATE-AF evaluated requirements of unfractionated heparin (UFH) and procedure-related bleeding in atrial fibrillation (AF) patients undergoing ablation with uninterrupted edoxaban or vitamin K antagonist (VKA) therapy. METHODS AND RESULTS : Patients were randomized 2:1 to once-daily edoxaban 60 mg (or dose-reduced 30 mg) or dose-adjusted VKA (target international normalized ratio: 2.0-3.0). Uninterrupted anticoagulation was mandated for 21-28 days' pre-ablation and 90 days' post-ablation. During ablation, UFH administration targeted an activated clotting time (ACT) of 300-400 s. Periprocedural bleeding was differentiated between procedure-related (bleeding at puncture side, cardiac tamponade) and unrelated events. Of 614 randomized patients, 553 received study drug and underwent catheter ablation (edoxaban n = 375; VKA n = 178). The median (Q1-Q3) time from last dose to ablation procedure was 14.8 (13.3-16.5) vs. 16.5 (14.8-19.5) h (edoxaban vs. VKA group, respectively). Mean ACT (SD) ≥300 s was observed in 52% edoxaban- vs. 76% VKA-treated patients, despite a higher mean (SD) UFH dose in the edoxaban vs. VKA group [14 261 (6397) IU vs. 11 473 (4300) IU; exploratory P-value < 0.0001]. In the edoxaban group, 13 patients (3.5%) had procedure-related bleeds of whom 9 had received an UFH dose above the median (13 000 IU). In the VKA arm, 7 patients (3.9%) had procedure-related bleeds of whom 3 had received an UFH dose above the median (10 225 IU). CONCLUSION : The rate of procedure-related major/clinically relevant non-major bleeding did not differ between the treatment arms despite higher doses of UFH used with edoxaban vs. VKA to achieve a target ACT during AF ablation

Identification of Candidate Genes for Dyslexia Susceptibility on Chromosome 18

Background: Six independent studies have identified linkage to chromosome 18 for developmental dyslexia or general reading ability. Until now, no candidate genes have been identified to explain this linkage. Here, we set out to identify the gene(s) conferring susceptibility by a two stage strategy of linkage and association analysis. Methodology/Principal Findings: Linkage analysis: 264 UK families and 155 US families each containing at least one child diagnosed with dyslexia were genotyped with a dense set of microsatellite markers on chromosome 18. Association analysis: Using a discovery sample of 187 UK families, nearly 3000 SNPs were genotyped across the chromosome 18 dyslexia susceptibility candidate region. Following association analysis, the top ranking SNPs were then genotyped in the remaining samples. The linkage analysis revealed a broad signal that spans approximately 40 Mb from 18p11.2 to 18q12.2. Following the association analysis and subsequent replication attempts, we observed consistent association with the same SNPs in three genes; melanocortin 5 receptor (MC5R), dymeclin (DYM) and neural precursor cell expressed, developmentally down-regulated 4-like (NEDD4L). Conclusions: Along with already published biological evidence, MC5R, DYM and NEDD4L make attractive candidates for dyslexia susceptibility genes. However, further replication and functional studies are still required.Publisher PDFPeer reviewe

Metodyka szacowania niezawodności układów sieciowych na przykładzie komunikacji miejskiej

Apart from reliability evaluation, the methodology of network systems reliability assessment presented in the article enables the design of modernisation of such systems targeted mainly at ensuring their required reliability. In practice the methodology can be applied for various network systems, e.g. computer, power, gas, water distribution, telecommunications and transport networks. A reliability analysis of a transport network in urban public transport is presented. Calculations were performed for selected criteria of network availability which actually conditions the quality of transport services provided. The basic calculation tool used was the factoring algorithm that enabled the assessment of the impact of individual connections failure (in particular those caused by physical factors) on the reliability of the whole network. The feasibility of modernisation of the network analysed is discussed and the results are presented in diagrams.W artykule zaprezentowano opracowaną metodykę szacowania niezawodności układów sieciowych. Rozwiązanie to umożliwia dokonywanie oceny niezawodności oraz projektowanie modernizacji rozpatrywanej sieci przede wszystkim w aspekcie zapewnienia jej wymaganej niezawodności. Praktyczne wykorzystanie omawianej metodyki może mieć miejsce w odniesieniu do różnych układów sieciowych, np. sieci komputerowych, energetycznych, gazowych, wodociągowych, telekomunikacyjnych i transportowych. W artykule przedstawiono analizę niezawodności sieci komunikacyjnej w miejskim transporcie zbiorowym. Obliczenia przeprowadzono dla wybranych kryteriów zdatności sieci, które praktycznie warunkują jakość świadczonych usług transportowych. Podstawowe narzędzie obliczeniowe stanowił algorytm faktoryzacji, który umożliwia ocenę wpływu uszkodzeń poszczególnych połączeń (spowodowanych w szczególności czynnikami fizycznymi) na niezawodność całej sieci. W opracowaniu uwzględniono możliwość modernizacji analizowanej sieci, a uzyskane wyniki przedstawiono na wykresach

Safety and effectiveness of a fixed-dose combination of olmesartan, amlodipine, and hydrochlorothiazide in clinical practice

Peter Bramlage,1 Eva-Maria Fronk,2 Wolf-Peter Wolf,3 R&uuml;diger Smolnik,3 Gemma Sutton,1 Roland E Schmieder4 1Institut f&uuml;r Pharmakologie und pr&auml;ventive Medizin, Mahlow, Germany; 2Daiichi Sankyo Europe GmbH, Munich, Germany; 3Daiichi Sankyo Deutschland GmbH, Munich, Germany; 4Abteilung f&uuml;r Nephrologie und Hypertensiologie, Universit&auml;tsklinikum Erlangen, Erlangen, Germany Background: Clinical trials indicate that the use of fixed-dose combinations (FDCs) is associated with a higher level of treatment adherence and prolonged blood pressure (BP) control. The aim of this study was to document the safety and effectiveness of the FDC olmesartan/amlodipine/hydrochlorothiazide in patients with essential hypertension in clinical practice. Methods: This multicenter, prospective, 24-week, noninterventional study enrolled 5,831 patients from primary care offices in Germany and Austria. Inclusion criteria were a diagnosis of essential hypertension and newly initiated treatment with the FDC. Results: The mean age of patients was 63.5 years, almost 50% of patients had a time since diagnosis of essential hypertension of over 5 years, and approximately 70% of patients had at least one cardiovascular risk factor, including 29.4% of patients with diabetes mellitus. Following approximately 24 weeks of treatment, the mean reduction in systolic/diastolic BP was 29.0/14.0 mmHg, a BP response was observed by 94.2% of patients, and a target BP of &lt;140/90 mmHg was attained in 67.5% of patients. At least one adverse drug reaction (ADR) was experienced by 1.2% of patients, with the most common being peripheral edema. Subanalyses demonstrated that the following factors did not have a significant influence on the ADR rate: age (&lt;65 years versus &ge;65 years), diabetes mellitus (no/yes), cardiovascular risk (low/high), and concomitant medication (no/yes). Conclusion: This study demonstrates that in clinical practice, treatment with the three-drug combination as an FDC tablet resulted in a very high proportion of patients with a BP response and control, accompanied by a very low rate of ADRs. Keywords: hypertension, clinical practice, fixed-dose combination, blood pressure, adverse drug reaction

Readout System and Data Processing for OCT Pachymetry

A complete system for measurement control, signal acquisition and data processing for an OCT pachymeter is described. Moreover, dedicated data processing algorithm used for noise reduction is presented. A simple OCT scanner was built and some measurements were performed to examine the capabilities of the system

Time Correlated Single Photon Counting System for Optical Measurements

The high sensitivity time correlated single photon counting system (with photomultiplier tube) for biomedical measurements was designed and tested. Photon time of flight through a parafine wax phantom was modeled by Monte Carlo simulation and next measured by the device. Mean time delay introduced by a phantom is in a good agreement with simulation results. The results presented in this paper demonstrate the feasibility of measuring the optical response with the device