Characterization and financial impact of implantable cardioverter-defibrillator patients without interventions 5 years after implantation

Background: Implantable cardioverter defibrillators (ICD's) are increasingly used for primary and secondary prevention of sudden cardiac death. However, data on how many ICD patients indeed receive appropriate ICD therapy during long-term follow-up is scarce. Aim: The aim of our study was to determine the number of patients without appropriate ICD therapy 5 years after ICD implantation, to identify predicting factors, to assess the occurrence of late first ICD therapy and to quantify the financial impact of ICD therapy in a real-world setting. Design: Prospective observational study. Methods: We prospectively enrolled 322 consecutive ICD patients. Baseline data were collected at implantation and patients were followed for a median of 7.3 years (IQR 5.8-9.2 years). Time to first appropriate ICD therapy (either antitachycardia pacing or cardioversion) was documented. Results: Five years after implantation, 139 patients (43%) had not received appropriate ICD therapy. In multivariable analysis, a primary prevention indication and negative electrophysiological studies prior to ICD implantation were independent predictors of freedom from ICD therapy. Of the patients without ICD therapy, 5 years after implantation, 25% had experienced inappropriate ICD shocks. Two hundred and seven devices (1.5 devices per patient) were needed for the 139 patients without ICD intervention within 5 years, accounting for €31 784 per patient. During an additional follow-up of 3 years, 12% of the patients with unused ICD received a late first appropriate ICD therapy. Conclusions: About half of the ICD patients receive appropriate ICD therapy within 5 years after implantation. Furthermore, there is a significant proportion of patients receiving late first shocks after five initially uneventful year

Holter monitoring for syncope: diagnostic yield in different patient groups and impact on device implantation

Background: Holter monitoring is routinely used in patients referred for the evaluation of syncope, but its diagnostic value in different patient groups is unclear, as is its impact on device implantation (pacemaker or cardioverter-defibrillator). Aim: To determine the diagnostic yield of Holter monitoring in the routine evaluation of syncope, and its impact on subsequent device implantation. Design: Retrospective record review. Methods: We reviewed all Holter studies in patients referred with syncope between 2000 and 2005. Strict criteria were applied to determine whether a study was diagnostic. The diagnostic value of Holter monitoring (overall and in five subgroups: age, gender, structural heart disease, ejection fraction, medication) and its impact on the implantation of devices, were determined. Results: Of 4877 Holter studies, 826 were performed in patients with syncope (age 72 ± 15 years): 71 (8.6%) were considered to explain the syncope. Structural heart disease, ejection fraction and age were significant predictors of a diagnostic study (all p < 0.01), whereas gender and cardiac medication were not. A device was implanted in 33 patients (4.4%) whose initial Holter did not explain their syncope, after mean 7 months, whereas 45 patients (5.4%) received a pacemaker based on the Holter results (p = 0.32). Discussion: The overall diagnostic yield of Holter monitoring in the evaluation of syncope was 8.6%, with dramatic differences between subgroups. Our data suggest that the impact of Holter monitoring on device implantation is generally overestimate

Temperature dependency of state of charge inhomogeneities and their equalization in cylindrical lithium-ion cells

The influence of cell temperature on the current density distribution and accompanying inhomogeneities in state of charge (SOC) during cycling is analyzed in this work. To allow for a detailed insight in the electrochemical behavior of the cell, commercially available 26650 cells were modified to allow for measuring local potentials at four different, nearly equidistant positions along the electrodes. As a follow-up to our previous work investigating local potentials within a cell, we apply this method for studying SOC deviations and their sensitivity to cell temperature. The local potential distribution was studied during constant current discharge operations for various current rates and discharge pulses in order to evoke local inhomogeneities for temperatures ranging from 10 °C to 40 °C. Differences in local potentials were considered for estimating local SOC variations within the electrodes. It could be observed that even low currents such as 0.1C can lead to significant inhomogeneities, whereas a higher cell temperature generally results in more pronounced inhomogeneities. A rapid SOC equilibration can be observed if the variation in the SOC distribution corresponds to a considerable potential difference defined by the open circuit voltage of either the positive or negative electrode. With increasing temperature, accelerated equalization effects can be observed

High intensity neutrino oscillation facilities in Europe

The EUROnu project has studied three possible options for future, high intensity neutrino oscillation facilities in Europe. The first is a Super Beam, in which the neutrinos come from the decay of pions created by bombarding targets with a 4 MW proton beam from the CERN High Power Superconducting Proton Linac. The far detector for this facility is the 500 kt MEMPHYS water Cherenkov, located in the Fréjus tunnel. The second facility is the Neutrino Factory, in which the neutrinos come from the decay of μ+ and μ− beams in a storage ring. The far detector in this case is a 100 kt magnetized iron neutrino detector at a baseline of 2000 km. The third option is a Beta Beam, in which the neutrinos come from the decay of beta emitting isotopes, in particular He6 and Ne18, also stored in a ring. The far detector is also the MEMPHYS detector in the Fréjus tunnel. EUROnu has undertaken conceptual designs of these facilities and studied the performance of the detectors. Based on this, it has determined the physics reach of each facility, in particular for the measurement of CP violation in the lepton sector, and estimated the cost of construction. These have demonstrated that the best facility to build is the Neutrino Factory. However, if a powerful proton driver is constructed for another purpose or if the MEMPHYS detector is built for astroparticle physics, the Super Beam also becomes very attractive

Modelling neurofibromatosis type 1 tibial dysplasia and its treatment with lovastatin

<p>Abstract</p> <p>Background</p> <p>Bowing and/or pseudarthrosis of the tibia is a known severe complication of neurofibromatosis type 1 (NF1). Mice with conditionally inactivated neurofibromin (Nf1) in the developing limbs and cranium (Nf1Prx1) show bowing of the tibia caused by decreased bone mineralisation and increased bone vascularisation. However, in contrast to NF1 patients, spontaneous fractures do not occur in Nf1Prx1 mice probably due to the relatively low mechanical load. We studied bone healing in a cortical bone injury model in Nf1Prx1 mice as a model for NF1-associated bone disease. Taking advantage of this experimental model we explore effects of systemically applied lovastatin, a cholesterol-lowering drug, on the Nf1 deficient bone repair.</p> <p>Methods</p> <p>Cortical injury was induced bilaterally in the <it>tuberositas tibiae </it>in Nf1Prx1 mutant mice and littermate controls according to a method described previously. Paraffin as well as methacrylate sections were analysed from each animal. We divided 24 sex-matched mutant mice into a lovastatin-treated and an untreated group. The lovastatin-treated mice received 0.15 mg activated lovastatin by daily gavage. The bone repair process was analysed at three consecutive time points post injury, using histological methods, micro computed tomography measurements and <it>in situ </it>hybridisation. At each experimental time point, three lovastatin-treated mutant mice, three untreated mutant mice and three untreated control mice were analysed. The animal group humanely killed on day 14 post injury was expanded to six treated and six untreated mutant mice as well as six control mice.</p> <p>Results</p> <p>Bone injury repair is a complex process, which requires the concerted effort of numerous cell types. It is initiated by an inflammatory response, which stimulates fibroblasts from the surrounding connective tissue to proliferate and fill in the injury site with a provisional extracellular matrix. In parallel, mesenchymal progenitor cells from the periost are recruited into the injury site to become osteoblasts. In Nf1Prx1 mice bone repair is delayed and characterised by the excessive formation and the persistence of fibro-cartilaginous tissue and impaired extracellular matrix mineralisation. Correspondingly, expression of Runx2 is downregulated. High-dose systemic lovastatin treatment restores Runx2 expression and accelerates new bone formation, thus improving cortical bone repair in Nf1Prx1 tibia. The bone anabolic effects correlate with a reduction of the mitogen activated protein kinase pathway hyper-activation in Nf1-deficient cells.</p> <p>Conclusion</p> <p>Our data suggest the potential usefulness of lovastatin, a drug approved by the US Food and Drug Administration in 1987 for the treatment of hypercholesteraemia, in the treatment of Nf1-related fracture healing abnormalities. The experimental model presented here constitutes a valuable tool for the pre-clinical stage testing of candidate drugs, targeting Nf1-associated bone dysplasia.</p

Efficacy of fixed-dose amlodipine and losartan combination compared with amlodipine monotherapy in stage 2 hypertension: a randomized, double blind, multicenter study

<p>Abstract</p> <p>Background</p> <p>The objective of this trial was to compare the blood-pressure lowering efficacy of amlodipine/losartan combination with amlodipine monotherapy after 6 weeks of treatment in Korean patients with stage 2 hypertension.</p> <p>Results</p> <p>In this multi-center, double-blind, randomized study, adult patients (n = 148) with stage 2 hypertension were randomized to amlodipine 5 mg/losartan 50 mg or amlodipine 5 mg. After 2 weeks, patients with systolic blood pressure (SBP) > 140 mmHg were titrated to amlodipine 10 mg/losartan 50 mg or amlodipine 10 mg. After 4 weeks of titration, hydrochlorothiazide 12.5 mg could be optionally added to both groups. The change from baseline in SBP was assessed after 6 weeks. The responder rate (defined as achieving SBP < 140 mmHg or DBP < 90 mmHg) was also assessed at 2, 6 and 8 weeks as secondary endpoints. Safety and tolerability were assessed through adverse event monitoring and laboratory testing. Baseline demographics and clinical characteristics were generally similar between treatment groups. Least-square mean reduction in SBP at 6 weeks (primary endpoint) was significantly greater in the combination group (36.5 mmHg vs. 31.6 mmHg; p = 0.0117). The responder rate in SBP (secondary endpoints) was significantly higher in the combination group at 2 weeks (52.1% vs. 33.3%; p = 0.0213) but not at 6 weeks (p = 0.0550) or 8 weeks (p = 0.0592). There was no significant difference between groups in the incidence of adverse events.</p> <p>Conclusion</p> <p>These results demonstrate that combination amlodipine/losartan therapy provides an effective and generally well-tolerated first line therapy for reducing blood pressure in stage 2 hypertensive patients.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01127217">NCT01127217</a></p