Regional Variations in Medical Device Diffusion

Despite established efficacy for cardiac implantable electrical devices (CIEDs), large differences in CIED implant rates have been documented across and within countries. The aim of this paper is to investigate the influence of socio‐economic, epidemiological and supply side factors on CIED implant rates across 57 Regions in 5 EU countries and to assess the feasibility of using administrative data for this purpose. A total of 1 330 098 hospitalizations for CIED procedures extracted from hospital discharge databases in Austria, England, Germany, Italy and Slovenia from 2008 to 2012 was used in the analysis. Higher levels of tertiary education among the labour force and percent of aged population are positively associated with implant rates of CIED. Regional per capita GDP and number of implanting centres appear to have no significant effect. Institutional factors are shown to be important for the diffusion of CIED. Wide variation in CIED implant rates across and within five EU countries is undeniable. However, regional factors play a limited part in explaining these differences with few exceptions. Administrative databases are a valuable source of data for investigating the diffusion of medical technologies, while the choice of appropriate modelling strategy is crucial in identifying the drivers for variation across countries. © 2017 The Authors. Health Economics published by John Wiley & Sons, Ltd

Pharmacological targeting of the ephrin receptor kinase signalling by GLPG1790 in vitro and in vivo reverts oncophenotype, induces myogenic differentiation and radiosensitizes embryonal rhabdomyosarcoma cells

EPH (erythropoietin-producing hepatocellular) receptors are clinically relevant targets in several malignancies. This report describes the effects of GLPG1790, a new potent pan-EPH inhibitor, in human embryonal rhabdomyosarcoma (ERMS) cell lines

Towards sustainability in European agricultural firms

Agricultural activity plays an important role in all 28 Member States (MS) of the European Union (EU) in terms of: -Economics, -Environmental, -Social, and -Political activity. The sector also provides: -agricultural goods and services to support food security; -exports and imports at European and World level; -creation of direct and indirect jobs; and -the maintenance of population living in rural and regional areas.N/

Five year trends (2008-2012) in cardiac implantable electrical device utilization in 5 European nations: a case study in cross-country comparisons using administrative databases

Aims Common methodologies for analysis of analogous data sets are needed for international comparisons of treatment and outcomes. This study tests using administrative hospital discharge (HD) databases in five European countries to investigate variation/trends in pacemaker (PM) and implantable cardioverter defibrillator (ICD) implant rates in terms of patient characteristics/management, device subtype, and initial implantation vs. replacement, and compares findings with existing literature and European Heart Rhythm Association (EHRA) reports. Methods and results HD databases from 2008 to 2012 in Austria, England, Germany, Italy and Slovenia were interrogated to extract admissions (without patient identification) associated with PM and ICD implants and replacements, using direct cross-referencing of procedure codes and common methodology to compare aggregate data. 1 338 199 records revealed 212 952 PM and 62 567 ICD procedures/year on average for a 204.4 million combined population, a crude implant rate of about 104/100 000 inhabitants for PMs and 30.6 for ICDs. The first implant/replacement rate ratios were 81/24 (PMs) and 25/7 (ICDs). Rates have increased, with cardiac resynchronization therapy (CRT) subtypes for both devices rising dramatically. Significant between- and within-country variation persists in lengths of stay and rates (Germany highest, Slovenia lowest). Adjusting for age lessened differences for PM rates, scarcely affected ICDs. Male/female ratios remained stable at 56/44% (PMs) and 79/21% (ICDs). About 90% of patients were discharged to home; 85-100% were inpatient admissions. Conclusion To aid in policymaking and track outcomes, HD administrative data provides a reliable, relatively cheap, methodology for tracking implant rates for PMs and ICDs across countries, as comparisons to EHRA data and the literature indicated

Novel frontiers in epilepsy treatments: preventing epileptogenesis by targeting inflammation

Currently available epilepsy drugs only affect the symptoms (seizures), and there is a need for innovative treatments that target the underlying disease. Increasing evidence points to inflammation as a potentially important mechanism in epileptogenesis. In the last decade, a new generation of etiologically realistic syndrome-specific experimental models have been developed, which are expected to capture the epileptogenic mechanisms operating in corresponding patient populations, and to exhibit similar treatment responsiveness. Recently, an intervention known to have broad-ranging anti-inflammatory effects (selective brain cooling) has been found to prevent the development of spontaneously occurring seizures in an etiologically realistic rat model of post-traumatic epilepsy. Several drugs used clinically for other indications also have the potential for inhibiting inflammation, and should be investigated for antiepileptogenic activity in these models. If results of such studies are positive, these compounds could rapidly enter Phase III trials in patients at high risk of developing epilepsy

THE INFLUENCE OF OLD AGE AND ENZYME INDUCING COMEDICATION ON THE PHARMACOKINETICS OF VALPROIC ACID AT STEADY STATE: A CASE-MATCHED EVALUATION BASED ON THERAPEUTIC DRUG MONITORING DATA.

PURPOSE: To evaluate the influence of aging on the pharmacokinetics of valproic acid (VPA) at steady-state and on the susceptibility of VPA metabolism to enzyme induction by antiepileptic comedication. METHODS: The database of the therapeutic drug monitoring service of a large neurological hospital was searched to identify patients aged > or = 65 years stabilized on VPA therapy. Apparent VPA oral clearance (CL/F) calculated for each elderly patient was compared with that determined in an equal number of VPA-treated controls aged 20-50 years and matched for gender, body weight and antiepileptic drug (AED) comedication. RESULTS: A total of 71 elderly patients aged 70.0+/-4.4 years, including 20 receiving enzyme inducing AEDs, was included in the main evaluation. In the absence of enzyme inducing comedication, VPA CL/F in the elderly was similar to that found in non-elderly controls (9.7+/-4.6 versus 10.2+/-4.6mlh(-1)kg(-1)). Elderly patients on enzyme inducing comedication, on the other hand, had lower CL/F values than enzyme induced younger controls (11.7+/-5.4 versus 16.0+/-6.3mlh(-1)kg(-1), p<0.05). Since VPA CL/F is known to increase with increasing dosage, a lower VPA dosage in elderly patients comedicated with enzyme inducers compared with controls may have contributed to differences in CL/F between the two groups. CONCLUSIONS: In the absence of enzyme inducing comedication, VPA clearance in the elderly was comparable to that observed in controls. VPA clearance in elderly patients receiving enzyme inducing AEDs was lower than in controls, the difference being probably due to an influence of age as well as to the fact that mean VPA dosage was lower in these patients than in controls. Since our measurements of clearance were based on total serum VPA concentrations and VPA binding to plasma proteins is known to be reduced in old age, it is likely that the clearance of unbound, pharmacologically active, VPA was decreased to an important extent in the elderly, presumably as a result of a decline in drug metabolizing capacity

Development and validation of an HPLC-UV detection assay for the determination of rufinamide in human plasma and saliva.

The development of a simple and rapid high-performance liquid chromatography (HPLC) method for the determination of the new antiepileptic drug rufinamide (RFN) in human plasma and saliva is reported. Samples (250 μl) are alkalinized with ammonium hydroxide (pH 9.25) and extracted with dichloromethane using metoclopramide as internal standard. Separation is achieved with a Spherisorb silica column (250 × 4.6 mm i.d., 5 μm) at 30 °C using as mobile phase a solution of methanol/dichloromethane/n-hexane 10/25/65 (vol/vol/vol) mixed with 6 ml ammonium hydroxide. The instrument used was a Shimadzu LC-10Av chromatograph and flow rate was 1.5 ml min(-1), with a LaChrom L-7400 UV detector set at 230 nm. Calibration curves are linear [r(2) = 0.998 ± 0.002 for plasma (n = 10) and r(2) = 0.999 ± 0.001 for saliva (n = 9)] over the range of 0.25-20.0 μg ml(-1), with a limit of quantification at 0.25 μg ml(-1). Precision and accuracy are within current acceptability standards. The assay is suitable for pharmacokinetic studies in humans and for therapeutic drug monitoring

Increased Apparent Oral Clearance of Valproic Acid during Intake of Combined Contraceptive Steroids in Women with Epilepsy

PURPOSE: To determine potential changes in total and unbound serum valproic acid (VPA) concentrations at steady-state during a cycle of intake of combined hormonal contraceptive (HC) steroids. METHODS: Blood samples were collected from nine women stabilized on VPA monotherapy on two separate randomized occasions: (i) at the end of the 4- to 7-day HC-free interval, and (ii) on the last day of the HC intake period. Trough concentrations of VPA in serum and serum ultrafiltrates were determined by fluorescence polarization immunoassay. RESULTS: In all women, total and unbound VPA concentrations were higher during the HC-free interval than during HC intake (means +/- SD: 425 +/- 184 vs. 350 +/- 145 micromol/L, respectively, for total VPA, p = 0.002, and 55 +/- 37 vs. 39 +/- 25 micromol/L, respectively, for unbound VPA, p = 0.005). Compared with the HC-free interval, HC intake was associated with a mean 21.5% increase in VPA total apparent oral clearance (from 8.0 +/- 5.2 to 9.7 +/- 6.4 ml/h/kg, p = 0.01) and a 45.2 % increase in VPA unbound apparent oral clearance (from 79 +/- 81 to 115 +/- 121 ml/h/kg, p = 0.029). CONCLUSIONS: The apparent oral clearance of total and unbound VPA increases during the HC intake period compared with the HC-free interval, probably due to induction of glucuronosyltransferase by ethinylestradiol. The magnitude of the change varies across individuals, being potentially clinically relevant in some cases. Serum VPA concentrations should be monitored when adding or discontinuing HC steroids, and possibly during the on-off intervals of a HC cycle