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Topiramate belongs to the second generation of antiepileptic drugs (AEDs) and has been approved for treatment of adults and children with different kinds of epilepsy as mono or as adjunctive therapy.1,2) The exact mechanism of topiramate action is unknown; however, it is considered that antiepileptic effects are exerted by modulation of voltage-dependent sodium channels, enhancement of g-aminobutyrate (GABA)ergic inhibition on the GABA A receptor, inhibition of carbonic anhydrase isoenzymes, and possibly, through the activity at non-N-methyl-D-aspartate receptors. 1,3,4) The effectiveness of topiramate in adults and children with partial onset and primary generalized seizures was established as initial monotherapy as well as adjunctive treatment. 5)Following oral administration of topiramate, absorption is rapid and almost complete with bioavailability ranging from 81 to 95%. 4,6) Peak plasma concentrations of the drug are reached within 1-4 h after administration. 4,6) Food delays topiramate absorption by approximately 2 h, but the extent of absorption remains unaffected.4) Plasma protein-bound fraction of topiramate varies from 9 to 17%. 4,6) In the dose range 100 to 1200 mg the mean apparent volume of distribution is between 0.6 and 1.0 l/kg. 4,6) In women the volume of distribution is about 50% less than in men, which is attributed to a higher percentage of body fat in women.6) This difference is not considered to be clinically relevant. Over 80% of topiramate is eliminated via the kidneys, predominantly as unchanged drug.6) To date, six trace metabolites formed by glucuronidation, hydroxylation and hydrolysis have been identified in humans. In animal seizure models the metabolites have little or no anticonvulsant activity. 4,6) At steadystate the renal clearance of topiramate is 1.02 l/h 6) and its elimination half-life (t 1/2 ) varies from 20 to 30 h. 1,4) Consequently, the steady-state is being reached in 4 to 8 d.2) Over the dose range 100-800 mg the relationship between topiramate dose and serum concentration is linear in both adults and children. 3,7,8) With the commonly used dosage regimen, serum topiramate concentrations in the range between 16 and 60 mmol/l have been reported.3) A wide range of doses and serum concentrations have been associated with optimal clinical response.3) Topiramate serum concentration was found to correlate with the time to the first seizure, 9) while in the majority of studies no clear relationship between average plasma concentration of topiramate and seizure reduction was found. 6,8,10) Based on these findings, clinical response, rather than blood concentrations is used to guide topiramate dosage adjustments. 1,6) Topiramate pharmacokinetic data mostly come from single dose studies with frequent blood sampling in healthy volunteers as well as from studies with sparse sampling in epileptic patients. However, both types of studies provide little information on inter-and intraindividual variability in pharmacokinetics of topiramate. So far there is no published study with a ...

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This study suggests that avoidance of major polypharmacy, use of nonpharmacological measures to improve lifestyle habits and decreasing the exposure of physicians to drug promotional material may reduce the risk of PIM use in older primary care outpatients. The only modifiable protective factors for PPOs were working environment of the patients chosen GPs and more frequent ambulatory visits to specialists.

BackgroundAlthough the costs of treating inflammatory bowel disease (IBD) in developed countries are well established, they remain largely unknown in countries with recent histories of socio-economic transition including Serbia.ObjectiveTo estimate the costs of treatment including the resources used by patients with IBD in Serbia from a societal perspective. This includes both Crohn’s disease and ulcerative colitis.MethodsThis cost-of-illness study was conducted to identify direct, indirect and out-of-pocket costs of treating patients with IBD in Serbia. Patients with IBD (n = 112) completed a semi-structured questionnaire with data concerning their utilisation of heath-care resources and illness-related expenditures. All costs were calculated in Republic of Serbia dinars (RSD) at a 1-year level (2014) and subsequently converted to Euros. Median values and ranges were reported to avoid potential distortions associated with mean costs.ResultsMedian total direct costs and total indirect costs per patient per year in patients with Crohn’s disease were 192,614.32RSD (€1602.97) and 28,014.00RSD (€233.13) and 142,267.15RSD (€1183.97) and 21,436.00RSD (€178.39), respectively, in patients with ulcerative colitis. In both groups, the greatest component of direct costs was hospitalisation.ConclusionsCosts of IBD in Serbia are lower than in more developed countries for two reasons. These include the fact that expensive biological therapy is currently under-utilised in Serbia and prices of health services are largely controlled by the State at a low level. The under-utilisation of biologicals may change with the advent of biosimilars at increasingly lower prices.Electronic supplementary materialThe online version of this article (doi:10.1007/s40258-016-0272-z) contains supplementary material, which is available to authorized users.

Simple, but well targeted educational interventions may improve polypharmacy and decrease inappropriate prescribing rate, contributing to a better care of elderly patients in nursing homes.

Sideritis scardica Griseb., Lamiaceae (ironwort, mountain tea), an endemic plant of the Balkan Peninsula, has been used in traditional medicine in the treatment of antimicrobial infections, gastrointestinal complaints, inflammation and rheumatic disorders. This study reports a comparison between conventional (hydrodistillation HD and solvent extraction SE) and alternative (supercritical carbon dioxide SC CO 2 ) extraction methods regarding the qualitative and quantitative composition of the obtained extracts as analyzed by GC and GC-MS techniques and their anitimicrobial activity. Different types of extracts were tested, the essential oil EO obtained by HD, EO-CO 2 and AO-CO 2 obtained by SC CO 2 at different preasures 10 and 30 MPa, at 40 °C, respectively, and the fractions A, B, C and D obtained by successive solvent extraction (SE) A: ethanol, B: diethyl ether, C: ethyl acetate and D: n-butanol). While EO was characterized by the presence of the OPEN ACCESSMolecules 2012, 17 2684 high percentage of oxygenated monoterpenes and sesquiterpenes (30.01 and 25.54%, respectively), the rest of the investigated samples were the most abundant in fatty acids and their esters and diterpenes (from 16.72 to 71.07% for fatty acids and their esters, and from 23.30 to 72.76%, for diterpenes). Microbial susceptibility tests revealed the strong to moderate activity of all investigated extracts against the tested microorganisms (MIC from 40 to 2,560 μg/mL). Although differences in the chemical compositions determined by GC and GC-MS analysis were established, the displayed antimicrobial activity was similar for the all investigated extracts.

Microwaves are non-ionizing electromagnetic waves with frequencies between 0.3 and 300 GHz. Both humans and microorganisms living on the human body are exposed to significant doses of microwave radiation in everyday life. Whether and how microwave radiation could influence the viability and growth of microorganisms is the subject of this educational paper. Studies on the effects of microwaves on the growth of microbial cultures were searched for in biomedical journals indexed in MEDLINE from 1966 to 2012. The published studies showed that microwaves produce significant effects on the growth of microbial cultures, which vary from the killing of microorganisms to enhancement of their growth. The nature and extent of the effect depend on the frequency of microwaves and the total energy absorbed by the microorganisms. Low energy, low frequency microwaves enhance the growth of microorganisms, whereas high energy, high frequency microwaves destroy the microorganisms. However, neither the effects of a wide spectrum of frequencies nor the effects of a wide range of absorbed energies have been investigated. Considering the potentially deleterious influence of microwaves on the symbiotic balance between microorganisms and the human host, further research on the effects of the complete frequency and energy spectra of microwave radiation on the growth of microorganisms is necessary.