BACKGROUND/AIM Chronic renal insufficiency (CRI), diabetes, hypertension, autosomal dominant polycystic kidney disease (ADPKD) are the main reasons for starting dialysis treatment in patients having kidney function failure. At present, dialysis treatments are performed in about 4,100 patients at 46 institutions in Serbia, out of which 90% are hemodialyses. At end-stage renal disease (ESRD) the only correct selection is kidney transplantation. The basic aim of the planned research was to compare ratio of costs and effects (Cost Effectiveness Analysis - CEA) of hemodialysis and kidney transplantation in patients at ESRD. METHODS As the main issue of treatment in patients from both groups the life quality measured by the validated McGill Questionary, was used. The study included 150 patients totally, divided into two groups. The study group consisted of 50 patients with kidney transplantation performed at the Clinical Center of Serbia and the control group consisted of 100 patients on hemodialysis at Clinical Center of Serbia, Clinical Hospital Center Zemun, Clinical Hospital Center "Zvezdara", Clinical Center Kragujevac and Health Center "Studenica", Kraljevo, comparable with respect to sex, age and length of treatment with the study group. RESULTS Effect of kidney transplantation in relation to hemodialysis being selection of treatment is expressed in the form of incremental ratio of costs and effects (Incremental Cost-Effectiveness Ratio - ICER). It is clear from the enclosed tables that the strategy of kidney transplantation is far more profitable considering the fact that it represents saving of EUR 132,256.25 per one year of contribution Quality Adjusted Life Years (QALY) within the period of 10 years. According to all aspects of live quality (physical symptoms and problems, physical well-being, phychological symptoms, existential well-being and support), difference is statistically important in favour of transplant patents. CONCLUSION The costs of patient therapy by hemodialysis at end-stage renal disease is far greater than by performing therapy of transplantation and maintenance, by almost three and a half times. Difference in total quality aspects of human life (physical, emotional, social, spiritual and financial) between dialysed and transplant patients is statistically significant and by 18.12% greater in transplant patients than in patients on hemodialysis.

Topiramate is biochemically classified as a fructopyranose sulphamate. Discovered as early as 1979, during middle 1980's it was approved in many countries for the treatment of epilepsies and migraine prevention. More recently, in the experimental stage, possible new indications have been disclosed: treatment of obesity, bipolar disorder, also cessation of smoking, neuropathic pain, cerebral pseudotumour, bulimia, periventricular leucomalatia in preterm infants and alcohol addiction. Most epileptologists consider it to be the first choice antiepileptic drug in severe pharmacoresistant epilepsies. A substantial corpus of evidence in paediatric population has been accumulated that confirms its efficiency in the treatment of generalised tonic-clonic seizures, Lenox-Gestaut syndrome, partial, absence and combined seizures. Having a unique monosaccharide chemical structure among other anticonvulsant drugs, characterizes it with special pharmacokinetic features. This substance exhibits a low interindividual variability in plasma levels and hence it features predictable pharmacokinetics. A steady state plasma concentration of topiramate increases linearly with higher dosages. Serum protein binding is approximately 15%, and biologic half-life in healthy volunteers is considered to range from 20 to 30 hours. Mean expected distribution volume rates from 0.55-0.8 l/kg, and accordingly, the drug shows a low and saturable binding capacity toward erythrocytes. It has not been present at the market for a sufficiently long time that would enable us to speak about a significant accumulation of data on its metabolism based on post-registration 4th stage clinical trials. For this purpose, we have done a literature review in order to summarise so far reported experience on topiramate pharmacokinetics in patients and healthy adults. Deeper understanding of its pharmacokinetic profile could enable a better technological design of the produced drug and the choice of the adequate route of its administration, and accordingly a more rational treatment of severe epilepsies resistant to other drugs.

BACKGROUND/AIM High morbidity and mortality rates, chronic course of disease and numerous clinical complications, make diabetes mellitus (DM) type 2 bear significant financial burden for healthcare system of Serbia. The aim of this study was to compare true disease-related expenses measured in the random sample of patients originating from the Central Serbia in 2007 and national estimate of total expenses based on available evidence on antidiabetic drugs and insulins acquisition costs in the same fiscal year. METHODS The study design was prevalence-based, bottom-up cost of illness analysis. It was implemented on a randomized sample of 99 adults with confirmed diagnosis of DM type 2. During 2007 all direct (drug acquisition, medical services, medical devices usage) and indirect costs associated with their primary disease (premature death, impaired working ability, early retirement, absentism), were taken into account. Other approach was to calculate average national rate of antidiabetic drugs and insulin utilization and sales at the domestic market during the mentioned period of time. Taking into consideration available estimate from the Institute of Public Health of Serbia of 475,000 people with this disease at the national level, we were able to compare these data. Assuming that our sample was enough representative and that the structure of costs was approximately similar at the local and national level, we were able to calculate an estimate of total cost of the disease. All costs were expressed in Serbian official currency, dinar (CSD). RESULTS Values of costs measured per patient in our sample in a given year were for drug acquisition 20,352.45 CSD, medical services 24,338.26 CSD, medical devices 3174.46 CSD and loss of productivity and absentism 5547.78 CSD. There were 2 cases of early retirement due to the disease and no cases of dialysis treatment or premature death. A total number of sickness absence days of employed patients, was 1025 and a total number of hospital treatment days was 360. A total amount of all costs was 53,412.96 CSD per patient per year. According to the National Medicines and Medical Devices Agency an overall value of oral antidiabetic drug sales for 2007 per patient was 1835.32 CSD and for insulins and analogs 2948.18 CSD. CONCLUSION Comparing true size of national financial burden of DM type 2 with experiences of other authors, we can see that it is comparable with European OECD average. But, if the structure of expenses is taken into account, Serbia is more similar tothose countries reported in the Third World economies. Ourlocal findings on a sample of diabetic population show that real patient expenses were even 2.28 times higher than those estimated at the national level.

BACKGROUND/AIM A cost-effectiveness analyses of immunomodulatory treatments for relapsing-remitting multiple sclerosis (RRMS) in developed countries have shown that any benefit from these drugs is achieved at very high cost. The aim of our study was to compare the cost-effectiveness of five treatment strategies in patients diagnosed with RRMS (symptom management alone and in combination with subcutaneous glatiramer acetate, intramuscular interferon beta-1a, subcutaneous interferon beta-1a, or intramuscular interferon [beta-1b) in a Balkan country in socio-economic transition. METHODS The Markov model was developed based on the literature about effectiveness and on local Serbian cost calculations. The duration of a cycle in the model was set to a month. The baseline time horizon was 480 months (40 years). The societal perspective was used for costs and outcomes, and they were discounted for 3% annually. Monte Carlo micro simulation with 1000 virtual patients was done. RESULTS Significant gain with immunomodulatory therapy was achieved only in relapse-free years, while the time spent in health states EDSS 0.0-5.5 was longer with symptomatic therapy only, and gains in life years and QALYs were only marginal. One QALY gained costs more than a billion of Serbian dinars (more than 20 million US dollars), making each of the four immunomodulatory therapies cost-ineffective. CONCLUSION Our study suggests that immunomodulatory therapy of RRMS in a Balkan country in socioeconomic transition is not cost-effective, regardless of the type of the therapy. Moderate gain in relapse-free years does not translate to gain in QALYs, probably due to adverse effects of immunomodulatory therapy.

Kvalitet i bezbednost upotrebe biljnih preparata ostaju i dalje prioritet koji treba zakonski urediti na svetskom nivou. Za registraciju biljnog preparata kao leka postoje isti zahtevi kao i za registraciju drugih lekova u pogledu dokumentacije koja treba da sadrži predklinicka i klinicka ispitivanja. Ovakva ispitivanja vrlo su zahtevna, a kako složenost molekulske građe, cak i jednokomponentnih biljnih preparata, ometa utvrđivanje jedinstvenih kriterijuma za jasno pracenje njihovih terapijskih efekata, ispunjavanje zahteva za registrovanje biljnih preparata kao lekova u praksi jos uvek je izazov i za naucnike i za proizvođace.