BACKGROUND Our team devised a real-time telemonitoring system (THYRPAN-TM) for measurement of the radiation exposure rate during the hospitalization of patients treated with high doses of radioiodine in the special premises with restricted access ("restricted area" [RA]). SUBJECTS AND METHODS The THYRPAN-TM prototype was tested for stability, efficacy, and linearity in a 32-day measurement of a 110 MBq (131)I source. Furthermore, it was tested on 15 patients with differentiated thyroid carcinoma who stayed in the RA for 3 days, following their radioiodine treatment. RESULTS Minor deviation from the theoretical values was detected when the (131)I source was measured by the THYRPAN-TM, but only at the beginning of the measurement (7.20%). CONCLUSIONS THYRPAN-TM is a stable, user-friendly detection system for the measurement of the exposure rate following radioiodine administration. It enables the telemonitoring of patients, as well as real-time and online measurement of the whole-body burden of (131)I.

Calcitonin gene-related peptide (CGRP) is present in nerve fibers that innervate the human ureter and may have important influence on the motility of this organ. The aim of our study was to investigate whether CGRP could affect the motility of an isolated human ureter. The tension and intraluminal pressure of the isolated ureteral segments were recorded and registered on a personal computer. Both phasic and tonic contractions of the isolated preparations were measured as area under the tension or pressure recordings. CGRP and CGRP fragment 8-37 were separately added to the organ baths in a cumulative way, thereby gradually increasing their concentration in the baths' solution. Alpha-CGRP did not affect either phasic, spontaneous activity or tone of isolated ureteral segments, as measured by both tension and intraluminal pressure. On the other hand, CGRP 8-37 caused concentration-dependent inhibition of spontaneous contractions of the isolated ureteral segments.

BACKGROUND/AIM Femoropopliteal bypass is a revascularization technique of lower extremities with excellent outcome. The great saphenous vein is the best graft material, but if it is not adequate or has been removed, synthetic grafts are an useful alternative. Graft occlusion is the most significant complication with the most serious consequences. The aim of this study was to analyse predictive factors for the synthetic femoropopliteal bypass occlusions. METHODS This retrospective case-control study included all patients who underwent synthetic femoropopliteal bypass due to peripheral arterial occlusive disease at the Vascular Surgery Center, Clinical Center of Kragujevac, Serbia, from 2007 to 2013. The cases group were the patients with femoropopliteal graft occlusion (n = 44), with the control group consisted of the patients without such an outcome (n = 88). RESULTS Significant effects to occlusion were: concomitant cardiovascular disease (adjustedOR 27.05; 95% CI 4.74; 154.35), a type of femoropopliteal bypass (adjustedOR 16.50; 95% CI 4.05; 67.24), previous vascular intervention (adjustedOR 4.67; 95% CI 1.20; 18.14), clinical stage of the disease (adjustedOR 3.73; 95% CI 1.94; 7.18), administration of postoperative oral anticoagulant therapy (adjustedOR 0.05; 95% CI 0.01; 0.23) and the use of angiotensin converting enzyme inhibitors (adjustedOR 0.14; 95% CI 0.03; 0.70). A significant synergism was shown for the following combinations of the observed risk factors: type of femoropopliteal bypass and cardiovascular disease, type of femoropopliteal bypass and previous vascular intervention, previous vascular intervention and cardiovascular disease, previous vascular intervention and beta blockers, cardiovascular disease and diabetes, type of femoropopliteal bypass and antiaggregant therapy, clinical stage of disease and cardiovascular disease, previous vascular intervention and antiaggregant therapy. CONCLUSION Concomitant cardiovascular disease, below-knee femoropopliteal bypass, advanced stage of vascular disease and non-use of anticoagulant therapy and angiotensin-converting enzyme inhibitors are the significant predictors of graft occlusion after synthetic femoropopliteal bypass. Their synergistic effect determines the importance of diabetes, use of beta blockers and platelet antiaggregant therapy.

Abstract Carbamazepine exhibits significant inter-individual variability in its efficacy and safety, which leads to unpredictable therapy outcomes for the majority of patients. Although its complex biotransformation depends on CYP3A5 activity, evidence of association between carbamazepine treatment outcomes and CYP3A5 functional variations remains inconclusive. The aim of the present study was to investigate the distribution of two of the functionally important CYP3A5 variants *2 and *3 as well as their effects on carbamazepine dose requirements, plasma concentrations and clearance in a Serbian population. The study involved 40 paediatric epileptic patients on steady-state carbamazepine treatment. Genotyping was conducted using the PCR-RFLP method, and carbamazepine plasma concentrations were determined using the HPLC method. CYP3A5*2 and *3 polymorphisms were found at frequencies of 0.0% and 97.5%, respectively, which corresponds well to previously published data for Caucasians. No differences in CYP3A5*3 allele frequencies were detected among epileptic patients in comparison to healthy volunteers within similar ethnic populations (p>0.08), indicating that CYP3A5 polymorphism does not represent a risk factor for epilepsy development. There was an observed tendency towards lower dosage requirements (mean±SD: 15.06±4.45 mg/kg vs. 18.74±5.55 mg/kg; p=0.26), higher plasma concentrations (mean±SD: 0.45±0.13 mg/kg vs. 0.38±0.03 mg/kg; p=0.47) and lower clearance (mean±SD: 0.14±0.05 mg/kg vs. 0.15±0.01 mg/kg; p=0.79) of carbamazepine in homozygous carriers of CYP3A5*3/*3 compared to heterozygous CYP3A5*1A/*3 Serbians. Because these genotype groups did not differ significantly in terms of their carbamazepine pharmacokinetics parameters, the proposed effects of CYP3A5*3 on carbamazepine metabolism could not be confirmed.

Abstract Depression is a disease of great social and medical importance. Quality of life can correlate with severity of manifested depression. The aim of our study was to determine whether people with unipolar depression have a poorer quality of life than healthy individuals, in what areas they have poorer quality of life and how socio-demographic characteristics and different therapies impact quality of life. The survey was conducted among 110 subjects, of which 55 were patients diagnosed with depression using ICD-10 criteria at the Psychiatric Clinic in Kragujevac and 55 were healthy subjects. Quality of life was evaluated by The Quality of Life Questionnaire compiled by the WHO. Quality of life was compared between the two groups and within research groups, depending on the applied therapy. There were statistically significant differences in quality of life between the groups: physical health - 49.64 versus 70.84, p=0.000; psychological health - 38.69 versus 69.85, p=0.000; social relations - 53.73 versus 64.89, p=0.004; living conditions - 54.58 versus 66.7, p=0.000, and in overall quality of life - 75.41 versus 96.00, p=0.000. The results showed that there was no statistically significant difference in quality of life between applied therapies. The overall quality of life of depressed patients did not depend on marital status or gender of the respondents. Depressed patients generally have a low quality of life in all domains and in overall quality of life. To improve of mental health, oOne of the primary goals to improve mental health should be to improve quality of life among depressed patients.

Abstract Acute necrotizing pancreatitis (ANP) is a severe form of acute pancreatitis that is associated with high morbidity and mortality. Thus, an adequate initial treatment of patients who present with acute pancreatitis (AP) based on correct interpretation of early detected laboratory and clinical abnormalities may have a significant positive impact on the disease course. The aim of the study was to determine patient- and initial treatment-related risk factors for the development of acute necrotizing pancreatitis. For the purpose of this study a case-control design was chosen, including adult patients treated for AP in the surgical Intensive Care Unit (sICU) of Clinical Center of Kragujevac, from January 2006 to January 2011. The cases (n=63) were patients who developed ANP, while the controls (n=63) were patients with AP without the presence of pancreatic necrosis. The controls were randomly selected from a study sample after matching with the cases by age and sex. Significant association with the development of ANP was found for the presence of comorbidity (adjusted OR 6.614 95%CI 1.185-36.963), and the use of somatostatin (adjusted OR 7.460, 95%CI 1.162-47.833) and furosemide (adjusted OR 2710.57, 95%CI 1.996-56.035) started immediately upon admission to the sICU. This study suggests that comorbidities, particularly the presence of serious cardio-vascular disease, can increase the risk for development of acute necrotizing pancreatitis. The probability for the development of ANP could be reduced by the avoidance of the initial use of loop diuretics and somatostatin.

ABSTRACT INTRODUCTION. Femoropopliteal bypass is revascularization technique of lower extremities with excellent outcome. AIM. The aim of this study was to analyse predictive factors for the synthetic femoropopliteal bypass occlusions. METHODS. This retrospective case-control study included all patients who underwent synthetic femoropopliteal bypass due to peripheral arterial occlusive disease at the Vascular Surgery Center, Clinical Center of Kragujevac, Serbia, from 2007 to 2013. The cases group were patients with femoropoliteal graft occlusion, and a control group consisted of patients without such an outcome. RESULTS. Significant effects for the occlusions were found for the concomitant cardiovascular disease( adjusted OR 27.05; 95%CI 4.74, 154.35), type of femoropopliteal bypass( adjusted OR 16.50; 95%CI 4.05, 67.24),  previous vascular intervention( adjusted OR 4.67; 95%CI 1.20, 18.14), clinical stage of disease ( adjusted OR 3.73; 95%CI 1.94, 7.18), the administration of postoperative oral anticoagulant therapy( adjusted OR 0.05; 95%CI 0.01, 0.23) and angiotensin converting enzyme inhibitors( adjusted OR 0.14 ; 95%CI 0.03, 0.70). A significant synergism was shown for the following combinations of observed risk factors: type of femoropopliteal bypass and cardiovascular disease, type of femoropopliteal bypass and previous vascular intervention, previous vascular intervention and cardiovascular disease, previous vascular intervention and beta blockers, cardiovascular disease and diabetes, type of femoropopliteal  bypass and antiaggregant therapy, clinical stage of disease  and car diovascular disease, previous vascular intervention and  antiaggregant therapy. CONCLUSIONS. Concomitant cardiovascular disease, below-knee femoropopliteal bypass, advanced stage of vascular disease and non-use of anticoagulant therapy and  angiotensin converting enzyme inhibitors were significant predictors of graft occlusion after synthetic femoropopliteal bypass. Synergistic effect has determined the importance of diabetes, use of beta blockers and platelet antiaggregant therapy. Earlier clinical stage of vascular disease, above-knee type of femoropopliteal  bypass, adequate treatment of chronic comorbidities with appropriate  therapy reduces the risk of graft occlusion. KEY WORDS : femoropopliteal bypass; synthetic; graft occlusion; predictive factors;

Introduction: South-eastern European socioeconomic transition followed by extensive health systems reforms has completely changed the pharmaceuticals market landscape in the region. Serbia, as the largest Western Balkans market, may serve as an example of such changes. Methods: Descriptive trend analysis of national-level dispensing of medicines in Serbia 2004–2012 was performed. Results: Total public health expenditure in Serbia increased sharply in less than a decade (€1,175,158,679 to €1,847,971,776); public spending on pharmaceuticals doubled (€339,279,304 to €742,013,976). Market growth was primarily driven by statins, novel platelet aggregation inhibitors, monoclonal antibodies and combined preparations indicated in asthma and chronic obstructive pulmonary disease. Conclusion: The pharmaceutical market of Serbia has undergone thorough and complete transformation from within. Serious crisis of medicine supply sustainability is currently shaking Balkan health systems due to increasing public debt worsened by global recession. More responsible reimbursement policy rooted in cost–effectiveness principle is needed in years to come.

Abstract The aim of this study was to develop a population pharmacokinetic (PK) model for clearance of mycophenolic acid (MPA) in adult renal transplant recipients, to quantify the PK parameters and the influence of covariates on the MPA pharmacokinetic parameters. Parameters associated with plasma concentrations of MPA at steady-state were analyzed in 70 renal transplant recipients (mean age 42.97 years; mean total body weight 75.33 kg) using nonlinear mixed-effect modeling (NONMEM). Characteristics of patients screened for influence on the pharmacokinetic parameters were gender, age, body weight, time after transplantation, whether the patient was diagnosed as having diabetes mellitus, organ source (living or deceased donor), biochemical parameters and co-therapy (tacrolimus, cyclosporine, prednisolone, omeprazole, bisoprolol, carvedilol, nifedipine). A validation set of 25 renal transplant recipients was used to estimate the predictive performance of population pharmacokinetic model. Typical mean value of MPA oral clearance, estimated by base model (without covariates) was 0.741 L h−1. During population modeling, the full model showed that clearance of the MPA was significantly influenced by age, total daily dose of MPA, creatinine clearance, albumin level, status and gender of a donor, and the nifedipine and tacrolimus co-therapy. In the final model, clearance of MPA was reported to be significantly influenced by age, total daily dose of MPA and thenifedipine co-therapy. The derived model describes adequately MPA clearance in terms of characteristics of our patients, offering basis for individual pharmacotherapy approach.

BACKGROUND Recent studies have shown that dronedarone is associated with significantly fewer adverse effects and treatment discontinuations, and a trend toward reduced all-cause mortality, compared with amiodarone. Introduction of dronedarone in clinical practice is limited by its higher cost than amiodarone, propafenone, and sotalol. AIM To estimate cost-effectiveness of dronedarone versus amiodarone, propafenone, and sotalol in patients with atrial fibrillation (AF). METHODS We constructed a Markov model, which was then simulated by Monte Carlo simulation using 1,000 virtual patients. Costs and outcomes were estimated from the societal perspective and discounted at 3% annually. A lifetime horizon and three-month cycle length were used. The main outcome measurement was the number of years spent without stroke. Values of transition probabilities and therapy outcomes were estimated from available literature. The prices of health services and drugs were obtained from the Republic Institute for Health Insurance Tariff Book and Drug List A and from the drug developer. RESULTS Cost-effectiveness shows that the dronedarone treatment option has the most advantageous relationship, where, for one year without a stroke, the total cost is €1,779.23. In the case of the amiodarone therapy option, for one year without a stroke €3,845.10 is needed, for propafenone €4,674.20, while for sotalol the sum is €14,973.89. Estimated annual costs for patients with first-detected AF in Serbia were €610. CONCLUSIONS The results of our model indicate that dronedarone is a cost-effective therapy compared with amiodarone, propafenone, and sotalol in patients with AF, if the outcome measurement is the number of years spent without stroke.

Introduction/Aim. Benign prostatic hyperplasia (BPH) is one of the most frequent diseases in men older than 50 years, and it is closely linked to ageing process. Considering rising life expectancy, further increase in prevalence of BPH could be expected.  The aim of our study was to analyze costs of treating patients with BPH in Montenegro, in order to estimate their impact on health budget. М ethods . The BPH treatment costs were analyzed in a random sample of 47 male patients, 50 years of age or older, taken from the population of patients with BPH treated in Hospital Niksic, Montenegro, during year 2013. The patients were in one of the five health states: mild symptoms of BPH, moderate symptoms of BPH, severe symptoms of BPH, acute urinary retention , and transurethral resection of the prostate (TURP). Only direct medical costs were taken into account when calculating costs of each health state. The costs were calculated on the basis of utilization of services, drugs and materials, taken from the patients’ medical records, and utilization figures were multiplied with prices recognized by the Health Insurance Fund, Montenegro. Total number of patients with BPH in Montenegro was taken from the database of Institute for Public Health, Montenegro. The costs are expressed in euros (EUR). Results. Average annual costs of treating a patient with certain BPH health state were: mild BPH - 266,63 ЕUR, moderate BPH - 343,26 EUR, severe BPH - 413,51 EUR, acute urinary retention - 493,93 ЕUR and  TURP - 1.013,16 ЕUR. Total costs of treating all patients with BPH in Montenegro are 2.338.008,66 ЕUR; this amount makes 1,43% of total Montenegrian health budget. The largest part of the costs make medication acquisition costs, especially those spent for finasteride (196.341,11 ЕUR) and antimicrobials. According to the data generated by Montenegrian Drug Agency, annual turnover of all drugs indicated for treatment of BPH in 2011 was 595.948,74 ЕUR, and from this amount, 251.157,66 ЕUR was paid by Montenegrian Health Insurance Fund. During the period 2006 – 2011, number of patients with BPH increased for 370%, and the annual amount spent for BPH drugs increased for 373%. Conclusion. Costs of treating BPH in Montenegro make significant percent of total healthcare costs, and there is trend of increase in costs due to constant increase in number of patients with BPH in Montenegro.

INTRODUCTION Problems with polypharmacy, adverse drug reactions and non-adherence are especially frequent among elderly nursing home residents. OBJECTIVE The aim of our study was to evaluate effectiveness of a specific form of staff education on appropriateness of prescribing in a cluster of nursing homes for the elderly. METHODS The study was designed as before-and-after trial of educational intervention on appropriateness of prescribing in nursing homes for the elderly. In total 20 nursing homes located in Belgrade, Serbia were included in the study with 104 elderly residents and 27 caring physicians. Appropriateness of prescribing was checked against Beers, START and STOPP criteria, before and 6 months after the intervention. RESULTS There were 349 inappropriately prescribed drugs according to Beers criteria before the intervention and 37 drugs six months after the intervention. According to STOPP criteria there were 70 drugs inappropriately prescribed before the intervention, and 20 drugs 6 months after. When both criteria are taken together, there is a significant difference between the average number of inappropriate drugs per patient before (3.4±0.5) and after (0.6±0.7) educational intervention (t=38.902; p<0.001). Finally, before the intervention 143 appropriate drugs were omitted according to START criteria, while 6 months after the intervention there were only 67 omissions. CONCLUSION 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.

ABSTRACT Acute pancreatitis (AP) is a common, potentially lethal, acute inflammatory process with a highly variable clinical course. The aim of this study was to analyse early changes in the serum concentrations of pro- and anti-inflammatory cytokines in the peripheral blood of patients with the interstitial form of acute pancreatitis (IAP) and necrotic acute pancreatitis (NAP), especially in those patients who had lethal outcomes. The prospective study enrolled 52 patients who were divided into IAP (65.38% of patients) and NAP (34.62% of patients) groups. The serum levels of interleukins (IL) 6, 8 and 10, together with tumour necrosis factor (TNF)-alpha were measured on the 1st and 3rd day of hospitalisation. Significantly higher values of IL-6, IL-8 and IL-10 were found on day 1 and 3 in NAP than in IAP. IL-6 was significantly higher on both days of measurement, whereas IL-10 on the first day and IL-8 on the third day were significantly higher in the group of patients who did not survive in comparison with patients who had the interstitial form of AP. In conclusion, the data from this study showed that immune suppression and excessive immune stimulation in the first three days after admission could indicate the development of NAP and a potentially lethal outcome.