Abstract Acute pancreatitis represents an acute nonbacterial inflammation of the pancreas caused by a premature and ectopic activation of pancreatic digestive enzymes. Two of the most important genes in pancreatic autodigestion, PRSS1 and SPINK1, were implicated in the earliest discoveries of the genetic background of pancreatitis. However, the distribution of their variations displays interethnic variability, which could significantly affect the magnitude of their proposed effects on this disease worldwide. The aim of the present study was to investigate the distribution of the most important functional variations of PRSS1 (86A>T and 365G>A) and SPINK1 (101A>G), and their influence on the clinical course of acute pancreatitis in Serbian patients. The study enrolled 81 subjects, the severity of disease course was determined using the Atlanta Classification system, and the genotyping was conducted using a PCR-RFLP method. PRSS1 86A>T and 365G>A SNPs were not observed in the study population, while SPINK1 101A>G was present with the frequency of 0.62% (95% CI: 0.00, 3.83%). Due to extremely low frequencies or absences of examined variations, the proposed effect of these SNPs on the severity of acute pancreatitis could not be confirmed. The results do not support routine genotyping of either PRSS1 or SPINK1 in Serbs.

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 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.

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 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.

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.