Background: The incidence of ventilator-associated pneumonia (VAP) among patients on mechanical ventilation ranges from 15% to 25%, and mortality ranges from 33% to 38%. Aim: The aim of our study was to analyse the importance of previously uninvestigated potential risk factors for death in intensive care unit (ICU) patients with VAP. Methods: A case-control design was chosen for this study. The study population consisted of all patients who developed ventilator-associated pneumonia in the central ICU of a tertiary care hospital (n = 65 ) during a period of 6 months. Cases (n=45) included patients who died during their treatments in the ICU, if their primary cause of death was ventilator-VAP. Controls (n=20) included patients with VAP who survived their treatments in the ICU and who subsequently were subsequently transferred to other hospital wards. Results: Significant associations were found between death and age over 65 (OR adjusted = 10.66; CI: 1.22, 93.12; p = 0.032), death and infection upon admission to the ICU (OR adjusted = 434.39; CI: 3.07, 61449.65; p = 0.016), and death and administration of ceftriaxone prior to VAP (OR adjusted = 69.32; CI: 1.74, 2768.92; p = 0.024). A synergistic effect on death was found only for age over 65 and infection upon admission to the ICU. Conclusions: ICU patients with VAP experience have increased risk of mortality if they receive ceftriaxone prophylactically, if they have an infection upon admission to the ICU and if their age is advanced.

Taken into consideration limited data about effects of palladium on cardiovascular system, the aim of our study was to compare toxicity of inorganic and organic palladium compounds on the isolated rat heart. The hearts (total number n=30, 6 for each experimental group) excised from Wistar albino rats, male sex, age 8 weeks, and body mass 180-200 g, were retrogradely perfused according to the Langendorff technique at constant perfusion pressure (70 cm H2O). After the insertion of sensor in the left ventricle, the parameters of heart function: maximum rate of left ventricular pressure development (dP/dt max), systolic left ventricular pressure (SLVP), diastolic left ventricular pressure (DLVP), mean blood pressure (MBP) and heart rate (HR)), were continuously registered. The experiments were performed during control conditions, and in the presence of perfusion with incresing concentration of the following: (triethanolamine (TEA), triethanolamine acetate (TEAA), palladium(II)chloride (PdCl2), and trans-dichlorobis(triethanolamine-N)palladium(II) complex (trans-[PdCl2(TEA)2])) started every 30 minutes (30, 60, 90, 120 minute). dP/dt max was not affected significantly by either TEAA, TEA, PdCl2 or Pd complex. SLVP was, also, not affected significantly by either TEAA, TEA, PdCl2, or Pd complex. DLVP was significantly decreased by both TEAA and PdCl2, while TEA and Pd complex did not show significant effect. MBP was significantly decreased only by PdCl2, while TEAA, TEA and Pd complex did not show significant effect. HR was significantly decreased by all compounds- PdCl2, TEAA, TEA and Pd complex. In our study, inorganic palladium compound (PdCl2) induced clear depression of the isolated rat heart contractility, manifested as drop in diastolic and mean blood pressure , and as decrease of the heart rate. On the other hand, it seems that palladium, when bound in an organic compound (linked to TEA in Pd complex), does not contribute significantly to cardio-toxicity in our experimental conditions.

Objective. The aim of this study is to determine and analyze the trend of consumption of NSAIDs on the Department of General and Endocrine Surgery, Clinical Center 'Kragujevac' for the five-year period (2005-2009.). Method. The utilization study was conducted for determining and monitoring the drug consumption in inpatient medical institution according to the adopted methodology of the World Health Organization based on the expression of drug consumption in accordance with the number of defined daily doses/1000 patients/day (DDD/1000 pat/day). Results. The results of this study indicated a relatively high rate of NSAIDs consumption in surgical department of the institution which performs health practice at the secondary and tertiary levels. According to the number of DDD/1000 pat/day, the following NSAIDs were within the DU 90% (drug utilization 90%): diclofenac and ketorolac. Ibuprofen was the least applied NSAIDs for the entire period of observation. The results are in accordance with the global trend of increased consumption of NSAIDs. Conclusion. Studies on inpatients utilization of NSAIDs in our country are necessary to establish their safety and quality of drug prescription.

INTRODUCTION Some research results point to significant benefit in the use of methadone substitution treatment in reduction of criminogenic activities in opiate addicts, as in positive affect on their somatic and mental state. OBJECTIVE The objective of the study was to indicate factors which lead to criminogenic activities in addicts with judicial problems before entering substitute, methadone program. METHODS Addicts were divided into two groups: addicts who had judicial problems before they entered substitution methadone program (group A-46 addicts) and addicts withoutjudicial problems (group B-20 addicts). A questionnaire containing basic data about the addicts in the treatment program (Pompidou questionnaire) was for questioning. RESULTS A statistically significant difference was recorded related to the way of taking PAS. The largest number of examinees from the group A took primal PAS intravenously (41; 89.1%), while from the group B 11 took it intravenously (55.0%). The majority of examinees in the group A committed the first criminal act before taking PAS (psychoactive substances) (19; 41.3%), then after taking so-called harder PAS (16; 34.8%), and finally after taking the so-called lighter PAS (11; 23.9%). In somewhat over half of the examinees in the group A (24; 52.2%) the measure of juvenile court was imposed. A suspended sentence was passed upon 19 (41.3%) examinee, then prison sentence in 16 (34.8%), multiple prison sentences in 6 (13.0%) and misdemeanour in 4 (8.7%). CONCLUSION Future research at our centre should show the efficiency of methadone program in a decrease of risky behaviour, degree of criminogenic activity and judicial problems, improvement of life quality, as well as show the ways for preventive acting.

INTRODUCTION In the last decades psychiatric patients' quality of life attracts great attention of researchers. Improving the quality of life of schizophrenic patients is increasingly becoming an imperative in pharmacological therapy. OBJECTIVE Analysis of certain aspects of quality of life in patients with schizophrenia treated with depot formulations of a typical antipsychotic (haloperidol) and injection preparation of a long-acting atypical antipsychotic (risperidone). METHODS Research was conducted as a cross-sectional study that included 60 patients of both genders. Examinees diagnosed with schizophrenia (ICD-10, F20.0-F20.9) were divided into two groups: the group of patients that received haloperidol depot (n = 30) and the group of patients that received injection preparation of long-acting risperidone (n = 30). In order to assess the quality of life, social functioning scale (SFS), satisfaction with life scale (SWLS), and short version of World Health Organization quality of life scale (WHO-QoL-Brief) were applied. RESULTS Results showed statistically significant differences when it comes to social activity and satisfaction with life in favour of patients treated with injection preparation of long-acting risperidone. Examinees from this group were much more satisfied with themselves, their health and sleep compared to those on haloperidol depot. There was no statistically significant difference found on the quality of life scale. CONCLUSIONS Applying the scales for the assessment of the quality of life of schizophrenic patients in terms of psychosocial functioning, statistically significant difference between groups was found. Results showed higher scores in the group of patients treated with injection preparation of long-acting risperidone concerning social activities and life satisfaction.

Increased aggregation of platelets during preeclampsia was shown in several studies, yet several others reported no change. The aim of our study was to investigate platelet aggregation in a group of patients suffering from preeclampsia. In a cross-sectional study blood samples were taken from 89 hospitalized patients in the third trimester of pregnancy: 38 were suffering from mild to moderate preeclampsia and 51 patients were without preeclampsia. From the blood samples platelet aggregation, secretion of adenine nucleotides from platelets, concentration of energy-rich adenine compounds and levels of cyclic adenosine-mono-phosphate and cyclic guanosine mono-phosphate in platelets were measured. In the patients with preeclampsia, the adenosine diphosphate threshold for biphasic aggregation [odds ratio (OR):.75; 95% Confidence Interval (CI): 0.55–1.02; p<0.05], total adenine nucleotides concentration in the metabolic pool of platelets (OR:0.99; CI: 0.62–1.57; p<0.01) and cyclic adenosine-mono-phosphate (OR:0.81; CI: 0.57, 1.14; p<0.05) and cyclic guanosine mono-phosphate (OR:.78; CI: 0.55–1.09; p<0.05) levels in platelets were decreased in comparison with the control group, while adenylate energy charge in the metabolic pool of platelets (OR: >100.00; CI: 0.00->100.00; p<0.05) and secretion of adenosine triphosphate (OR:.13; CI: 0.00–14.26; p<0.05) and adenosine diphosphate (OR:.77; CI: 0.08–36.79; p<0.05) were increased. The results of our study show increased activation and aggregation of platelets in pregnant females with preeclampsia.

The aim of this study was to investigate N‐acetyltransferase 2 (NAT2) genetic polymorphism and enzyme activity in Serbs, and to examine the influence of NAT2 genotype, sex, and smoking on the phenotype. Genotyping for 190C>T, 282C>T, 341T>C, 403C>G, 411T>A, 481C>T, 590G>A, 803A>G, and 857G>A in the NAT2 gene, was performed in 140 healthy Serbs. NAT2 activity was determined as AFMU/(AFMU + 1X + 1U) urinary ratio in 100 subjects using caffeine as a probe. The most frequent NAT2 haplotypes were NAT2*5B (38.2%), NAT2*6A (26.0%), and NAT2*4 (24.4%). The log‐transformed NAT2 activity indices exhibited trimodal distribution with 9%, 36%, and 55% of slow, intermediate, and rapid acetylators, respectively. Significant NAT2 genotype‐phenotype correlation was observed (P < .0001). The frequency of NAT1*10 and NAT1*11 were 27.5% and 6.9%, respectively. There was no significant influence of sex or cigarette smoking on NAT2 enzyme activity. Eight subjects displayed rapid NAT2 acetylators phenotype despite being homozygous for NAT2 slow alleles, and NAT1 fast acetylators genotype (NAT1*10 and NAT1*11) had no implication. In contrast to other white populations described hitherto, rapid acetylator is the predominant NAT2 phenotype in Serbs. NAT2 genotype, but not sex and cigarette smoking, influence enzyme activity. NAT1 fast acetylators genotypes do not contribute for NAT2 genotype‐phenotype discordance.

OBJECTIVE The aim of the present study was to build population pharmacokinetic models for the clearance of carbamazepine (CBZ) in two separate populations of Serbian patients with epilepsy, children and adults. METHODS Analysis was performed using 114 and 53 steady-state concentrations of CBZ collected from 98 children and 53 adult epileptic patients, respectively. Mean values of total body weight and age were 31 ± 13 kg and 8 ± 3 years in the population of children, and 67 ± 13 kg and 32 ± 15 years in the population of adults. The one-compartment model with first order elimination and without absorption was used from the PREDPP (Prediction for Observation Population Pharmacokinetics) library of NONMEM software. RESULTS The derived final models of CBZ clearance were similar in the target populations. The most important factors which affected typical mean value of CBZ clearance in both populations studied were age of the patients and total daily dose; the CBZ clearance linearly followed increase of these factors. However, the influence of the patients' age was almost 3.4 times higher in the pediatric population than that in adults while the influence of total daily dose of CBZ is similar. On the other hand, final model in the adult population revealed also influence of concomitant therapy with phenobarbital (PB). The magnitude of this effect was +1.61 l h-1. The pharmacokinetic models obtained were validated in groups of 18 children and 13 adults with epilepsy. CONCLUSIONS The derived models describe well CBZ clearance in terms of Serbian pediatric and adult epileptic patient characteristics, offering a basis for rational individualization of CBZ dosage regimens.

INTRODUCTION Angiotensin-converting enzyme inhibitors are leading cause of drug-induced angioedema, with incidence of 0.1 to 0.2%. The angioedema is not of immune nature; in predisposed individuals it is caused by accumulation of vasoactive mediators due to reduced activity of angiotensin-converting enzyme. CASE REPORT We presented a 63-year old male patient suffering from hypertension and chronic obstructive pulmonary disease, who had developed two episodes of angioedema during a 5-year long therapy with enalapril. The first episode happened after three, and the second after five years of the therapy. On both occasions, the patient was admitted to the hospital and tracheotomy was avoided in the last moment. CONCLUSION Long-term therapy with angiotensin-converting enzyme inhibitors could be associated with delayed angioedema, especially in patients with inflammation of airways caused by infection or chronic irritation.

PURPOSE To evaluate the early clinical experience associated with percutaneous imaging-guided radiofrequency ablation (RFA) in patients with renal cell carcinoma (RCC). METHODS Eighteen consecutive patients with RCC were treated with percutaneous RFA sessions (24 sessions for 19 solitary RCC in 18 patients: 15 patients underwent a single RFA session, 3 had 2 sessions and one 3 sessions). Treatment indications were localized, solid renal mass <4.5 cm, comorbidities precluding surgery, high operation risk, and refusal to perform surgery. During 23 sessions, RFA was performed using computed tomography (CT) guidance and in one session it was guided by ultrasonography. The average patient age was 76.8±7.6 years (range 64-89), and the average renal mass size 3.3 ±0.7 cm (range 2.0-4.5). Follow-up imaging was performed at 3- and 6-month intervals and yearly thereafter. Successful treatment was defined as lack of enhancement of the treated region on follow-up CT studies. RESULTS RFA was technically successful in all patients. After the last imaging control, 17 of the 19 tumors were completely necrotic according to the imaging criteria (the secondary clinical success rate was 89.5%). Thirteen tumors were not visible on the first follow-up imaging control (the primary clinical success rate was 68.4% - 13 of 19). In 4 of the 6 patients residual tumors were successfully re-ablated, while in 2 patients repeated RFAs were not performed at the time of writing this report. Five patients (20.8%) developed treatmentrelated complications, including mild pain, large perirenal abscess, mild perirenal hematoma and transient elevation of the white blood cell count. The mean follow-up period was 25.3±16.8 months (range 1-51). CONCLUSION RFA is effective and safe treatment option of exophytic RCC <5 cm in diameter in patients not suitable for surgery due to serious concomitant diseases or advanced age.

Introduction. Th e objective of this study was to obtain accurate data about adverse events (AEs) related to antimicrobial therapy, including rate, causality, outcome and circumstances in which they occurred. Methods. Hospitalizised patients undergoing treatment with one or more anti-infective drugs were eligible for the study. Th e main outcome measures were any adverse clinical signs, symptoms or laboratory test abnormalities that had likely been induced by an anti-infective agent. Th e seriousness and causality of the AEs were classifi ed on the basis of WHO recommendations and compared with results from the Naranjo Probability Scale, European Causality Categories (ABO system) and French Imputation System assessments. Results. During the 6-month study period, 421 patients (72.84%) received at least one anti-infective drug. Th irtyone patients (7.36%) were found to have anti-infectiveinduced AEs. Anti-tuberculosis agents caused the highest percentage of AEs (38.7%) during the period of observation. Th e majority of AEs presented as disorders of the gastrointestinal tract (41.9%). Conclusion. AEs in females tend to last longer than in males. Males have a greater risk of experiencing AEs caused by fluoroquinolones (e.g., ciprofloxacin), while female patients have a greater risk of experiencing AEs caused by anti-tuberculosis agents. The incidence of AEs in inpatients receiving anti-infectives in our study (7.36%) is within the range reported from other studies. There is a great need for the development of new causality assessment scales that have better sensitivity and specificity.