Drug-drug interactions (DDIs) with serious adverse consequences for patients at intensive care unit (ICU) occur with the prevalence of 5.3%. The aim of our study was to reveal the risk factors for potential DDIs among the ICU patients. This retrospective cohort analysis took place in the ICU of the Clinical Center Podgorica, Montenegro, between June 1, 2017 and September 30, 2018. The study was conducted as a chart review of the ICU patients (n = 99) who spent ≥ 2 days in the ICU. The main outcome measure was the number of DDIs per patient. Ninety-four percent of patients had at least one potential DDI, while 20% of patients had at least one potential DDI which required a change of therapy. The number of potential DDIs per patient according to the Medscape was 6.6 ± 9.1 and 3.8 ± 4.9 according to the Epocrates. A higher number of drugs (or therapeutic groups) prescribed per patient increased the number of potential DDIs, including those which required a change of therapy. The patients who were prescribed antiarrhythmics, anticoagulants or two antiplatelet drugs experienced more DDIs than patients without these therapeutic groups, while delirium, dementia and drug allergy were protective factors. The main limitation of our study was its uni-centerdness, which allowed for certain degree of bias. Routine screening of the ICU patients with high number of prescribed drugs who receive antiarrhythmics, anticoagulants or double antiplatelet therapy for potential DDIs may prevent a great deal of DDIs with potentially deleterious effects.

Pandrug-Resistant Pseudomonas Aeruginosa Isolated from Qualitative Endotracheal Aspirate Could Rather be Contaminant than Causative Agent of Respiratory Infections in Intensive Care Unit Patients: Case Study A Slobodan M. Janković1,2, Zorana М. Đorđević2, Danijela B. Jovanović2, Tatjana V. Vulović1,2 A 1 Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia 2 Clinical Center Kragujevac, Serbia

Background/Aim. Despite the widespread use of procalcitonin, C-reactive protein (CRP), and soluble CD14 subtype (sCD14-ST), their diagnostic accuracy in children with sepsis is not yet clear. The aim of the study was to establish and compare the diagnostic accuracy of procalcitonin, CRP, and sCD14-ST in children admitted to the hospital under suspicion of having sepsis. Methods. The study was designed as a retrospective cross-sectional study on children admitted to the Pediatrics Clinic in Kragujevac, Serbia, under suspicion of sepsis, during a 6-month period. Diagnostic accuracy was tested by the construction of receiver operating characteristic (ROC) curves and their comparison in terms of area under the curve (AUC). Results. Procalcitonin had the largest AUC [0.75; 95% confidence interval (CI) 0.63?0.88], followed by CRP (0.68; 95% CI 0.54?0.81) and sCD14-ST (0.65; 95% CI 0.52 ? 0.79). Differences between the areas under the ROC curves were not significant (CRP vs. procalcitonin z = 1.054, p = 0.291; CRP vs. sCD14-ST z = 0.238, p = 0.812; procalcitonin vs. sCD14-ST z = 1.089, p = 0.286). Conclusion. Our study showed relatively low sensitivity and moderate specificity of procalcitonin, C-reactive protein and sCD14-ST in diagnosing sepsis among children, as well as similar diagnostic accuracy of the three biomarkers.

Background/Aim. The Headache Under-Response to Treatment (HURT) questionnaire and the Migraine Disability Assessment Test (MIDAS), which are intended for assessing the headache-related disability, impact (MIDAS) and management (HURT), were not yet translated to Serbian and validated in the population of Serbia. The aim of this study was to translate the HURT and MIDAS from English to Serbian, to make necessary cultural adaptations and to test their psychometric properties in a sample of outpatients with the headache. Methods. The HURT and MIDAS questionnaires were translated and adapted according to the internationally accepted guidelines, and then tested on a sample of Serbian patients with various headache types. Internal consistency was checked through the calculation of Cronbach?s alpha for the questionnaires, and by correlation of each question with the corrected total score. The criterion validity of the translation was tested by correlating scores of individual items, domains and whole questionnaire with the headache characteristics (severity, duration, frequency), and convergent validity was tested by correlating the abovementioned scores with results of an instrument for measurement of headache-related quality of life. Results. There were 171 (79.2%) females and 45 (20.8%) male study participants. The mean age of the patients was 42.3 years, (standard deviation ? SD 13.35; range 18?75); 27 (12.5%) suffered from a migraine and 189 (87.5%) from the episodic tension-type headache (TTH). The Serbian translation of HURT and MIDAS questionneires showed excellent internal consistency, with high values of the Cronbach?s alpha: 0.764 and 0.731, respectively. The validity of the instruments in all aspects (criterion, convergent and discriminant validity) was also excellent for the whole sample and for the subgroup of patients with TTH, while the results for the patients with the migraine were less favorable. The factor analysis suggested the existence of one domain of MIDAS and two domains of HURT questionneires. Conclusion. The Serbian translations of HURT and MIDAS could be used as the reliable and valid specific instruments for measuring a headache-related disability, impact (MIDAS) and management (HURT) in the patients with TTH and probably in the patients with the migraine.

Background/Aim. Nausea after oral administration of iron is frequent phenomenon (11% of patients) and it is believed to be consequence of accumulation of free radicals in mucosa of gastrointestinal tract. The aim of our study was to measure the extent of nausea in outpatients taking oral supplementation with iron, and to investigate possible factors that may have an influence on it. Methods. The study was of the cross-sectional type, and conducted on a sample of outpatients on oral iron supplementation. The sample was consecutive, including all patients coming to a community pharmacy for oral iron supply during the study period. Frequency and severity of nausea were measured by the 5- item Drug-Induced Nausea Scale (DINS). Results. The mean score of the DINS from the sample of 128 patients was 8.56 ? 5.07 (range from 5 to 25). Each additional cup of coffee per week increased the DINS score for 0.143 points, the history of gastrointestinal disease had protective effect and decreased the DINS score for 5.923 points. Conclusion. Frequency and severity of oral iron-induced nausea are not dependent on oral iron burden, but rather on coffee intake and previous experience of patients with symptoms of gastrointestinal diseases. Modification of diet and education about types and severity of symptoms of gastrointestinal diseases could be useful preventive measures to avoid or at least mitigate oral iron-induced nausea and/or vomiting.

Introduction: A gap between evidence-based recommendations for prescribing antipsychotics and its implementation in practice could be overcome by local guidelines. Aim: The aim of our study was to locally adapt the national guideline for schizophrenia and evaluate its impact on prescribing practice as well as on clinical and humanistic outcomes in a long-stay psychiatric hospital Dobrota in Kotor, Montenegro. Subjects and Methods: This was academic, prospective, IV phase interventional study, which measured outcome before and after investigators intervention within healthcare system. The study was conducted in two six-months phases separated by implementation of the local guidelines. Prescribing practices and treatment outcomes were monitored in both phases of the study. Results: Study included 111 patients. Although the guidelines did not infl uence total volume of prescribed antipsychotics, social functioning and environmental aspects of quality of life were improved. Conclusions: Writing and adopting the guidelines for local use might be associated with some benefi t in humanistic outcomes, but multi-faceted intervention should be considered in order to achieve more substantial impact on prescribing practices and clinical outcomes.

Introduction/Objective. Although effectiveness of atypical antipsychotics in patients with schizophrenia is mostly similar, there are significant differences in adverse effects rate and treatment costs, making comparison of their cost/effectiveness ratios essential for optimal drug choice. The aim of this study was to compare cost/effectiveness of aripiprazole and olanzapine in long-term treatment of schizophrenia. Methods. A four-state, three-month cycle Markov model was built to compare aripiprazole and olanzapine. The model assumed that patients who relapse on treatment with both aripiprazole and olanzapine are further treated with clozapine. The perspective of the National Health Insurance Fund was chosen, and the period covered by the model was 10 years. The model results were obtained after Monte Carlo microsimulation of a sample with 1,000 virtual patients. Both multiple one-way and probabilistic sensitivity analysis was made. Results. After base-case analysis aripiprazole was dominated by olanzapine, as net monetary benefit was negative (-390,341.96 ?} 29,131.53 RSD) and incremental cost/effectiveness ratio (ICER) was above the willingness-to-pay line of one Serbian gross domestic product per capita per quality-adjusted life year (QALY) gained. Multiple one-way and probabilistic sensitivity analysis confirmed results of the base case simulation. Conclusion. Olanzapine has more beneficial cost/effectiveness ratio than aripiprazole for long-term treatment of schizophrenia in Serbian milieu.

Background/Aim. There are several questionnaires for measuring intensity of nausea after drug administration, but they are either too settings specific (like those measuring chemotherapy-induced nausea), or they were not properly tested for reliability and validity. The aim of this study was to develop and validate a reliable instrument that can measure drug-induced nausea. Methods. The cross-sectional study for assessing reliability and validity of a questionnaire was performed. The questionnaire with 5 items and answers according to the Likert?s scale was developed during two brainstorming sessions of the research team. Its reliability, validity and temporal stability were tested on the sample of 128 outpatients taking iron salts orally. Results. The final version of the Drug-Induced Nausea Scale (DINS) with 5 items showed excellent reliability, both when rated by the investigators (Cronbach?s alpha 0.892) and by the patients themselves (Cronbach?s alpha 0.897). It was temporally stable, and both divergent and convergent validity tests had very good results. Factorial analysis revealed only one factor, which means that the whole scale is measuring only one phenomenon, intensity of nausea, as was originally intended. Conclusion. The DINS is reliable and valid instrument for measuring intensity of drug-induced nausea. Identification of patients with high intensity of druginduced nausea by this questionnaire will help prescribers to decide whether the therapy should be stopped or the patient switched to less emetogenic therapy.

Introduction/Objective. Making a calculator that would recognize patterns of abnormal liver function tests and link them to the most probable etiology could help clinicians in their initial orientation towards a definitive diagnosis in patients with liver damage. The aim of our study was to design, construct, and validate a calculator that based on a pattern of abnormalities in liver function tests of a patient with liver damage would propose the most probable etiology. Methods. Patterns of abnormal liver function tests for certain etiology of liver damage were extracted from distributions of actual values taken from reports in medical literature about patients whose etiology of liver damage was proven by reliable diagnostic tests. After setting up the calculator with the patterns extracted, its diagnostic value was checked under real-life conditions, on a sample of patients with liver damage whose etiology was established by the gold standard of diagnostics (biopsy or else). The calculator validation study was carried out at the Military Medical Academy in Belgrade during a two-year period (2015?2016). Results. For all tested diagnoses, the calculator demonstrated a highly significant difference between the area under the receiver-operator curves? values and the value of 0.5 (p < 0.001), and high level of sensitivity (more than 90%, except for the model for chronic hepatitis) as well as relatively high specificity (more than 75%) were noted, indicating good ability of the calculator to detect etiology of liver damage. Conclusion. New calculators showed satisfactory sensitivity and specificity for revealing major liver damage etiologies.

Background/Aim. The two-part questionnaire called Injection Phobia Scale (IPS)-Anxiety and IPS-Avoidance represents one of the most commonly used questionnaires for assessing the fear of injections. The aim of the present study was to translate and culturally adapt this questionnaire from English into Serbian as well as to assess reliability and validity of the translation. Methods. The translation and cultural adaptation of the IPS?Anxiety and IPS?Avoidance was performed in accordance with the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) guidelines. Reliability testing, factor analysis and validation of Serbian translation of IPS-Anxiety and IPS-Avoidance were carried out on a sample of 485 students of pharmacy, or medicine at the University of Kragujevac, Serbia. Results. Serbian translation of IPS-Anxiety and IPSAvoidance demonstrated high internal consistency with Cronbach?s alpha of 0.934 for IPS-Anxiety and 0.911 for IPS-Avoidance. Factor analysis of IPS-Anxiety showed that there are two domains, which we have called as Direct Experience (9 items) and Indirect Experience (9 items); factor analysis of IPS-Avoidance also pointed out on two domains referring to direct and indirect fear of injections. Female students scored higher on the scale showing more extensive injection phobia than male students. It is also interesting that students of pharmacy have higher level of injection phobia than students of medicine, and those students of the fifth year of study feel more fear of injections than students from the first four years. Conclusion. Serbian translation of IPS-Anxiety and IPS-Avoidance showed good psychometric properties on population consisted of students medicine and pharmacy.

The district heating system in Serbia, with an installed capacity of 6600 MW, currently supplies 58 towns with thermal energy. As a candidate country for accession to the European Union, Serbia faces the obligation to reduce the level of its GHG emissions as part of environmental reforms. This paper presents a basic scenario and three alternatives for final energy consumption in the district heating sector for the years 2015, 2020, and 2025. It is suggested that demand for heating will increase 10% up to 2020 and by 15% up to 2025, in relation to 2015 levels, while the share of each energy carrier will not change. Changing the structure of energy sources for heat supply assumes a decrease in the share of coal and liquid fuel, and increases in the use of biomass and natural gas. The results obtained were compared to the General Index of Sustainability which is a measure of the complexity of the proposed energy scenario. The paper considers the formation of related energy indicators as quantitative tools for the analysis of changes. It also proposes a methodology for multi-criteria analysis in the sustainability assessment of complex energy systems based on the stochastic evaluation of criteria (sets of indicators and sub-indicators). In this way, the results of the multi-criteria assessment can help in the decision-making process in cases where economic, social and ecological criteria are considered to be influential.