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Snježana N. Mirković, S. Janković, Jelena Džudović, V. Gužvić

Summary Phytopreparations, in addition to the pharmacological activity and positive effects on health, can lead to side effects, toxic effects, allergic reactions, as well as the interaction of conventional and herbal medicines. Despite this, there is a generally positive attitude that herbal medicines and herbal dietary supplements are safe and harmless to health and are most often used on its own initiative, without consultations with a pharmacist or a doctor. The aim of this study was to develop and validate a questionnaire for measuring the general knowledge about phytopreparations. The study was designed as an observational, prospective cross-sectional study, intended for the valiation of the original epidemiological questionnaire to evaluate the knowledge about phytopreparations. The sample consisted of 218 respondents, who were visiting private pharmacies at the territory of Bijeljina, in February and March 2016. The final version of the questionnaire for the evaluation of knowledge about herbal preparations had good internal consistency (α= 0.849) and homogeneity when randomly splitting the questionnaire into two parts (α=0.731; 0.788). Exploratory factor analysis singled out two factors. Based on the results of the study, it can be concluded that the questionnaire was a valid and reliable instrument for the evaluation of general knowledge about safety of use of phytopreparations. This is very important because the evaluation of knowledge could lead to undertaking measures for improving it, which would reduce the potential adverse reactions and interactions of herbal preparations with conventional drugs, and the application would become safe and optimal.

M. Matović, D. Nikolić, N. Filipovic, Dongfang Chen, M. Jeremić, S. Janković, S. Ninkovic, A. Cvetkovic et al.

OBJECTIVE To describe a new method of 3D interactive modeling which integrates images obtained by separate SPET and multi slice computed tomography (MSCT) modalities using an original software in order to better localize SNL in BC patients. SUBJECTS AND METHODS We used technetium-99m-colloid rhenium sulphate for identifying SNL in seven patients with BC. Markers were made of lead pearls wrapped with cotton wool soaked in 99mTc-pertechnetate and placed on the skin of the patients forming of a triangle. Using an original software, two separate 3D models were made after SPET and MSCT imaging and then merged into a hybrid 3D model which enabled precise visualization and localization of the SNL. RESULTS In all cases the position of the SNL established by our method was successfully verified using a gamma probe. Duration of SNL identification and extirpation were significantly reduced in less than 10 minutes per patient. The reproducibility of this method was confirmed by precise identification and biopsy of the SNL. CONCLUSION We found this integrated SPET/MSCT 3D model to be much faster and easier to use as compared with the "classic" method, which was based on a radioactivity detection probe. In addition, our method was reproducible, accurate and of low cost. In other words, the method described in this paper could be very useful for health facilities with modest budget, because it obviates the need for buying expensive integrated SPET/MSCT hybrid imaging systems while detecting SNLs more accurately and in shorter time.

Ivana R. Vasić, S. Janković, M. Jelić

Summary Anxiety, depression and fear in general are the most common emotional problems in people with cancer and it is necessary to recognize them. The patients’ attitude towards the side effects of chemotherapy has changed significantly in recent years and psychological effects, rather than physiological ones, are becoming increasingly important. The aim of this study was to develop and validate a reliable questionnaire that can measure cancer patients’ fear of the chemotherapy side effects (CheSeFS). A cross-sectional observational study involved 208 oncology and haematology patients at the Clinical Centre of Kragujevac, Serbia and the Institute for Oncology and Radiology of Vojvodina in Sremska Kamenica. The internal reliability of the questionnaire was estimated by calculating Cronbach's alpha coefficient, while the external reliability was calculated by the split-half method with approximately the same number of respondents. In order to test the construct validity of the CheSeFS, all participants filled out the Scale of Depression, Anxiety and Stress-21 (DASS-21) and the Short Subjective Well-being Scale (SSWS), validated in Serbian language. Cronbach’s α coefficient reveals strong internal consistency, with a value of 0.922. The questionnaire demonstrated good structure and uniformity when randomly split into two parts. Exploratory component analysis revealed two factors with the same number of items that explain 61.691% of variance. The components are objective physiological effects of the treatment, and factor that depends on the patient’s psychological and sociological status, with approximately the same percentage of variance. The CheSeFS was positively correlated with the DASS-21 scale (ϱ = 0.595, p = 0.000). CheSeFS is a unique, reliable and valid two-factor 14-item instrument, a clinically useful tool to assess fear of the chemotherapy side effects in cancer patients.

Aleksandra Petrović-Kitić, S. Janković

Summary The Quality of Life Enjoyment and Satisfaction Questionnaire – Short Form is the most often used scale for measuring the quality of life of patients with psychiatric diseases. The aim of this research was to analyze the possibilities for measuring the quality of life in clinical conditions on the sample of patients with schizophrenia by using this scale. The study was conducted on the group including 153 patients with schizophrenia at the Institution for Accommodation of Adults “Male Pčelice”, Kragujevac. The study was observational and cross-sectional. The reliability of questionnaire was examined by using Cronbach’s alpha. The two tests of factor analysis adequacy were used, Spherical Bartlett’s Test and Keiser-Meyer-Olkin test (sampling adequacy). Validation was performed by calculating the correlation (validation by criteria). The Quality of Life Enjoyment and Satisfaction Questionnaire – Short Form was reliable (Cronbach’s alpha coefficient was 0.730) and valid. According to Catell criterion two domains were applied. This two-component solution explained the total of 37.80% variance, whereby the contribution of the first domain was 27.1% and the second 10.7%. The Quality of Life Enjoyment and Satisfaction Questionnaire – Short Form is suitable for everyday clinical evaluation of the patients with schizophrenia.

R. Pavlović, S. Stefanovic, Z. Lazic, S. Janković

BACKGROUND/AIM Exacerbations are key events in chronic obstructive pulmonary disease (COPD). Frequent exacerbations occurring during the natural course of COPD lead to deterioration of health-related quality of life and are major causes of morbidity and mortality. The aim of this study was to identify factors independently associated with frequent severe exacerbations of COPD that require hospitalization. MATERIALS AND METHODS A case-control study was performed to analyze risk factors and frequency of severe exacerbations, which were defined by the GOLD guideline criteria. Stepwise multivariate regression was used to determine the significant predictors of frequent exacerbations. RESULTS Results revealed five independent predictors of frequent exacerbations: age, length of hospital stay, FEV1/FVC ratio, CRP level above 10 mg/L, and respiratory comorbidities. CONCLUSION COPD patients should be more carefully assessed in terms of age, length of hospital stay, FEV1/FVC ratio, CRP level, and respiratory comorbidities. Patients under 65 years of age with respiratory comorbidities, longer hospital stay, lower FEV1/FVC ratio and CRP of <10 mg/L are more prone to experiencing a minimum of one additional hospitalization in the following year. Patients could spend less time in the hospital environment and increase their quality of life by adjusting these risk factors for hospitalization due to COPD.

M. Spasić, S. Janković, S. Stefanovic, Irena Kostić, D. Radovanovic, N. Djordjevic, I. Radosavljević, A. Divjak et al.

Background/Aim. Acute pancreatitis is an inflammatory condition having the significant mortality rate in the case of severe forms of the disease. The aim of this study was to investigate putative factors of increased mortality in patients with acute pancreatitis with contradictory prior evidence, and to reveal factors that were insufficiently explored previously. Methods. This prospective cohort study with nested case/control design included all adult patients treated for acute pancreatitis in the Clinical Center of Kragujevac, Serbia, during the 3-year period (from October 2011 to December 2014). The cases (n = 19) were patients who died, while the controls (n = 113) were patients who survived. The associations between putative risk factors and the study outcomes were tested by univariate and multivariate logistic regressions, and expressed as crude and adjusted odds ratios (OR) with corresponding 95% confidence intervals (CI). Results. Significant association with the lethal outcome in acute pancreatitis was found for advanced age (adjusted OR 1.12, 95%CI 1.02–1.23), presence of significant comorbidities (adjusted OR 10.62, 95%CI 1.01–111.39), higher interleukin- 8 (IL-8) value on third day from onset of symptoms (adjusted OR 1.05, 95%CI 1.02–1.08), use of tramadol and/or morphine (adjusted OR 47.34, 95%CI 3.21–699.08), the Bedside index for severity in acute pancreatitis (BISAP) score ≥ 3 in the first 24 hours (adjusted OR 48.11, 95%CI 3.14–736.29), and prophylactic use of antibiotics (adjusted OR 0.07, 95%CI 0.01–0.85). Conclusion. Advanced age, significant comorbidities, use of tramadol and/or morphine and more severe disease as assessed by BISAP score can increase the risk of death in acute pancreatitis, while prophylactic use of antibiotics may have a protective role.

Vlada Injac, U. Batranović, J. Matijašević, M. Vukoja, M. Hadnadjev, Z. Bukumirić, G. Trajkovic, S. Janković

Ventilator-associated pneumonia (VAP) incidence, causative pathogens, and resistance patterns are different between countries and intensive care units (ICUs). In Europe, resistant organisms have progressively increased in the last decade. However, there is a lack of data from Serbian ICUs. The aims of this study were to evaluate etiology and antimicrobial resistance for pathogens causing VAP in ICU patients, to examine whether there were differences between pathogens in early-onset and late-onset VAP and to identify mortality in patients with VAP after 30 and 60 days of hospitalisation. A retrospective cohort study was conducted in the respiratory ICU and all adult patients diagnosed with VAP from 2009 to 2014, were included. Gram negative organisms were the major pathogens (80.3%). The most commonly isolated was Acinetobacter spp (59.8%). There was statistical significant increase in incidence of infection with Klebsiella pneumoniae (8.9% vs 25.6%, p = 0.019). Extensively drug-resistant strains (XDR) were the most common (78.7%). Late-onset VAP was developed in 81.1% of patients without differences between pathogens in comparison with early-onset VAP. Acinetobacter spp was susceptible to tigecycline and colistin with a significant increase in resistance to ampicillin/sulbactam (30.2% vs 58.6%; p = 0.01). Resistance rate of Pseudomonas aeruginosa and Klebsiella pneumoniae to carbapenems was 38% and 11%, respectively. In methicillin-resistant Staphylococcus aureus no resistance was observed against vancomycin and linezolid. In conclusion, Gram negative organisms were the primary cause of bacterial VAP of which the most common was the XDR strain of Acinetobacter spp. Patients with early- and late-onset VAP have the same pathogens.

Dubravka Vukadinović, N. Samardžić, S. Janković, Marijana Tomić-Smiljanić, R. Pavlović, S. Stefanovic

Background/Aim. Early treatment failure (ETF) in patients hospitalized for community-acquired pneumonia (CAP) is associated with prolonged hospitalization, increased risk of mortality and high treatment costs. The aim of this study was to analyze relative importance of factors influencing ETF in hospitalized adult patients with CAP that are still insufficiently explored. Methods. A retrospective case-control study was carried out on a sample of 126 adult patients treated for serious CAP at the Clinic for Pulmonary Diseases, Clinical Center of Serbia, Belgrade, Serbia, during the 5-year period (2007-2011.). The cases (n=63) were consecutive patients with ETF, observed within the three days upon the admission to hospital, while the control group consisted of the equal number of randomly selected patients without such an outcome. The association between potential risk/protective factors and ETF was estimated using logistic regression analysis. Results. The coexistence of gastrointestinal disorders (adjusted OR 18.83, 95%CI 1.15-309.04), higher CURB-65 score on admission (adjusted OR 2.57, 95%CI 1.05-6.25), initial use of nonsteroidal anti-inflammatory drugs (NSAIDs) in hospital (adjusted OR 38.19, 95%CI 3.61-404.51) and previous outpatient use of inhaled corticosteroids(adjusted OR 22.41, 95%CI 1.03-489.06) were found to be significant risk factors for ETF. On the other hand, older age and use of antibiotics before the hospitalization were associated with a significantly lower chance of experiencing ETF, reducing the odds for 98% and almost 90%, respectively. Conclusions. The avoidance of routine in-hospital use of NSAIDs as well as outpatient use of appropriate antibiotics may be beneficial for patients hospitalized for CAP in terms of reducing risk of ETF. The CURB-65 score could be better predictor of ETF than Pneumonia Severity Index. Further prospective studies are required to confirm these findings.

S. Janković, S. Lukić

Background/aim. Ganaxolone is an allopregnanolone analogue devoid of hormonal activity which potentiates inhibitory action of GABA through positive allosteric modulation of GABA-A receptor. This review summarizes preclinical and clinical development of ganaxolone for treatment of epilepsy in children and adults. Methods. Published preclinical and clinical studies with ganaxolone were retrieved from multiple searches of MEDLINE and SCINDEKS databases of published scientific articles. Published European and USA patents with ganaxolone were also used as data source for writing this article, as well as the feedback from the company which is developing ganaxolone (Marinus Pharmaceuticals). Results. Ganaxolone prevented seizures in animal models of partial and generalized tonic-clonic seizures, while in the models of absence seizures it was either ineffective or prolonged spike wave discharge. Phase I clinical trials pointed to linear pharmacokinetics of ganaxolone, its high protein-binding and metabolism in the liver, and predominant excretion in feces. Ganaxolone showed certain efficacy as add-on therapy against partial seizures with or without secondary generalization in adult patients and a phase III clinical trial is currently being prepared to test ganaxolone in this indication. Although tried in several small studies on children suffering from infantile spasms, it failed to produce significant response. Conclusions. If future clinical trials confirm efficacy of ganaxolone as add-on therapy in adult patients with partial onset seizures, it could become useful adjunct to existing anti-epileptic therapy of patients who did not achieve satisfactory seizure control. [Projekat Ministarstva nauke Republike Srbije, br. 175007]

Zorana Đorđević, M. Folic, S. Janković

Background/Aim Urinary tract infections (UTIs) are among the most common infections in outpatients. The aim of this study was to define the causative agents of urinary tract infections and their resistance to antimicrobial drugs in the urban area of central Serbia, as well as to evaluate eventual differences associated with age and gender of the patients. Methods This retrospective study analysed data taken from routine, consecutively collected urine cultures of outpatients with symptomatic UTIs, collected from the Department of Microbiology, Institute of Public Health in Kragujevac, Serbia, from January 2009 to December 2013. Results There were 71,905 urine cultures, and 24,713 (34.37%) of them were positive for bacterial pathogens. The most common pathogen was Escherichia coli (E. coli) (56.56%), followed by Klebsiella spp. (16.20%), Proteus spp. (14.68%), Enterococcus spp. (5.29%) and Pseudomonas aeruginosa (3.74%). E. coli and Enterococcus spp. isolation rates were lower in males ≥ 60 years old (23.71% and 4.87%, respectively), while Klebsiella spp. was more prevalent in this group (32.06%). The most common causative agents isolated from 15–29 years old male patients were Enterococcus spp. and Pseudomonas aeruginosa (13.28% each). Among women, the isolation rate of E.coli was high in all age groups (around 70%). Proteus spp. was frequently isolated from females ≤ 14 years old (13.27%), while Klebsiella spp. was the most frequent in the oldest age female group (10.99%). Conclusion Choice of antibiotics for treatment of UTIs should be governed not only by the local resistance patterns, but also by gender and age of patients.

Nevena Folic, Z. Djordjevic, M. Folic, S. Markovic, Biljana Vuletić, D. Savić, O. Gajović, S. Janković

Abstract Low birth weight newborns (≤1500 grams) are at a high risk of acquiring hospital infections due to the immaturity of the immune system, lack of efficient structural barriers, and an incomplete development of endogenous microbial flora. The aim of this study was to reveal the potential risk factors for hospital-acquired pneumonia in low birth weight newborns. This study was a prospective cohort design with a nested case-control study and was conducted between January 1st, 2012 and June 30th, 2015 at the Neonatology Department, Clinical Centre Kragujevac, Serbia. There were 1140 newborns hospitalized at the Neonatology Department for longer than 48 hours during the study period, and 169 of them (14.82%) weighed less than 1500 grams at birth. In total, 73 (43.19%) newborns with low birth weights developed HIs. The most prevalent HI was hospital pneumonia (n=64, 87.67%). Although univariate analyses identified many risk factors with a significant influence on the occurrence of hospital pneumonia, multivariate analysis identified only the following two independent risk factors for hospital pneumonia in newborns with birth weights below 1500 grams: mechanical ventilation (p=0.003, OR=68.893, 95% CI=4.285-1107.699) and longer hospitalization (p=0.003, OR=1.052, 95% CI=1.017-1.088). Almost all of the pathogens isolated from the patients with pneumonia were gram-negative bacteria (98.50%). More than half of all of the isolates were Acinetobacter spp (37.50%) and Enterobacter spp (18.75%). Our study showed that mechanical ventilation and prolonged hospitalization were significant risk factors for the development of hospital pneumonia in newborns with birth weights below 1500 grams.

Danijela Jakšić-Gvozdić, S. Janković, Danka Pajović, S. Vidojević, S. Stefanović, J. Milovanović

Abstract The aim of this study was to investigate the possible potential of preschool staff through a newly designed questionnaire and evaluate their role in the prevention of early childhood caries (EEC) in Serbia where extremely high prevalence of this preventable disease was recorded. We preformed a cross-sectional study of 268 preschool staff using specially prepared semi-structured questionnaire for measuring potential of secondary children’s caregivers to prevent EEC. The questionnaire was tested on a pilot sample and after that all collected data were analyzed trough construction of correlation matrix with the evaluation of the value of each question, reliability testing, factorial analysis and estimating of its validity using SPSS software. The tested questionnaire had good internal consistency based on the Cronbach’s alpha coefficient value of 0.873 calculated directly and similar value (0.899) after applied Spearman-Brown “prediction” formula. Using exploratory factorial analysis and orthogonal rotation, we identified two domains that emerged with similar loadings (4.043 and 3.183). The first factor (domain) reflected attitudes of the study participants towards prevention of EEC, and the second factor (domain) showed behaviour of the study participants, which includes preventive actions against EEC. The total score of the questionnaire was correlated positively with oral health knowledge (Spearman’s correlation coefficient 0.331, p=000) and inversely with the length of employment, where each additional year of employment decreased the total score of the questionnaire by 1.20. These findings could partially explain an extremely high prevalence of EEC in young children and indicate that preschool teachers should be more engaged in health education activities and motivation programs.

Z. Djordjevic, M. Folic, Nevena Folic, N. Gajović, O. Gajović, S. Janković

INTRODUCTION Acinetobacter baumannii is one of major causative agents of severe, life-threatening hospital infections (HIs), especially in intensive care units (ICUs). Our aim was to discover the risk factors associated with the emergence of HIs caused by carbapenem-resistant Acinetobacter baumannii (CRAB), as well as those associated with death in patients who suffer from such infections. METHODOLOGY A prospective cohort study was conducted over a five-year period in the medical-surgical ICU of the Clinical Centre in Kragujevac, Serbia. The study group comprised patients who had HIs caused by CRAB, while the control group comprised patients infected with carbapenem-sensitive Acinetobacter baumannii. RESULTS In total, 137 patients developed HIs caused by Acinetobacter baumannii. The mean age of the patients was 59.65 ± 16.08 years, and 99 (72.26%) of them were males. In 95 patients (69.35%), the infection was caused by CRAB. There were six independent risk factors for CRAB infections: use of mechanical ventilation, previous stay in another department, stay in ICU for more than a month, and previous use of carbapenems, aminoglycosides, and metronidazole. Three independent risk factors were found for death in patients with HIs caused by CRAB: use of mechanical ventilation, previous stay in another department, and previous use of carbapenems. CONCLUSIONS The results of this study can be helpful when identifying patients with risk of HIs caused by CRAB and in planning preventive measures. Modification of known risk factors and appropriate institutional policy of antibiotic utilization are important measures that may decrease the incidence and mortality of such infections.

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