Correct choice and administration of a statistical test are absolutely essential for meaningful interpretation of research data, yet mistakes are still frequent and could be easily found in published scientific papers or PhD theses. The aim of this study was to analyze mistakes made by PhD students in statistical analysis of data collected during research within the framework of their thesis. PhD students frequently use Excel and SPSS for data processing, while SAS, Stata and R are also available. The study was designed as cross-sectional analysis of random sample (n=15) of PhD theses in pre-approval stage at Faculty of Medical Sciences, University of Kragujevac, Serbia. In total 14 (93%) theses had at least one mistake. The most frequent mistakes were as the following: insufficient statistical power due to small sample size, inappropriate presentation of results at tables and graphs, andinappropriate choice of statistical tests. In order to improve the situation, training courses in statistics during PhD studies should be re-evaluated and improved in regard to relevance, delivery methods and motivating potential, and mentors should invest more effort to review the data and guide students through statistical analysis.

Summary Background: During reproductive life of women, adenosine causes both contraction (with low concentrations) of fallopian tubes and inhibition of their spontaneous motor activity (with high concentrations). Objective: The aim of this study was to investigate effects of natural agonists of adenosine, P2X and P2Y receptors on motility of isolated fallopian tubes taken from postmenopausal women. Materials and Methods: Isolated preparations of isthmus and ampoule were made from fallopian tubes of 21 women in post-menopause, and then tested for reactivity on increasing concentrations of adenosine and P2X/P2Y selective agonists. Results: Adenosine showed concentration-dependent inhibitory effect on spontaneous contraction of both isthmic and ampullary segments of fallopian tubes, while P2X and P2Y agonists (adenosine-5-diphosphate, adenosine-5-triphosphate, uridine-5-diphosphate, and uridine-5-triphosphate) did not influence motility of the isolated preparations. Contractile effect of adenosine was not observed throughout the concentration range used in the experiments. Conclusions: Fallopian tubes of postmenopausal women are unresponsive to P2X and P2Y agonists, unlike those of women in reproductive period. Only an inhibitory effect of adenosine on spontaneous contractions of fallopian tubes is maintained in post-menopause, while a contractile effect is observed in younger women at low concentrations is lost.

Stenotrophomonas maltophilia can cause serious infections in immunocompromised patients. The aim of this systematic review was to establish what invasive infections in humans are caused by S. maltophilia and to evaluate the optimal choice of antibiotics for their treatment. MEDLINE, EBSCO, SCOPUS, SCINDEKS and GOOGLE SCHOLAR were systematically searched for clinical trials, observational studies, case reports or case series describing invasive infections with S. maltophilia in patients of any age. S. maltophilia may cause invasive infections of various tissues in hospitalized patients. In the great majority of cases it was susceptible to co-trimoxazole, levofloxacin and ceftazidime. In about three fourths of the cases, the treatment was successful, while less than 20% of the patients died. S. maltophilia is increasingly associated with serious invasive infections in hospitalized patients and due to growing trend of resistance to almost all antibiotics requires a careful approach to patients who is harboring this bacterium.

INTRODUCTION Chronic diseases with disabilities have a huge pharmacoeconomic impact on the health budget, especially in countries with recent history of social and economic transition. The aim of this study was to identify total costs of treating patients with lumbar pain in medical facilities in the central part of the Republic of Serbia. MATERIAL AND METHODS This study was designed as a cost of illness study, using a bottom-up approach and it was conducted from a societal perspective. This study included 97 patients with lumbar syndrome who were treated in outpatient facilities in the Central part of Serbia. RESULTS Total costs of treating lumbar pain were about €200.40 ± €86.65 per patient per year, where the largest volume of direct costs were costs due to visits to specialists in primary health care institutions (€9.39 ± €6.66). Total indirect costs were €182.00 ± €78.66. DISCUSSION Our findings highlight the need to estimate the total costs of treating lumbar pain and evaluate the correlation between costs and other variables for larger population of these patients. CONCLUSION This study distinguished two important pharmacoeconomic aspects of treating lumbar pain. Firstly, indirect costs represent major part of total costs of treating lumbar syndrome. Secondly, differences in valuing medical services between countries with recent history of social and economic transition and countries within European Union are one of crucial reasons for difference in total costs of treating low back pain among patients in neighboring regions.

Abstract: To date, many questions about the extent and cause of pharmacokinetic (PK) variability of even the most widely studied and prescribed &bgr;1-adrenergic receptor blockers, such as metoprolol and bisoprolol, remain unanswered. Given that there are still no published population pharmacokinetic (PopPK) analyses of bisoprolol in routinely treated patients with acute coronary syndrome (ACS), the aim of this study was to determine its PK variability in 71 Serbian patients with ACS. PopPK analysis was conducted using a nonlinear mixed-effects model (NONMEM), version 7.3.0 (Icon Development Solutions). In each patient, the same formulation of bisoprolol was administered once or twice daily at a total daily dose of 0.625–7.5 mg. We separately assessed the effects of 31 covariates on the PKs of bisoprolol, and our results indicated that only 2 covariates could have possible influence on the variability of the clearance of bisoprolol: the mean daily dose of the drug and smoking habits of patients. These findings suggest that possible autoinduction of drug metabolism by higher total daily doses and induction of cytochrome P450 isoform 3A4 (CYP3A4) by cigarette smoke in liver could be the potential causes of increased total clearance of bisoprolol in patients with ACS.

Vitamin D is one of the keys to bone health, and the serum levels of this vitamin are a major concern for postmenopausal women. The aims of this study were to develop a population pharmacokinetic (PPK) model for the clearance of 25-hydroxy vitamin D in non-elderly postmenopausal women and to identify the factors which have a significant influence on its clearance. The study population consisted of postmenopausal women who had been referred for evaluation of bone mineral density (BMD) by DEXA (dual-energy x-ray absorptiometry) scanner. The population pharmacokinetics modeling was conducted using the ADVAN 1 subroutine from a non-linear mixed effects (NONMEM) program, and thirty-two covariates were assessed. A total of 75 serum concentrations were obtained from the same number of postmenopausal women and used for PPK analysis. The mean value of the participantsí age was 57.92 ± 3.93 years and their body weight was 69.76 ± 11.49 kg. A wide range of 25-hydroxy vitamin D concentrations was observed (from 3.41 to 61.92 ng/mL) with a mean value of 26.19 ± 10.95 ng/mL. A total of 32 covariates were examined and preliminary results suggested the influence of six covariates on 25-hydroxy vitamin D clearance. In the final PPK model, however, only one covariate was shown to have a significant impact on the clearance value ñ the mean daily dietary intake dose of vitamin D (DD). These findings offer a preliminary basis on which to determine the level of vitamin D supplementation required by individual postmenopausal women. It could prove particularly important in achieving optimal serum levels of vitamin D in this vulnerable population.

Objective of this systematic review was to establish whether and what invasive infections in humans were caused by Kocuria kristinae, and to evaluate outcomes of administered antibiotic treatment. MEDLINE, EBSCO, SCOPUS, SCINDEKS and GOOGLE SCHOLAR were systematically searched for primary case reports or case series describing invasive infections with K. kristinae. K. kristinae is a pathogen microorganism that could cause invasive infections of various tissues in patients of any age. Majority of the patients had K. kristinae isolated from blood. It was also found in peritoneal fluid, pus, sputum, synovial fluid, bile, fluid from abdominal abscess, throat swab, urine catheter tip and mid-stream urine. Antibiotic treatment was almost universally effective, with only one death reported. Susceptibility was highest to vancomycin, linezolid, rifampicin, teicoplanin, tigecycline, cefotaxime, ampicillin/sulbactam, minocycline and meropenem. Initial treatment of Kocuria kristinae infections should involve parenteral vancomycin in combination with some other antibiotic to which it is susceptible.

Abstract Background Clinically relevant potential drug-drug interactions are considered preventable adverse drug reactions. Objective The aim of this study was to ascertain the frequency of potential drug-drug interactions in acute ischemic stroke patients and to explore factors associated with occurrence of potentially contraindicated drug-drug interactions. Methods This observational retrospective cohort and nested case-control study was carried out among patients treated for acute ischemic stroke at the Neurological Intensive Care Unit in the Clinical Centre Kragujevac, Serbia. The potentially drug-drug interactions for each day of hospitalization were identifi ed using Micromedex® soft ware. Based on the existence or absence of potentially contraindicated drug-drug interactions, the participants were divided into a group of cases (n=111) and the control group (n=444). Results A total of 696 patients were analysed. All patients had a minimum of one potential drug-drug interaction during hospitalization. The most common drugs involved in potential drug-drug interactions were aspirin (8.02%), diclofenac (7.49%) and warfarin (7.14%). The number of medications prescribed for simultaneous use during hospitalisation and the use of antipsychotics in therapy signifi cantly increased the likelihood of potentially contraindicated drug-drug interactions aft er adjustment by means of logistic regression for 1.2 and 3 times, respectively. Conclusions This study suggests that patients with acute ischemic stroke are frequently exposed to potential drug-drug interactions. It is essential to identify potentially drug-drug interactions in these patients as early as possible in order to prevent adverse drug reactions and ensure safe recovery. Besides, full attention should be paid when adding each new medication in therapy, particularly when a neurologist decides to prescribe antipsychotics, such as risperidone.

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.

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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. 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.

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.

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.