OBJECTIVE The aim is to analyze how schizophrenia is pharmacologically treated in seven CEE countries: Croatia, Estonia, Hungary, Poland, Serbia, Slovakia and Slovenia. METHODS Psychiatrists from selected centers in each of participating countries were asked to complete a pre-defined questionnaire on their current clinical practice. Information on protocols and resource utilization in schizophrenia treatment was included and derived from randomly selected patient medical records. Expert opinions on country-wide treatment patterns were additionally sought. This sub-analysis focuses on pharmacological treatment patterns in the last six months and over the course of the disease. RESULTS 961 patients' data show that during last six months the most commonly prescribed medications were oral atypical antipsychotics: olanzapine (n=268), clozapine (n=234) and risperidone (n=160). The most frequently prescribed atypical antipsychotics over course of disease were: risperidone (54.5%), olanzapine (52.4%) and clozapine (35.1%), along with haloperidol (39.3%). Experts reported risperidone (four countries) and olanzapine (three countries) as first-line treatment, with the same two medications prescribed as second-line treatment. Clozapine was the most reported medication for refractory patients. Approximately 22% of patients received polypharmacy with antipsychotics in at least one period over the disease course. Mean time since diagnosis was 13.1 years and on average 4.8 treatment courses received during that period. Anxiolytics (70%), antidepressants (42%), mood-stabilizers (27%) were also prescribed, with diazepam (35.4%), sertraline (10.5%), valproic acid (17.5%) the most commonly reported, respectively, in each group. The most frequently reported treatment change was switch from one oral atypical antipsychotic to another (51%). CONCLUSION Oral atypical antipsychotics, mostly older drugs (risperidone, olanzapine, clozapine), were most commonly prescribed for schizophrenia treatment in participating countries. Given that results are from the first large-scale analysis of RWD, we believe these findings can be a benchmark for future real-world studies, which could contribute to the optimization of treatment for this debilitating disease.

Summary The aim of the paper was to determine the factors related to the initial therapy that may contribute to death from severe necrotizing acute pancreatitis and to analyze their clinical importance as well as possible additive effects. A retrospective case-control study included all adult patients treated for severe necrotizing acute pancreatitis in the Clinical Center of Kragujevac, Serbia, during the five-year period (2006-2010.). The cases (n = 41) were patients who died, while the controls (n = 69) were participants who survived. In order to estimate the relationship between potential risk factors and observed outcome, crude and adjusted odds ratios (OR) with 95 % confidence intervals (CI) were calculated in logistic regression models. Significant association with observed outcome was shown for the use of gelatin and/or hydroxyethyl starch (adjusted OR 12.555; 95 % CI 1.150-137.005), use of albumin (adjusted OR 27.973; 95 % CI 1.741-449.373), use of octreotide (adjusted OR 16.069; 95 % CI 1.072-240.821) and avoiding of enteral feeding (adjusted OR 3.933; 95 % CI 1.118-13.829), while the use of nonsteroidal anti-inflammatory drugs had protective role (adjusted OR 0.057; 95 % CI 0.004-0.805). The risk of death in patients with predicted severe necrotizing acute pancreatitis could be reduced with avoidance of treatment with colloid solutions, albumin and octreotide, as well as with an early introduction of oral/enteral nutrition and use of nonsteroidal anti-inflammatory drugs.

Background/Aim Delirium is an acute or subacute, and most frequently reversible syndrome of higher cortical functions disturbances that is manifested as generalized disorder. If not prevented, it is associated with various adverse outcomes. The aim of this study was to determine the connection between the markers of inflammation and lethal outcome in patients diagnosed with delirium, hospitalized in the psychiatric intensive care unit. Methods This retrospective study included 120 patients hospitalized in the psychiatric intensive care unit in whom examination of differences in inflammation markers was done. The examinees have been divided into two groups: the case group of 40 patients who died during the hospitalization, and the control group of 80 examinees who were discharged with the diagnosis Post delirium status. The following variables were taken into account: age, gender, clinical diagnosis of infection (pneumonia and urinary tract infection), laboratory parameters (total of white blood cells, granulocytes, monocytes, C-reactive protein − CRP) and type of delirium (withdrawal or organic). Results The average age of patients was 50.3 ± 13.1 years. The patients who survived delirium, were on the average 10.5 years younger than the deceased (p < 0.001). More than half (57.5%) of the deceased had pneumonia. There was a statistically significant correlation between pneumonia and lethal outcome in the patients with delirium (p < 0.001). The examinees with lethal outcome had significantly higher median CRP levels than the group of examinees who survived (75.6% ± 54.0 vs 30.3 ± 42.5 ng/L, p < 0.001). Conclusion Aiming to better and more precise diagnostics of this complicated and still unclear neuropsychiatric syndrome it would be useful to consider introduction of more precise diagnostic algorithms in every unit of intensive care. That would significantly reduce the number of delirium diagnosis overlook, decrease complication of clinical features and would also reduce the unfavorable outcome rate, therefore the total cost of treatment.

Background Colorectal cancer is one of the leading causes of cancer deaths in both sexes in the world. Improvement of existing therapy modalities and implementing new ones in order to improve survival of patients with colorectal cancer represents a great challenge for medicine. The aim of this paper was to assess the impact that adding bevacizumab to chemotherapy has on survival in patients with metastatic colorectal cancer, compared to the use of chemotherapy alone. Methods Hazard ratios (HRs) with their 95% confidence intervals (CI) were determined from the studies and pooled. Two-sided p values were reported and considered to indicate statistical significance if less than 0.05. Results A total of 12 studies that meet the inclusion criteria were identified in the literature search, 3 phase II studies and 9 phase III studies. Based on the random effects meta-analysis, a statistically significant improvement was identified for both overall survival (HR = 0.84; 95% CI: 0.74–0.94; p = 0.003) and progression free survival (HR = 0.64; 95% CI: 0.55–0.73; p<0.00001) in patients with metastatic colorectal cancer when bevacizumab was added to chemotherapy, compared to chemotherapy treatment alone. Conclusion The findings of this meta analysis confirm the benefit of adding bevacizumab to chemotherapy in terms of survival and progression free survival, but the magnitude of this effect is not consistent throughout the included studies. This suggests the need for further research of interaction of bevacizumab with chemotherapeutic agents as well as recognition of patients’ characteristics important for the treatment selection criteria.

BACKGROUND AND AIM Drugs used chronically by patients with diseases of the cardiovascular system (group C of the ATC classification) may act on adrenergic receptors and/or certain ion channels, which gives them the potential to interact with the action of local dental anesthetics. The aim of the study was to investigate the effect of systemically administered chronic cardiovascular medication (oral route) on the efficacy of intraoral local anesthesia in patients with diseases of the cardiovascular system. PATIENTS AND METHODS This was a prospective cohort study which analyzed the efficacy of local terminal anesthesia (onset of anesthesia, duration anesthetized area) in the upper jaw of 70 patients: 40 patients on medication for cardiovascular system disorders and 30 patients who were not using these drugs (the control group). The following cardiovascular drugs were used: beta blockers, angiotensin converting enzyme inhibitors, calcium channel blockers, vasodilatators, diuretics, angiotensin receptor blockers, antiarrhythmics, statins and alfa blockers. RESULTS The onset of anesthesia on the vestibular side was faster in those taking cardiovascular drugs (40.50±19.87 s) than the control patients (58.93±31.07 s; P = 0.004) and duration of anesthesia on this side was shorter. Although the difference was not significant, it was evident that on vestibular and palatal side the anesthetized area was more rapidly reduced in the patients taking cardiovascular drugs. The duration of cardiovascular therapy also had a significant impact on the anesthetized area. CONCLUSION Drugs acting on cardiovascular system may influence the effect of local anesthetics used in dentistry, possibly through interaction with autonomic receptors and ion channels.

OBJECTIVE Hypothyroidism is one of most common endocrine disorders resulting from deficiency of thyroid hormones. The aim of our study was to investigate whether cardiovascular drugs as well as gender, age, body-mass index, and habits, like smoking or drinking coffee affect thyroid-stimulating hormone (TSH) level in hypothyroid patients with thyroxine replacement therapy who suffer from cardiovascular disease. MATERIALS The study was conducted on 150 hypothyroid patients who underwent total thyroidectomy for benign reasons; they were divided into five treatment groups: levothyroxine only group and, according to the drugs they had in therapy alongside levothyroxine, the angiotensinconverting enzyme inhibitors group, the selective β-blockers group, the calcium antagonists group, as well as the nitrates group. A retrospective cohort study was conducted in the Clinical Center Kragujevac, Serbia, during the period of January 2012 to October 2014. All patients' data were collected both from participants' health records and questionnaires that patients completed, including data about habits, like smoking or drinking coffee. RESULTS TSH values were significantly higher in the group of patients with selective β-blockers in therapy alongside levothyroxine, compared to all the other study groups. The values of TSH level did not significantly differ among the other therapy groups. On the other hand, cigarette smoking was a risk factor that decreased TSH levels in patients on thyroid replacement therapy. CONCLUSIONS Our study shows that selective β-1 blockers can increase, while cigarette smoking can decrease TSH serum levels in hypothyroid patients on thyroid-replacement therapy.

Aim: CAM- ICU is instrument for brief delirium screening in the intensive care unit (ICU) for ventilated and non-ventilated patients. The aim of this study was to translate, validate and evaluate the applicability of this instrument in the Serbian speaking area. Methods: Translation of the CAM-ICU was made according to International Society for Pharmacoeconomics and Outcomes Research guidelines. In this prospective cohort study, CAM-ICU was applied to 301 adult surgical ICUs by two different raters. We tested CAM-ICU for interrater reliability by correlation between them. The scale was validated by comparison with the reference evaluation, wich was done by a psychiatrist using the Diagnostic and Statistical Manual of Mental Disorders V (DSM-V). Interrater agreement was measured using weighted kappa (k) and correlation used Spearman´s test. Results: The Spearman correlation coefficient was highly significant for rater 1 (r=0.672, p<0.001) and for rater 2 (r=0.625, p<0.001). The inter-rater reliability expressed by the kappa coefficient between rater 1 and rater 2 was highly significant (k= 0.859, 95% CI, 0.910-0.99, p<0.001). Conclusion: CAM- ICU, the first validated instrument for early detection of delirium in the Serbian speaking area, is reliable, valid and easily applied in daily clinical practice.

BACKGROUND Schizophrenia is a serious public health problem and is ranked among the most disabling diseases in the world. The sub-study presented here was part of a larger project to characterize the burden of schizophrenia on healthcare systems and on individuals living with the disease in Central and Eastern Europe (CEE). AIMS This sub-study aimed to assess and analyze the impact of schizophrenia on many aspects of the lives of patients and caregivers. METHODS Psychiatrists from selected centers in seven Central and Eastern European countries were asked to complete a questionnaire in order to collect information about the disease history, characteristics, treatment protocols and resources used for each randomly selected patient. All data were statistically analyzed and compared between countries. RESULTS Data from 961 patients with schizophrenia (mean age 40.7 years, 45.1% female) were included in the analysis. The mean number of days spent in hospital per patient per year across all seven countries was 25.3 days. Hospitalization occurred on average once per year, with psychiatrist visits 9.4 times per year. Of the patients in the study, 61% were single, 12% divorced and 22% married or cohabiting. Almost 84% were living with relatives or a partner; only 17% lived alone and, on average, 25% of patients received support from social workers. Relatives provided care for approximately 60% of patients and 4% of them had to stop working in order to do so. Twenty-nine percent of the patients were unemployed, and 56% received a disability pension or were retired, with only 19% in full-time employment or education. CONCLUSION Schizophrenia has a significant effect on the lives of patients and caregivers and impacts their social integration.

ABSTRACT Introduction: Linezolid is an oxazolidinone antibiotic active against Gram-positive bacteria, and is most commonly used to treat life-threatening infections in critically ill patients. The pharmacokinetics of linezolid are profoundly altered in critically ill patients, partly due to decreased function of vital organs, and partly because life-sustaining drugs and devices may change the extent of its excretion. Areas covered: This article is summarizes key changes in the pharmacokinetics of linezolid in critically ill patients. The changes summarized are clinically relevant and may serve as rationale for dosing recommendations in this particular population. Expert opinion: While absorption and penetration of linezolid to tissues are not significantly changed in critically ill patients, protein binding of linezolid is decreased, volume of distribution increased, and metabolism may be inhibited leading to non-linear kinetics of elimination; these changes are responsible for high inter-individual variability of linezolid plasma concentrations, which requires therapeutic plasma monitoring and choice of continuous venous infusion as the administration method. Acute renal or liver failure decrease clearance of linezolid, but renal replacement therapy is capable of restoring clearance back to normal, obviating the need for dosage adjustment. More population pharmacokinetic studies are necessary which will identify and quantify the influence of various factors on clearance and plasma concentrations of linezolid in critically ill patients.

OBJECTIVES The aim of this study was to investigate associated risk factors for dysmenorrhea in a sample of Serbian university students. METHODS A case-control study was conducted among undergraduate students (n = 288) attending lectures during 2014/2015 academic year at the Faculty of Medical Sciences, University of Kragujevac. RESULTS The only significant associations were between dysmenorrhea and age at menarche (OR adjusted = 0.74; 95% CI 0.58-0.95; p = 0.017), family history of dysmenorrhea (OR adjusted = 3.39; 95% CI 1.74-6.63; p = 0.000), duration of menstrual flow (OR adjusted = 1.52; 95% CI 1.16-1.99; p = 0.002) and smoking at least one cigarette a day (OR adjusted = 5.09; 95% CI 1.83-14.15; p = 0.002). The factors associated with dysmenorrhea were not interacting with each other. CONCLUSION Our results suggest that earlier age at menarche, longer duration of menstrual flow, prior family history of dysmenorrhea and smoking at least one cigarette a day are important risk factors associated with dysmenorrhea. Smoking cessation should be strongly encouraged.

BACKGROUND/AIM Drug-related problems are especially frequent among patients suffering from non-communicable diseases, like osteoporosis, leading to suboptimal treatment response. The aim of this study was to identify drug-related problems in patients with osteoporosis. METHODS This cross-sectional prospective study was conducted in January 2014 on outpatients with osteoporosis from three health facilities in Belgrade, Serbia. The patients included in the study were older than 50 years, and they were offered an anonymous questionnaire with open-ended questions. RESULTS There were 355 study participants, 329 (92.7%) females and 26 (7.3%) males. The patients who experienced at least one osteoporotic fracture (n = 208) were significantly less adherent to the therapy, less engaged in sports and regular physical activities, and more prone to nutrition with inadequate intake of calcium and vitamin D than patients without fractures (n = 147). CONCLUSION The effectiveness of osteoporosis treatment is decreased by several drug-related problems encountered by both physicians and patients. However, the majority of the drug-related problems could be greatly influenced by appropriate educational programs.