Backgroun/Aim. Although majority of guidelines recommend triazoles (voriconazole, posaconazole, itraconazole and isavuconazole) as first-line therapeutic option for treatment of invasive aspergillosis, echinocandins (caspofungin, micafungin and anidulafungin) are also used for this purpose. However, head-to-head comparison of triazoles and echinocandins for invasive aspergillosis was rarely target of clinical trials. The aim of this meta-analysis was to compare efficacy and safety of triazoles and echinocandins when used for treatment of patients with invasive aspergillosis. Methods. This meta-analysis was based on systematic search of literature and selection of high-quality evidence according to pre-set inclusion and exclusion criteria. The literature search was made for comparison of treatment with any of triazoles (isavuconazole, itraconazole, posaconazole or voriconazole) versus any of echinocandins (caspofungin, anidulafungin or micafungin). The effects of triazoles (itraconazole, posaconazole or voriconazole) and echinocandins (caspofungin, anidulafungin or micafungin) were summarized using RevMan 5.3.5 software, and heterogeneity assessed by the Cochrane Q test and I? values. Several types of bias were assessed, and publication bias was shown by the funnel plot and Egger?s regression. Results. Two clinical trials and three cohort studies were included in this meta-analysis. Mortality in patients with invasive aspergillosis who were treated with triazoles was significantly lower than in patients treated with echinocandins [odds ratio 0.29 (0.13, 0.67)], and rate of favorable response (overall treatment success) 12 weeks after the therapy onset was higher in patients treated with triazoles [3.05 (1.52, 6.13)]. On the other hand, incidence of adverse events was higher with triazoles than with echinocandins in patients treated for invasive aspergillosis [3.75 (0.89, 15.76)], although this difference was not statistically significant. Conclusion.Triazoles (voriconazole in the first place) could be considered as more effective and somewhat less safe therapeutic option than echinocandins for invasive aspergillosis: However, due to poor quality of studies included in this meta-analysis, definite conclusion should await results of additional, well designed clinical trials.

Background/Aim. After having established an indication for surgery, some patients experience sense of fear, unpleasantness and embarrassment due to the expectance of adverse consequences of surgical intervention. Recently an instrument for measuring fear of surgery - the Surgical Fear Questionnaire (SFQ) - was developed and validated on a sample of Dutch patients awaiting surgery. The objective of this study was to translate the SFQ to Serbian language, make cultural adaptation of the translation and test its reliability and validity in a sample of outpatients in Serbia. Methods. The SFQ was translated and adapted according to the accepted international standards (double forward translation, harmonization, backward translation, and piloting). The study was multicentric, involving patients from 7 cities in 3 countries: Serbia, Montenegro, Bosnia and Hercegovina. It was conducted at state-owned health facilities. The sample was of consecutive nature and consisted of 330 outpatients who visited specialists of either internal medicine or general surgery. Results. Translated SFQ showed excellent reliability, both when rated by the investigators (Cronbach’s alpha 0.915), and by the patients themselves (Cronbach’s alpha 0.917). It is temporally stable, and both divergent and convergent validity tests had good results. Factorial analysis revealed one domain on the whole study sample and two domains like in original on the subsample of patients without experience with surgery in general anesthesia. Conclusion. Identification of patients with high level of fear of surgery by this questionnaire should help clinicians to administer measures which may decrease fear and prevent avoidance of absolutely necessary surgery by such patients.

Objective. To determine reasons and their actual role in occurrence of complications in users of soft contact lenses. Methods. This was a qualitative study in which a constructivist grounded theory approach was used to analyze obtained data. The study population consisted of two groups of subjects: 10 students who were identified as users of soft contact lenses and 4 ophthalmologists. Each of the respondents participated ina single interview. Based on audio recordings of these interviews appropriate transcripts of conversations were made and analyzed. After elimination of waste words 11 key categories were crystallized. Results. Recommendations of the ophthalmologists perhaps have the decisive role in the formation of attitude that users will have regarding the adequate hygiene of soft contact lenses: hand hygiene, proper cleanliness of storage for soft contact lenses and using the solution in the allotted time are imperative for users of soft contact lenses. Sleeping with soft contact lenses for a long period and more frequently than it was specified in the recommendation of an ophthalmologist is one of the greatest reasons for development of dry eye symptoms, while swimming with soft contact lenses increases the risk for occurrence of eye

Risk Factors for Healthcare-Associated Infections Caused by Cefepime-Resistant Pseudomonas Aeruginosa A Marko M. Folić1,2, Zorana M. Djordjević3, Dragan R. Milovanović1,2, Dejana T. Ružić Zečević1,2, Nikola V. Rosić1, Slobodan M. Janković1,2 A 1 Clinical Centre Kragujevac, Clinical Pharmacology Department, Kragujevac, Serbia 2 University of Kragujevac, Faculty of Medical Science, Kragujevac, Serbia 3 Clinical Centre Kragujevac, Department of Hospital Infections Control, Kragujevac, Serbia

Background/Aim. Measuring health-related quality of life is of great help to clinicians when they have to choose optimal therapy for their patients or estimate its effects. The aim of this study was to translate the oral health-related quality of life [OHQoL-UK(W)] questionnaire from English to Serbian, to make necessary cultural adaptations of the translation, and to test its reliability in a sample of adult Serbian patients. Methods. After obtaining permission from the authors, translation and cultural adaptation of the OHQoL- UK(W) was made according to the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) guidelines. Reliability of the Serbian translation was tested on a sample of 250 patients through calculation of Cronbach?s alpha, as a measure of internal consistency. Results. Serbian translation of the OHQoL-UK(W) had very similar degree of internal consistency (Cronbach?s alpha 0.947), and correlated satisfactorily with the visual analogue scale (VAS) score and inversely with the Decay-missingfilled teeth (DMFT) index. Factorial analysis revealed only one factor, as in the original scale. Conclusions. Serbian translation of the OHQoL-UK(W) is reliable instrument for measuring oral health-related quality of life in adult dentistry patients.

Objective. Until now, there have been no guidelines for the use of drugs in patients with COVID 19 in the Republic of Serbia that have been authorized and published in the professional or scientific literature, or on the official websites of the Ministry of Health or healthcare institutions. The aim of this paper is to present a local guideline for the use of drugs in patients with COVID 19 and the process of its development and adoption. Methods. The guideline proposal was prepared by a working group based on the results of a systematic research of the medical literature, and quality control of found publications from the category "clinical practice guidelines". The proposal of the working group was considered and adopted at the sessions of the Drug / Therapeutics Committee and the Quality Assurance Committee of the University Clinical Centre Kragujevac. Results. The guideline's recommendations are based on the type of patient, and all have the same degree of recommendation and the same quality of evidence on which they are based. Patient types are formed according to the severity of the disease and the need for respiratory support, as well as according to the risk of secondary bacterial infection. Conclusion. The local guideline to the use of drugs in patients with COVID 19 was developed and adopted in a short period of time, primarily due to the need for its urgent use. A revision of this guide is planned after 6 months from the moment of adoption.

Background/Aim. Liver damage, with potentially serious consequences, is not uncommon in hospitalized cardiac patients. The aim of our study was to determine the risk factor profile for liver damage in patients hospitalized from a deterioration of their acute or chronic cardiac illness. Methods. The study had observational case-control design with retrospective data collections from medical files of adult patients hospitalized in a tertiary health care center. The cases (n = 140) were subjects with novel liver injury (which emerged during hospital stay) and three control subjects were matched (age, date) for each case subject (n = 420). The primary outcome was hepatotoxicity (present or absent) and independent variables were proposed risk factors. Statistical analysis included descriptive methods, hypothesis testing and univariate and multivariate binary logistic regression, with p ? 0.05. Results. In the whole study population, there were 432 (77.1%) females and the mean age of patients was 64.1 years [standard deviation (SD) = 10.7, range 24?85 years]. The most common illnesses were coronary heart disease (n = 385), hypertension (n = 334) and arrhythmia (n = 115). Mean value of Charlson Comorbidity Index (CCI) score was 3.8 (SD=1.7; range 1-10) corresponding to estimated CCI 10-years survival rate of 54.4% (SD = 33.5%). In the group of cases, 114 (81.4%) of the patients had hepatocellular, 9 (6.4%) cholestatic and 17 (12.2%) mixed type of hepatic injury. Factors independently associated with hepatotoxic event were previous occasional alcohol intake odds ratio (OR) 96.47; 95% confidence interval (CI) 28.95?321.43; p < 0.001), amiodarone (OR 3.70; 95% CI 1.82?7.53; p < 0.001), enoxaparin (OR 3.29; 95% CI 1.79?6.05; p < 0.001), obesity (OR 2.78; 95% CI 1.15? 6.71; p < 0.023), atorvastatin (OR 2.67; 95% CI 1.33?5.38; p < 0.006) and CCI total score (OR 1.89; 95% CI 1.53?2.34; p < 0.001). Conclusion. Major factors associated with acute liver damage in patients hospitalized in cardiology ward of a tertiary health care institution were patient?s constitutional and habitual characteristics (occasional alcohol intake, obesity, CCI total score) and drugs with known hepatotoxic properties (amiodarone, enoxaparin, atorvastatin).

Introduction. Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome (sy) to carbamazepine has a heterogeneous clinical presentation. The aim of this report is to indicate the efficacy of immunoglobulin G in the treatment of corticosteroidresistant DRESS sy. Case outline. An adolescent suffering from epilepsy treated with carbamazepine and Na-valproate was hospitalized for fever, elevated transaminases, lymphadenopathy, splenomegaly. There was an eruption of skin efflorescence daily. On the sixth day of hospitalization, the number of eosinophils increased to 24% (780/ml absolute number). There was no desired response to methylprednisolone during the first eight days of treatment or to prednisolone during further treatment, with concomitant administration of antihistamines from day one of hospitalization, to Na-valproate, metformin hydrochloride, elimination diets, and carbamazepine withdrawal. Significant clinical, hematologic, and biochemical improvement occurred the day after the first dose of intravenous immunoglobulin G (IVIG). Conclusion. We point out the need to change the DRESS sy treatment recommendations in favor of the IVIG (as soon as the third or fourth day of treatment) in patients in whom the treatment with corticosteroids has no effect. Until new cases of the proven role of IVIG in the treatment of DRESS sy are published, corticosteroids remain the first therapeutic choice.

The COVID-19 pandemic required rapid response to the needs of critically ill patients, and one of the solutions was re-purposing of drugs with wide spectrum of antiviral action for treatment of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection. The re-purposing characteristically started with outof-label use in single or series of cases, to continue after the first promising results with randomised clinical trials. There are several drugs that are currently tested in ongoing clinical trials: antimalarials hydroxychloroquine and chloroquine, HIV protease inhibitors lopinavir/ritonavir, broad spectrum antivirals umifenovir (anti-influenza drug) and favipiravir, antiparasitary drug ivermectin and nucleotide analogue remdesivir. However, up to date only a few trials are completed and published, precluding definitive conclusions about efficacy and safety of these drugs. Until major clinical trials are completed, physicians who decide to use these drugs out-of-label should properly inform their patients of all potential risks and benefits and seek for their consent before administration of the drugs.

Previous research suggested that several genetic polymorphisms are associated with increased risk of ischaemic stroke (IS) in young adults. However, the predictive biomarkers of IS in young adults are still unclear. Our aim was to assess the contribution of modifiable and genetic factors in IS in young adults. In total, 40 stroke patients and 40 healthy controls aged 20 to 50 years were recruited. Data on modifiable factors were collected, then participants were genotyped for seven SNPs linked to thrombophilia: ACE rs1799752, PAI-1 rs1799889, APOE rs1412 and rs429358, FV rs6025 and rs1800595, and FII rs62623459. Significantly increased risk factors: hypertension and dyslipidaemia in stroke patients compared with the controls: 50.0 % vs 27.5 % and 75.0 % vs 40.0% (P = 0.039 and P = 0.002, respectively) were observed. Stroke patients compared with controls did not differ in distribution of ACE, APOE, FV, and FII variants. The 4G4G homozygotes of the PAI-1 gene were significantly more prevalent in stroke patients compared to the controls: 42.5 % vs 17.5 %, (P = 0.033). In the group with the small vessel occlusion subtype of stroke, statistically significant overrepresentation of 4G4G homozygotes and frequency of the 4G allele compared with controls: 57.1 % vs 17.5 % and 0.7 vs 0.45 (P = 0.026 and P = 0.03, respectively) were observed. Independent predictors of stroke incident were: dyslipidaemia (OR (95% CI) = 4.2 (1.4-12.4)) and 4G4G genotype (OR (95% CI) = 3.9 (1.1-13.7)). These results confirm the contribution of dyslipidaemia and 4G4G genotype in the increased risk of IS in young Bosnian adults.

OBJECTIVE The objective of our study was to investigate the effects of carbamazepine (CBZ) and lamotrigine (LTG) treatment on bone metabolism in epileptic patients. PATIENTS AND METHODS A cross-sectional study was performed on normal controls (N=30) and 100 patients with symptomatic epilepsy caused by a primary brain tumor, divided into two groups according to the treatment: LTG monotherapy group (N=50) and CBZ monotherapy group (N=50). For each participant serum levels of 25-OHD and osteocalcin (OCLN) were measured, and bone mineral density (BMD) was evaluated by the dual-energy X-ray absorptiometry method. RESULTS There was no statistically significant difference in the average values of vitamin D in serum between the CBZ and LTG groups (Vitamin D CBZ 17.03±12.86 vs. Vitamin D LTG 17.97±9.15; F=0.171, P=0.680). There was no statistically significant difference in the average values of OCLN between the CBZ and LTG groups (OCLN CBZ 26.06±10.87 vs. OCLN LTG 27.87±28.45; F=0.171, P=0.674). The BMD value was lower in both groups using antiepileptic agents compared to the controls, but when comparing the CBZ group to the LTG group, a statistically significant difference was only observed for the Z score (T-score CBZ: 0.08± 1.38 vs. T-score LTG: 0.37± 1.02; F=1.495, P=0.224; Z score CBZ: -0.05±1.17 vs. Z. score CBZ: 0.38±0.96; F=4.069, P=0.046) (Table 3). CONCLUSION The choice of antiepileptic agents for treating seizures in patients with brain tumors should be carefully evaluated in relation to their impact on bone health. These patients could benefit from supplementation and regular measurement of biochemical markers of bone turnover and BMD.

Similar to other European countries experiencing growth in their 65+ populations, Bosnia and Herzegovina have also been affected by an intensive population ageing process. This national phenomenon affects the pension system, the health system and the labour market. A brief description of extending working life in the socio-economic context in Bosnia and Herzegovina, including gendered statistics on employment for older workers and pension coverage, is presented in this chapter. There is a discussion on extended working life policies, pension reforms, pensions systems and policy, and relevant employment and health policies for older workers. Flexible employment policies and training for older workers have not yet been introduced in Bosnia and Herzegovina. Future policy recommendations are also discussed.