Background In last two decades, there have been substantial changes in the pattern of lipid-modifying medicines utilisation following the new treatment guidelines based on clinical trials. The main purpose of this study was to analyse the overall utilisation and expenditure of lipid-modifying medicines in the Republic of Srpska, Bosnia and Herzegovina during an 11-year follow-up period and to express its share in relation to the total cardiovascular medicines (C group) utilisation. Methods In this retrospective, observational study, medicines utilisation data were analysed between 2010 and 2020 period using the ATC/DDD methodology and expressed as the number of DDD/1000 inhabitants/day (DDD/TID). The medicines expenditure analysis was used to estimate the annual expenditure of medicines in Euro based on DDD. Results During the analysed period, the use of lipid-modifying medicines increased almost 3-times (12.82 DDD/TID in 2010 vs 34.32 DDD/TID in 2020), with a rise in expenditure from 1.24 million Euro to 2.15 million Euro in the same period. This was mainly driven by an increased use of statins with 163.07%, and among these, rosuvastatin increased more than 1500-fold, and atorvastatin with 106.95% increase. With the appearance of generics, simvastatin showed a constant decline, while the other lipid-modifying medicines in relation to the total utilisation had a neglecting increase. Conclusion The use of lipid-modifying medicines in the Republic of Srpska has constantly increased and strongly corresponded to the adopted treatment guidelines and the positive medicines list of health insurance fund. The results and trends are comparable with other countries, but still the utilisation of lipid-lowering medicines represents the smallest share of total medicines use for the treatment of cardiovascular diseases, compared to high-income countries.

Background/Aim: Clinical research nursing is a well-known concept in Europe and other countries. The purpose of this study was to investigate the nurses' knowledge and attitudes towards clinical research and their opinions and self-evaluation about clinical research nursing and factors affecting them. Methods: A cross sectional study was conducted at the University Clinical Centre of the Republic of Srpska (UCCRS). A questionnaire included 50 questions/ statements was created in order to address the aims of the research and afterwards distributed to 120 nurses from 6 departments. Results: Response rate was 91.6 %. Most of the respondents showed a low level of knowledge, but positive attitude related to clinical research. Nurses who participated in clinical research were confident in their competencies according to their self-evaluation. Conclusion: Systematic approach to the additional nurses education could have a significant impact on a success of clinical research.

Background: In last 2 decades, there have been substantial changes in the utilization patterns of antihypertensive medicines following new clinical trials and the introduction of new treatment guidelines. The aim of this study was to analyze utilization and prescribing patterns regarding antihypertensive medicines in the Republic of Srpska, Bosnia and Herzegovina during an 11-years follow-up according to national and European treatment guidelines. Methods: In this retrospective, observational study, medicine utilization data were analyzed between 2009–2019 period using the ATC/DDD methodology and expressed as the number of DDD/1,000 inhabitants/day (DID/TID). The medicine utilization 90% (DU90%) method was used for determine the quality of prescribing. Results: During the observed period, the use of antihypertensive medicines increased more than 3-times (125.97 DDD/TID in 2009 vs 414.95 DDD/TID in 2019), corresponding to a rise in the prevalence of hypertensive patients from 91.7/1,000 to 186.3/1,000 in the same period. This was mainly driven by increased use of angiotensin converting enzyme inhibitors with 241.69%, beta blockers with 146.87%, calcium channel blockers with 251.55%, and diuretics with 178.95%. Angiotensin receptor blockers were the fastest growing group of antihypertensive medicines in this period and their utilization increased nearly 40 times. Conclusions: The overall antihypertensive medicines utilization was largely influenced by national and ESH/ESC guidelines and strongly corresponded to the positive medicine list of the national health insurance fund. Antihypertensive medicines utilization is comparable with medicine utilization trends in other countries.

Background and Objectives: Cigarette smoking among the youth population has increased significantly in developing countries, including Bosnia and Herzegovina. However, no extant literature assesses the prevalence of tobacco use, nor identifies factors associated with smoking. This study determined the prevalence of cigarette smoking among a specific cohort of students and assessed factors related to tobacco use in this population. Materials and Methods: This cross-sectional study included 1200 students at all faculties of Banja Luka University. Data were collected from questionnaires adapted from the Global Youth Tobacco Survey (GYTS) and the Global Health Professional Student Survey (GHPSS) standardized questionnaires and were analyzed using descriptive statistics, Pearson’s χ2 test, and logistic regression. Results: When the prevalence of cigarette smoking within the last thirty days was recorded, we found that 34.1% of students smoked within this period. Nearly three-quarters (74.9%) of the student population had smoked or experimented with cigarette smoking. However, medical students were 27.2% less likely to smoke than their counterparts from other faculties. Overall, 87% of all students were aware of the harmful effects of cigarette smoking, 79% were aware of the harmful effects of secondhand smoke, and 65% reported that it was difficult to quit. Increased spending of personal money was associated with a higher probability of smoking, while exposure to secondhand smoke increased the odds of smoking by 62%. Conclusion: Policies, strategies, and action plans should be introduced in order to reduce the prevalence of smoking among university students and to create a smoke-free environment at the various universities involved.

Abstract The enzymes of the cytochrome P450 superfamily play a critical role in phase I drug metabolism. Among them, CYP2C9 and CYP2C19 are clinically important, as they can mediate severe toxicity, therapy failure, and increased susceptibility to cancer and other diseases caused by chemicals. The aim of this study was to determine the prevalence of pharmacologically most important allelic variants of the CYP2C9 and CYP2C19 genes in the general population of the Republic of Srpska (Bosnia and Herzegovina) and to compare them with other populations. For this purpose we determined the genotype profile and allele frequency of 216 randomly selected healthy volunteers using real-time polymerase chain reaction (RT-PCR). The prevalence of the CYP2C9 *2 and *3 alleles was 13.6 and 7.4 %, respectively. Based on these frequencies, of the 216 participants four (1.86 %) were predicted to be poor metabolisers, 78 (36.11 %) intermediate, and the remaining 134 (62.03 %) normal metabolisers. Based on the prevalence of CYP2C19 *2 and *17 variants – 16.2 and 20.4 %, respectively – nine (4.17 %) were predicted to be poor, 57 (26.39 %) rapid, and nine (4.17 %) ultra-rapid metabolisers. We found no significant differences in allele frequencies in our population and populations from other European countries. These findings suggest that genetically determined phenotypes of CYP2C9 and CYP2C19 should be taken into consideration to minimise individual risk and improve benefits of drug therapy in the Republic of Srpska.

Background: Monitoring and measuring of the medicine utilisation enables to assess the quality of use of medicines, providing the evidence-based data for the improvement of the prescribing practice and a more rational use of medicines. The aim of this study was to analyse utilisation patterns of medicines and to compare the results with other countries. Methods: A retrospective, observational study to analyse outpatient medicines utilisation in the Republic of Srpska between 2009 and 2017. Data of medicines utilisation were retrieved from the national database in the Public Health Institute of the Republic of Srpska and calculated and analysed by using the Anatomical Therapeutic Chemical/Defined Daily Dose (ATC/DDD) methodology. The results were expressed as Defined Daily Doses (DDDs) per 1,000 inhabitants per day. Results: Total medicines utilisation increased, from 448 DDDs in 2009 to 1,036 DDDs in 2017. Cardiovascular medicines (group C) were the most used medicines, and their share in the total utilisation increased from 36.6% in 2009 to 44.4% in 2017. Among them, the most frequently used were angiotensin-converting enzyme inhibitors, plain and in combinations with diuretics, namely enalapril. The share of medicines used in diabetes in the total utilisation increased from 3.9% in 2009 to 5.1% in 2017. Metformin and glimepiride accounted for about 83% of the blood glucose lowering medicines group (A10B). Among the antithrombotic medicines, the most frequently used were platelet aggregation inhibitors (B01AC), mainly acetylsalicylic acid whose use tripled since 2009. Diclofenac was the most frequently used non-steroidal anti-inflammatory and antirheumatic drug (M01). Conclusion: The trend of increased medicines utilisation was observed in this study. This finding is comparable with other countries. Variations between countries in the preferred medicines within a class as well as the extent of medicines use were observed. These differences were probably consistent, but not solely attributable, to differences in local guidelines and reimbursement policies.

Renalni kalikrein-kinin sistem igra veoma važnu ulogu u regulaciji lokalnogprotoka krvi u bubrezima i u procesu izlučivanja soli i vode, te predstavlja važnu karikuu održavanju homeostaze organizma.

Uvod. Infekcije urinarnog trakta (IUT) su poslije respiratornih, najcesce infekcije u djecjem uzrastu.Cilj rada je bio utvrditi ucestalost urinarnih infekcija, njihove etioloske i klinicke osobitosti kod djece u prvoj godini života, koja su hospitalizovana na Klinici za djecje bolesti tokom jednogodisnjeg perioda. Metode. Istraživanje je provedeno u periodu od 01.01.2010. do 31.12.2010. god. na Klinici za djecje bolesti Banja Luka. Analizirano je ukupno 126 pacijenata uzrasta 0–12 mjeseci kod kojih je verifikovana IUT. Svi pacijenti su podijeljeni u 4 starosne grupe (I: 0-28 dana života; II: 29 dana-3 mjeseca; III: 4-8 mjeseci; IV: 9-12 mjeseci). Ispitanici su podvrgnuti ispitivanjima koja su, zavisno od indikacija, obuhvatala laboratorijske i mikrobioloske testove, ultrazvuk abdomena i mikcionu cistouretrografiju. Rezultati. Djeca hospitalizovana zbog IUT u prvoj godini života ucestvuju u strukturi ukupnog hospitalnog morbiditeta sa 3,18%. Infekcije se cesce javljaju kod djecaka, sto je posebno izraženo u novorođenackom periodu, (79% djecaka prema 21% djevojcica). Infekciju po tipu akutnog pijelonefritisa imalo je 110 (87,3%) djece. Kod 50% dojencadi IUT se ispoljila u prva 3 mjeseca života, zatim od 4–8 mjeseca. Najcesci izolovan uropatogen je Escherichia coli (52,38%), oblik terapije parenteralni (96,03%), a ukupno trajanje terapije 8–10 dana. Na ultrazvucnom pregledu abdomena znake prosirenog pijelokanalnog sistema imalo je 31,75% djece. Od ucinjene 43 mikcione cistouretrografije vezikoureteralni refluks je nađen u 23,2% djece. Zakljucak. IUT su se najcesce javljale u prva 3 mjeseca života, po tipu akutnog pijelonefritisa sa nespecificnom simptomatologijom, cesce kod djecaka. Najcesci uropatogen je bila Escherichia coli, a nacin lijecenja parenteralni. Vezikoureteralni refluks je nađen kod 23,2% djece kod koje je ucinjena mikciona cistouretrografija.

We surveyed 27 anesthesiology residents to determine their basic understanding of biostatistics. We wanted to see how well they could interpret statistical presentation in biomedical literature and assess research outcomes. The questionnaire included three sections: demographics of the participants, their knowledge of statistics (21 questions) and their attitude and self reported confi dence about biostatistics. Recognition of a meta-analysis was the highest scoring question (85% gave the correct answer), and recognition of a case-control study scored the lowest (22%). There was no effect of gender, the year of study, the number of years elapsed since graduation at the medical school, or country in which the participants had attended medical school (US or foreign schools). The only factor that increased the number of correct answers signifi cantly was an additional course in biostatistics that two participants had attended after graduation. Sixty six percent indicated they did not understand all of the statistics they encountered in journal articles, but all of the participants felt it was important to be able to understand the literature. We conclude that most residents in this study lack the knowledge in biostatistics needed to interpret results in medical publications. Most participants in this survey expressed the desire to improve their knowledge on this subject, even though it would require taking special courses in basic epidemiology, and statistics for the non-statistician during their residency training.

Introduction. Information on antibiotic utilization in the Republic of Srpska is limited. The aim of this study was to analyze antibiotic utilization in the community from 2007 to 2011 and to compare this data with antibiotic use in other European countries. Materials and Methods. We did a population-based study to analyze systemic antibiotic utilization by an outpatient population using Anatomical Therapeutic Chemical/Defi ned Daily Dose methodology. The results were expressed as the defi ned daily dose (DDD) per 1000 inhabitants per day. The data were obtained from the annual reports of the Agency for Drugs and Medical Devices of the Republic of Srpska and Public Health Institute. Results. Outpatient use of systemic antibiotics ranged between 21.51 DDD in the year with the highest use (2010) and 17.01 DDD in the year with the lowest use (2011). Penicillins were the most frequently prescribed antibiotic group, and amoxicillin was the most frequently prescribed drug. Cefalexin was the most frequently prescribed cephalosporin. Increased use of a second-generation cephalosporin, cefuroxime constituted almost a third of cefalexin consumption in 2011. Second-generation quinolones, mostly ciprofl oxacine, accounted for about 70% of total quinolones consumption, with rising third-generation drugs also in proportion to the increasing use. Erythromycine was the most frequently used macrolide, followed by long-acting azithomycin. Conclusion. Outpatient use of systemic antibiotics in the Republic of Srpska, at about 19 DDD, does not exceed that in Europe. As in other European countries, a shift between generations of drugs was noted for antibiotic use. Additional studies, including monitoring of seasonal variation impact on antibiotic use, are needed.

The Activity of Proximal Tubule Enzymes in the Urine of Cephalexin-Treated Patients The activities of alanine aminopeptidase (AAP), γ-glutamyltransferase (GGT) and N-acetyl-β-D-glucosaminidase (NAG), enzymes dominantly localised in the epithelial proximal tubule cells, were measured with an aim of determining the nephrotoxicity of a cephalosporin antibiotic cephalexin. Enzymatic activities were measured in the 12-h urine samples of patients receiving cephalexin orally for 15 days in daily doses of 50 mg/kg body mass against Gram-positive infections of the respiratory or urinary tract. The same enzymes were determined in the 12-h urine samples of the corresponding control. Both the control and the experimental group consisted of 30 examinees of both sexes, age range 3-10 years. Statistically significant differences in AAP and GGT activities expressed as U/mmol creatinine were recorded after 12 days of cephalexin therapy in comparison with the control (p < 0.01). At the same time, no significant differences in NAG activity of the patients in relation to the control were observed during the entire course of the therapy. Based on the obtained results it can be concluded that treatment of 3-10 years old patients with the applied cephalexin doses for 15 days results in mild nephrotoxic changes close to the end of therapy accompanied by increased activities of AAP and GGT, the enzymes known as very sensitive indicators of nephrotoxicity. The results showing that during the entire period of cephalexin application no changes in NAG, as a lysosomal enzyme, were observed, could be taken as a proof that this antibiotic did not lead to severe injuries of epithelial proximal tubule cells at the level of cell organelles. Aktivnost Enzima Proksimalnih Tubula u Urinu Pacijenata Tretiranih Cefaleksinom Radi određivanja nefrotoksičnosti cefalosporinskog antibiotika cefaleksina, praćena je aktivnost enzima dominantno lokalizovanih u ćelijama epitela proksimalnih tubula, alaninaminopeptidaze (AAP), gama-glutamil-transferaze (GGT) i N-acetil-beta-D-glukozaminidaze (NAG). Određivanje aktivnosti enzima je vršeno u uzorcima 12-časovnog urina kod 30 ispitanika kojima je, zbog grampozitivnih infekcija respiratornog i urinarnog trakta, per os apliciran cefaleksin u dozama od 50 mg/kg telesne mase dnevno za vreme sprovođenja terapije do 15 dana. Aktivnosti istih enzima su određivane i u 12-časovnom urinu 30 ispitanika kontrolne grupe. I eksperimentalna i kontrolna grupa sastojale su se od ispitanika oba pola, starosti od 3 do 10 godina. Statistički značajne razlike u aktivnostima AAP i GGT, izražene u U/mmol kreatinina, registrovane su između ispitanika eksperimentalne i ispitanika kontrolne grupe nakon dvanaestog dana sprovođenja terapije (p < 0,01). Aktivnost NAG ispitanika eksperimentalne grupe u odnosu na ispitanike kontrolne grupe se nisu značajno menjale za čitavo vreme petnaestodnevne terapije. Može da se zaključi da petnaestodnevni tretman ispitanika starosti od 3 do 10 godina preporučenim dozama cefaleksina izaziva blage nefrotoksične promene pri kraju terapije koje su praćene porastom aktivnosti AAP i GGT, veoma osetljivih indikatora nefrotoksičnosti. Za čitavo vreme sprovođenja terapije nije došlo do porasta aktivnosti lizozomalnog enzima NAG, što znači da ne dolazi do težih oštećenja ćelija epitela proksimalnih tubula na nivou organela.

Great scientifi c discoveries rarely originate from small and poor countries, especially if they are frequently engulfed in wars, like it was the case with Serbia, and other parts of the former Yugoslavia. Despite the odds, quite a few well educated, curious, wise, and brave minds have made signifi cant contributions under such circumstances. For example, the achievements of Laza K. Lazarević (18511891), Milutin Milankovic (1879-1958), Ivan Djaja (18841957), Pavao Stern (1913-1976), and several other Yugoslav researchers clearly show that some scientists are able to make great discoveries under limited resources. 1 Nikola Tesla (1856-1943), and two Nobel laureates of Yugoslav origin, Leopold Ruzicka (1887-1976) and Vladimir Prelog (1906-1998), are only mentioned here because their major scientifi c contributions had been mostly conducted in the USA and Switzerland.

Scientists rely upon statistics to report their findings accurately and to interpret the published findings of others. The proper application of this discipline provides confidence in statements based upon experimental results. Professional statisticians may help at some phases of planning experiments even before results are obtained, but not all scientists avail themselves of such services. As a result, errors can occur in presentation of variability of data, and more often than not, such errors are ultimately published in biomedical journals. This paper examines the most common descriptive statistics for quantitative and categorical data. Standard deviation (SD), standard error of the mean (SEM), confidence intervals (CI), and various technical details, including how to present data in publications, and when to use particular statistical tools, are discussed as well.