Search

Dragan Kalinić,1 Ranko Škrbić,2 Duško Vulić,3 Svjetlana Stoisavljević-Šatara,2 Nataša Stojaković,2 Miloš P Stojiljković,2 Vanda Marković-Peković,4 Ana Golić Jelić,4 Nataša Pilipović-Broćeta,5 Nevena Divac6 1Centre for Biomedical Research, Faculty of Medicine, University of Banja Luka, Banja Luka, 78000, Republic of Srpska, Bosnia and Herzegovina; 2Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Banja Luka, Banja Luka, 78000, Republic of Srpska, Bosnia and Herzegovina; 3Centre for Specialisations and Continuous Medical Education, Faculty of Medicine, University of Banja Luka, Banja Luka, 78000, Republic of Srpska, Bosnia and Herzegovina; 4Department of Pharmacy, Faculty of Medicine, University of Banja Luka, Banja Luka, 78000, Republic of Srpska, Bosnia and Herzegovina; 5Family Medicine Teaching Centre, Primary Healthcare Centre of Banja Luka, Banja Luka, 78000, Republic of Srpska, Bosnia and Herzegovina; 6Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, 11000, SerbiaCorrespondence: Dragan Kalinić, Centre for Biomedical Research, Faculty of Medicine, University of Banja Luka, Save Mrkalja 14, Banja Luka, 78000, Republic of Srpska, Bosnia and Herzegovina, Tel/Fax +387 51 234 101, Email dragan.kalinic@med.unibl.orgBackground: 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.Keywords: lipid-modifying medicines, medicines utilisation, ATC/DDD methodology, medicines expenditure, medicines positive list

BACKGROUND. Endotoxemia provokes excessive host response to bacteria or microbial compounds, resulting in systemic inflammation, organ injury and mortality. Aim: This study examined the effects of simvastatin on survival and liver injury in endotoxic shock in a rat model of endotoxemia. METHODS. Male Wistar rats were injected intraperitoneally with E.coli-lipopolysaccharide (LPS) and the medial lethal dose (LD50) was determined. Simvastatin was given orally (5-40 mg/kg body weight) for five days prior to either a single LD50 dose of LPS or 2, 2.5 or 3x LD50. Liver damage was assessed by histological examination and expressed as a tissue damaged score (TDS). Another group of rats was treated with simvastatin and then challenged with LPS to determine the degree of apoptosis in hepatocytes, liver immune cells, and cleaved caspase-3 activity after 24h of endotoxemia. RESULTS. Endotoxemia caused substantial mortality with associated leukocyte infiltration, liver injury (TDS = 3.67, SD = 0.55), as well as notable apoptosis of hepatocytes and resident liver macrophages. Simvastatin, in a dose-dependent manner significantly reduced LPS-induced mortality, hepatocellular damage (TDS = 1.5, SD = 0.55), inflammatory infiltration, and dte drug markedly decreased apoptosis and expression of cleaved caspase-3. CONCLUSIONS. Simvastatin improves survival in endotoxic shock and prevents endotoxemic liver injury by inhibiting leukocyte infiltration and hepatocellular apoptosis. These results suggest that simvastatin could be used to prevent endotoxemia-associated liver dysfunction by simvastatin.

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.

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.

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/Defined Daily Dose methodology. The results were expressed as the defined 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 ciprofloxacine, 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.

Great scientific discoveries rarely originate from small and poor countries. The Balkan region, an area with frequent wars and numerous invasions, is not considered an appropriate base for scientific research. Despite such opinions, a number of well educated, curious, wise, and brave minds from Serbia and the former Yugoslavia have been able to make significant scientific contributions. As an example, we briefly outline the lives and achievements of two scientists: Milutin Milanković (1879-1958) and Ivan Đaja (1884-1957). Nikola Tesla (1856-1943), and two Nobel laureates of Yugoslav origin, Leopold Ružička (1887-1976) and Vladimir Prelog (1906-1998), are not included here because their scientific contributions were mainly conducted in the USA or Switzerland. Milanković and Đaja overcame many obstacles, including wars, to contribute significantly to science. Unfortunately, each generation in Serbia and in the former Yugoslavia has been severely disturbed by at least one war. However, some researchers, despite wars and limited resources were able to complete their great scientific projects. Notably, such scientists stayed in the country or returned home as soon as peace returned. However, following the recent civil war that split Yugoslavia, many capable scientists did not return to their prewar homes.

The activities of alanine aminopeptidase (AAP), g-glutamyl transferase (GGT) and N-acetyl-b-D-glucosaminidase (NAG), enzymes dominantly localized 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.

Background the aim of this study was to analyze the total outpatient utilization of antibacterials for systemic use (ATC class J01) and the outpatient utilization of antibiotics on the reimbursable medication list of the Health Insurance Fund, in the Republic of Srpska, in 2007 and 2008. Methods in the retrospective study outpatient utilization of prescription-only antibacterials for systemic use dispensed in pharmacies was analyzed. Anatomical therapeutic chemical/defined daily dose methodology was used to monitor drug utilization. Results It was observed that penicillins accounted more than 50% of both total and reimbursable antibiotic use, and that broad-spectrum penicillins were more prescribed than narrow-spectrum. Amoxicilline was the most prescribed antibiotic. Cephalosporins, namely cefalexin, were widely prescribed as well as tetracyclines and combination of sulfametoxazole and trimethoprim. Increased utilization of a macrolide antibiotic claritromycin was observed. The list of reimbursable antibiotics was comprised of the first-generation antibiotics. Utilization of all reimbursable antibiotics increased in 2008, except phenoxymethylpenicillin, due to marketing authorization renewal process. Conclusions the outpatient utilization of antibiotics was comparable with trends worldwide. Utilization increase of almost all reimbursable antibiotics suggested that more patients were able to achieve their rights deducible form the health insurance, and that the spending out-of pocket for medicines was reduced. Utilization of amoxicillin, solely or in combination with clavulanic acid, as the most prescribed antibitotic was similar to other countries.

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 confidence 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 significantly 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.

The aims of this study were to analyze the utilization of antibiotics before (2018, 2019) and during the COVID-19 pandemic (2020) and the practice of prescribing antibiotics in outpatient settings for COVID-19 patients during the 2020-2022 period. The Anatomical Therapeutic Chemical Classification/Defined Daily Dose methodology was used for the analysis of outpatient antibiotic utilization in the Republic of Srpska. The data was expressed in DDD/1000 inhabitants/day. The rate of antibiotics prescribed to COVID-19 outpatients was analyzed using medical record data from 16,565 patients registered with B34.2, U07.1, and U07.2 World Health Organization International Classification of Diseases 10th revision codes. During 2020, outpatient antibiotic utilization increased by 53.80% compared to 2019. At least one antibiotic was prescribed for 91.04%, 83.05%, and 73.52% of COVID-19 outpatients during 2020, 2021, and the first half of 2022, respectively. On a monthly basis, at least one antibiotic was prescribed for more than 55% of COVID-19 outpatients. The three most commonly prescribed antibiotics were azithromycin, amoxicillin/clavulanic acid, and doxycycline. The trend of repurposing antibiotics for COVID-19 and other diseases treatment might be a double-edged sword. The long-term effect of this practice might be an increase in antimicrobial resistance and a loss of antibiotic effectiveness.

Background and objectives: the aim of this study was to analyse the utilisation of proton pump inhibitors (PPIs) during a 12-year period and to show the characteristics and patterns of their prescribing. Materials and methods: firstly, in the pharmacoepidemiological analyses the ATC/DDD methodology was used to assess the utilisation of PPIs in the Republic of Srpska. The annual PPI utilisation was expressed as a number of DDD/1000 inhabitants/year. Secondly, the cross-sectional surveys were used to reveal the characteristics of PPIs prescribing and medicines use, namely the dose, duration and indication, and possible adverse reactions. For the purposes of the surveys, the adapted version of questionnaires related to physicians’ and patients’ perspectives of medicines prescribing and use were performed. Results: the utilisation of medicines for alimentary tract and metabolism (group A/ATC classification) increased by almost threefold in a 12-year period, which was consistent with the total medicine utilisation. Pantoprazole was the most prescribed medicine among the PPIs. With the exclusion of PPIs in the therapy of Helicobacter pylori eradication, more than half of family physicians prescribed PPIs with antibiotics, and only 53/239 physicians, noticed some adverse reactions of PPIs in their patients. Most of the patients knew how to use PPIs and were taking these medicines in recommended daily doses, but approximately 45% of them were using PPIs for a long period of time (>6 months). Conclusions: the overuse of PPIs is a major concern due to potential serious adverse reactions, especially in elderly patients and in a case of prolonged exposure.

Background and Objectives : Benzodiazepines (BZDs) are among the most prescribed psychotropic drugs and significant number of patients use these drugs for longer periods than recommended. The objective of this study was to determine the factors associated with prescribing of BZDs at the primary healthcare level. Materials and Methods : A retrospective analysis of family physicians' prescriptions from the databases of family medicine teams of the Republic of Srpska was performed. The number of BZDs users, as well as the total number of prescriptions, were determined. Thereafter, it was determined which specific BZD had been prescribed, in which dose, for how long, as well as the specific social and demographic characteristics of patients to whom the drugs were prescribed. Results : The results showed that 38.47% of patients used the BZDs for a period longer than six months. The most frequent BZDs prescribed were the intermediate-acting BZDs, primarily bromazepam (58.69%). Two thirds of patients were women. The average age of the patients was 60, 60.46% of patients were single, and 69.68% lived in urban areas. The longer uses of BZDs were recorded in women, the elderly, single people and those who lived in urban areas, while higher doses of BZDs were prescribed to men, as well as younger and married people. The highest positive correlation was found between the dose and length of use of BZD. Conclusions : A significant percentage of patients used BZDs for a time period longer than recommended. Caution is necessary when prescribing BZDs to women, the elderly, patients that live in urban areas and patients who are single. When prescribing BZDs, family physicians should be aware of their potential interactions and addictive potentials.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kalinić, Škrbić, Vulić, Stojaković, Stoisavljević-Šatara, Stojiljković, Marković-Peković, Golić Jelić, Pilipović-Broćeta, Wong and Godman.)

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.

Purpose: To determine the potential value of an adapted questionnaire to discover the predictors of preceptors' higher interest in precepting pharmacy interns and to evaluate preceptors' motivational factors and incentives for teaching as well as their professional satisfaction., Method: A link to the survey study of adapted questionnaire (JSAMPPP) was e-mailed to all pharmacists registered with the Pharmaceutical Chamber of the Republic of Srpska. Pharmacists' demographic and work experience characteristics, their attitudes related to motivation for precepting, value of incentives for precepting, job satisfaction, and influence of interns on pharmacists' professional practice were obtained., Results: Half of the preceptors who reported feeling satisfied with their professional life also showed interest in teaching. In addition, teaching pharmacy students positively contributed to the overall job satisfaction of the preceptors. Pharmacy preceptors were found to be most motivated by intrinsic factors. The most valued incentives reported were those related to continuing education., Conclusions: The adapted questionnaire has potential value and it revealed the following predictors of preceptors' higher interest in precepting: enjoyment of teaching, satisfaction with professional life, satisfaction as a pharmacy preceptor, and interns' influence on preceptors. These identified predictors can be emphasized to improve pharmacy students' internship experiences, thereby reinforcing the pharmacy profession.