Introduction: Antimicrobial resistance and the rapid spread of multiresistant bacteria represent one of the main public health problem in limited resources countries. This issue is significantly worsening since the COVID-19 pandemic due to the unreasonably increased antibiotics prescription to patients with confirmed SARS-CoV-2 infection. The aim of this study was to examine whether COVID-19 pandemic (2020, 2021) was associated with increased antibiotic consumption in inpatient and outpatient settings in the middle size urban region (Republic of Srpska/Bosnia and Herzegovina) in comparison to period before the pandemic (2019). Additionally, we aimed to determine antimicrobial resistance and the presence of multiresistant bacteria in the regional hospital (“Saint Apostol Luka” Hospital Doboj) in 2021. Methodology: The consumption of antibiotics in inpatient was calculated as Defined Daily Dose per one hundred of patient-days. The consumption of antibiotics in outpatient was calculated as Defined Daily Dose per thousand inhabitants per day. Resistance of bacteria to antibiotics is expressed as a rates and density for each observed antibiotic. The rate of resistance was calculated as a percentage in relation to the total number of isolates of individual bacteria. The density of resistance of isolated bacteria against a specific antibiotic was expressed as the number of resistant pathogens/1000 patient days. Results: Antibiotic consumption in hospital setting registered during 2019, 2020 and 2021 was as follows: carbapenems (meropenem: 0.28; 1.91; 2.33 DDD/100 patient-days, respectively), glycopeptides (vancomycin: 0.14; 1.09, 1.54 DDD/100 patient-days, respectively), cephalosporins (ceftriaxone: 6.69; 14.7; 14.0 DDD/100 patient-days, respectively) and polymyxins (colistin: 0.04; 0.25; 0.35 DDD/100 bed-days, respectively). Consumption of azithromycin increased drastically in 2020, and dropped significantly in 2021 (0.48; 5.61; 0.93 DDD/100 patient-days). In outpatient setting, an increase in the consumption of oral forms of azithromycin, levofloxacin and cefixime, as well as parenteral forms of amoxicillin-clavulanic acid, ciprofloxacin and ceftriaxone, was recorded. In 2021, antimicrobial resistance to reserve antibiotics in hospital setting was as follows: Acinetobacter baumanii to meropenem 66.0%, Klebsiella spp to cefotaxime 67.14%, Pseudomonas to meropenem 25.7%. Conclusion: Recent COVID-19 pandemic was associated with increased antibiotic consumption in inpatient and outpatient settings, with characteristic change of pattern of azithromycin consumption. Also, high levels of antimicrobial resistance to reserve antibiotics were registered in hospital setting with low prevalence of identified pathogen-directed antimicrobial prescription. Strategies toward combat antimicrobial resistance in the Doboj region are urgently needed.

Antibiotics are often misused, especially for the treatment of upper respiratory tract infections (URTIs) in children, where their use is unnecessary and leads to antimicrobial resistance. This study sought to explore the knowledge, attitudes and practices (KAP) of parents and pediatricians on the use of antibiotics among children and whether the level of education of parents has an impact on their KAP. The research was carried out among 1459 parents of children under 6 years of age and among 18 pediatricians. Sixty percent of pediatricians (61.1%) were prescribed antibiotics daily in their practice. Most of the surveyed parents (98.4%) state that doctors are their main source of information when deciding on the use of antibiotics in the treatment of their children. Parents with a higher level of education use television less often as a source of information when making this decision compared to parents with a lower level of education (p = 0.039, i.e., p = 0.003). The majority of parents (80.7%) knew that Panklav (amoxicillin/clavulanic acid) is an antibiotic, while 52.5% identified Pancef (cefixime) as an antibiotic. Parents with a higher level of education correctly identified antibiotics significantly more often (p < 0.001). This study shows that in the Republic of Srpska, parents have adequate knowledge about antibiotics, especially those with a higher level of education, who show better KAP when it comes to antibiotic use.

Many drugs with different mechanisms of action and indications available on the market today are capable of inducing hepatotoxicity. Drug-induced liver injury (DILI) has been a treatment challenge nowadays as it was in the past. We searched Medline (via PubMed), CENTRAL, Science Citation Index Expanded, clinical trials registries and databases of DILI and hepatotoxicity up to 2021 for novel therapies for the management of adult patients with DILI based on the combination of three main search terms: 1) treatment, 2) novel, and 3) drug-induced liver injury. The mechanism of action of novel therapies, the potential of their benefit in clinical settings, and adverse drug reactions related to novel therapies were extracted. Cochrane Risk of bias tool and Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment approach was involved in the assessment of the certainty of the evidence for primary outcomes of included studies. One thousand three hundred seventy-two articles were identified. Twenty-eight articles were included in the final analysis. Eight randomized controlled trials (RCTs) were detected and for six the available data were sufficient for analysis. In abstract form only we found six studies which were also anaylzed. Investigated agents included: bicyclol, calmangafodipir, cytisin amidophospate, fomepizole, livina-polyherbal preparation, magnesium isoglycyrrhizinate (MgIG), picroliv, plasma exchange, radix Paeoniae Rubra, and S-adenosylmethionine. The primary outcomes of included trials mainly included laboratory markers improvement. Based on the moderate-certainty evidence, more patients treated with MgIG experienced alanine aminotransferase (ALT) normalization compared to placebo. Low-certainty evidence suggests that bicyclol treatment leads to a reduction of ALT levels compared to phosphatidylcholine. For the remaining eight interventions, the certainty of the evidence for primary outcomes was assessed as very low and we are very uncertain in any estimate of effect. More effort should be involved to investigate the novel treatment of DILI. Well-designed RCTs with appropriate sample sizes, comparable groups and precise, not only surrogate outcomes are urgently welcome.

Introduction Infective endocarditis is relatively rare in pediatric population, but can result in significant morbidity and mortality. Children with bicuspid aortic valve are at higher risk of developing infective endocarditis as compared to general population. Our objective is to emphasize the importance of rapid diagnosis and proper treatment of infective endocarditis in patients with bicuspid aortic valve with aim to prevent serious adverse events. Case outline We report a case of a 13-year-old girl with newly diagnosed bicuspid aortic valve who developed infective endocarditis with severe complications and underwent cardiac surgery. Recurrent fever and anemia, as well as cardiac murmur were present for six months prior to diagnosing infective endocarditis. During the course of illness, only one of many blood cultures taken was positive for Streptococcus sanguinis. Conclusion Patients with bicuspid aortic valve require careful evaluation for infective endocarditis, especially if recurrent fever associated with anemia is present. Delayed diagnosis of infective endocarditis is associated with serious complications.

Introduction: Treatment is generally not available for drug-induced liver injury (DILI) patients except in some specific circumstances. The management of DILI is based on the withdrawal of the responsible drug and monitoring the patients and only a few patients need to be referred to a transplant center. Some studies on the role of ursodeoxycholic acid (UDCA) in DILI have been published. The aim of this study was to perform a systematic review of the role of UDCA in the treatment and prevention of DILI. Methods: A search was undertaken in PubMed, with the key words ursodeoxycholic acid, drug-induced liver injury and hepatotoxicity following the PRISMA guidelines. Results: A total of 33 publications were identified: 25 case reports and 8 case series. In 18 of the 25 cases reports (22 patients), authors reported improvement of liver injury associated with UDCA therapy whereas 7 case reports did not show clinical or biochemical improvement after UDCA treatment. There were 4 studies evaluating the role of UDCA in the treatment of DILI, three prospective (one being a clinical trial) and one retrospective studies. Three studies observed liver profile improvements associated with UDCA. In addition, four studies evaluated UDCA in the prevention of DILI: one pilot study, two randomized clinical trials (RCT) and one retrospective study. Three of these studies observed a lower percentage of patients with an increase in transaminases in the groups that used UDCA for DILI prevention. Conclusion: According to available data UDCA seems to have some benefits in the treatment and prevention of DILI. However, the design of the published studies does not allow a firm conclusion to be drawn on the efficacy of UDCA in DILI. A well designed RCT to evaluate the role of UDCA in DILI is needed.

Background/Aim: The prevention of cardiovascular risk factors and cardiovascular disease management contributes to the cardiovascular mortality reduction. The effects of these activities have been measured by quality indicators. The aim of this study was to determine the effects of family medicine team training workshop and implementation of clinical guidelines on the cardiovascular risk factors and diseases management in primary health care in the Republic of Srpska/Bosnia and Herzegovina. Methods: The "CardioVascular Risk Assessment and Management" study included a sample of 373 teams from 41 primary health care centres trained to provide adequate services and to compare the quality of cardiovascular risk management before and after the training workshop and implementation of clinical guidelines. The comparison was based on nine project defined performance indicators related to hypertension, type 2 diabetes mellitus, hyperlipidaemia, tobacco smoking and obesity. Results: Significant improvements were observed in six indicators after the training workshop and implementation of guidelines. Target values for blood pressure and HbA1c were achieved in over 80 % of patients (82.12 ± 15.81 vs 84.49 ± 12.71 and 84.49 ± 12.71 vs 85.49 ± 24.55; before and after the training workshop, respectively), while the target values for LDL cholesterol were achieved in 54.98 % ± 20.33 before and 57.64 % ± 16.66 after the training workshop. The number of teams that had less than 20 % of recorded data significantly decreased after the training workshop and guidelines implementation, and adequate recording of all indicators was improved. Conclusion: The training workshop of family medicine teams and implementation of clinical guidelines resulted in significant quality improvement of cardiovascular diseases management in primary health care.

Introduction While medicine shortages are complex, their mitigation is more of a challenge. Prospective risk assessment as a means to mitigate possible shortages, has yet to be applied equally across healthcare settings. The aims of this study have been to: 1) gain insight into risk-prevention against possible medicine shortages among healthcare experts; 2) review existing strategies for minimizing patient-health risks through applied risk assessment; and 3) learn from experiences related to application in practice. Methodology A semi-structured questionnaire focusing on medicine shortages was distributed electronically to members of the European Cooperation in Science and Technology (COST) Action 15105 (28 member countries) and to hospital pharmacists of the European Association of Hospital Pharmacists (EAHP) (including associated healthcare professionals). Their answers were subjected to both qualitative and quantitative analysis (Microsoft Office Excel 2010 and IBM SPSS Statistics®) with descriptive statistics based on the distribution of responses. Their proportional difference was tested by the chi-square test and Fisher's exact test for independence. Differences in the observed ordinal variables were tested by the Mann-Whitney or Kruskal-Wallis test. The qualitative data were tabulated and recombined with the quantitative data to observe, uncover and interpret meanings and patterns. Results The participants (61.7%) are aware of the use of risk assessment procedures as a coping strategy for medicine shortages, and named the particular risk assessment procedure they are familiar with failure mode and effect analysis (FMEA) (26.4%), root cause analysis (RCA) (23.5%), the healthcare FMEA (HFMEA) (14.7%), and the hazard analysis and critical control point (HACCP) (14.7%). Only 29.4% report risk assessment as integrated into mitigation strategy protocols. Risk assessment is typically conducted within multidisciplinary teams (35.3%). Whereas 14.7% participants were aware of legislation stipulating risk assessment implementation in shortages, 88.2% claimed not to have reported their findings to their respective official institutions. 85.3% consider risk assessment a useful mitigation strategy. Conclusion The study indicates a lack of systematically organized tools used to prospectively analyze clinical as well as operationalized risk stemming from medicine shortages in healthcare. There is also a lack of legal instruments and sufficient data confirming the necessity and usefulness of risk assessment in mitigating medicine shortages in Europe.

Introduction. Asthma and obesity are the most common chronic health disorders in children. Although heredity plays a significant role in their development, environmental factors and early exposure have contributed to the increasing incidence of both disorders in recent decades. The aim of the study was to estimate asthma prevalence in schoolchildren in Indjija, Srem District, Serbia, and to investigate differences in nutritional status of children with asthma as well as differences between their nutritional status and prescribed asthma medications. Material and Methods. A cross-sectional retrospective cohort study was conducted at the Primary Health Center in Indjija. Of all the medical records of children aged 6 - 14 years, a cohort of children with asthma was formed. The retrospective study evaluated their nutritional status and the prescribed asthma medications. Results. The prevalence of asthma in children aged 6 - 14 was 6.9%. Children with asthma were significantly more overweight and obese (40.5%) than children without asthma. Boys accounted for 63.7% of children with asthma, with a statistically significant gender difference. Abnormal nutritional status was found in 44.3% of children with asthma and boys with asthma were significantly more obese (23%) compared to girls (7.8%). Overweight and obese children with asthma were not prescribed significantly more medications to relieve asthma symptoms than normal-weight children. Conclusion. The prevalence of asthma among schoolchildren in Indjija was 6.9%. Children with asthma were more likely to be overweight and obese than children without asthma, whereas boys with asthma were significantly more obese than girls. No significant differences were found between their nutritional status and prescribed asthma medications.

Centre for Biomedical Research, Faculty of Medicine, University of Banja Luka, Banja Luka, the Republic of Srpska, Bosnia and Herzegovina. Public Health Institute of the Republic of Srpska, Banja Luka, the Republic of Srpska, Bosnia and Herzegovina. Agency for Certification, Accreditation and Healthcare Quality Improvement of the Republic of Srpska (ASKVA), Banja Luka, the Republic of Srpska, Bosnia and Herzegovina.

Rare diseases ('orphan diseases') (RDs) count for 5000-8000 diseases with low prevalence and most commonly of genetic origin. Although most of rare diseases are manifested in early childhood, many are diagnosed in adults, even in elderly. Common characteristics, such as severity, debilitating and life-threatening features, with the lack of a specific drugs, make the treatment of RD a significant public-health problem. Even though randomized controlled trials (RCTs) are the most ideal design for evaluating new drugs, the aim of this review was to present the aggravating circumstances that development of so-called orphan drugs faces in context of RD. We searched the PubMed/Medline for publications on studies and ethics in RDs and applying of 'omics' technologies in analysing tissue samples at biobanks published between 2010 and 2017. In this review, we presented the most significant obstacles in conducting clinical trials in RD as well as main alternative clinical trial designs aiming to decrease the number of patients recruited with increased access to innovative medicines as many as possible. Furthermore, we have presented the possibility of accessing innovative drugs outside of clinical trials as well as ethics violations by the involvement of the subject in clinical trial. Modern technologies in molecular biology will enable the development of 'precision medicine' aimed at identifying the best therapeutic goal, depending on the genetic and epigenetic factors in the affected person. That is why RD biobanks have great significance in the preservation and distribution of tissue samples, in the research of diagnostic biomarkers and the drug development.

BACKGROUND/AIM Recurrent aphthous stomatitis (RAS) is defined as multifactor immunologic inflammatory lesions in the oral cavity, characterized by painful, recurrent single/multiple, shallow, round or ovoid ulcerations of mucosal tissues. To date, a considerable number of RAS treatment protocols have been suggested, but since the etiology of RAS is idiopathic, these treatment options have symptomatic rather than curative or preventive effect. Recently, it has been suggested that laser therapy could be successfully used as an efficient treatment approach in therapy of RAS. Therefore, the aim of this review was to estimate the effects of laser therapy in treatment of RAS analyzing results of clinical studies published in peer reviewed journals. METHODS The studies published until 31 December 2013 were obtained from the Medline/PubMed, Science Direct and Cochrane Library of the Cochrane Collaboration (CENTRAL) online databases, using following search terms and key words: "laser" AND "recurrent aphthous stomatitis", "laser" AND "aphthous", and "laser" AND "aphthae". In total 4 original research articles met the all required inclusion/exclusion criteria, and were used for this review. The main outcome measures assessed were: a reduction of pain associated with RAS and a reduction in episode duration (faster RAS healing). RESULTS The assessed literature demonstrates the benefits of laser therapy mainly due to immediate analgesia and ability to speed up a RAS healing process. CONCLUSION Even thoughthe assessed literature suggests beneficial outcomes of laser therapy in treatment of RAS, these results should be interpreted with caution. The issues related to the study designs and different sets of laser irradiation parameters of a limited number of available studies with the same treatment outcomes prevent us from making definite conclusions.

Background/Aim. Recurrent aphthous stomatitis (RAS) is defined as multifactor immunologic inflammatory lesions in the oral cavity, characterized by painful, recurrent sin- gle/multiple, shallow, round or ovoid ulcerations of mucosal tissues. To date, a considerable number of RAS treatment protocols have been suggested, but since the etiology of RAS is idiopathic, these treatment options have symptomatic rather than curative or preventive effect. Recently, it has been suggested that laser therapy could be successfully used as an efficient treatment approach in therapy of RAS. Therefore, the aim of this review was to estimate the effects of laser therapy in treatment of RAS analyzing results of clinical stud- ies published in peer reviewed journals. Methods. The stud- ies published until 31 December 2013 were obtained from the Medline/PubMed, Science Direct and Cochrane Library of the Cochrane Collaboration (CENTRAL) online data- bases, using following search terms and key words: "laser" AND "recurrent aphthous stomatitis", "laser" AND "aphthous", and "laser" AND "aphthae". In total 4 original research articles met the all required inclusion/exclusion cri- teria, and were used for this review. The main outcome measures assessed were: a reduction of pain associated with RAS and a reduction in episode duration (faster RAS healing). Results. The assessed literature demonstrates the benefits of laser therapy mainly due to immediate analgesia and ability to speed up a RAS healing process. Conclusion. Even though the assessed literature suggests beneficial outcomes of laser therapy in treatment of RAS, these results should be inter- preted with caution. The issues related to the study designs and different sets of laser irradiation parameters of a limited number of available studies with the same treatment out- comes prevent us from making definite conclusions.