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Introduction: Prior to the 1990s, the most common sources of HCV infections were blood transfusions, unsafe injections and I.V drug use. Screening of blood products for HCV has eradicated transfusion-transmitted hepatitis C in most countries since 1992–in Bosnia and Herzegovina, however, since 1995, due to the war. Aim: To investigate the impact of the source of HCV infection on the therapeutic response in patients treated for chronic HCV infection with dual combined therapy. Methods: We diagnosed chronic HCV infections amongst 246 patients over a period of five years and selected them according to the reported source of infection. Pegylated interferon alfa 2a or alfa 2b with ribavirin was administered during the time that was genotype-dependent. HCV RNA levels in sera were measured by real time PCR. Liver histology was evaluated in accordance with the level of necroinflammation activity and the stadium of fibrosis. Results: Regardless of the genotype of the virus and the source of infection, SVR was achieved in 67% of the patients. Therapeutic response (ETR) was not achieved in 25% of the patients who were infected with an untested blood transfusion and 6% of the patients who had had wartime surgery. Amongst the different sources of infections, patients with a war-surgery source of infection responded better to therapy than those with a blood transfusion source of infection (p = 0.023). A blood transfusion source of infection implies a larger fibrosis stage than in blood donors; (g = 1.177; s2 = 0.577). A blood transfusion source of infection implies a significantly larger necroinflammatory activity than in blood donors; (g = 1.456; s2 = 0.618). Conclusions: An untested blood transfusion was a significant risk factor for more advanced liver diseases in regards to necroinflammatory activity and the fibrosis stage. This source of infection was also a risk factor for low responses to antiviral therapy. At the same time, I.V. drug users had more progressive necroinflammatory activity, but a high therapeutic response to antiviral therapy.

Elmedin Bajrić, S. Kobašlija, A. Huseinbegović, Mediha Selimović-Dragaš, A. Muratbegović, N. Marković

Background: Dental fear and anxiety (DFA) are present worldwide globally, as well as in children. These psychological clinical entities in its progressive phase lead to avoiding of dentists and dental appointments, and consequtive impairments of oral health. If we ignore these facts, we would have the strenghtening of this relationship in a way of further oral health impairments and lost of dental hard and soft tissues, as well as appearance of dental phobia as the most negative form of psychological reaction to dental stimuli. Original CFSS-DS scale and its modifications, as the most used instruments for evaluation of DFA presence so far, showed various disadvantages. These were the reasons why we wanted to design new psychometric instrument for better evaluation of DFA presence in children compared to evaluation which the existed scales could offer nowadays, in a form of the Modified Version of CFSS-DS scale (CFSS-DS-mod scale). Materials and methods: There were 809 schoolchildren from 8 cities of Bosnia and Herzegovina aged 9-12 years that participated in the study. There was one school per city where the schoolchildren answered to the questions from the CFSS-DS-mod scale. Results: 636 schoolchildren correctly answered to the scale questions. The CFSS-DS-mod scale showed excellent internal consistency reliability values (with Cronbach α>0.9), and also validity results (mostly over 60% of explained variance of obtained results) with two-dimensional concept of DFA presence. Conclusion: The CFSS-DS-mod scale represents good psychometric instrument for evaluation of the DFA presence in 9-12 year old schoolchildren in Bosnia and Herzegovina. Some of normative values of this psychometric instrument should be determined, in order to expand its usage in children.

D. Pérez, L. Stojanovich, L. Naranjo, N. Stanisavljevic, G. Bogdanovic, M. Serrano, A. Serrano

Background Several manifestations strongly associated with APS have been excluded as classification criteria.1 2 Objectives The aim of this study was to investigate correlation between circulating immune-complexes of IgG or IgM antibodies bound to B2GPI (B2G-CIC and B2M-CIC) and clinical manifestations in Serbian cohort of APS patients. Methods A total of 57 patients with APS were evaluated: 35 with PAPS and 22 patients with SAPS. Mean age was 47.6±1.6 years; 36 (63.2%) were women. All patients have met the 2006 revised Sydney criteria for APSQuantification of B2G-CIC and B2M-CIC levels was performed as previously, for detect B2G-CIC was used anti-human IgG HRP-conjugate and for B2M-CIC human IgM HRP- conjugate, both from INOVA (INOVA Diagnostics Inc., San Diego, CA, USA). Results In our cohort Serbian APS patients the prevalence of CIC was 19.29% (11/57); 8 patients with B2M-CIC and the remain 3 patients with B2G-CIC. Livedo reticularis was diagnosed with higher prevalence in patients with CIC compared with patients without CIC; 63.6% and 23.9%, respectively (OR: 5.57, p=0.01). In patients with CIC, thrombocytopenia and leukopenia were more prominent; 54.4% vs 17.4% (OR: 5.70, p=0.01) and 45.5% vs 13.0% (OR: 5.56, p=0.01), respectively. Ophthalmic sicca was more prevalent in patients with CIC; 54.4% vs 8.7% (OR: 12.6, p<0.001). Although complement consumption was more frequent in patients with CIC (figure 1). Figure 1 Mean levels of C3 (A) and C4 (B) complement in groups. Mean levels of C3 (115.6±9.2 mg/dL and 140.9±4.3 mg/dL, group-1 and group-2 respectively) and mean levels of C4 (140.9±4.3 mg/dL and 30.8±1.6 mg/dL, group-1 and group-2, respectively). Conclusions B2G-CIC and B2M-CIC are strongly associated with clinical manifestations related to APS. Widening the APS spectrum is indispensable to better understand this syndrome. References [1] Stojanovich L, Kontic M, Djokovic A, Marisavljevic D, Ilijevski N, Stanisavljevic N, et al. Association between systemic non-criteria APS manifestations and antibody type and level: results from the Serbian national cohort study. Clin Exp Rheumatol. 2013 Mar-Apr;31(2):234–42. [2] Stojanovich L, Markovic O, Marisavljevic D, Elezovic I, Ilijevski N, Stanisavljevic N. Influence of antiphospholipid antibody levels and type on thrombotic manifestations: results from the Serbian National Cohort Study. Lupus. 2012Mar;21(3):338–45. Acknowledgements This work was supported by research grant number 175041, and TR 32040 for 2011–2018, issued by the Ministry of Science of the Republic of Serbia. Disclosure of Interest None declared

F. Koopman, A. Musters, M. J. Backer, D. Gerlag, S. Miljko, S. Grazio, S. Sokolovic, Y. Levine et al.

Background: Rheumatoid arthritis (RA) is a debilitating chronic disease with an unmet need for additional therapeutic approaches. Activating neuro-immune reflex pathways by stimulation of the vagus nerve (VNS) could represent a novel means of treating RA [1] and other immune-mediated inflammatory diseases. Last year we reported a 12-week proof-of-concept study using a VNS device, approved for drug-resistant epilepsy, showing reduction in the DAS28-CRP clinical disease activity score, with concomitant reductions in TNF and IL-6 levels [2]. Objectives: To understand the long term safety and efficacy of this novel treatment approach, we followed the patients in a 24 months long-term extension study and report on the safety and clinical efficacy data. Methods: VNS devices were implanted into 17 RA patients, mostly with insufficient response to multiple conventional and biologic disease-modifying antirheumatic drugs (DMARDs), on stable background of methotrexate (≤25 mg weekly) therapy. The devices electrically stimulated the vagus nerve, 1–4 min/day, over a 12 week open label period. On completion, subjects were offered to enroll into a follow-up study, where the study physicians were given flexibility to alter VNS dosing parameters and/or to add a biologic DMARD to the treatment regimen. DAS28-CRP and Health Assessment Questionnaire-Disability Index (HAQ-DI) were collected over 2 years. Results: All subjects electively continued on VNS treatment through 24 months of the long term follow-up study. Biologic DMARDs were started in 1 and restarted in 8 of 17 subjects; of these, 4 were non-responders to VNS, and 5 had stable improvement but had not yet achieved disease remission on VNS alone (table 1). At the start of the follow-up study, the mean DAS28–28 and HAQ-DI were significantly reduced compared to the pre-implant baseline (mean difference±SE in DAS28-CRP=-1.60±0.37, p<0.0001; mean difference±SE in HAQ-DI = -0.44±0.21, p<0.037), and the depth of effect was retained through 24 months. At 24 months, there was no significant difference in DAS28-CRP between the subjects using VNS monotherapy or those using a combination of VNS and biologic DMARDs (VNS monotherapy= 3.76±1.77 vs. VNS and biologic DMARD= 3.21±1.44, p<0.54). No difference in the adverse events profile between the two groups was seen.Table 1 Two Year Efficacy of VNS Treatment. Mean DAS28-CRP at primary study baseline (month -3-5) and at visits over 2 years of long term follow up (months 0-24). Conclusions: The data presented here demonstrate that VNS in subjects with RA is associated with a substantial reduction in disease activity that is sustained for 24 months without untoward safety signals. In addition, the data suggest that biological DMARDs can be initiated safely in combination with VNS treatment, though this requires further study in larger cohorts. These results support further development of VNS devices as an alternative therapeutic approach for RA treatment, which potentially can safely be combined with biologic DMARDs. References [1]Van Maanen M, et al. The cholinergic anti-inflammatory pathway: towards innovative treatment of rheumatoid arthritis. Nat Rev Rheumatol2009;5:229–32. [2]Koopman FA, et al. Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis. Proc Natl Acad Sci USA2016;113(29):8284–9. Disclosure of Interest: F. Koopman: None declared, A. Musters: None declared, M. Backer: None declared, D. Gerlag Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, which has an interest in SetPoint, S. Miljko: None declared, S. Grazio: None declared, S. Sokolovic: None declared, Y. Levine Shareholder of: SetPoint Medical, Employee of: SetPoint Medical, D. Chernoff Shareholder of: SetPoint Medical, Adamas Pharmaceuticals, OLLY Nutrition, NAIA Pharma, Aquinox Pharma, Consultant for: Adamas Pharmaceuticals, OLLY Nutrition, NAIA Pharma, Aquinox Pharma, Crescendo BioScience, Employee of: SetPoint Medical, N. de Vries Grant/research support from: Abbvie, Janssen Biologics BV, Ergomed Clinical Research, GlaxoSmithKline, Pfizer, Boehringer Ingelheim, Roche, Consultant for: MSD, Pfizer, P.-P. Tak Shareholder of: GlaxoSmithKline, Employee of: GlaxoSmithKline, which has an interest in SetPoint

D. Kuiš, Ivan Matoš, I. Mišković, Filip Matija Vuković, J. Prpić

Abstract This paper uses a DEA-VRS methodology for the estimation of municipal efficiency to provide empirical evidence of the impact of decentralization in BiH under the Dayton Peace Agreement (DPA) on overall municipal efficiency. In particular, the paper focuses on the analysis of the overall efficiency of 33 new municipalities established under DPA. The findings suggest that the average municipal efficiency in BiH is rather low, and only 23 or 16% of municipalities in BiH are efficient. The average efficiency achieved is around 0.71. This means that with the same level of inputs (budget revenue) outputs may be increased by almost 30%, on average. The results of DEA-VRS efficiency estimation suggest that new municipalities have lower average efficiency (0.60) in comparison to “older” municipalities (0.74). In our sample, only six percent of newly created municipalities are efficient, 12% exhibit some level of efficiency, while the remaining 82% are inefficient, with significant share (39%) of very inefficient municipalities

Introduction: Neuropathic pain resulting from injury to the nervous system. Up to 7% to 8% of the European population is affected. A number of different treatments for neuropathic pain have been studied including antiepileptic. Pregabalin and gabapentin are often considered first-line treatments. Pregabalin provides equivalent efficacy to gabapentin, showing greater potency at much lower doses and is considered as cost-effective intervention. In Federation of Bosnia and Herzegovina (FB&H), gabapentin is fully reimbursed, while pregabalin is enlisted on list B with copayment. Aim: To develop simple budget impact (BI) model and assess BI of introducing pregabalin into full reimbursement in FB&H. Material and methods: Budget impact model was developed using Microsoft Excel 2010. Local epidemiology data and data on drug consumption from government reports in 2016 were used. Two scenarios with three-year time horizon have been developed: 1) without and 2) with pregabalin reimbursed at the same level as gabapentin. Two developed scenarios have been compared from health insurance fund (HIF) perspective. Results: In scenario 1 consider both drugs fully reimbursement and without patient switch among alternatives the total cost would be increased for 780,025 KM; 852,027 KM and 943,830 KM over a 3-year period. In scenario 2 considering both drugs fully reimbursed but with patient switch topregabalin total annual cost would be increased for 732,241 KM; 742,395 KM and 751,761 KM. Comparing scenario 1 and 2 it is found that scenario 2 is more favorable from HIF perspective. Conclusion: Implementation of pharmacoeconomic principles in reimbursement decisions in Bosnia and Herzegovina would improve access to medicines and contribute rationale resource consumption.

V. Causevic, A. Falsone, D. Ioli, M. Prandini

We address a cooling energy management problem in a multi-building setting where buildings need to maintain comfort conditions for the occupants by keeping their zones temperature within a certain range. To this purpose, each one of them has its own chiller and is connected to a shared cooling network. The goal is to minimize the overall district electricity cost over some finite time horizon by optimally setting the temperature set-points in the buildings and the energy exchange with the cooling network, compatibly with comfort and actuation constraints, while accounting for uncertainty, mainly due to outside temperature, people occupancy, and solar radiation. To this purpose, a distributed version of the scenario approach to stochastic constrained optimization is adopted, which allows to guarantee by design a predefined robustness level of the obtained solution against uncertainty.

U. Glamočlija, B. Tubić, Martin Kondža, Aleksandar Zolak, N. Grubiša

Aim To compare individual case safety reports (ICSR) rates and characteristics between Croatia, Serbia, Montenegro, and Bosnia and Herzegovina (B&H). Methods This retrospective pharmacoepidemiological study used the data from ICSR received by the Agency for Medicines and Medical Devices in B&H in 2011-2016. The number, characteristics, and sources of reports, suspected drugs, and patient characteristics were analyzed. The results were compared with the publicly available data from Croatia, Serbia, and Montenegro. Results The number of reported adverse drug reactions per one million of inhabitants was lowest in B&H and highest in Croatia. There were significant differences in reporter characteristics, sources of reports, and the percentage of missing data in ICSR, while the Anatomical Therapeutic Chemical product classes, patient’s sex, and adverse drug reaction System Organ Classes were similar. Conclusion Despite the historical and geographical vicinity of B&H and its neighboring countries, there were significant differences in indicators of pharmacovigilance development.

Z. Pilić, Herzegovina

The effect of the aqueous extract of Achillea millefolium L . (AM) on the electrochemical behaviour of iron in a simulated acid rain solution (pH 4.5) was studied by electrochemical techniques cyclic voltammetry, potentiodynamic polarization and electrochemical impedance spectroscopy. Experiments were carried out over a wide range of AM concentrations. The results of all techniques showed that AM extract contributes to iron passivation. The films formed in the presence of AM extract were thinner and more resistive then the films formed in pure simulated acid rain solution. The AM extract adsorbed on the iron according to the Freundlich isotherm. The thermodynamic data indicated physical adsorption of the AM extracts on the iron surface. The concentration of the metallic ions released into solution, measured by atomic absorption spectroscopy, was in accordance with the results obtained from the electrochemical techniques.

Background: The gene for 5,10-methylenetetrahydrofolate reductase (NAD(P)H) or MTHFR gene encodes protein methylenetetrahydrofolate reductase (MTHFR), an enzyme important in folate metabolism. Aim: The aim of this study was to determine the frequencies of 677C>T and 1298A>C polymorphisms in the MTHFR gene of healthy subjects from the population. Material and methods: The blood samples were collected from 164 unrelated and healthy donors from population consisted of 98 females and 66 males. Both the MTHFR 677C>T and 1298A>C single nucleotide polymorphisms (SNPs) were analyzed by Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Linkage disequilibrium (LD) between pair of SNPs was calculated through Haploview analysis. Results: The frequency of MTHFR 677T allele in the population (32.62%) was in agreement with the frequency of this allele in most other populations, however, the frequency of MTHFR 1298C allele (38.41%) was higher than that reported for most other populations in the world. Haploview analysis showed a relatively strong LD between 677C>T and 1298A>C SNPs with D′ values of 0.87. Conclusion: Regarding the two MTHFR polymorphisms, three of the nine combined genotypes were present in 87.2% of the population. 33.54% subjects were complex heterozygous (677CT/1298AC genotype), 34.15% subjects had 677CC/1298AC and 19.51% of 677CT/1298AA genotype. The subjects with 677TT genotype had a 1298AA or 1298AC genotype while subjects with 1298CC genotype had only 677CC genotype. The subjects with 677CC/1298AA genotype were only 3.05%. We were not found triple 677CT/1298CC and quadruple 677TT/1298CC mutation suggesting decreased viability of embryos with increased numbers of mutant alleles.

Denis Jurečić, Vilko Žiljak, M. Kudumovic, Božica Kelčec Pester, Herzegovina

In the article is presented the design for security graphics on packaging with invisible information. The color choice is underlined by the INFRAREDESIGN® theory. Individual solutions for joining two independent images are realized with digital printing and interpreted with computer animation. Separation of the dye is performed for the default response of the hidden drawing that is released by the infrared camera. Product recognition is with IRD process as a "visual information identity". Hidden graphics are designed with a protective line solution. Experiments have been carried out in the pharmaceutical field, on the packaging of drugs. Proving the authenticity of the content is carried out by recording the packaging and comparing it with the specimen that was recorded as photographs of the twenty light blockades in the visual and infrared spectrum.

V. Becirovic, S. Smaka, Roko Jerčić, S. Hanjalic, V. Helać

Phasor estimation is an essential task in power system since the voltage angle and voltage RMS determine the available active power and its flow. This paper proposes fast and simple algorithm for harmonic phasor estimation in a three-phase system. Harmonics are considered the most serious power quality (PQ) problem in the emerging scenario with a growing proportion of power electronic based devices in the power system. The algorithm is based on well-known mathematical transform and recommendations given in relevant IEC and IEEE standards. The presented algorithm can be used to generate input data for Harmonic State Estimation.

V. Becirovic, V. Helać, S. Hanjalic, S. Smaka, H. Šamić

The paper describes a photovoltaic system (PVS) composed of a group of photovoltaic (PV) panels and presents the initial evaluation of power quality (PQ) in the low-power microgrid connected to these PV panels. This PVS is called solar tree and it is built as a research platform at our faculty to conduct teaching and research on renewable energy sources. The solar tree can operate in two modes: on-grid and off-grid (autonomous operation). An off-grid mode was analysed and experiments were carried out in order to determine the maximum power that can be delivered to the load connected to this autonomous photovoltaic system (APVS). Also, the various consumer's responses to a sudden load changes in this APVS were analysed. The experiments were carried out by using modern power quality monitoring devices and PQ of this single-phase APVS with energy storage is examined in terms of compatibility with the relevant international standards.

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