Treatment non-adherence for chronic diseases such as diabetes is a common problem. The aim of the study was to assess the pattern of non-adherence among among type 2 diabetic patients in Republic of Srpska. Medication non-adherence was measured using pill counts in primary care setting. Univariate and multivariate logistic regression model was used to identify factors related to non-adherence. The study was approved by the Ethical Committees of the Medical Faculty in Novi Sad. Participants have signed an informed consent. Among the total of 323 publicly insured type 2 diabetic patients (mean age 66.5±10.6) the prevalence of non-adherence was 47,7%. About 40% patients were on metformin monotherapy and 37% on metformin/sulphonylurea based combination therapy. Although univariate logistic regression model analysis revealed that the presence of lower education (B=–0.479; p<0.001), widowed patients (B=0.704; p=0.007), longer duration od diabetes (B=0.445; p=0.001), higher BMI (B=0.508; p=0.020), copayments for prescriptions (B=0.727; p=0.001) were significantly associated with non-adherence, whereas in a multivariate logistic regression model analysis only patients with copayments were 1.9 fold more likely to be non-adherent (OR=1.89, B=0.637; p=0.015) than those without copayment for presciption. The present study revealed that publicly insured patients with type 2 diabetes could be especially susceptible to medication non-adherence when copayment is required. Patients with copayments were about two fold more likely to be non-adherent than those without copayment for presciption. Policy-makers should be wary of potential negative clinical outcomes resulting from non-adherence.

A substantial evidence has shown that the general community plays a role in the increase and spread of antibiotic resistance. Thus, the objective of this study was to determine the public knowledge, beliefs, and behavior regarding the use of antibiotics in Serbia. The survey was conducted on a random sample of 325 adult subjects who consulted general practitioners (GP) at health centers. A self-administered questionnaire included questions on demographic characteristics, knowledge about antibiotics, beliefs and behaviours toward antibiotic use. The study was approved by the Ethical Committees of the Medical Faculty in Novi Sad and the Health Center Bačka Topola.Participants have signed an informed consent. A total of 253 adults participated. The average age was 50.56 ± 17.05 years, and 64.82% of the respondents were women. The mean antibiotic knowledge score was 8.77±2.27. Respondents with with higher education, employed, with a family member working in the heath care sector were significantly more knowledgeable of antibiotics (p<0.001). Overall, 47.83% of respondents believed that antibiotics could be used to treat common cold. 86.56% believed that frequent and inappropriate antibiotic use was dangerous Among the respondents, 31.62% stated that they used antibiotics without previous physicians’ consultation (self-medication). Although 85% of respondents claimed that antibiotic treatment should be taken as long as their GP prescribed (knowledge), only 61% followed this advice during the last infection (behaviour). Respondents had a relatively adequate knowledge about antibiotics (scoring 8.77 out of maximum 13). However, in further rationalization of the use of antibiotics, effective public education initiative should provide practical and appropriative means to change their behavior.

Consumption and expenditure of drugs for malignancy varies between countries. One of the main reason is the high price of this innovative drugs. Developed countries have more resources for the treatment of malignant diseases and better access to expensive drugs than countries with midle income. We compared the data on expenditure and consumption of innovative anticancer drugs in middle income country Serbia (13,020 USD), and high income country with different GDP: Slovakia (26,497USD) and Norway (64,406 USD) during the year 2012. Consumption data were expressed in grams of active ingredient per million in one year, expenditure in EU. In Norway 144 drugs for malignancy is on market, while in Serbia only 92 drugs are available for ttreatemnt of malignancy. In Norway in year 2012 440 million eur was spent for drugs for malignancy, or about 80 million euros per million inhabitans. Slovakia had more than half lower consumption of anticancer medicines, 190 million euros, or about 37 million euros per million inhabitants. In Serbia only 73 million euros was spent for anticancer drugs, or about 10 million euros per million ihabitants, which is much less compared to the other two countries. Data on consumption 10 most expensive oncology drugs, show that the least of these drugs are consumed in Serbia when comparing to Norway and Slovakia. Among them, the most frequently used drug in Serbia is trastuzumab(treatment of metastatic breast cancer). For this indication is also marketed lapatinib, which has the highest consumption among the most expensive drugs in Norway and Slovakia. Countries with lower GDP have less availability of anticancer medicines in amount and in quantity. Countries with lower GDP must control the usage of drugs for malignancy treatemnt if they want to allocated their resurses for treatment of other diseases as well.

Consumption of drugs for malignancy treatment varies between countries. Developed countries have higher allocations for health protection, more resources for the treatment of malignant diseases and better access to expensive drugs.

Background: Pre-emptive strategies have been suggested as a desirable and efficient way to implement pharmacogenetics in the routine clinical practice.In order to obtain the best possible evidence we have designed a randomized pragmatic "proof-of-concept" clinical trial to test this strategy.Design: Five groups of predefined patients expecting to receive the target treatment will be recruited in this multicentre study.In the initial visit all patients will be genotyped after informed consent has been obtained.Those patients receiving the target treatment and carring the target mutation(s) will be under stratified randomization to: 1) Pharmacogenetic arm: doctor will contact with the Pharmacogenetic Unit (PGx Unit) to obtain a prescription/dosing recommendation mainly based in reviews from CPIC and DPWP (http://www.pharmgkb.org);2) Control arm: patients will be treated as usual without pharmacogenetic information.Selection Criteria: patients to be enrolled are: 1) Metastatic/advanced colorectal cancer, 2) High risk cardiovascular patients, 3) Patients under bone marrow transplant, 4) Patients with major unipolar depression and 5) Post-surgery patients.Target Drug and Biomarker(s) Pairs for Each Group: 1) fluoropyrimidines-DPYD and irinotecan-UGT1A1, 2) high dose statins-SLCO1B1, 3) voriconazole-CYP2C19, 4) SSRIs-CYP2D6 and 5) tramadol/oxicodone-CYP2D6. Outcomes: 1) neutropenia and gastrointestinal toxicity, 2) myopathy, 3) lack of efficacy (persistent fever), 4) lack of efficacy (need to switch therapies) and 5) lack of efficacy (need of rescue medication) or toxicity (gastrointestinal toxicity).Genotype Assay: We will use an Open Array® technology (Life Technologies Corporation) designed and patented by our group (PharmArray®, Application MC011608403).It allows to genotype 192 SNPs from 57 genes.The cost per patient, including DNA extraction, is 23 € .Conclusions: This "proof of concept" clinical trial will allow to test in a risky selected population the effectiveness of a preemptive pharmacogenetic strategy and it implementation in clinical practice.

Uncomplicated urinary tract (UTI) infections are the commonest bacterial infections in community. Recently ciprofloxacin has become a popular treatment option. However, with increasing resistance to ciprofloxacin, adequacy of current dosing regimens became questionable.

Respiratory diseases, including asthma and chronic obstructive pulmonary disease (COPD), cause about 1 million deaths annually in the WHO European Region. Xanthines (e.g. theophylline, aminophylline) are recommended for treating severe exacerbations of COPD, when short-acting bronchodilators do not produce adequate response. The aim of this study was to compare use of xanthines in the treatment of chronic respiratory diseases between Serbia and the Scandinavian countries in the period from 2004 to 2013. The data on utilization of drugs for obstructive airway diseases (ATC group R03) during the ten-year period (2004-2013) were retrieved by a retrospective, observational, population-based study, from the Medicines and Medical Devices Agency of Serbia, Finnish Medicines Agency Fimea, Danish Statens Serum Institut and Norwegian Institute of Public Health. ATC/DDD methodology was applied and the results were expressed in defined daily doses per 1000 inhabitants per day (DID). While the utilization of xanthines (R03DA) showed a significant tendency to decrease in all Scandinavian countries during the whole observed period of time (4.4-fold in Denmark, 3.46-fold in Norway and 2.38-fold in Finland), in Serbia on the other hand, xanthines represented the most used drugs in the R03 group, with no clear decrease tendency. In 2013, xanthines accounted for less than 2% of total use of drugs in R03 group in Finland, Norway and Denmark (1.25 DID, 0.61 DID and 0.50 DID, respectively), versus 26% (7.11 DID) in Serbia. The large differences in utilization of xanthines between Serbia and other observed countries may suggest considerable lower number of exacerbations of COPD in the Scandinavian countries due to better control of chronic respiratory diseases.

Cefaclor was one of the commonly used antimicrobials in Serbia, but due to fast development of resistance, other oral cephalosporins rapidly upstaged cefaclor and cefaclor was removed from the list of the drugs reimbursed by the National Health Insurance Fund. Use of recommended dosing regimen (250-500mg/8-12h) is likely to result in sub-therapeutic concentrations for a wide portion of dosing interval due to short half-life of cefaclor, which may facilitate development of resistance. The aim of this study was to determine adequate dosing interval for cefaclor in treatment of systemic infections using Pharmacokinetic (PK) and pharmacodznamic (PD) parameters with special regard to postantibiotic effect (PAE). PK profile of cefaclor in healthy volunteers and PK/PD indices relating to efficacy of cephalosporins were determined, as well as minimum inhibitory concentration (MIC) and PAE of cefaclor on 4 susceptible bacteria. Cmax of 23.142 ± 5.67 µg/mL was measured after 40-60 minutes. Tmax was 0.72 ± 0.13 hours. Calculated AUC(0-t) was 29.148 ± 9.27 µg/mL/h. MICs were in range of 1-2 µg/mL. Cefaclor induced PAE of 1-2h. There was inconsistency between standard dosing regimen and PK/PD parameters. Main PK/PD index relating to efficacy of cephalosporins (%t>MIC) for the 750mg dose was 33.5–42.1%. PK/PD breakpoints for cefaclor were between 0.3-1µg/mL. Even the maximum doze with standard dosing intervals is not appropriate for eradication of susceptible organisms. Short PAE can't compensate for sub-inhibitory concentrations at the half of the dosing interval. In reference to PK/PD parameters cefaclor should be administered every 6h for the doses of 500mg and 750mg, and every 4-4.5h for the 250mg dose in order to maximize its therapeutic efficacy and minimize development of resistance.

Hypertension is one of the major risk factors for occurrence cardiovascular disease. Drugs of the first choice in the treatment of hypertension are: diuretics, beta adrenergic blockers, calcium channel blockers, angiotensin converting enzyme inhibitors and inhibitors of angiotensin II receptor. Fixed combinations of antihypertensive drugs simplify treatment and enhance patient compliance. The aim of this study was to analyze consumption fixed combinations of drugs for the treatment of hypertension in the Republic of Serbia in the 2011-2012 year and to compared it with the results of Finland and Norway in the same period. Consumption of officinals is expressed by the number of defined daily doses per 1000 inhabitants per day (DDD) according to the anatomical therapeutic chemical classification. Data on consumption of drugs are taken from the official web site for the period 2007– 2012. year from the Agency for drugs and medical devices of Serbia, Finnish Medicines Agency Fima and Norwegian Institute of Public Health. Fixed combination of converting enzyme inhibitors with diuretics are most frequently used drugs in Serbia (2007 (18,86 DDD), 2008 (26,61 DDD), 2009 (30,77 DDD), 2010 (27,30 DDD), 2011 (43,72 DDD) and 2012 (55,52 DDD)) compared with Norway and Finland. The use of these drugs is on the rise in Serbia. In the opposite side use of angiotensin II antagonists and diuretics in Serbia is significantly lower (2007 (0,10 DDD), 2008 (0,07 DDD), 2009 (0,12 DDD), 2010 (0,19 DDD), 2011 (0,73 DDD) and 2012 (1,70 DDD)) compared with Norway and Finland. Based on the results, we concluded that the use of fixed combination of drugs in therapy of hypertension in Serbia must be modified. This research was supported by Provincial Secretariat for Science and Technological Development, Autonomous Province of Vojvodina project No 114-451-2458/2011 and by Ministry of Science, Republic of Serbia, project no 41012

Arterial hypertension represents a major cause of morbidity and mortality among elderly population in Novi Sad, Serbia. The aim of this study was to analyze patterns and address financial aspects of antihypertensive drug utilization among elderly outpatients (>60). Data on antihypertensive issued on prescription were collected from all state-owned pharmacies in Novi Sad (population 350,000) from September 2011 to February 2012. Consumption was calculated using the ATC/DDD methodology, and results were expressed in DDD/1000 inhabitants/day. DU90% (drug utilization 90%) segment and price per DDD were determined. The total use of antihypertensives among population >60 years in Novi Sad, Serbia was 203.1 DDD/1000inh/day. ACE inhibitors were the most frequently used drugs and accounted for 58.44% of total consumption, followed by calcium channel blockers (23.51%) and beta-blockers (11.10%). Consumption of diuretics (4.29%) and angiotensin receptor antagonists (<3%) was low. High use of ACE inhibitors was also reflected in DU90% profile. Even though most commonly prescribed drug was amlodipine (18.49%), out of 16 drugs within DU90% segment, 10 were ACE inhibitors or ACE inhibitors/diuretics fixed combinations. Average price per DDD within DU90% was 0.09 euro per DDD whereas it was 0.12 euro per DDD for drugs beyond the DU90% segment. High consumption of ACE inhibitors and disregard to other antihypertensive agents points to therapeutic irrationalities which can have considerable clinical and economic consequences. Targeted education may both improve efficacy of treatment of hypertension in elderly and provide significant savings. Acknowledgement: This work was supported by the Ministry of Science and Technological Development, Republic of Serbia, project No. 41012.

Therapy of acute lymphoblastic leukemia includes the use of high doses of glucocorticoides (prednisone and dexamethasone), which significantly increase the success of therapy because of its limphocitolitic.

Diuretics are drugs of first choice in the treatment of hypertension. The aim of this study was to analyze the consumption of diuretics in Serbia in the period from 2008 to 2012 year. The data about the use of drugs were taken from the Agency for Drugs and Medical Devices of the Serbia. The use of diuretics during the observed period in Serbia is quite small and it ranged from 5 to 6% of the total consumption of all drugs from the C group. Furosemide was the most frequently used diuretic from 2008-2010. In the observed period consumption of furosemide ranged about 61 % of the total consumption of all diuretics. On the second place in consupmtion during first three years of the study was indapamide. Indapamid records decline in consumption in next two years. In 2011. and 2012. hydrochlorothiazide takes second place in consumption and marks a possitive trend. In 2012. it ranged 7.92 DDD/1000 inh/day. Spironolactone takes the fourth position in the first three years. During the 2011. and 2012. consumption of spironolactone has increased and took the third position in consumption. Consumption of all other diuretics was small. In Serbia, in the observed period, consumption of diuterics were uneven. It is two to three times lower in comparison with the consumption of diuretics in Norway and Finland. This research was supported by Provincial Secretariat for Science and Technological Development, Autonomous Province of Vojvodina project No 114-451-2458/2011 and by Ministry of Science, Republic of Serbia, project no 41012.

Benzodiazepines (BZD) are often administered to patients with arterial hypertension in addition to antihypertensive agents. The aim of this study was to analyze patterns of BSD usage among hypertensive outpatients in Serbia according to sex and age. Data on BZD issued on prescription for the International classification of diseases (ICD) code I10 (essential arterial hypertension) were collected from all state-owned pharmacies in Novi Sad (population 350,000) from September 2011 to February 2012. Consumption was calculated using the ATC/DDD methodology. BZD accounted for 2% of all drugs issued in treatment of hypertension. The total amount of BZD issued was 2.27 DDD/1000inh/day. Bromazepam (51.38 %) and diazepam (37.56 %) were the most commonly used BSD and accounted for almost 90% of all BSD utilized. Lorazepam accounted for 8.36% of total consumption. Other agents (alprazolam, nitrazepam, midazolam, klonazepam) accounted for less than 3% altogether. The BZD consumption increased with patient’s age – 91% being prescribed to the patients over the age of 50. Consumption was highest in age group 70-80 years. BZD were more often prescribed to female (68.63%) than to male outpatients (31.37%). This study confirmed consumption of BZD among outpatients with hypertension. It is most common in hypertensive female and elderly population. However, since the benefits of BZD administration in hypertension control remain unclear, the adequacy of this practice is questionable. This work was supported by the Ministry of Science and Technological Development, Republic of Serbia, project No. 41012.

Medications in households offer a variety of opportunities for irrational consumption and development of adverse drug reactions (ADR). One of the medicines most commonly associated with ADR are non-steroidal anti-inflammatory drugs (NSAIDs), one of the most frequently used medications in Serbia. Therefore, the aim of this study was to analyze the amount and structure of NSAIDs present in household drug supplies, and address the issue of possible inadequate use. This was an observational, cross-sectional study of drug storage and self-medication practice in households in the city of Novi Sad, Serbia over the 8 months period. Study consisted of personal insight into the drug inventory, and drugs were classified according the Anatomical Therapeutic Chemical (ATC) classification system. Out of 383 surveyed households, 280/383 (73%) households held at least one box of NSAID in their home-pharmacy and a total of 473 packages of NSAID have been inventored. Most commonly encountered NSAIDs were ibuprofen (52.64%), diclofenac (31.92%), nimesulide (8.03%) and meloxicam (3.38%). Other NSAIDs accounted for less than 4% altogether. Over 70% of all NSAIDs present have been bought without prescription. Majority of ibuprfoen (91.3%) and diclofenac (65.74%) were obtained without a prescription even though in Serbia all NSAIDs (except ibuprofen 200mg) are prescription only medication (POM). According to European Medicine Agency, ibuprofen is classified as OTC, but diclofenac is strictly POM. Large amount of diclofenac used without consulting a physician presents a serious issue. Nimesulide and meloxicam were almost exclusively bought with prescription (>80%). NSAIDs were present in most of Serbian home-pharmacies and were usually bought without prescription. This present a serious problem, especially for unsupervized diclofenac use. Financial Sources: This work was supported by the Ministry of Science and Technological Development, Republic of Serbia, project No. 41012.

Was to determine the percentage of drug interactions' risk in elderly population receiving three or more drugs at the same time, also and degree of risk of severe, moderate and mild interactions. This study was retrospectively-observational. The study included 50 patients of both genders, aged at least 65 years, who were treated in the first half 2012th in the Health Center Novi Sad which prescribed three or more drugs. Three sources of information about possible drug interactions were used: www.drugs.com, British National Formulary (BNF) and SPC of drug. The study included a total of 50 patients with mean age of 73.62 years. According to the number of possible drug interactions, most of them were from BNF (n = 204 or 45.43% compared to the number of possible drug combinations), then www.drugs.com (n = 203 or 45.21%) and from SPC source were significantly less (n = 150 or 33.40%). In relation to the degree of relevancy of drug interactions, according to the source www.drugs.com, the incidence of serious interactions was 3%, 29% moderate and 13% mild. Out of 50 patients analyzed, only in 9 patients (18%) were found complete compatibility in the number of interactions in all three data sources. A significantly higher number of interactions were at the level of pharmacodynamic (167 or 77.68%). With the increasing number of taken drugs at the same time, increases the total number of interactions with a correlation coefficient of 0.71. Publications and Internet could provide useful information of drug interactions, but we could not say what else is important in a particular patient. This research was supported by Provincial Secretariat for Science and Technological Development, Autonomous Province of Vojvodina project No 114-451-2458/2011 and by Ministry of Science and Technological Development, Republic of Serbia project No 41012.

The aim of the study was to analyze of use of anti-infective drugs for systemic administration (ATC-group J) in Serbia in 2011 year. Data about use of anti-infective drugs for systemic administration in Serbia in 2011 was taken from the Agency for Drugs and Medical Devices of Serbia. Use of all drugs in Serbia in 2011 was 1,104.57 DDD/1000 inhabitants/day. ATC-group J was on the seventh place according to amount of DDDs with 27.35 DDD/1000 inh/day or 2.48% of total consumption. According to the funding spent, this group was on the second position with 77,800,748.63€. In this group, subgroup with highest consumption were antibacterial drugs for systemic use (subgroup J01), with 26.68 DDD/1000 inh/day or 97.55% of total use in group J. This subgroup takes first place in funding spent with 52,801,780.13€ or 67.87% of total expended finances in this group in 2011. Beta-lactam antibacterial drugs with 14.98 DDD/1000 inh/day or 56.15% were drugs with highest use in this subgroup, macrolides and lincosamides were at second place with 5.11 DDD/1000 inh/day or 19.15%, while on the third place were quinolones with 2.66 DDD/1000 inh/day or 9.97% of total drug utilization inside this subgroup. Funding spent on beta-lactam antibacterial drugs was 29,522,197.18€ or 55.91%, macrolides and lincosamides 10,811,308.09€ or 20.48%, and for quinolones 6,286,373.19€ or 11.91% of total funding spent for subgroup J01 in 2011 year. In comparison to 2010 spending of group J in Serbia in 2011 year was increased for 7.72 DDD/1000 inh/day or 39.33%. However the amount of funding spent in this group of drugs was decreased for 12,850,895.28€ or 14.18%. This research was supported by Provincial Secretariat for Science and Technological Development, Autonomous Province of Vojvodina project No 114-451-2458/2011 and by Ministry of Science and Technological Development, Republic of Serbia project No 41012.

Arterial hypertension represents a major cause of cardiovascular morbidity and mortality in the city of Novi Sad, Serbia, with every fourth adult inhabitant suffering from it. The aim of this study was to analyze patterns of antihypertensives usage within different age groups of patients (30–40, 50–60, 70–80 years) and between genders.