Increase and Change in the Pattern of Antibiotic Use in Serbia (2010-2019).

The aim of this study was to determine and describe trends in antibiotics utilization in Serbia over a ten-year period. Data were retrieved from publicly available annual reports (2010-2019). The results were expressed as Defined Daily Dose (DDD) per 1000 inhabitants per day (DID). All calculations were performed using the DDD values for the 2020 Anatomical Therapeutic Chemical/Defined Daily Dose (ATC/DDD) version for each year of the study, to account for the DDD changes during the study period. Antibiotics were classified using the WHO Access, Watch, Reserve (AWaRe) classification. Total utilization of antibacterials for systemic use increased from 17.25 DID in 2010 to 28.65 DID in 2019. A statistically significant increasing trend in the use of the Watch category antibiotics was observed. A tendency towards use of broad-spectrum antibiotics, apparent by a statistically significant increase in the rate of utilization of broad-spectrum macrolides, quinolones and third-generation cephalosporins vs. narrow-spectrum ones, as well as a significant increasing trend in the use of quinolones was identified. Total antibiotic utilization was found to be well above the European average. Several specific problem areas were identified, which requires further efforts to improve antibiotic prescribing. The present study provides the information needed to facilitate antibiotic stewardship in Serbia further and proposes specific interventions to optimize antibiotic use in Serbia.

Five-year surveillance and correlation of antibiotic consumption and resistance of Gram-negative bacteria at an intensive care unit in Serbia.

A surveillance study was performed in an intensive care unit in the largest tertiary health care center in Vojvodina, Serbia from 2014 to 2018. Antibiotic prescription data were collated in the WHO anatomical therapeutic chemical (ATC)/defined daily dose (DDD) format, while antibiotic resistance was expressed as incidence density adjusted for total inpatient-days. Individual trends were determined by linear regression, while possible associations between antibiotic prescription and resistance were evaluated using cross-correlation analysis. An overall decrease in antibiotic utilization was observed. The prescription rates of piperacillin-tazobactam increased significantly, while consumption of 3rd and 4th generation cephalosporins and fluoroquinolones decreased. There were rising incidence densities of doripenem resistant Acinetobacter spp., piperacillin-tazobactam resistant Pseudomonas aeruginosa and carbapenem and colistin resistant Klebsiella pneumoniae. These results can serve as a basis for the development of antimicrobial stewardship strategies in the current setting.

Kidney, skeletal muscle and myocardium as potential target sites of Pygeum africanum toxicity in Wistar rats / Riñón, musculoesquelético y miocardio como posibles lugares diana de los efectos tóxicos de Pygeum africanum en las ratas de raza Wistar

Objective: Extract of Pygeum africanum (PAE) is commonly used herbal medication in the treatment of benign prostatic hyperplasia. In Montenegro and neighboring countries, PAE is primarily advertised as dietary supplement in the treatment of erectile dysfunction. The purpose of this study was to broaden the current cognition concerning its safety profile. Material and methods: Twenty-four adult male Wistar rats were used. The first control group (O) received water and second control group (OO) received olive oil for 30 days. The third and fourth groups (PA5 and PA10) were treated with PAE dissolved in olive oil (50 and 100mg/kg p.o. daily). The behavior of animals was observed continuously, bodyweight gain (BWG) was calculated weekly and the weight of selected organs was measured at the end of experiment. Total protein and glutathione content of the liver were analyzed. Standard biochemical analyses were also performed. Results: BWG was higher in PA5 compared to both controls at all measuring intervals. Liver weight/body weight ratio was significantly higher in PA10 in comparison with O. Prostate weight/body weight ratio was lower in both PA5 and PA10 compared to OO, achieving statistical significance in PA5. The value of creatinine was higher in PA5 and PA10 compared to both control groups, but achieving statistical significance in PA10 only. LDH was also increased in PA5 and PA10 compared to both controls. Conclusions: Both dosage regimens of PAE, particularly PA10, caused some toxicological effects in Wistar rats after one month of application. Kidney, skeletal muscle and/or myocardium are suspected as target sites of PA toxicity most likely. In order to provide more reliable conclusion it is necessary to conduct an additional research on the basis of these findings

Objetivo: El extracto de Pygeum africanum (PAE) es un producto de origen vegetal que frecuentemente se utiliza en el tratamiento de la hiperplasia benigna de próstata. En Montenegro y en los países limítrofes, el PAE se anuncia principalmente como suplemento dietético en el tratamiento de la disfunción eréctil. El propósito de este estudio fue ampliar el conocimiento actual respecto a su perfil de seguridad. Material y métodos: Se utilizaron 24 ratas macho adultas de raza Wistar. El primer grupo de control (O) recibió agua y el segundo grupo de control (OO) recibió aceite de oliva durante 30 días. El tercer y cuarto grupos (PA5 y PA10) se trataron con PAE disuelto en aceite de oliva (50 y 100mg/kg vo diariamente). Se observó continuamente el comportamiento de los animales, semanalmente se calculó el incremento del peso corporal (IPC), y el peso de los órganos seleccionados se midió al final del experimento. Se analizaron el contenido total de proteína y glutatión del hígado. También se realizaron análisis bioquímicos habituales. Resultados: El IPC fue mayor en PA5 que en los 2 grupos control en todos los intervalos de medición. La relación entre peso del hígado y peso corporal fue considerablemente mayor en PA10 que en O. La relación entre peso de la próstata y peso corporal de la próstata fue menor tanto en PA5 como en PA10 en comparación con OO, por lo que se obtuvo significación estadística en PA5. El valor de la creatinina fue más elevado en PA5 y PA10 en comparación con ambos grupos de control, pero alcanzó significación estadística solo en PA10. La LDH también se incrementó en PA5 y PA10 en comparación con los 2 grupos control. Conclusiones: Las 2 pautas de dosificación de PAE, sobre todo en PA10, provocaron algunos efectos toxicológicos en ratas de raza Wistar después de un mes de aplicación. Se sospecha que muy probablemente el riñón, el musculoesquelético o el miocardio sean lugares diana de los efectos tóxicos de PAE. Para ofrecer una conclusión más fiable, es necesario llevar a cabo más investigación sobre la base de estos hallazgos

Use of microdialysis for the assessment of fluoroquinolone pharmacokinetics in the clinical practice.

Antibacterial drugs, including fluoroquinolones, can exert their therapeutic action only with adequate penetration at the infection site. Multiple factors, such as rate of protein binding, drug liposolubility and organ blood-flow all influence ability of antibiotics to penetrate target tissues. Microdialysis is an in vivo sampling technique that has been successfully applied to measure the distribution of fluoroquinolones in the interstitial fluid of different tissues both in animal studies and clinical setting. Tissue concentrations need to be interpreted within the context of the pathogenesis and causative agents implicated in infections. Integration of microdialysis -derived tissue pharmacokinetics with pharmacodynamic data offers crucial information for correlating exposure with antibacterial effect. This review explores these concepts and provides an overview of tissue concentrations of fluoroquinolones derived from microdialysis studies and explores the therapeutic implications of fluoroquinolone distribution at various target tissues.

Kidney, skeletal muscle and myocardium as potential target sites of Pygeum africanum toxicity in Wistar rats.

OBJECTIVE: Extract of Pygeum africanum (PAE) is commonly used herbal medication in the treatment of benign prostatic hyperplasia. In Montenegro and neighboring countries, PAE is primarily advertised as dietary supplement in the treatment of erectile dysfunction. The purpose of this study was to broaden the current cognition concerning its safety profile. MATERIAL AND METHODS: Twenty-four adult male Wistar rats were used. The first control group (O) received water and second control group (OO) received olive oil for 30 days. The third and fourth groups (PA5 and PA10) were treated with PAE dissolved in olive oil (50 and 100mg/kg p.o. daily). The behavior of animals was observed continuously, bodyweight gain (BWG) was calculated weekly and the weight of selected organs was measured at the end of experiment. Total protein and glutathione content of the liver were analyzed. Standard biochemical analyses were also performed. RESULTS: BWG was higher in PA5 compared to both controls at all measuring intervals. Liver weight/body weight ratio was significantly higher in PA10 in comparison with O. Prostate weight/body weight ratio was lower in both PA5 and PA10 compared to OO, achieving statistical significance in PA5. The value of creatinine was higher in PA5 and PA10 compared to both control groups, but achieving statistical significance in PA10 only. LDH was also increased in PA5 and PA10 compared to both controls. CONCLUSIONS: Both dosage regimens of PAE, particularly PA10, caused some toxicological effects in Wistar rats after one month of application. Kidney, skeletal muscle and/or myocardium are suspected as target sites of PA toxicity most likely. In order to provide more reliable conclusion it is necessary to conduct an additional research on the basis of these findings.

Are There Striking Differences in Outpatient Use of Antibiotics Between South Backa District, Serbia, and Some Scandinavian Countries?

There is little published information about antibiotic utilization in outpatients in Serbia. The objective of this study was to determine the amount and structure of outpatient antibiotic use in South Backa District (SBD) in Serbia, to assess prescibing quality of antibiotics and to compare with results from Scandinavian countries. Data on the antibiotic use were collected from all private and state-owned pharmacies from January through March 2008 in SBD. Results were expressed as the number of defined daily doses/1,000 inhabitants/day. The drug utilization 90% method was also used. Penicillins were the most frequently used antibiotic subgroup in SBD (35.20%), followed by cephalosporins (19.16%) and macrolides (13.18%). Thirteen drugs accounted for 90% of total antibiotics consumption (DU90% segment). The average cost/DDD within the DU90% segment was 0.95 euros, whereas the average cost/DDD beyond the DU90% segment was 1.89 euros, indicating that less expensive antibiotics were more frequently used. High use of ampicillin, third-generation cefalosporins, co-trimoxazole, and gentamicin, will aggravate the alarming problem of resistance in Serbia. Differences in the amount and structure of antibiotic consumption between SBD and Scandinavian countries indicate the need of updated national guidelines for rational antimicrobial drug use in Serbia.

Factors associated with non-adherence among type 2 diabetic patients in primary care setting in eastern Bosnia and Herzegovina.

AIMS: The aims of this study were to assess patients' non-adherence and associated factors to antidiabetic medication in the primary care setting in the eastern part of Bosnia and Herzegovina (BiH). METHODS: We conducted a retrospective chart review of 323 patients with type 2 diabetes mellitus (T2DM) attending the primary health care center of the Foca municipality in eastern part of BiH and measured adherence to antidiabetic medication. Adherence was measured using a pill count method. RESULTS: The majority of patients were treated with oral therapy (84.21%). Half of the patients (48%) treated pharmacologically were non-adherent and patients on oral and insulin combination therapy showed better adherence than those on oral therapy. Age (B=-0.749; p=0.004), copayment (B=0.549; p=0.028) and oral therapy (B=0.827; p=0.045) were the strongest predictors of poor adherence. CONCLUSION: About half of the patients were non-adherent to antidiabetic medication. Interventions oriented towards policy changes regarding availability of antidiabetic medication through copayment reductions, and providing healt education to younger population and patients on oral therapy could lead to better adherence among T2DM patients in eastern part of BiH.

Is the level of knowledge a predictor of rational antibiotic use in Serbia?

INTRODUCTION: The objective of this study was to investigate the knowledge, attitudes and behavior regarding antibiotics of the general population. METHODS: The study sample consisted of adult subjects who consulted general practitioners at health centers in Serbia and agreed to complete the questionnaire. A total of 668 questionnaires were distributed; 500 respondents completed the entire questionnaire (response rate 74.85%). RESULTS: The average age was 51.65 ± 16.56 years, 60.80% of the respondents were women. The median antibiotic knowledge score was 9. Predictors of adequate antibiotic knowledge were higher education level and a family member whose ocuppation was related to health-care. Overall, 58.4% of respondents believed that antibiotics could be used to treat common cold. Around a half of the respondents (47.2%) self-medicated with antibiotics at least once during their life-time, and around a quarter (24.2%) during the last treatment of infection. Patients with inadequate knowledge had 3 times higher chances of self-medicating with antibiotics compared to those with adequate knowledge. Although 98.20% of respondents claimed that antibiotic treatment should be started after a visit to a doctor and receiving a prescription, only 65.8% obtained antibiotics with prescription from a doctor during the last infection. CONCLUSIONS: Although these results demonstrate that respondents had a relatively adequate level of knowledge regarding antibiotics use, some areas of misconceptions and improper behavior were identified. Therefore, further rationalization should be focused on educational campaigns targeting the behavior of patients with regard to antibiotic use.

Self-medication with antibiotics in Serbian households: a case for action?

Background Irregular antibiotic use, including self-medication contributes to the development of antibiotic resistance. One method of accessing antibiotic use in the community is through obtaining an in house inventory of drugs. Objective The aim of this study was to investigate the extent of storage and self-medication with antibiotics agents in households in Novi Sad, Serbia. Setting Households in Novi Sad. Method The study was performed during a 4-month period (October 2015-January 2016) using a sample of 112 households in Novi Sad, Serbia. Two trained interviewers performed the survey by visiting each household. The study consisted of making an inventory of all drugs in household and a semi-structured interview about drug use practices and perceptions. Main outcome measure Number of antibiotics obtained without prescription. Results Out of 112 surveyed households, antibiotics were encountered in 55 (49.1%). Antibiotics constituted 11.98% (92/768) of total number of drug items in households. Out of all antibiotics in households, 41 (44.57%) were not in current use, and presented left-overs from previous treatment. Antibiotics were usually acquired with prescription (67, 67.7%), while about a quarter of packages were used for self-medication-purchased at pharmacy without prescription (19, 20.65%) or obtained through friends or family member (6, 6.52%).The most commonly used antibiotics for self-medication was amoxicillin (reported indications included common cold, cough, pharyngitis and tooth-ache). Conclusion Antibiotics were present in large share of households in Novi Sad. Self-medication with antibiotics and sale of antibiotics without prescription represent an important problem in Serbia.

Analysis of expired medications in Serbian households.

INTRODUCTION: An ongoing issue of expired medications accumulating in some households is a universal problem around the world. The aim of the study was to investigate the extent and structure of expired medications in Serbian households, and to determine which therapeutic groups generated the most waste. METHODS: This was an observational, cross-sectional study conducted in households in the city of Novi Sad, Serbia. The study had been performed over 8 month period (December 2011 - July 2012) and it consisted of personal insights into the medication inventory in households. RESULTS: Of 1008 families, 383 agreed to participate and complete the questionnaire (38.3% response rate). In almost a half of households (44.4%), expired medications were maintained. The amount of expired medications was 402 items, corresponding to 9.2% of total medications presented in surveyed households. The majority of expired medications (64.7%) was in solid dosage (tablets, capsules, granules, lozenges), following semisolid (ointments, creams, gel, suppositories) and liquid dosage forms (drops, syrups). Expired medications in the households belonged mostly to 3 categories: antimicrobials for systemic use (16.7%), dermatological preparation (15.9%) and medications for alimentary tract and metabolism (14.2%). CONCLUSIONS: This study revealed that there were relatively large quantities of expired medications in Serbian households, with a high prevalence of antibiotics for systemic use, anti-inflammatory and antirheumatic products, and medications for alimentary tract and metabolism.

Patterns of prescription antihypertensive drug utilization and adherence to treatment guidelines in the city of Novi Sad.

BACKGROUND/AIM: Hypertension is one of the leading causes of cardiovascular morbidity and mortality and more than a half of all health insurance expenditures for reimbursed medicines are allocated to antihypertensive drugs in Serbia. The aim of this study was to identify the antihypertensive drug utilization patterns among hypertensive outpatients in the city of Novi Sad, Serbia, determine the adherence to clinical guidelines and address the economic aspects of current prescribing practices. METHODS: This retrospective observational study was conducted in Novi Sad over a period of six months. The data on the number of packages, size their, and retail price of antihypertensives issued on prescription in outpatients with the diagnosis of essential arterial hypertension was collected from all state-owned pharmacies in Novi Sad. Drug consumption was analyzed using the Anatomical Therapeutic Chemical (ATC)/ defined daily dose (DDD) methodology. RESULTS: Total consumption of antihypertensives issued on prescription over a 6-month period in the city of Novi sad, Serbia was 283.48 DDD per 1,000 inhabitans per day (DID). Angiotensin converting enzyme inhibitors (ACEi) were most commonly prescribed drugs, and were used 3 times more often than calcium channel blockers and 5 times more than beta-blockers. The consumption of diuretics and angiotensin receptor antagonists was low within all the groups of outpatients. Both national and international guidelines state superiority and effectiveness of diuretics in treatment of hypertension in the elderly, but their consumption was unreasonable low despite the fact that over 70% of all antihypertensive drugs in the city of Novi Sad were dispensed in people aged > 60. The use of more expensive ACEi was observed despite the guidelines deeming all the drugs of this class equally effective in treatment of hypertension. CONCLUSION: Large differences in utilization of different groups of antihypertensive agents were noted in this study. Underutilization of valuable, efficacious, and cost-effective thiazide diuretics and overuse of expensive ACE inhibitors is unjustifiable. There is a potential for large savings with switching to low-price ACEi, modeling the practice of Scandinavian countries.

DRUG UTILIZATION IN TREATMENT OF THYROID DISORDERS DURING PREGNANCY IN SERBIA.

INTRODUCTION: Depleted uranium radiation and pollution with polychlorinated biphenyls resulting from bombings the territories of Serbia as well as the additional long-term stress may have affected the function of thyroid gland. The objective of this study was to determine the trend of drug utilization in the treatment of thyroid dysfunction during pregnancy in Novi Sad. MATERIAL AND METHODS: Women who had given birth at the Department of Gynecology in 1989, 1999, 2007 and 2011 were interviewed during a one-month period about thyroid diseases in the pregnancy as well as the drugs they had taken. RESULTS: Not a single pregnant woman was reported to have a thyroid disorder in 1989 and 1999, while in 2007 four women were reported to have a thyroid dysfunction. In 2011, fourteen out of 18 women with thyroid dysfunction were using levothyroxine and in most cases hypothyroidism was diagnosed as autoimmune Hashimoto thyroiditis. CONCLUSION: The study results suggest the necessity of performing more detailed analyses of the correlation between the frequency of the thyroid gland dysfunction and the effects of environmental pollution in Serbia.

Do We Bury Antibacterials When Launching? Cefaclor Example.

This study aimed to compare existing dosing regimens of cefaclor with recommended pharmacokinetic/pharmacodynamic (PK/PD) parameters and to see if the proposed dosing regimen could have been the reason for development of bacterial resistance. PKs of cefaclor were determined after administrating the highest therapeutic dose of 750 mg in standard release (SF) and modified release form (MRF) in 12 volunteers. The study was performed on clinical isolates of the most frequent causative agents in urinary and respiratory infections. Minimum inhibitory concentration (MIC), postantibiotic effect, and PK/PD efficacy indices were determined. Peak plasma concentrations of 23.142 ± 5.67 (SF) and 8.7 ± 2.09 µg/mL (MRF) were observed after 40-60 min and 3.04 ± 0.75 h, respectively. MIC for investigated bacterial strains ranged from 1 to 4 mg/L. Postantibiotic effect lasted from 2.10-2.18 ± 0.2 h for Gram-positive to 0.58-0.90 ± 0.05 h for Gram-negative bacteria. PK/PD indices (t > MIC) ranged from 27.08 ± 5.93% to 43.23 ± 6.54% of 8-h dosing interval (SF) and 22.57 ± 8.93% to 49.65 ± 1.95% of 12-h dosing interval (MRF). Plasma levels were below MIC for more than 50% of the dosing interval even for the most sensitive pathogens (MIC = 1 mg/L). During both dosing intervals the total "antibacterial activity" was not longer than 6 h for Gram-positive and 5 h for Gram-negative bacteria for SF and 9 h for Gram-positive and 5 h for Gram-negative bacteria for MRF.

Home pharmacies in Serbia: an insight into self-medication practice.

BACKGROUND: Worldwide data indicate that self-medication is frequently used inappropriately. Although self-medication is encouraged in most of the countries by introducing over-the-counter drugs, it bears the risk of misuse of drugs issued on prescription due to low observance of legislation of medicines requiring prescription by some pharmacies. OBJECTIVE: The objective of this study was to explore the self-medication practice, with an emphasis on self-medication with prescription-only medications. SETTING: Households in Novi Sad city, Serbia. METHOD: The study was conducted over 8 month period (December 2011-July 2012) and involved a random sample of households. The questionnaire-based study and personal insight into household drug supplies was performed by a trained interviewer. Main outcome measure Number of drugs obtained without prescription or without consulting a physician in surveyed households. RESULTS: The total number of drug items present in the 383 households was 4,384 with a median of 11 drugs per household. More than a half of drugs in households were prescription-only medication (58.5 %). Approximately one third of prescription-only medications were obtained without prescription. The most common drugs obtained without prescription were anti-inflammatory and antirheumatic products and antibacterials for systemic use. Ibuprofen and diclofenac were the most common self-medicated drugs. Number of prescription-only medications bought with ought prescription was significantly higher in households with children under 12 years of age compared to other types of households. CONCLUSION: Our survey indicated that self-medication with prescription drugs appeared to be a rather common practice, which is far away from the concept of "responsible self-medication", especially regarding antibiotics.

Antibiotics in Serbian Households: a Source of Potential Health and Environmental Threats?

AIM: Worldwide data indicate that antibiotics are frequently used inappropriately. The objective of this study was to investigate the extent of storage and wastage of antibacterial agents in households in Novi Sad, Serbia. METHODS: The study was performed in 8 months period (December 2011-July 2012) in households in Novi Sad, Serbia. The households were randomly selected from the telephone directory. The interviewer performed the survey visiting each household. RESULTS: The total number of antibacterial agents in the 383 surveyed households was 318, constituting 7.3% of the total stored medications. From 383 families included in the study antibiotics were found in 178 (46.5%). In 13 (7.3%) families were found more than one pack of the same antibiotics. The median number of antibacterial agents per household was 1 (range 1-5). The most common antibacterial agents that were not in current use were cephalexin (22.1%) and amoxicillin (16.6%), followed by doxycycline (11.4%), sulfamethoxazole/trimethoprim (11.4%) and amoxicillin/clavulanic acid (9.2%). The percentage of expired antibacterial agents was 20.8%, while 85.2% were not currently in use. CONCLUSION: Antibacterial agents were commonly encountered in Serbian households, and a relatively large percentage was wasted. Informational and educational activities aimed at improving the public knowledge about antimicrobials play the leading role in reducing imprudent use of antibiotics.

Hormonal contraception--habits and awareness female students of the University of Novi Sad, Vojvodina, Serbia.

INTRODUCTION: Despite a large number of modern contraceptive methods available in the market today, numerous studies have shown insufficient awareness of young women about these forms for birth control. The aim of this study was to compare characteristics of common use of contraceptives as well as the awareness of hormonal contraception among female students of the Faculty of Medicine and the Faculty of Technical Sciences in Novi Sad. MATERIALS AND METHODS: In the study which was conducted in 2012 240 female students of the Faculty of Medicine and the Faculty of Technical Sciences participated. The average age of students of the Faculty of Medicine and the Faculty of Technical Sciences was 24.06 ± 3.24 and 22.72 ± 0.90 years, respectively. They completed an anonymous questionnaire, which consisted of three parts. The first part comprised general questions, the second part included characteristics of the sexual life of students and their contraceptive habits, while in the third part students were asked to evaluate the accuracy of statements about hormonal contraception. The obtained data were statistically processed by using appropriate methods. RESULTS: The average age when the students of the Faculty of Medicine and the Faculty of Technical Sciences had the first sexual intercourse was 18.74 ± 2.61 and 18.75 ± 2.59, respectively. One third of students from both faculties (30.91% from the Faculty of Medicine and 35% from the Faculty of Technical Sciences) had only one sexual partner. Modern contraception was used by 83.64% of the medical students and by 80% of those from the Faculty of Technical Sciences. Contraception was used regularly by 54.54% of the medical students and 43% of those from the Faculty of Technical Sciences. The most frequently applied contraceptive method was condom (90% of the medical students and 93% of the Faculty of Technical Sciences students, respectively). Oral contraceptives were used by 24.54% of the medical students and 11% of those from the Faculty of Technical Sciences. There was a statistically significant difference in the knowledge level between the two groups since the medical students gave quantitatively higher range of expected responses than the students from the Faculty of Technical Sciences. CONCLUSION: It is necessary to increase the availability of adequate information on various types of contraception to student population in Vojvodina.

Cost-effectiveness of everolimus for second-line treatment of metastatic renal cell carcinoma in Serbia.

BACKGROUND: New targeted therapeutics for metastatic renal cell carcinoma (mRCC) enable an increment in progression-free survival (PFS) ranging from 2 to 6 months. Compared with best supportive care, everolimus demonstrated an additional PFS of 3 months in patients with mRCC whose disease had progressed on sunitinib and/or sorafenib. The only targeted therapy for mRCC currently reimbursed in Serbia is sunitinib. OBJECTIVE: The aim of this study was to estimate the cost-effectiveness and the budget impact of the introduction of everolimus in Serbia in comparison to best supportive care, for mRCC patients refractory to sunitinib. METHODS: A Markov model was designed corresponding with Serbian treatment protocols. A health care payer perspective was taken, including direct costs only. Treated and untreated cohorts were followed up over 18 cycles, each cycle lasting 8 weeks, which covered the lifetime horizon of mRCC patients refractory to the first-line treatment. Annual discounted rates of 1.5% for effectiveness and 3% for costs were applied. Transitions between health states were modeled by time-dependent probabilities extracted from published Kaplan-Meier curves of PFS and overall survival (OS). Utility values were obtained from the appraisals of other mRCC treatments. One-way and probabilistic sensitivity analyses were done to test the robustness and uncertainty of the base-case estimate. Lastly, the potential impacts of everolimus on the overall health care expenditures on annual and 4-year bases were estimated in the budget-impact analysis. RESULTS: The incremental cost-effectiveness ratio for everolimus was estimated at €86,978 per quality-adjusted life-year. Sensitivity analysis identified the hazard multiplier, a statistical approximator of OS gain, as the main driver of everolimus cost-effectiveness. Furthermore, probabilistic sensitivity analyses revealed a wide 95% CI around the base-case incremental cost-effectiveness ratio estimate (€32,594-€425,258 per quality-adjusted life-year). Finally, an average annual budgetary impact of everolimus in first 4 years after its potential reimbursement would be around €270,000, contributing to <1% of the total budget in Serbian oncology. CONCLUSIONS: Everolimus as a second-line treatment of mRCC is not likely to be a cost-effective option under the present conditions in Serbia, with a relatively limited impact on its budget in oncology. A major constraint on the estimation of the cost-effectiveness of everolimus relates to the uncertainty around the everolimus effect on extending OS. However, prior to a final decision on the acceptance/rejection of everolimus, reassessment of the whole therapeutic group might be needed to construct an economically rational treatment strategy within the mRCC field.

Storage and disposal of unused medications: knowledge, behavior, and attitudes among Serbian people.

BACKGROUND: Improper disposal of medications potentially poses a significant environmental risk and storage of expired and unused medications in households provides an increased risk of accidental childhood poisonings. OBJECTIVE: The objective of this study was to investigate the storage and disposal habits of medications amongst the population in the South Backa District of Serbia, and to gain insight into the attitudes and knowledge of the population about the proper disposal of medications. Setting Households in South Backa District. METHOD: The study was conducted during the 6-month period from February 2010 to July 2010 and involved a random sample of households. The questionnaire-based study was performed by a trained interviewer. MAIN OUTCOME MEASURE: number of expired and unused medications in families, behavior and knowledge about the disposal of medications. RESULTS: Of 230 families, 208 (108 urban and 100 rural) agreed to participate and complete the questionnaire(90 % response rate). The drugs were mostly kept in a specific place-home pharmacy (89.8 % [urban] and 89.0 % [rural]). Exposure of children to medications in the home environment was similar in urban and rural families (19.6 % [urban] and 23.1 % [rural]). The frequency of expired medications was not observed to be different between the urban and rural households (10.3 % [urban] and 11.8 % [rural]). The most common method for disposal of household medications is disposal in the garbage (85.6 % [urban] and 74.5 % [rural]) or in the toilet (8.7 % [urban] and 6.4 % [rural]). However, inconsistent with disposal practices, half of the urban and rural participants thought that throwing medications in the garbage, toilet, or sink has a detrimental effect on the environment. CONCLUSION: Public services in Serbia, including government and health sectors, need to be more proactive about educating people on how to store and dispose medications, as well as finding a way for implementation of the law on medications wastage destruction.