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Optimal vitamin D status is very important for reflecting not only bone but overall woman's health. The aim of the study was to determine pharmacokinetic variability of 25-hydroxy vitamin D, to reveal and quantify the most significant factors that affect its variability in the population of healthy non-menopausal women using the population pharmacokinetic (PopPK) approach. The study population consisted of 74 healthy reproductive women aged from 35 to 50 years, without the use of any supplement. A population pharmacokinetics analysis was conducted using a nonlinear mixed-effects model software. A total of 35 factors were assessed: demographic, clinical, biochemical data and lifestyle factors. The average age and bodyweight of our participants were 40.11 ± 4.35 years 65.30 ± 6.80 kg, respectively. The observed mean serum concentration of 25-hydroxy vitamin D was 26.51 ± 13.49 ng/mL with a wide range of 6.97 to 59.89 ng/mL. Development final PopPK model of the clearance of 25-hydroxy vitamin D showed that only the average daily dose of vitamin D intake from food had a significant influence, with a magnitude of its effects of 0.00401. These results could help when individualizing vitamin D intake in the form of supplements, especially during the wintertime, in healthy reproductive women.

Background/Aim: The purpose of the conducted study was to show the frequencies of PIM in the elderly population with cardiovascular diseases and to describe factors with significant impact on PIM present in the elderly population. Methods: The study was performed as a retrospective, cross-sectional study. The research was performed during 2018 , the relevant data collected during the period from January 2016 to December 2017. Study sample included 1500 patients over 65 years with cardiovasculares disease who had medical records at the Institute for Gerontology and Palliative Care, Belgrade. Assessment of PIM was done by standard international criteria American Geriatrics Society 2015 updated Beers Criteria for potentially inappropriate medication use in older adults. Results: PIM frequency in elderly population was 70, 3%. In relation to gender, it was more frequent in female elders. Mean number of prescribed drugs was similar for 2016 and 2017, respectively 7, 2 and 7, 3. The most common were: medium acting benzodiazepines (70, 9%), central α blockers (23, 98%), and antipsychotics (typical and atypical) (20,94%). The most common comorbidity was noted in a group labelled with the international disease classification I00-I99 which inlcudes heart and blood vessel diseases (n=2658; 36.9%). The most common diagnoses belonged to the subgroup I10-I15 hypertensive diseases (n=1298; 18%), I20-I25 ischemic heart diseases (n= 542; 7.5%), I30-I52, other forms of heart disease (n=705; 9.8%), I60-I69 cerebrovascular diseases (n =94; 1.3%), and I80- I89 diseases of veins, lymph vessels and lymph nodes (n=12; 0.17%). Predictor for PIM were numerous: polypharmacy, gender, nicotine use, cognitive status, nutrition state and number of diseases registered at study sample. Conclusion: Cardiovascular diseases in the elderly population are associated with a high prevalence of potentially inappropriate drug prescribing. Creating health recommendations for prescribing drugs in the elderly that would emphasize these factors could reduce the prevalence of PIM in this population

The aim of this pilot study is a preliminary evaluation of previous models / modalities of online teaching at the Faculty of Medical Sciences in Serbia and to examine the attitudes of students and academic staff about education during the COVID-19 pandemic, as well as their previous experiences. The research was designed as an observational qualitative epidemiological study which was conducted on a population of students and academics staff at the Faculty of biomedical sciences, University of Kragujevac during the pandemic of SARS-CoV-2 infection in Serbia. The first phase is a pilot study which included 332 participants performed between December 2020 and January 2021. The pilot study questionnaire is formed for the purposes of the research and consists of 17 closed-ended questions with graduated answers. Students and academic staff completed the questionnaire through an online learning platform in all environments and from all electronic devices. The importance of this study is reflected in the fact that it provides detailed and valid data that can serve the purpose of improving the efficiency of online teaching at the faculties of medical sciences in Serbia In general, the results of our study indicate that in addition to great inexperience, both students and academic staff cope well during online education and the changed environment and learning conditions despite all the difficulties.

(1) Background: the purpose of this study was a preliminary analysis of current methods of online teaching at the Faculty of Medical Sciences, University of Kragujevac, Republic of Serbia, in order to define the attitudes of biomedical students about education during the COVID-19 pandemic and to validate of the education medical questionnaire (eMedQ), a new tool for the assessment of the students’ perceptions about digital education. (2) Methods: this was a qualitative cross-sectional observational study that used the originally developed 45-item questionnaire (eMedQ) as an assessment instrument conducted on biomedical students (n = 209) of all study years at the Faculty of Medical Sciences, University of Kragujevac (Republic of Serbia), during winter semester or between September 2021 and January 2022. (3) Results: In this study, a Cronbach’s alpha value of 0.904 was obtained, which indicated good internal consistency; the correlation matrix revealed many coefficients greater than 0.3, denoting high correlations between the items. The Kaiser–Meyer–Olkin measure of sampling adequacy was 0.866 and Bartlett’s test of sphericity was significant (p < 0.001). The PCA revealed the presence of seven components with characteristic values over one, while three factors explained the highest percentage of variance. (4) Conclusions: this research developed and validated a new tool for evaluation of biomedical student perceptions about digital education.

Over-the-counter drugs are medicines that are available to consumers without a prescription. The most common оver - the-counter preparations in self - medication are nasal decongestants that can be used systemically or locally in the form of drops or nasal sprays. The most common indications for nasal decongest-ants are viral infections and allergic conditions in order to alleviate the symptoms so it is necessary to inform the users about the type of drug, the active substance it contains and the correct dosage regimen. Given their availability and the prevailing safety precaution, these preparations can lead to numerous prolonged conditions and complications. The mechanism of action of nasal decongestants is based on the reduction of blood vessels’ swelling in the nose, which helps the opening of the airway. As a result, most nasal decongestants cause vasoconstriction (narrowing of blood vessels). There are nasal decongestants that block histamine and have a good effect on people who suffer from seasonal allergies. Availability (free sale) and prolonged use of the decongestant lead to a decrease in the sensitivity of the alpha receptor, which leads to the need to increase the dose at shorter time intervals to achieve the same effect. As a consequence, patients use excessive, uncontrolled doses of nasal decongestants, which is a public problem and warns of the necessity of identification and the taking of measures to prevent their uncontrolled procurement and use.

Atrophic vaginitis is a relatively common adverse effect of aromatase inhibitors used as an adjunctive treatment for breast cancer. Vaginal estrogen therapy is a treatment option, but the safety of its use in estrogen receptor-positive breast cancer remains understudied. The aim of our study was to determine the safety of local hormonal treatment of vulvovaginal atrophy in women treated with aromatase inhibitors. Our meta-analysis was based on a systematic search of the literature and selection of high-quality evidence. The safety of local hormonal therapy of vaginal atrophy in women on aromatase inhibitors were summarized using calculators built by the authors; heterogeneity was assessed by the Cochrane Q test and I2 values. Several types of bias were assessed; publication bias was calculated by a funnel plot and the Egger regression. Eleven studies fulfilled the inclusion criteria for our study. After 8 weeks of local hormonal treatment, there was no change in the serum levels of luteinizing hormone and estradiol, whereas sex hormone binding globulins were low, and follicle stimulating hormone was almost doubled compared with the baseline. Adverse effect rates of vaginal discharge, facial hair growth, urinary tract or yeast infection, and vaginal or vulvar itching and/or irritation did not show significant changes in the sensitivity analysis, with exception of a single trial. Current evidence suggests that vaginal estrogen administration in postmenopausal women with a history of breast cancer is not associated with systemic absorption of sex hormones and may provide indirect evidence for the safety of their use.

Vitamin D, also known as the “sun vitamin” in the literature, has been examined for many years and still arouses researchers’ interest due to the pleiotropic effects achieved in the human body. Because of the influence on mineral homeostasis, the initially observed effects of vitamin D on the prevention and treatment of rickets, have now been extended to a large number of diseases with different aetiologies such as cardiovascular, autoimmune, endocrine, infectious, neurological, malignant and other diseases. Due to the large number of experimental studies in animals and humans, we have exact information about the role of vitamin D in many of these conditions. Reaching an adequate level of 25(OH)D in the human body is a basic requirement for the realization of these effects; 25(OH)D is a metabolic product that reflects the vitamin D status but that does not have any biological activity. The biological activities of vitamin D can occur only after the formation of a second metabolic product, 1,25(OH)2D, in the kidneys. The three main sources of acquiring vitamin D are through food, skin and supplementation. Food is not a rich source of vitamin D; it is clear that the most important influences to achieve an optimal vitamin D status in the human body are vitamin D synthesis at the skin and adequate supplementation intake. An alarming fact is that vitamin D deficiency is detected in an increasing number of people from one day to another in the general world population and that this condition has pandemic dimensions. Introducing the beneficial effects and sources of vitamin D to the general population and to medical experts with adequate supplementation regime can decrease the number of people who are vitamin D deficient.

The aim of this study is to determine modifiable risk factors contributing to potentially inappropriate prescribing in older primary care outpatients (≥65 years).Two separate, age- and sex-matched case-control studies were carried out simultaneously at the Primary Health Care Center Kragujevac, Serbia, during the period September 2013-September 2014. The cases were defined as patients with at least one prescription for potentially inappropriate medication (PIM) according to Screening Tool of Older Persons potentially inappropriate Prescriptions (STOPP) criteria (n = 122), and patients who had at least one potential prescribing omission (PPO) listed in Screening Tool to Alert doctors to the Right Treatment (START) criteria (n = 108), while the control groups consisted of patients without such outcomes (n = 244 and n = 216, respectively).A total of 138 PIM and 161 PPO events were identified using 26 (41.3 %) of STOPP criteria and 17 (77.3 %) of START indicators, respectively. The unhealthy behaviors including at least two of the following: sedentary lifestyle, improper nutrition, active smoking or heavy alcohol consumption (adjusted OR 2.57, 95 % CI 1.28-5.20), use of multiple drugs (five to eight drugs, adjusted OR 3.05, 95 % CI 1.59-5.85; ≥9 of drugs adjusted OR 7.17, 95 % CI 3.07-16.74) and frequent contacts between patients chosen general practitioners (GPs) and pharmaceutical sales representatives (adjusted OR 2.28, 95 % CI 1.10-4.75), were identified as major risk factors for PIM use. Patients who were handled by GPs from smaller practices (adjusted OR 0.51, 95 % CI 0.29-0.93), those with more organ systems affected by the extremely severe disorders and those who often visited the outpatient specialist services (adjusted OR 0.88, 95 % CI 0.81-0.95), had a significantly reduced risk of PPO.This study suggests that avoidance of major polypharmacy, use of nonpharmacological measures to improve lifestyle habits and decreasing the exposure of physicians to drug promotional material may reduce the risk of PIM use in older primary care outpatients. The only modifiable protective factors for PPOs were working environment of the patients chosen GPs and more frequent ambulatory visits to specialists.

Classical homeopathy is a method belonging to complementary and alternative medicine and is used in treatment of both people and animals. In human medicine, classical homeopathy has a different status within the European Union, depending on legislation that applies in the member countries Veterinary homeopathy has currently being developed in three directions: scientific researches are being conducted, animals are being treated by homeopathy and education for homeopathic treatment of animals is being organised as well. European Council for Classical Homeopathy (ECCH) in 2007. published a report on homeopathic treatment of animals in Europe. The report encompassed a variety of issues related to homeopathic treatment in veterinary medicine in the countries of the European Union (EU) as well as ECCH members, wherein the situation in Serbia is also mentioned. The current veterinary homeopathy in Serbia is in the early development. Compared to the moment of publication of the report, there is a slight positive change, but there still lacks a standardized education and licencing system in this field. Klasična homeopatija je metod koji pripada komplementarnoj i alternativnoj medicini (KAM) i koristi se za lečenje ljudi i životinja. U humanoj medicini klasična homeopatija ima različit status u različitim zemljama članicama Evropske unije, u zavisnosti od zakonske regulative koja važi u svakoj od zemalja. Veterinarska homeopatija se trenutno razvija u 3 pravca: sprovode se naučna istraživanja, homeopatski se leče životinje i organizuje edukacija za homeopatsko lečenje životinja. Evropski savet za klasičnu homeopatiju (European Councile of Classical Homeopathy, ECCH) je 2007. godine objavio izveštaj o homeopatskom lečenju životinja u Evropi. Izveštaj je obuhvatio različita pitanja u vezi sa homeopatskim lečenjem u veterinarskoj medicini u zemljama Evropske unije (EU) i članovima ECCH, pri čemu je navedena i situacija u Srbiji. Aktuelna veterinarska homeopatija u Srbiji je u ranom razvoju. U odnosu na trenutak objavljivanja izveštaja postoje blage pozitivne promene, ali još uvek nedostaje standardizovan način obrazovanja i licenciranja u veterinarskoj homeopatiji.

Helianthus tuberosus L. (Jerusalem artichoke) tubers are good source of dietary fiber (inulin) due to which are beneficial to human health. The objective of this study was to characterize wheat bread enriched with content of Jerusalem artichoke powder by organoleptic properties, nutritional and caloric value, microbiological safety, glycemic index (GI) and glycemic load (GL). The bread was made from yeast dough of the following content: 75% of wheat flour and 25% of Jerusalem artichoke powder. Glycemic index and load were determined according to the FAO/WHO protocol. The bread contained 41.64% of water, 58.36% of dry matter, 0.27% of lipids, 8.25% of proteins, 47.64% of carbohydrates, and 6.15% of dietary fiber. Caloric value of was 226 Kcal / 100 g of bread. The glycemic index was 53.70, while glycemic load value was 7.67. The bread enriched with J. artichoke powder showed optimal nutritional and caloric value, low glycemic index and low glycemic load values.

Sea buckthorn oil (Hippophae rhamnoides L.) is medically used both externally and internally, but the external application is unsuitable due to its liquid, lipophilic and highly coloured nature. These difficulties could be overcome by a formulation of semisolid emulsion with sea buckthorn oil. Previous research on this formulation showed that it has higher wound healing potential than sea buckthorn oil, possessing an enhanced structure of liquid crystals, stability and suitability for topical use. The aim of this investigation was to completely characterizise a proposed emulsion by testing skin effects, such as moisturising potential, skin pH and potential to cause skin irritation. The emulsion was prepared by standard emulsifying techniques using a combination of surfactants that form an enhanced structure of liquid crystals. Approximately 40% of sea buckthorn oil was incorporated. The moisturising potential and skin pH were tested on the healthy skin of volunteers. Skin tolerance was tested on a rabbit skin model and evaluated by the Draize test. The tested emulsion containing sea buckthorn oil did not cause a significant change in skin pH, while it significantly increased skin hydration. Th ere was an absence of edema or erythema type of irritation after 2 h, 24 h, 48 h, 72 h and 7 days of application of the emulsion with sea buckthorn oil. The tested formulation shows good moisturizising effects and does not cause human or animal skin irritation. Th e study confi ms that the combination of the proposed ingredients in a sea buckthorn oil emulsion is adequate and could be safe for skin application

To conduct a study on attitudes, knowledge, and use of complementary and alternative medicine (CAM) therapies in Serbia. Available data about CAM therapies in the region are scarce, opinions lacking from health sector. Balkan region countries had a delay in issuing national policies on CAM therapies. The questionnaire used was based on previously validated CAM Health Belief Questionnaire (CHBQ), formulated as 5-item Likert type scale, adjusted for local environment. Health care students and professionals were evaluated. The questionnaire comprehended 10 closed questions on attitudes, knowledge and use of CAM therapies. This survey was conducted in eight cities of Serbia, January 2010–July 2011. A total of 797 participants was included. The second group of participants was 145 healthcare professionals (50 academic staff, 64 clinical staff, 19 pharmacists, 6 other clinical branch specialists and 6 nurses). Data were collected by an interview. Examinees could acquire maximum of 70 points, 35 representing neutral attitude. Students of dentistry (54.65±6.07) were better informed on CAM therapies than medicine students (50.26±7.92). Pharmacy students (51.16±7.10) accepted low-scientific CAM. Pharmacists scored better than university professors (55.12±6.55 vs. 50.29±9.50). Primary health care professionals had better awareness than pharmacists in dispensing pharmacies. Both groups of participants preferred use of vitamins over any other CAM therapy. These pioneering efforts in the region exposed weaknesses in CAM attitudes of current and future health care professionals. Nevertheless, awareness on alternative medicine treatment choices is growing among Balkan prescribers. Supportive legal framework would facilitate dissemination of CAM medical practices.

Background Disability either due to illness, aging, or both causes remains an essential contributor shaping European labor markets. Ability of modern day welfare states to compensate an impaired work ability and absenteeism arising from incapacity is very diverse. The aims of this study were to establish and explain intercountry differences among selected European OECD countries and to provide forecasts of future work absenteeism and expenditures on wage replacement benefits. Methods Two major public registries, European health for all database and Organization for Economic Co-operation and Development database (OECD Health Data), were coupled to form a joint database on 12 core indicators. These were related to disability, work absenteeism, and sickness benefits in European OECD countries. Time horizon 1989–2013 was observed. Forecasting analysis was done on mean values of all data for each single variable for all observed countries in a single year. Trends were predicted on a selected time horizon based on the mean value, in our case, 7 years up to 2020. For this purpose, ARIMA prediction model was applied, and its significance was assessed using Ljung–Box Q test. Results Our forecasts based on ARIMA modeling of available data indicate that up to 2020, most European countries will experience downfall of absenteeism from work due to illness. The number of citizens receiving social/disability benefits and the number being compensated due to health-related absence from work will decline. As opposed to these trends, cancer morbidity may become the top ranked disability driver as hospital discharge diagnoses. Concerning development is the anticipated bold growth of hospital discharge frequencies due to cancer across the region. This effectively means that part of these savings on social support expenditure shall effectively be spent to combat strong cancer morbidity as the major driver of disability. Conclusion We have clearly growing work load for the national health systems attributable to the clinical oncology acting as the major disability contributor. This effectively means that large share of these savings on public expenditure shall effectively be spent to combat strong cancer morbidity. On another side, we have all signs of falling societal responsibility toward the citizens suffering from diverse kinds of incapacity or impaired working ability and independence. Citizens suffering from any of these causes are likely to experience progressively less social support and publicly funded care and work support compared to the golden welfare era of previous decades.

Health care quality, prescribing drugs and adequate consumption could be defined with terms compliance, adherence, persistency and concordance. Compliance is a measure of administration of therapy exactly as prescribed. Adherence is often substituted for term 'compliance', but it assumes greater involvement of the patient in decision making regarding his therapy. A failure to measure adherence can partially be attributed to the phenomenon of 'white coat adherence'. That is why researchers are trying to establish a new measure such as 'persistency'. Nonadherence can be classified in two categories: primary ('intention') and secondary ('non-intention'). For measuring adherence various methods are used, the two becoming a standard nowadays: direct and indirect. Depending on research targets, one of the methods is chosen from the group of direct (e.g. measuring drug blood levels) or indirect methods (counting pills, patient's logs, prescribing rates, questionnaires for patients, patients' self-report). Abundant evidence indicates that poor adherence in therapeutic procedures is extremely expensive and represents significant problem affecting all ages, both sexes and people of all socio-economic groups. In order to improve compliance, adherence, persistence and concordance it is necessary to implement a more comprehensive strategy, with complementary interventions, aiming to achieve the overall results which could be more important for public health. Decision-makers in health care and experts engaged in regular, clinical practice and health care system have an important task of implementing the valid strategy because there is already abundant valid evidence for many of them. The guidelines for translational medicine, in this regard, are of particular benefit.

Background: Serbia, as the largest market of the Western Balkans, has entered socioeconomic transition with substantial delay compared to most of Eastern Europe. Its health system reform efforts were bold during the past 15 years, but their results were inconsistent in various areas. The two waves of global recession that hit Balkan economies ultimately reflected to the financial situation of healthcare. Serious difficulties in providing accessible medical care to the citizens became a reality. A large part of the unbearable expenses actually belongs to the overt prescription of pharmaceuticals and various laboratory and imaging diagnostic procedures requested by physicians. Therefore, a broad national survey was conducted at all levels of the healthcare system hierarchy to distinguish the ability of cost containment strategies to reshape clinician’s mindsets and decision-making in practice. Aims: Assessment of healthcare professionals’ judgment on economic consequences of prescribed medical interventions and evaluation of responsiveness of healthcare professionals to policy measures targeted at increasing cost-consciousness. Study Design: Cross-sectional study. Methods: A nationwide cross-sectional survey was conducted through a hierarchy of medical facilities across diverse geographical regions before and after policy action, from January 2010 to April 2013. In the middle of the observed period, the National Health Insurance Fund (RFZO) adopted severe cost-containment measures. Independently, pharmacoeconomic guidelines targeted at prescribers were disseminated. Administration in large hospitals and community pharmacies was forced to restrict access to high budget-impact medical care. Economic Awareness of Healthcare Professionals Questionnaire–29 (EAHPQ-29), developed in Serbian language, was used in face-to-face interviews. The questionnaire documented clinician’s attitudes on: Clinical-Decision-Making-between-Alternative-Interventions (CDMAI), Quality-of-Health-Care (QHC), and Cost-Containment-Policy (CCP). The authors randomly and anonymously recruited 2000 healthcare experts, with a total of 1487 responding; after eliminating incomplete surveys, 649 participants were considered before and 651 after policy intervention. Results: Dentists (1.195±0.560) had a higher mean CDMAI score compared to physicians (1.017±0.453). The surgical group compared to the internist group had a higher total EAHPQ-29 score, CCP score and CDMAI score. Policy intervention had a statistically significant negative impact on the QHC score (F=4.958; df=1; p=0.027). There was no substantial impact of policy interventions on professional behavior and judgment with regard to the CDMAI, CCP, and total EAHPQ-29 scores. Conclusion: Although cost savings were forcibly imposed in practice, the effects on clinical decision-making were modest. Clinicians’ perceptions of quality of medical care were explained in a less effective manner due to the severely constrained resources allocated to the providers. This pioneering effort in the Balkans exposes the inefficiency of current policies to expand clinicians’ cost consciousness. JEL code: I180 Health Total Times Cited: 20 (Updated on Sep. 2018- WoS)

HIGHLIGHTS Since the geopolitical developments of 1989, former centrally planned economies of Eastern Europe followed distinctively different pathways in national pharmaceutical expenditure evolution as compared to their free market Western European counterparts.Long term spending on pharmaceuticals expressed as percentage of total health expenditure was falling in free market economies as of 1989. Back in early 1990s it was at higher levels in transitional Eastern European countries and actually continued to grow further.Public financing share of total pharmaceutical expenditure was steadily falling in most Central and Eastern European countries over the recent few decades. Opposed scenario were EU-15 countries which successfully increased their public funding of prescription medicines for the sake of their citizens.Pace of annual increase in per capita spending on medicines in PPP terms, was at least 20% faster in Eastern Europe compared to their Western counterparts. During the same years, CEE region was expanding their pharmaceuticals share of health spending in eight fold faster annual rate compared to the EU 15.Private and out-of-pocket expenditure became dominant in former socialist countries. Affordability issues coupled with growing income inequality in transitional economies will present a serious challenge to equitable provision and sustainable financing of pharmaceuticals in the long run.

The blooming of incidence and prevalence of “prosperity diseases” among the broad layers of modern day populations is rather novel phenomenon in demographic history of the human race (1). Illnesses such as obesity (2), diabetes mellitus, hypertension, cerebrovascular and cardiovascular consequences of atherosclerosis, renal insufficiency, mental disorders, and even cancer are closely related to the increased longevity of most contemporary societies (3). In previous centuries, they were mostly reserved for elite social groups enjoying rather luxurious life style. Vast majority of citizens of the time were living in rural communities on the verge of poverty. Their structure of morbidity even in Europe until late 19th century was dominated by burden of infectious diseases and injury while neonatal and maternal mortality rates were huge. Industrial revolution led to the growth of living standards, invention of vaccines, and antibiotics, and ultimately development of organized publicly funded health systems. The prominent European health policy makers in the 19th century properly believed that effective public health measures will diminish huge burden of infectious diseases. Consecutively, they expected that overall costs of medical care provision should decrease substantially and ultimately reach plateau level. This second step turned out to be a great miscalculation and a surprise. Like no time in written past, people began living longer and healthier lives. But it happened at the cost. Simultaneously, from many industrialized nations, evidence were accumulating of accelerated occurrence of non-communicable diseases. Accomplishment of evidence-based medicine succeeded to control many of these initially incurable diseases, thereby transforming them into life time disorders as in the typical cases of diabetes and terminal renal insufficiency. Acute bacterial infections, dominating morbidity in the old days, were usually successfully treated within few weeks. Unlike these, chronic illnesses were bringing long-term burden for both the patients and the society. Malignant disorders with its complex treatment strategies present particularly demanding medical conditions. Cancer leaves permanent footprint in a life of a patient in terms of poor survival rates, decreased life quality, and working ability.

Humanity has almost won its battle with many infectious diseases, thus increasing longevity, but is now confronted with challenges arising from population aging (1). A blessing turned into a curse as modern societies began struggling with prosperity diseases proliferation (2). Such obstacles are notable in the largest Western Balkan country (1). One-fifth of the Serbian population is aged 65, where that age group holds 8% globally (3). Serbia has a negative population growth and descending fertility rates, which places its population among the oldest in Europe (4). Following these trends, it is estimated that population older than 75 will make up amajority in the next two decades forming a T shaped age pyramid (5). Within the broader South East European region, population aging trend is clearly present for decades and shows clear signs of acceleration (6). This phenomenon originated from tumultuous changes in terms of political and economic stability affecting the Balkans in past decades. During the civil war in the 1990s, there has been an exodus of refugees from former parts of Yugoslavia to Serbia. This influx of people accounted for 5% of the total Serbian population count, but left no positive mark on the overall fertility rates due to similar reproductive behavior of internally displaced people (7). Destitution caused by sanctions placed by the Security Council of the UN forced indigenous people to embark on massive emigrations toward richer and more viable economies. Additional impacts on renewal of demographic potential were “brain drain” consisting of almost 50% of skilled emigrants younger than 40 (8). Difficulties in finding a partner of the opposite sex are also noteworthy. Even though the ratio of men and women is even at reproductive age, the proportion of each gender in rural and urban settings is significantly off-balance (9). Also, the age for womenwhen couples decide on having their first child has shifted from 25 in 2001 to 27 in 2011 (5).

Objectives: The aim of our study was to develop a population pharmacokinetic (PPK) model for 25-hydroxyvitamin D clearance in a healthy young adult population in Serbia. Methods: Study sample consisted of 70 healthy young students of the Faculty of Medical Science, University of Kragujevac, Serbia, with a mean age and body mass index of 22.39 +/- 1.82 years and 21.31 +/- 2.69 kgm(-2), respectively. Non-linear mixed-effect modeling (NONMEM) software was used for data analysis. A validation set of 16 participants was used to estimate the predictive performance of the pharmacokinetic model. Results: In the base model (without covariates), we had parameter estimates of 0.01 L/h for apparent clearance, 0.25 L for apparent volume of distribution, while value of minimum objective function (MOF) was 383.468. The full regression model was established by estimating the effects of 12 covariates. Mean intake of vitamin D from foods (DD) and value of phosphate in serum (PHO) were covariates included in the final model, while others were excluded in this process. The estimated value in the final MOF model was 274.555. The final regression model formula was: clearance (CL) (L/h) = 0.0711 + 0.738 x DD + 0.618 x PHO. Conclusions: The PPK model obtained determined clearance of 25-hydroxyvitamin D in a healthy young adult population in Serbia. Mean intake of vitamin D from foods and serum phosphate level are the most important covariates that influence value of 25-hydroxyvitamin D clearance in healthy young adults.

To assess and compare the costs of first-line monoclonal antibodies (mAbs) treatment protocols in breast cancer, non-Hodgkin lymphoma and colorectal carcinoma in South-Eastern Europe.A retrospective, bottom-up case series study design was implemented with one-year time horizon and payer's perspective. The study sample size was 265 patients (breast cancer, N=137; colorectal cancer, N=44; and non-Hodgkin lymphoma, N=84), while treatment protocols included adjuvant mAbs: trastuzumab (N=137), bevacizumab (N=28), rituximab (N=16) and cetuximab (N=84). ICD-10 related resources use included history of medical services utilization, chronology (time out of service provision) and unit consumption of examinations, drugs prescribed, imaging, radiotherapy and surgical procedures provided etc., direct medical and lost productivity costs (€) across treatment groups during 2010-2013.The average length of observation was 125+97 days per patient. Total mean direct and indirect costs of care were: trastuzumab for breast cancer group € 17,740 per patient; bevacizumab for colorectal carcinoma group €8,775 per patient; cetuximab for colorectal carcinoma group € 27,181 per patient; and rituximab for non-Hodgkin lymphoma group €19,431 per patient. An average mAbs-treated patient incurred €17,897 costs of medical care. The total combined budget of these 330 patients was €4,742,775.The use of mAbs strongly correlated with high costs in first-line cancer medical care and dominated other cost domains. Cetuximab-based treatment protocols in colorectal carcinoma patients was substantially more expensive compared to trastuzumab (C50), bevacizumab (C20), and rituximab (C80) alternatives. Extremely high costs of mAbs are the key-issue for Eastern European policy makers by crossing the upper limits of affordability in middle-income economies.

Background/Aim. Severe dental anxiety (SDA) is the most severe form of dental anxiety, thus the aim of this study was to determine the factors associated with SDA in students of health-related disciplines. Methods. In this case-control study the cases were students with severe dental anxiety. The study was conducted at the Faculty of Medical Sciences, University of Kragujevac, Serbia. The participants were undergraduate students attending lectures during spring semester 2010/2011 (n = 1,812). A random sample of 800 students was assessed for the association between various risk factors and the severe dental anxiety. The main outcome measures were the data on demographics, dental anxiety, habits concerning oral hygiene, nutrition, general anxiety and (co)morbidity which were collected from the study participants by semi-structured questionnaire. Results. Less frequent visits to the dentist (OR adjusted = 7.02 [2.65; 18.60]) and visiting the dentist only when there is a dental problem (OR adjusted = 8.08 [1.28; 50.93]) were associated with severe dental anxiety. The same was true for improper oral hygiene (OR adjusted = 4.25 [1.16; 15.60]). Factors as changing toothbrush more frequently (OR adjusted = 0.33 [0.14; 0.76]) and having chronic disease (OR adjusted = 0.01 [0.00; 0.09]) were inversely associated with severe dental anxiety. The level of education of students was not associated with severe dental anxiety. Conclusion. Inappropriate oral hygiene, less frequent changes of a toothbrush and less frequent visits to the dentist are important risk factors for severe dental anxiety. [Projekat Ministarstva nauke Republike Srbije, br. 175007]

BACKGROUND: Pegylated interferon alfa plus ribavirin protocol is currently considered the most efficient hepatitis C treatment. However, no evidence of costs comparison among common viral genotypes has been published.OBJECTIVES: We aimed to assess core drivers of hepatitis C medical care costs and compare cost effectiveness of this treatment among patients infected by hepatitis C virus with genotypes 1 or 4 (group I), and 2 or 3 (group II).PATIENTS AND MATERIALS: Prospective bottom-up cost-effectiveness analysis from societal perspective was conducted at Infectious Diseases Clinic, University Clinic Kragujevac, Serbia, from 2007 to 2010. There were 81 participants with hepatitis C infection, treated with peg alpha-2a interferon plus ribavirin for 48 or 24 weeks. Economic data acquired were direct inpatient medical costs, outpatient drug acquisition costs, and indirect costs calculated through human capital approach.RESULTS: Total costs were significantly higher (P = 0.035) in group I (mean ± SD: 12,751.54 ± 5,588.06) compared to group II (mean ± SD: 10,580.57 ± 3,973.02). In addition, both direct (P = 0.039) and indirect (P < 0.001) costs separately were significantly higher in group I compared to group II. Separate comparison within direct costs revealed higher total cost of medical care (P = 0.024) in first compared to second genotype group, while the similar tendency was observed for total drug acquisition (P = 0.072).CONCLUSION: HCV genotypes 1 and 4 cause more severe clinical course require more care and thus incur higher expenses compared to HCV 2 and 3 genotypes. Policy makers should consider willingness to pay threshold differentially depending upon HCV viral genotype detected. (Less)

Basic principle of homeopathy is individualized therapy, which finds application also in posology of homeopathic medicines. Posology in homeopathy depends on the state of the patient. Hahnemann's 'Organon', which presents important instructions for correct homeopathic treatment, was published in six editions. Homeopathic medicines are most often prepared in two scales - decimal and centizimal (ratio 1:10 and 1:100), but they also get prepared in M and LM scale (ratio 1:1000 and 1:50 000). Homeopathic aggravation is not necessary confirmation of action of medicine. Evolution of conclusions on posology of homeopathic medicine had a crucial moment: in the forth edition of 'Organon' Hahnemann said that medicines should be administered in form of several granules, while in the fifth edition he introduced the main correction in posology, that medicines should be adminstered in water solutions. In the sixth edition of 'Organon' Hahnemann confirmed this postulate by adding new ones about the use of LM potencies. In order to dose homeopathic medicine correctly, it is necessary to have thorough knowledge of classical homeopathy, requiring sometimes, for the sake of patient's benefit, corrections in already well established posology practice.