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Introduction : To assess incidence and mortality trends of acute myeloid leukemia (AML) in Belgrade (Serbia) in a 15-year period (from 1999 to 2013). Material and Methods: Data were obtained from the Cancer Registry of Serbia, Institute of Public Health of Serbia. Standardized incidence and mortality rates per 100,000 inhabitants were calculated by direct standardization method using World Standard Population. Analysis of raw data indicated single-digit numbers per year and per 5-year age cohorts. Therefore, we merged years of diagnosis to three-year intervals, creating so-called "moving averages". We also merged study population to 10-year age cohorts. Results: Both incidence and mortality rates increased with age, i.e., the lowest rates were observed in the youngest age groups and the highest rates were observed in oldest age groups. In all age groups, except the youngest (15⁻24 years), AML incidence was statistically significantly higher in men compared with women. Average age-adjusted incidence was 2.73/100,000 (95% confidence interval (CI) 2.28⁻3.71). Average age-adjusted mortality was 1.81/100,000 (95% CI 1.30⁻2.26). Overall, there were no significant changes in incidence trend. Age-adjusted incidence rates had increasing tendency among men aged 65⁻74 years (B = 0.80, standard error (SE) = 0.11; p = 0.005) and in total population aged 65⁻74 years (B = 0.41, SE = 0.09; p = 0.023). Increasing tendency in incidence of AML among women was observed in age group >75 years (B = 0.63, SE = 0.14; p = 0.019). No changes of mortality trend were observed. Conclusion: There was no significant change in trends of AML from 1999 to 2013 in the population of Belgrade., Competing Interests: The authors declare no conflict of interest.

Aim: Our aim was to explore the influence of 9-bp insertion/deletion and variable number of 9 bp elements (63/91) length polymorphism in noncoding interfering RNA and major promoter of DHFR gene on methotrexate (MTX) efficacy and toxicity in patients with rheumatoid arthritis (RA)., Patients & Methods: Response to the MTX therapy and adverse effects were estimated in 243 RA patients genotyped for the selected polymorphism., Results: The presence of allele 1 of analyzed polymorphism had significant protective effect against MTX toxicity (odds ratio: 0.37 [95% CI: 0.19-0.70]; p = 0.002). Results remained significant in multiple logistic regression analysis with the inclusion of disease and treatment features in the model (p = 0.03)., Conclusion: Polymorphism 63/91 in DHFR gene promoter can modulate the onset of MTX-related adverse effects in RA patients.

Nitric oxide (NO) is a mediator in autoimmune responses and thus involved in the pathogenesis of a variety of rheumatic diseases. Genetic factors that influence the expression of the enzyme endothelial nitric oxide synthase (eNOS) that catalyzes NO synthesis are important for the control of NO level and consequently its activity. We have analyzed three functionally relevant polymorphisms of eNOS gene: T-786C, G894T and VNTR (4a/b), to investigate whether they are predisposing factors in pathogenesis of RA in Serbian population and to evaluate their role in clinical manifestations of RA. We performed genotyping of 196 patients with RA and the control group of 132 healthy individuals from Serbian population, using PCR and polymerase chain reaction-restriction fragment length polymorphism methods. Disease activity was prospectively assessed using number of tender joints, number of swollen joints and 28-joints disease activity score (DAS28). There were no differences between the patients and control groups in the genotypes and alleles frequencies of the three analyzed SNPs. Our results showed statistically significant differences in all three analyzed parameters of disease severity between 786TT/786CT and 786CC genotypes and between 894GG/894GT and 894TT genotypes. In the case of 4a/b polymorphism, carriers of minor allele had significantly lower DAS28 values. In conclusion, our results do not support the implication of analyzed eNOS gene polymorphisms in susceptibility to RA but associate them with the disease activity and give assumption that minor alleles are indicators of better clinical course.

The aim of this study was to determine whether e-learning as a new teaching concept was acceptable for second-year undergraduates and to compare attitudes and exam results of students who followed electronic compared with classroom seminars. The electronic seminars (e-seminars) were developed several months prior to start of the epidemiology course for second-year students at the Faculty of Medicine, University of Belgrade. The students who applied for e-seminars accessed their content during summer semester (February-May) 2014. E-seminars were set according to the existing topics in practical workbook and designed using Moodle, a free, open-source, personal home page web application for producing modular internet-based courses. To evaluate the motives for enrollment and satisfaction with seminars, two surveys (pre- and post-course) were administered. Students' exam grades were registered over 4 exam sessions (June-October 2014) and compared according to seminar program. Out of 516 students in the second year, 60 (11.6 %) applied for e-seminars (mean age 21 years). Students considered the reason "It's easier to do assignments from home" as the strongest motive to participate. When compared to classroom seminars, students in e-seminars had significantly more fun (p = 0.003), thought that e-seminars were better mode to learn epidemiology (p = 0.030) and would recommend them to other colleagues (p = 0.001). There was no significant difference in average grade received at the oral exam in epidemiology (t = 0.071, p = 0.944). E-seminars in undergraduate epidemiology course add a novel, easy-to-follow and amusing mode of learning. Based on this pilot study, e-seminars in epidemiology will be available for next generations of students, while further improvement of e-seminars could include expansion of seminar syllabus and development of discussion fora.

Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy during childhood. Mutations in dystrophin (DMD) gene are also recognized as a cause of cognitive impairment. We aimed to determine the association between intelligence level and mutation location in DMD genes in Serbian patients with DMD. Forty-one male patients with DMD, aged 3 to 16 years, were recruited at the Clinic for Neurology and Psychiatry for Children and Youth in Belgrade, Serbia. All patients had defined DMD gene deletions or duplications [multiplex ligation-dependent probe amplification (MLPA), polymerase chain reaction (PCR)] and cognitive status assessment (Wechsler Intelligence Scale for Children, Brunet-Lezine scale, Vineland-Doll scale). In 37 patients with an estimated full scale intelligence quotient (FSIQ), six (16.22%) had borderline intelligence (70

Developmental delay and intellectual disabilities (DD/ID) are significant health problems affecting 3% of the human population. Submicroscopic chromosomal rearrangements involving subtelomeric regions are often considered to be the cause of unexplained DD/ID. Screening of subtelomeric regions was performed in 80 unrelated patients with DD/ID and normal GTG-banded chromosomes using the MLPA method with two kits (SALSA P070-B1 and P036-E1). The MLPA screening revealed subtelomeric chromosome aberrations in four cases (5%). The aberrations detected were: 1p deletion, 1p deletion combined with 12q duplication, 4p deletion, and 9p deletion combined with 15q duplication. The deletions detected were classified as causative for the patients' observed phenotypes. This study confirms the high frequency of subtelomeric rearrangements in unexplained DD/ID and reinforces the argument for routine subtelomeric screening in order to get a correct diagnosis, establish genotype-phenotype correlations and offer accurate genetic counseling.

Objectives: The aim of this study was to examine the epidemiology of occupational accidents and self-reported attitude of health-care workers (HCWs) in Serbia., Subjects and Methods: A cross-sectional study was conducted among HCWs in selected departments of five tertiary care hospitals and in one secondary care hospital in February 2012. A previously developed self-administered questionnaire was provided to HCWs who had direct daily contact with patients. χ(2) test and Student's t test were used for statistical analysis of the data., Results: Of the 1,441 potential participants, 983 (68.2%) completed the questionnaire: 655 (66.7%) were nurses/medical technicians, 243 (24.7%) were physicians and 85 (8.6%) were other personnel. Of the 983 participants, 291 (29.6%) HCWs had had at least one accident during the previous year and 106 (40.2%) of them reported it to the responsible person. The highest prevalence (68.6%) of accidents was among nurses/technicians (p = 0.001). Accidents occurred more often in large clinical centers (81.1%; p < 0.001) and in the clinical ward, intensive care unit and operating theater (p = 0.003) than in other departments. Seventy-six (13.1%) nurses/medical technicians had an accident during needle recapping (p < 0.001). Of all the HCWs, 550 (55.9%) were fully vaccinated, including significantly more doctors (154, 63.4%) than participants from other job categories (p < 0.001)., Conclusion: There was a relatively high rate of accidents among HCWs in our hospitals, most commonly amongst nurses and staff working in clinical wards, intensive care units and operating theaters. The most common types of accidents were needlestick injuries and accidents due to improper handling of contaminated sharp devices or occuring while cleaning instruments or by coming into contact with blood through damaged skin or through the conjunctiva/mucous membranes., (© 2014 S. Karger AG, Basel.)

Purpose: Gamma-glutamyl hydrolase (GGH), cyclin D1 (CCND1) and thymidylate synthase (TS) genes encode enzymes that are involved in methotrexate (MTX) action. In a group of 184 RA patients treated with MTX, we have investigated whether selected polymorphisms in these genes modulate MTX efficacy and/or have impact on adverse drug effects (ADEs)., Methods: The efficacy of the MTX therapy has been estimated using the disease activity score in 28 joints (DAS28-ESR) based on EULAR criteria and relative DAS28 values (rDAS28). All adverse drug events were recorded. Patients were genotyped for selected polymorphisms of the GGH (-354 G > T and 452 C > T), CCND1 (870 A > G) and TYMS (variable number of tandem repeats, VNTR, and G to C substitution of triple repeat, 3R allele) gene. Association studies have been performed between obtained genotypes and the efficacy and toxicity of MTX., Results: According to the EULAR response criteria, 146 RA patients (79.3 %) were classified as responders (good/moderate response) and 38 (20.7 %) as non-responders (poor response). Higher frequency of the TYMS 3 G/3 G genotype has been found among non-responders as compared to individuals with remaining genotypes (p = 0.02). ADEs were recorded in 53 patients. Among those patients eight experienced bone marrow toxicity, all of them carried GGH -354GG genotype (p = 0.003). No other significant association were observed., Conclusion: The 3 G/3 G genotype of the TYMS gene may indicate predisposition of poor response to MTX and GG genotype of GGH -354 T > G polymorphism may have high predictive value for myelosuppression in RA patients.

Objectives: Identifying genetic predictors of methotrexate (MTX) treatment response in patients with rheumatoid arthritis (RA) may have great importance for optimising drug doses required for clinical benefit without toxicity. In a group of 125 RA patients treated with MTX we investigated whether selected polymorphisms in genes relevant for MTX action (aminoimidazole-4-carboxiamide ribonucleotide transformylase, ATIC, and dihydrofolate reductase, DHFR) modulate disease activity and/or have impact on therapy side effects., Methods: The efficacy of treatment was estimated both by the disease activity score in 28 joints (DAS28), based on EULAR criteria, and relative DAS28 (rDAS28) score. Adverse drug events (ADEs) were also recorded. RA patients were genotyped using the PCR-RFLP method, followed by an association study between ATIC -129T>G, DHFR -216T>C and DHFR -317A>G polymorphisms and the efficacy and toxicity of MTX., Results: According to the EULAR response criteria, 96 RA patients (76.8%) were classified as responders (good/moderate response) and 29 (23.2%) as non-responders (poor response). rDAS28 values ranged from -0.01 to 0.80 (mean value 0.31±0.19). Among 125 patients enrolled in this study 39 experienced at least one side effect. The DHFR -317AA genotype was associated with the less favourable response (reduction in rDAS28 score, p=0.05). None of the analysed polymorphisms was associated with MTX toxicity., Conclusions: RA patients with DHFR-317AA genotype had less favourable response to MTX. Further studies in larger patient populations are necessary to confirm the relationship between the analysed polymorphisms and MTX treatment response.

Introduction: Assuming that spina bifida (SB) is a genetically controlled disease, the aim of our study was to evaluate the degree of genetic homozygosity and the distribution of AB0 blood types among patients with SB occulta and SB aperta by the homozygously recessive characteristics (HRC) test., Material and Methods: Our study included an analysis of the presence, distribution and individual combination of 15 selected genetically controlled morpho-physiological traits in a sample of 100 patients with SB (SB occulta N = 50 and SB aperta N = 50) and a control group of individuals (N = 100)., Results: We found a statistically significant difference between the mean values for genetic homozygosity (SB 4.5 ±0.3; control 3.0 ±0.2, p < 0.001) and also differences in the presence of certain individual combinations of such traits. In 12 (80.0%) of the 15 observed characteristics, recessive homozygosity was expressed to a greater degree among the group of SB patients, while for 9 (60.0%) of the traits this level of difference was statistically significant (Σ(χ) (2) = 266.3, p < 0.001). There was no difference in average homozygosity of such genetic markers between groups of SB occulta and SB aperta patients, but the type of individual variation in the two studied groups significantly differed. In the group of patients with SB the frequency of 0 blood group was significantly increased while B blood group was significantly decreased., Conclusions: Our results clearly show that there is a populational genetic difference in the degree of genetic homozygosity and variability between the group of patients with SB and individuals without clinical manifestations, indicating a possible genetic component in the aetiopathogenesis of spina bifida.

A case-control study of 110 consecutive psoriatic outpatients and 200 unmatched controls was carried out in order to analyze the association of psoriasis with smoking habits, alcohol consumption, family history of psoriasis and stressful life events. Stressful life events were assessed with Paykel's Interview for Recent Life Events, a semi-structured interview covering 63 life events. According to our results, the risk of psoriasis is higher in urban dwellers (odds ratio [OR] = 3.61; 95% confidence interval [CI] = 0.99-13.18), patients who were divorced (OR = 5.69; 95% CI = 2.26-14.34) and those exposed to environmental tobacco smoke at home (OR = 2.29; 95% CI = 1.12-4.67). Alcohol consumption (OR = 2.55; 95% CI = 1.26-5.17), family history of psoriasis (OR = 33.96; 95% CI = 14.14-81.57) and change in work conditions (OR = 8.34; 95% CI = 1.86-37.43) are also risk factors for psoriasis. Separate analyses for men and women showed that the risk of developing psoriasis was stronger in men with a family history of psoriasis (OR = 30.39; 95% CI = 6.72-137.42) than in women (OR = 16.99; 95% CI = 7.21-40.07). The effect of environmental tobacco smoke at home was found only in women (OR = 2.44; 95% CI = 1.26-4.73). Future well-designed epidemiological studies need to be performed in order to determine whether lifestyle factors and stress could be risk factors triggering or aggravating psoriasis.

Background: In the last decade of the 20th century, a considerable effort has been put into the development of summary measures of population health that combine information on mortality and non-fatal health outcomes. We used the DALYs (Disability adjusted life years) method to assess the burden of disease and injury in the population of Serbia., Methods: Our study, largely based on the methods developed for the Global burden of disease study, was conducted between October 2002 and September 2003. DALYs, stratified by gender and age, were calculated for 18 selected health conditions for the population of Serbia, Serbia and Montenegro for 2000. Years of life lost (YLL) were calculated using country mortality statistics, while years lived with disability (YLD) were calculated using different sources of information. Also, the YLD/YYL ratio and age-adjusted rates of DALYs were calculated., Results: Ischaemic heart disease, cerebrovascular diseases, lung cancer, unipolar depressive disorders, and diabetes mellitus were responsible for almost two-thirds (70%) of the total burden of 18 selected disorders in Serbia 2000. The leading five causes for males were ischaemic heart disease (26.1 DALY per 1000), stroke (17.9), lung cancer (12.7), road traffic accidents (6.5), and self-inflicted injuries (5.5). For females, the leading five causes were stroke (18.1 DALY per 1000), ischaemic heart disease (14.1), depression (8.7), breast cancer (6.1), and diabetes mellitus (5.2)., Conclusions: The final results of the study have shown that the national health priority areas should cover cardiovascular diseases, cancers, and mental health.