Assessment and Prediction of Adherence to Methotrexate Using Three Self-Report Questionnaires in Patients with Rheumatoid Arthritis.

Introduction: Methotrexate (MTX) reduces rheumatoid arthritis activity and ameliorates the long-term functional status in these patients. To achieve this aim, patients need to take their medication regularly. Nevertheless, non-adherence to MTX still remains a considerable issue in the management of rheumatoid arthritis. Objective: This study aimed to estimate the adherence to methotrexate in patients with rheumatoid arthritis and to identify specific non-adherence risk factors. Methods: A cross-sectional study included 111 patients (mean age 56.2 ± 10.6 years, 78.4% female, and mean disease duration 6 years (3-13)). Three adherence self-assessment questionnaires were used: the Compliance-Questionnaire-Rheumatology (CQR19), the Medication Adherence Reports Scale (MARS-5), and the Visual Analogue Scale (VAS). We also collected demographic data, disease and treatment characteristics, and anxiety/depression estimation results (Hospital Anxiety and Depression Scale, HADS). Results: Adherence was identified in 48.6% of patients (COR19), 70.3% of patients (MARS-5), and 82.9% of patients (VAS questionnaire). All three questionnaires displayed a significant positive mutual correlation: CQR19 with MARS-5 and VAS (r = 0.364, r = 0.329, respectively, p < 0.001 for both) and between the VAS and MARS-5 scores (r = 0.496, p < 0.001). A significant positive prediction was shown for urban residence (0.347 (0.134-0.901), p = 0.030) using the MARS-5, female sex (0.264 (0.095-0.730), p = 0.010) according to the CQR19, and for a dose of methotrexate (0.881 (0.783-0.992), p = 0.036) using the VAS, while negative predictions were shown for comorbidity number (3.062 (1.057-8.874), p = 0.039) and depression (1.142 (1.010-1.293), p = 0.035) using the MARS-5 and for older age (1.041 (1.003-1.081), p = 0.034) according to the CQR19. The use of steroids was a significant positive predictor in all three questionnaires and remained an independent predictor for methotrexate adherence in the multivariate logistic regression. Conclusions: We showed non-adherence to methotrexate in a significant number of patients using all three questionnaires. Concomitant steroid therapy emerged as an independent positive predictor for adherence.

Are pediatricians responsible for maintaining high MMR vaccination coverage? Nationwide survey on parental knowledge and attitudes towards MMR vaccine in Serbia.

AIM: To assess parental knowledge and attitudes related to MMR vaccination and to determine factors associated with parental decision whether to vaccinate their child with MMR vaccine in Serbian population. METHODS: The selection of participants was performed using multi-phase sampling. Seventeen out of the total 160 public health centers on the territory of Republic of Serbia were randomly selected. All parents of children up to the age of 7 who visited the pediatrician at the public health centers from June to August 2017 were recruited. Parents filled in an anonymous questionnaire regarding their knowledge, attitudes and practices in immunization with MMR vaccine. The relative contribution of different factors was explored by univariable and multivariable logistic regression analysis. RESULTS: The majority of parents were female (75.2%), with mean age of 34.3 ± 5.7 years, and the average age of children was 4.7 ± 2.4 years, 53.7% of them were girls. In the multivariable model, getting information on vaccination from a pediatrician was associated with 7.5 fold increased probability to vaccinate child with MMR vaccine (OR = 7.52; 95% CI 2.73-20.74; p<0.001), while previous vaccination of the child increased this chance two times (OR = 2.07; 95% CI 1.01-4.27; p = 0.048), and having two children was associated with 84% increase in chance of vaccinating child with MMR vaccine compared to having one child or three or more children (OR = 1.84; 95% CI 1.03-3.29; p = 0.040). CONCLUSION: Our study emphasized the key role of pediatricians in the formation of parental attitude on MMR vaccination of their child.

Linguistic adaptation and psychometric properties of the health literacy questionnaire in serbian language among people with chronic diseases.

OBJECTIVE: To translate the Health Literacy Questionnaire (HLQ) to Serbian language and examine its psychometric characteristics. METHODS: This cross-sectional study was conducted among 295 people with chronic diseases from the Foca region (Republic of Srpska, Bosnia and Herzegovina). The HLQ was translated according to the translation integrity procedure. Construct validity was tested using confirmatory factor analysis (CFA) using the maximum likelihood estimator and reliability was estimated using the α and ω coefficients. RESULTS: Minor linguistic differences in 17 items were observed between the original and the initial forward translation and were corrected. The parameters of one-factor CFA on domains 3 and 8 fitted well. The parameters of the CFA for domains 1, 2, 4, 5, 6, 7 and 9 were acceptable after modification using residuals' correlation. The α and ω coefficients for all domains were good to excellent (>0.80). CONCLUSION: Each domain of the HLQ in Serbian has acceptable construct validity and overall good reliability. This study adds to the growing evidence that the HLQ is a useful tool to provide in-depth multidimensional information on health literacy to improve researchers and policymakers understanding of the health literacy strengths, needs and preferences across cultures and languages.

Immunogenicity and Reactogenicity of the Booster Dose of COVID-19 Vaccines and Related Factors: A Panel Study from the General Population in Serbia.

The Republic of Serbia applied the booster dose of the following COVID-19 vaccines: BNT162b2 mRNA (Pfizer-BioNTech), Sinopharm BBIBP-CorV (Vero Cell®), Gam-COVID-Vac (Sputnik V) and ChAdOk1 nCoV-19 (AstraZeneca). We aimed to examine the immunogenicity and reactogenicity of the booster dose and identify factors related to immune response and adverse events. Panel study, conducted during August and September 2021, included 300 persons receiving the booster dose at the Institute of Public Health of Serbia. Blood samples were taken on the day of receiving the booster dose, and after 7 and 28 days. When applying homologous regimen, the average increase in anti-spike immunoglobulin G was 8782.2 (after 7 days), 1213.9 after 28 days, while 9179.5 (after 7 days) and 16,728.1 after 28 days of heterologous regimen. Sinopharm BBIBP-CorV (p < 0.001) and Sputnik V (p < 0.001), age 65 and over (p = 0.001) and currently smoking (p < 0.001) were independently associated with lower levels of anti-spike immunoglobulin G. Female sex (OR = 1.77; 95%CI = 1.01−3.12), previous COVID-19 infection (OR = 3.62; 95%CI = 1.13−11.63) and adverse events after the second dose (OR = 2.66; 95%CI = 1.33−5.32) were independently associated with intense systemic adverse events 7 days after. Booster dose significantly increased antibodies titers, especially 28 days after heterologous regimen, without a significant increase in reactogenicity.

Trend in mandatory immunisation coverage: linear and joinpoint regression approach, Serbia, 2000 to 2017.

BackgroundAnalyses of temporal trends in immunisation coverage may help to identify problems in immunisation activities at specific points in time. These data are essential for further planning, meeting recommended indicators, monitoring, management and advocacy.AimThis study examined the trends of mandatory vaccination coverage in the period 2000-2017 in Serbia.MethodsData on completed immunisations were retrieved from annual national reports of the Institute of Public Health of Serbia during the period 2000-2017. To assess the trends of immunisation coverage, both linear and joinpoint regression analyses were performed. A probability p < 0.05 was considered significant.ResultsOver the period 2000-2017 linear regression analysis showed a significant decline in coverage with the primary vaccination against poliomyelitis, diphtheria, tetanus, pertussis and measles, mumps, rubella (MMR) (p ≤ 0.01). In the same period, coverage of all subsequent revaccinations significantly decreased, namely, first revaccination for pertussis (p < 0.01); first, second and third revaccination against diphtheria, tetanus and poliomyelitis (p < 0.01); and second dose against MMR before enrolment in elementary school (p < 0.05). Although linear regression analysis did not show change in vaccination coverage trend against tuberculosis (Bacillus Calmette-Guérin; BCG), hepatitis B (HepB3) in infants and diseases caused by Haemophilus influenzae type b (Hib3), the joinpoint regression analysis showed that the coverage declined for BCG after 2006, HepB3 after 2010 and Hib3 after 2008.ConclusionTo achieve and keep optimum immunisation coverage, it is necessary to address barriers to immunisation, such as the availability of all vaccines and vaccine-hesitancy among parents and healthcare workers in Serbia.

Is exposure to indoor secondhand smoke associated with poor mental health? Results from non-conflict and post-conflict setting.

The purpose of this study was to examine the association between exposure to indoor SHS and self-reported HRQoL among healthy non-smoking students at the University of Belgrade, Serbia and Kosovska Mitrovica located in the post-conflict Kosovo province. Students who presented at Student Public Health Center in Belgrade in 2009 and Kosovska Mitrovica in 2015 for mandatory health checks were invited to participate. Data were collected using socio-demographic and behavioral questionnaire, health-related quality of life questionnaire Short Form-36 (SF-36) and Beck Depression Inventory (BDI). A total of 82.3% students in Belgrade sample and 76.0% in Kosovska Mitrovica sample reported daily exposure to indoor SHS. After adjustment for socio-demographic characteristics and behavior, daily exposure to indoor SHS for more than 6 hours was associated with poorer Vitality (ß = -5.55, 95% confidence interval [CI] -9.49, -1.61) and Mental Health (ß = 5.00, 95% CI-8.94, -1.07) only among students at the University of Belgrade. This study showed that the association between longer daily indoor SHS exposure and poor mental health HRQoL was not consistent in non-conflict and post-conflict setting. This association was not found in a post-conflict setting. Strict no smoking policies are needed in student housing, university campuses and all public spaces.

The prevalence of comorbidities in patients with multiple sclerosis: population-based registry data.

BACKGROUND: Comorbidities occur frequently in persons with multiple sclerosis (MS). The aim of the present study was to determine the prevalence of the most common comorbidities in the population of MS patients in Belgrade, Serbia. MATERIAL AND METHODS: Data on diagnosed and fully documented comorbidities were taken from the Belgrade MS population registry. The list of explored comorbidities included cardiovascular, malignant, and autoimmune diseases; psychiatric disorders; epilepsy; and type 2 diabetes. In the data analysis, crude, age- and gender-specific, and age-adjusted prevalence was calculated. Additionally, comorbidities were analyzed in patients with various MS phenotypes. RESULTS: The most prevalent group of comorbidities were psychiatric (prevalence (Prev) = 20.59%, 95% CI 19.10-22.17) and cardiovascular comorbidities (Prev = 15.23%, 95% CI 13.93-16.63). The most prevalent single comorbidities were depression (Prev = 11.82%, 95% CI 10.64-13.11) and hypertension (Prev = 11.41%, 95% CI 10.25-12.68). Type 2 diabetes was significantly more prevalent in patients with primary progressive MS compared with the patients with relapsing-remitting and secondary progressive MS (p < 0.001). We found statistically significant positive correlation between number of comorbidities and progression index (p < 0.001). Patients treated with disease-modifying therapies (DMTs) had significantly higher risk of developing comorbidity, after treatment initiation, compared with those who were untreated (p = 0.001). CONCLUSIONS: Our study demonstrated high prevalence of comorbidities in persons with MS, with psychiatric and cardiovascular diseases being the most common. Furthermore, our findings confirmed the association of comorbidities with progression of disability and emphasized their role in treatment decision-making in MS.

Epidemiology, diagnosis and management of sexual dysfunction in multiple sclerosis.

Multiple sclerosis (MS) is the most common chronic neurological disorder in young adults, with numerous potential effects on neurologic function. Sexual dysfunction (SD) is a common and very stressful one in persons with MS and represents a significant burden of disease. It has been shown that proportion of SD in MS is greater than in other neurological diseases, and almost five times higher than in the general population. Since there is no consistent definition in the literature for the diagnosis of SD, various studies reported a prevalence of SD of 40-80% in women and 50-90% in men with MS. The nature of sexual changes in this chronic illness is best defined as primary, secondary, and tertiary. Recently, it has been emphasized that detailed sexual history is crucial for all SD assessments and diagnoses. Committee 3 of the international consultation on sexual medicine suggested an updating algorithm for diagnostic evaluation of SD in both genders, with specific recommendations related to sexual history taking and diagnostic evaluation. Because treatments and preventive strategies might manage SD, it is necessary to increase the focus on these aspects of the disease when counselling patients. Management of SD should be comprehensive because the symptoms could be somatic, psychological, or related to relationship problems.

Tobacco smoking and health-related quality of life among university students: Mediating effect of depression.

The aim of this study was to assess the association between cigarette smoking and health-related quality of life (HRQoL) among students in two different universities, and the potential mediating effect of depression. Participants were students who came for mandatory check-ups at Student Health Care Centers in two Universities in Serbia, differing by socio-politically and economically environments. Students completed socio-demographic questionnaire, Beck Depression Inventory (BDI) and the SF-36 questionnaire for assessment of HRQoL. In both populations, after adjustment for socio-demographic, behavioral and health factors, smoking was associated with poorer Mental Composite Score (MCS) and Physical Composite Score (PCS) (Belgrade 1,624 students: MCS ß = 3.38, 95% confidence interval [CI] 1.31, 5.44, PCS ß = 1.01, 95% CI -0.50, 2.52; Kosovska Mitrovica 514 students: MCS ß = 5.06, 95% CI 1.74, 8.37, PCS ß = 3.29, 95% CI 0.75, 5.83). After additional adjustment for BDI score, the observed associations were lost (Belgrade: MCS ß = 1.12, 95% CI -0.57, 2.80, PCS ß = -0.40, 95% CI -1.71, 0.92; Kosovska Mitrovica: MCS ß = 0.77, 95% CI -2.06, 3.60, PCS ß = 0.56, 95% CI -1.75, 2.87). Higher BDI score was associated with poorer PCS and MCS across all quintiles. The association of smoking with impairment of HRQoL among university students in two different settings was mediated by higher levels of depressive symptoms. These findings highlight the need for further research on the interaction between smoking, mental health and quality of life, with implications for prevention, diagnosis and treatment.

Towards a Framework for Research Ethics Education for Physicians in Serbia.

With growing opportunities for medical doctors to work either in academia and industry, research ethics education for health sciences research, meaning research which includes humans and animals and/or their tissues and cells with the goal to understand underlying mechanisms of disease occurrence and disease treatment, is of paramount importance, especially in regions, such as Serbia, where comprehensive research ethics curricula for physician researchers are lacking. This article addresses the spectrum of research ethics topics that were identified through analysis of the existing research ethics curricula in medical schools, international organizations, Serbian legislative codes and the PubMed database applying the key search terms: ethics, research, biomedical, education, curriculum, program, course and their combinations. Selected topics were classified in eight syllabi based on their similarity: #1 Responsible conduct of research, #2 Justice in human subjects research, #3 Research on human subjects, #4 Vulnerable population groups, #5 Conflict of interest, #6 Research on animals, #7 Research on genes, cells and embryos, and #8 Organization of research ethics. Justifications for each syllabus are discussed based on empirical evidence and local context. Higher education authorities could use this framework to strengthen, adjust or refine research ethics education for physician researchers in Serbia.

PERCEPTION OF FIRST-YEAR VERSUS SIXTH-YEAR MEDICAL STUDENTS IN SERBIA ON STUDYING MEDICINE AND POSTGRADUATE CAREER.

Self-perceived stress during undergraduate medical training could influence forthcoming career choices. The aim of this study was to explore the attitudes and potential differences between 1st and 6th year students regarding aspects of medical training and career plans. As many as 570 students in 1st and 400 in 6th year of studies at the Faculty of Medicine, University of Belgrade, were recruited on December 2-9, 2013. Data were acquired through a self-administered questionnaire. Students in both years rated "Helping other people" as the most important reason to study medicine. Freshmen rated statistically significantly higher 'good incomes' and 'social status' as reasons to study medicine (p=0.003 and p=0.037, respectively). The most desirable fields of specialization were surgery and internal medicine (36.4% and 18.7% for 1st year, and 26.3% and 36.6% for 6th year, respectively). Significantly more freshmen would prefer working abroad (χ2=3.891, p=0.029). In terms of careers abroad, students in both years expressed the highest interest in working in western and northern Europe. Desires for specialty training among medical students follow the pattern of the most frequent disciplines in the Serbian physician population, with gender differences comparable to other populations. A certain percentage of students would likely emigrate.

Longitudinally extensive transverse myelitis in a patient infected with West Nile virus.

Until now, longitudinally extensive transverse myelitis (LETM) was reported in association with various viral infections. We describe the case in which a diagnosis of LETM was established as a clinical manifestation of West Nile virus (WNV) infection. We report a 39-year old man with WNV infection and LETM. In neurological examination, there was a left periscapular hypotrophy, moderate weakness of left arm, decreased left brachioradialis reflex, tandem instability and gait ataxia. Cervical spine MRI showed enhancing intramedullary lesion extending from C3-C7 level. According to the neurological, EMG and MRI findings, a diagnosis of LETM, with affection of anterior horn cells of the cervical spinal cord, induced by WNV infection was established. The patient was treated with antibiotics, acyclovir and high dose-steroids, methylprednisolone (MP) 1 g/daily in intravenous infusion, for 5 consecutive days, followed by tapering doses of prednisone during the next four months. Six weeks after onset of symptoms, previously described lesion on cervical spine MRI resolved, and the patient gradually clinically improved.

Long-term disability outcomes in relapsing-remitting multiple sclerosis: a 10-year follow-up study.

OBJECTIVE: The aim of this study is to assess the impact of interferon (IFN) beta treatment on the development of worsening disability in relapsing-remitting (RR) multiple sclerosis (MS) patients in the single-center observation cohort. METHOD: This is a prospective study of 236 IFN-beta-treated and 183 untreated RRMS patients recruited consecutively at the Clinic of Neurology in Belgrade (Serbia). Out of this original cohort, 10-year follow-up data were available for 233 IFN-beta-treated and 131 untreated subjects. The median time since recruitment was 9.7 years. RESULTS: IFN-beta treatment significantly delayed (p < 0.001) the time to reach each of the clinical outcomes (secondary progression-SP, EDSS scores 4 and 6) since recruitment. Time from the first visit to SP was reached after 9.7 years for IFN-beta-treated vs. 7.8 years for untreated patients. The delay for the development of EDSS score ≥ 4 from the first visit was 1.6 years (8.7 years for IFN-beta-treated vs. 7.1 years for untreated patients). Time from the first visit to EDSS score of 6 was reached after 9.8 years for IFN-beta-treated vs. 8.8 years for untreated patients. The IFN-beta-treated group showed significant reduction (p < 0.001) in the risk of conversion to SP when compared with untreated patients (HR = 0.22). There was also a significant difference in reaching EDSS scores 4 and 6 (p < 0.001), in favor of the IFN-beta-treated group (HR = 0.40 and HR = 0.27, respectively). CONCLUSION: Comparison of outcomes in our IFN-beta-treated vs. untreated RRMS patients suggests that this treatment may delay development of long-term disability in MS.

Flu vaccination among older persons: study of knowledge and practices.

BACKGROUND: Surveys of older adults' knowledge relative to flu immunization have highlighted its relevance in the improvement of vaccination coverage. The purpose of this study was to estimate the proportion of older persons who have ever been immunized against seasonal flu in the municipality of Vracar (Belgrade, Serbia), assess their knowledge related to flu and flu vaccination, and to determine factors associated with flu immunization. METHODS: In the period November 2012-January 2013, 480 persons aged above 65 years were recruited at the Community Health Center, of which 354 persons were finally included in the study. Data were collected using a questionnaire. To assess the level of knowledge, correct answers were awarded 1 point. The total knowledge score ranged from 0 to 17 and was divided into three levels: poor (0-4 points), moderate (5-8 points), good (9-13 points), and excellent (14-17 points). RESULTS: The proportion of ever vaccinated older persons was 47.7%. Of those, one third (29.1%) had been immunized regularly. Most seniors (61.9%) demonstrated good, whereas one third (29.8%) demonstrated excellent level of knowledge. In terms of reasons for non-compliance, the highest proportion of older persons declined vaccination because "they were in good health" (33.5%) and because "they did not believe that vaccine protects from flu" (31.5%). Independent predictors of being ever immunized against seasonal flu were having higher level of education, being more knowledgeable relative to flu vaccination, and taking more medications. CONCLUSIONS: Our results indicate that health care sector requires well-coordinated promotion campaigns to enhance acceptance of flu vaccination. Organized immunization counseling could provide accurate, evidence-based information in order to transform misbeliefs, prejudice, and negative attitude towards vaccination.

Association of uPA and PAI-1 tumor levels and 4G/5G variants of PAI-1 gene with disease outcome in luminal HER2-negative node-negative breast cancer patients treated with adjuvant endocrine therapy.

BACKGROUND: The aim of this study was to evaluate the prognostic potential of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) tumor tissue levels and examine the association between these biomarkers and classical prognostic factors in early node-negative luminal breast cancer patients. The clinical value of 4G/5G variants of PAI-1 gene was evaluated. PATIENTS AND METHODS: This study involved 81 node-negative, estrogen receptor-positive and/or progesterone receptor-positive and human epidermal growth factor receptor 2-negative operable breast cancer patients who underwent radical surgical resection and received adjuvant endocrine therapy. Determination of uPA and PAI-1 concentrations in the breast cancer tissue extracts was performed using FEMTELLE® uPA/PAI-1 ELISA. An insertion (5G)/deletion (4G) polymorphism at position - 675 of the PAI-1 gene was detected by PCR-RFLP analysis. RESULTS: Our research showed that patients with uPA tumor tissue levels higher than 3 ng/mg of protein had significantly reduced disease-free survival (DFS) and overall survival (OS) when compared to patients with uPA tumor tissue levels lower or equal to 3 ng/mg of protein. Patients with PAI-1 tumor tissue levels higher than 14 ng/mg of protein had significantly decreased OS in comparison with patients with PAI-1 tumor tissue levels lower or equal to 14 ng/mg of protein. ROC analysis confirmed the uPA and PAI-1 discriminative potential for the presence/absence of relevant events in these patients and resulted in higher cut-off values (5.65 ng/mg of protein for uPA and 27.10 ng/mg of protein for PAI-1) than standard reference cut-off values for both biomarkers. The prognostic importance of uPA and PAI-1 ROC cut-off values was confirmed by the impact of uPA higher than 5.65 ng/mg of protein and PAI-1 higher than 27.10 ng/mg of protein on poorer DFS, OS and event-free survival (EFS). We observed that patients with dominant allele in PAI-1 genotype (heterozygote and dominant homozygote, - 675 4G/5G and - 675 5G/5G) had significantly increased DFS, OS and EFS when compared with patients with recessive homozygote genotype (- 675 4G/4G). CONCLUSION: Our study indicates that uPA and PAI-1 tumor tissue levels and 4G/5G variants of PAI-1 gene might be of prognostic significance in early node-negative luminal HER2-negative breast cancer patients treated with adjuvant endocrine therapy.

Self-confidence and clinical skills: the case of students who study medicine in English in a non-English speaking setting.

BACKGROUND: An increasing number of international students has been enrolling in medical studies in the English language offered by the countries of Eastern Europe. Development of practical skills is likely more challenging when students learn in the English language, while their patients are non-English speaking persons. AIMS: To evaluate self-perception of practical skills of medical students in the English language program. METHODS: From December 2016 to December 2017, a total of 52 students from the Studies in English program of two universities in Serbia were included in the study. Data were obtained by a previously validated questionnaire. RESULTS: Participants were most confident when measuring blood pressure, checking the arterial pulse, and taking history. Students were the least confident when placing urinary catheters, performing rectal examinations, and suturing wounds. Male students reported higher confidence in "Major interventions" compared to females (p = 0.004), and no difference between male and female students was found in the total skill score of "knowledge of Serbian language" (p = 0.339). Adjusted analysis showed that a higher grade point average remains associated with a more confident perception of one's practical skills (B 26.48, 95% confidence interval 8.98-43.98). Rasch analysis showed that because the scores were distributed around the mean value between "not confident at all" and "quite confident," the majority of students had similar perceptions of their skills. CONCLUSION: Active supervision by teaching staff is also recommended in an attempt to rectify the lack of confidence at performing a range of clinical procedures which is present among international students.

Incidence and Mortality Patterns of Acute Myeloid Leukemia in Belgrade, Serbia (1999⁻2013).

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.

Management and treatment of children with medulloblastoma in Serbia, a middle-income country.

PURPOSE: The aim of this study was to present the management and treatment of children with medulloblastoma in Serbia, a middle-income country (MIC). METHODS: The data of 87 children diagnosed with medulloblastoma and treated at the Institute for Oncology and Radiology of Serbia from 2000 to 2013 were analyzed. RESULTS: The children's median age was 8.3 years (range 2.5-17.3). Eighty-two (94.2%) were 3 years or older. Sixtytwo (71.3%) patients had stage M0 medulloblastoma, 12 (13.8%) had stage M1 and 13 (14.9%) had stage M2 or M3. As of October 2015, 51 (58.6%) patients were alive and 31 (35.6%) had died. Five patients (5.7%) were lost to followup. Twenty-six patients relapsed. The median follow-up time was 58 months (range 4-187). Mean overall survival (OS) was 76.4% at 3 years, 66.2% at 5 years and 59.2% at 10 years. Mean disease-free survival (DFS) was 75.8% at 3 years, 62.8% at 5 years and 56.6% at 10 years. Mean OS of stage M0 patients was 86.4% at 3 years, 74% at 5 years and 63.1% at 10 years. The OS of stage M1, M2 and M3 patients combined was 48.9% at 3 years, 44.0% at 5 years and 37.7% at 10 years. CONCLUSION: In Serbia, a MIC, it is possible to achieve good treatment results in children with medulloblastoma using international treatment guidelines and recommendations, available resources and an experienced team of professionals dedicated to pediatric neurooncology.

Illict drug use and academia in North Kosovo: Prevalence, patterns, predictors and health-related quality of life.

PURPOSE: The purpose of this study were to estimate the prevalence and patterns of illicit drug use in a sample of University students from North Kosovo, to assess factors associated with illicit drug use and to assess health-related quality of life (HRQoL) among students according to illicit drug use. METHODS: A cross-sectional study was conducted at the Student Public Health Center, where 514 University students were enrolled from April to June 2015 in North Kosovo. Participants completed the general socio-demographic and behavioral questionnaire, Beck Depression Inventory (BDI) and the SF-36 questionnaire for HRQoL assessment. Data on lifetime illicit drug use were self-reported. RESULTS: As much as 16.0% of students reported ever illicit drug use. The most frequently used drugs were marijuana (9.3%) and bromazepam (7.6%). Factors associated with ever illicit drug use were: being smoker and alcohol user, having chronic diseases and having higher depressive symptoms score. Ever illicit drug users reported all domains of HRQoL as worse. CONCLUSION: These results could serve as a tool for implementation of preventive strategies and University policies to promote healthy lifestyles and behaviors. Measurement of HRQoL could also be used as indicator of the effect of interventions designed to reduce and/or prevent illicit drug use at institutions of higher education.

Psychological factors as predictors of early postoperative pain after open nephrectomy.

PURPOSE: There is an increasing interest in the identification of predictors for individual responses to analgesics and surgical pain. In this study, we aimed to determine psychological factors that might contribute to this response. We hence investigated patients undergoing a standardized surgical intervention (open nephrectomy). PATIENTS AND METHODS: Between May 2014 and April 2015, we conducted a prospective observational cohort study. The following psychological tests were administered preoperatively: Mini-Mental State Examination, Amsterdam Preoperative Anxiety and Information Scale (APAIS), Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, and Pain Catastrophizing Scale. The primary outcome, postoperative pain intensity (11-point numerical rating scale, [NRS]), was assessed in the "immediate early" (first 8 hours), "early" (12 and 24 hours), and "late early" periods (48 and 72 hours). RESULTS: A total of 196 patients were assessed, and 150 were finally included in the study. NRS scores improved from 4.9 (95% confidence interval [CI]: 4.7-5.1) in the "immediate early" to 3.1 (95% CI: 2.9-3.3) in the "early" and 2.3 (95% CI: 2.1-2.5) in the "late early" postoperative period. Most (87%) patients received intravenous opioids, while 13% received analgesics epidurally. Repeated measures analysis of variance indicated better pain management with epidural analgesia in the first two postoperative periods (F=15.01, p<0.00). Postoperative pain correlated strongly with analgesic strategy and preoperative psychological assessment. Multiple linear regression analysis showed "expected pain" was the only predictor in the "immediate early" phase, and "anxiety" was most important in the "early" postoperative period. In the "late early" phase, catastrophizing was the predominant predictor, alongside "preoperative analgesic usage" and "APAIS anxiety". CONCLUSION: After open nephrectomy, epidural analgesia conveys a clear advantage for pain management only within the first 24 hours. Moreover, as the psychological phenotype of patients changes distinctively in the first 72 postoperative hours, psychological variables increasingly determine pain intensity, even surpassing employed analgesic strategy as its main predictor.