Zoran Bukumirić

The prognostic significance of the circulating neuroendocrine markers chromogranin A, pro-gastrin-releasing peptide, and neuron-specific enolase in patients with small-cell lung cancer

Lung cancer is the most common cancer, and small-cell lung cancer (SCLC) accounts for around 20xa0% of lung cancers. SCLC has a neuroendocrine cellular origin, and the tumor cells usually express neuroendocrine markers. There have been major recent advances in the management of SCLC, and multimodal approaches are now the norm. An improved knowledge of the prognostic variables would assist in defining which patients were better candidates to receive these newer intensive therapies. This single-center retrospective study of 97 previously untreated and histologically proven SCLC patients analysed the circulating neuroendocrine markers chromogranin A (CGA), pro-gastrin-releasing peptide (ProGRP), and neuron-specific enolase (NSE) in addition to the other more classical variables. Fifty patients had limited-stage disease and 47 had extensive disease. Sixty patients had an ECOG performance status (PS) of 0–1 and 37 had PS 2–4. Median survival for the whole study population was 13xa0months. Univariate analysis and univariate Cox regression modeling found a statistically significant association between survival and PS, disease stage, and CGA, ProGRP, and NSE levels. Age and sex were not prognostic. A shorter survival time was found in patients with a PS equal to or >2, extensive stage disease, a serum CGA level >56xa0ng/ml, a serum ProGRP level >58xa0pg/ml, and a serum NSE level >19xa0ng/ml. This study has found that there is a potential role for ProGRP, NSE, and CGA in both staging and prognosing survival in SCLC patients.

Improving Education in Medical Statistics: Implementing a Blended Learning Model in the Existing Curriculum

Background Although recent studies report on the benefits of blended learning in improving medical student education, there is still no empirical evidence on the relative effectiveness of blended over traditional learning approaches in medical statistics. We implemented blended along with on-site (i.e. face-to-face) learning to further assess the potential value of web-based learning in medical statistics. Methods This was a prospective study conducted with third year medical undergraduate students attending the Faculty of Medicine, University of Belgrade, who passed (440 of 545) the final exam of the obligatory introductory statistics course during 2013–14. Student statistics achievements were stratified based on the two methods of education delivery: blended learning and on-site learning. Blended learning included a combination of face-to-face and distance learning methodologies integrated into a single course. Results Mean exam scores for the blended learning student group were higher than for the on-site student group for both final statistics score (89.36±6.60 vs. 86.06±8.48; p = 0.001) and knowledge test score (7.88±1.30 vs. 7.51±1.36; p = 0.023) with a medium effect size. There were no differences in sex or study duration between the groups. Current grade point average (GPA) was higher in the blended group. In a multivariable regression model, current GPA and knowledge test scores were associated with the final statistics score after adjusting for study duration and learning modality (p<0.001). Conclusion This study provides empirical evidence to support educator decisions to implement different learning environments for teaching medical statistics to undergraduate medical students. Blended and on-site training formats led to similar knowledge acquisition; however, students with higher GPA preferred the technology assisted learning format. Implementation of blended learning approaches can be considered an attractive, cost-effective, and efficient alternative to traditional classroom training in medical statistics.

Reliability of the witness descriptions of epileptic seizures and psychogenic non-epileptic attacks: a comparative analysis

Abstract Background: The diagnosis of epilepsy primarily depends on description of the observed seizure. The aim of this study was to determine the reliability of witness’ description among groups with different medical education. Methods: A group of 44 respondents (15 laymen, 15 medical students, and 14 doctors at neurology residency program) were shown video footages of focal epileptic seizure (ES) with secondary generalization and psychogenic non-epileptic seizure (PNES) of the same patient. The ability to describe ES and PNES characteristics, to estimate duration of seizures, and to detect of accurate seizure type was evaluated using a questionnaire. For the analysis of primary data obtained from questionnaires, we used descriptive statistical methods and methods for testing statistical hypotheses. Results: The sensitivity (Sn) and specificity (Sp) for accurate recognition of ES are different in the examined groups (laymen Sn u200a=u200a 53·3%, Sp u200a=u200a 33·3%; medical students Sn u200a=u200a 100%, Sp u200a=u200a 13·3%; neurology residents Sn u200a=u200a 100%, Sp u200a=u200a 71·4%). Evaluated duration of PNES and ES do not differ between examined groups. The impression that ES and PNES are distinct events is reciprocal for medical students and neurology residents, but not in laymen group. Neurology residents notice the essential characteristics of ES in high percentage. Conclusion: Accurate classification of the attacks is associated with the observers’ level of medical knowledge. Witnesses with specific, neurological knowledge with higher probability, compared to the laity and medical students, differentiate ES from PNES.

Assessing attitudes towards statistics among medical students: psychometric properties of the Serbian version of the Survey of Attitudes Towards Statistics (SATS).

Background Medical statistics has become important and relevant for future doctors, enabling them to practice evidence based medicine. Recent studies report that students’ attitudes towards statistics play an important role in their statistics achievements. The aim of the study was to test the psychometric properties of the Serbian version of the Survey of Attitudes Towards Statistics (SATS) in order to acquire a valid instrument to measure attitudes inside the Serbian educational context. Methods The validation study was performed on a cohort of 417 medical students who were enrolled in an obligatory introductory statistics course. The SATS adaptation was based on an internationally accepted methodology for translation and cultural adaptation. Psychometric properties of the Serbian version of the SATS were analyzed through the examination of factorial structure and internal consistency. Results Most medical students held positive attitudes towards statistics. The average total SATS score was above neutral (4.3±0.8), and varied from 1.9 to 6.2. Confirmatory factor analysis validated the six-factor structure of the questionnaire (Affect, Cognitive Competence, Value, Difficulty, Interest and Effort). Values for fit indices TLI (0.940) and CFI (0.961) were above the cut-off of ≥0.90. The RMSEA value of 0.064 (0.051–0.078) was below the suggested value of ≤0.08. Cronbach’s alpha of the entire scale was 0.90, indicating scale reliability. In a multivariate regression model, self-rating of ability in mathematics and current grade point average were significantly associated with the total SATS score after adjusting for age and gender. Conclusion Present study provided the evidence for the appropriate metric properties of the Serbian version of SATS. Confirmatory factor analysis validated the six-factor structure of the scale. The SATS might be reliable and a valid instrument for identifying medical students’ attitudes towards statistics in the Serbian educational context.

Heavy Metals Fractionation in Agricultural Soils of Pb/Zn Mining Region and Their Transfer to Selected Vegetables

Improved understanding of the relationships between heavy metals fractionation in agricultural soils and biological uptake could be obtained by analysing samples of biota in parallel with sequential extraction of their grown media. The overall goals of this study were to identify the characteristics of metal fractions and their bioavailability to maize and potato plants in the agricultural land of the Ibar River in southern Serbia and northern Kosovo. The concentrations of Pb, Zn, Cd, Ni, Cr and Cu in soil and vegetable samples were determined by the ICP-OES method. Pb/Zn production and industrial waste disposal significantly increased the pseudo-total concentrations of heavy metals in the soil together with their mobile and potentially bioavailable amounts. The Pb concentrations in the vegetable samples were generally above the EU maximum permitted concentrations in foodstuffs. However, the concentrations of Zn, Ni, Cr and Cu in the vegetables were below the critical levels. The results of the present study indicated that the intensive industrial production of Pb/Zn over the years and permanent pollution were responsible for the environmental contamination by heavy metals in the study area, particularly by Pb and Zn. The quantity of the mobile and potentially bioavailable heavy metals in the studied soils threatens the quality of Zea mays L. and Solanum tuberosum L. crops, with a real risk that these elements could enter the food chain.

The Importance of Medical Students' Attitudes Regarding Cognitive Competence for Teaching Applied Statistics: Multi-Site Study and Meta-Analysis.

Background The scientific community increasingly is recognizing the need to bolster standards of data analysis given the widespread concern that basic mistakes in data analysis are contributing to the irreproducibility of many published research findings. The aim of this study was to investigate students’ attitudes towards statistics within a multi-site medical educational context, monitor their changes and impact on student achievement. In addition, we performed a systematic review to better support our future pedagogical decisions in teaching applied statistics to medical students. Methods A validated Serbian Survey of Attitudes Towards Statistics (SATS-36) questionnaire was administered to medical students attending obligatory introductory courses in biostatistics from three medical universities in the Western Balkans. A systematic review of peer-reviewed publications was performed through searches of Scopus, Web of Science, Science Direct, Medline, and APA databases through 1994. A meta-analysis was performed for the correlation coefficients between SATS component scores and statistics achievement. Pooled estimates were calculated using random effects models. Results SATS-36 was completed by 461 medical students. Most of the students held positive attitudes towards statistics. Ability in mathematics and grade point average were associated in a multivariate regression model with the Cognitive Competence score, after adjusting for age, gender and computer ability. The results of 90 paired data showed that Affect, Cognitive Competence, and Effort scores demonstrated significant positive changes. The Cognitive Competence score showed the largest increase (M = 0.48, SD = 0.95). The positive correlation found between the Cognitive Competence score and students’ achievement (r = 0.41; p<0.001), was also shown in the meta-analysis (r = 0.37; 95% CI 0.32–0.41). Conclusion Students subjective attitudes regarding Cognitive Competence at the beginning of the biostatistics course, which were directly linked to mathematical knowledge, affected their attitudes at the end of the course that, in turn, influenced students performance. This indicates the importance of positively changing not only students’ cognitive competency, but also their perceptions of gained competency during the biostatistics course.

Distribution and mobility of heavy elements in floodplain agricultural soils along the Ibar River (Southern Serbia and Northern Kosovo). Chemometric investigation of pollutant sources and ecological risk assessment.

This work investigates the influence of a high-magnitude flood event on heavy elements (HEs) pollution and mobility in the agricultural soils along Ibar River in Southern Serbia and Northern Kosovo. The study area was one of the most important Pb/Zn industrial regions in Europe. Soil samples (nu2009=u200950) collected before and after the floods in May 2014 were subjected to the sequential extraction procedure proposed by the Community Bureau of Reference (BCR). The results indicated that the floods significantly increased not only the pseudo total concentrations of HEs in the soil but also their mobile and potentially bioavailable amounts. Moreover, higher concentrations (both pseudo total and potentially bioavailable) were found in the agricultural soils closer to the industrial hotspots. Principal component analysis and hierarchical cluster analysis successfully grouped the analyzed elements according to their anthropogenic or natural origin. The floods significantly increased the potential ecological risk of HEs associated with Pb/Zn industrial activities in the study area. The potential ecological risk of Cd after the floods was highest and should be of special concern.

Meta-analysis of the changes in correlations between depression instruments used in longitudinal studies.

BACKGROUNDnCorrelations between instruments measuring the same construct reflect their concurrent validity. Little is known about changes in correlations between such instruments employed in studies with repeated assessment. The aim of this meta-analysis was to examine the changes in correlations between depression instruments in the course of longitudinal studies.nnnMETHODSnA literature search was conducted using MEDLINE and PsycINFO for the period from 1960 to 2013. The total number of collected articles was 3723, of which 61 were included. Three meta-analyses were performed for the changes in correlations between each pair of the three depression scales: Hamilton Rating Scale for Depression (HAMD), Montgomery-Asberg Depression Rating Scale (MADRS) and Beck Depression Inventory (BDI). The effect size in these meta-analyses was obtained by the z-transformation of correlation coefficients.nnnRESULTSnCorrelations between depression scales increased over time in 52 studies. Significant changes in correlation coefficients were found for correlations between HAMD and BDI (p<0.001) and for correlations between HAMD and MADRS (p<0.001). An increase in correlations between the scales was associated with a decrease in depression scores and increase in their variability.nnnLIMITATIONSnUnivariable and multivariable meta-regression models were not obtained in all three meta-analyses because of the lack of data.nnnCONCLUSIONSnA finding that correlations between depression instruments tended to increase over time has significant implications for assessment of the concurrent validity of these instruments. In longitudinal designs it is important to estimate correlations between depression scales over time because different thresholds for scale correlations indicate acceptable concurrent validity at different times.

PREDICT score and CYP2C19 polymorphism independently predict lack of efficacy of clopidogrel in cardiology patients

Sne zana Mugo sa,* Nata sa Djordjevi c, Zoran Bukumiri c, Nina Djukanovi c, Jelena Cuki c, Ivan Radosavljevi c, Dejan Baski c, Dragana Proti c, Marija Zdravkovi c** and Zoran Todorovi c** *Faculty of Pharmacy, University of Montenegro, Podgorica, Montenegro, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, , Faculty of Medicine, University of Belgrade, High Medical School “Milutin Milankovi c”, Belgrade, Public Health Institute, Kragujevac, and **Medical Center “Be zanijska kosa”, Belgrade, Serbia

The Rationale for Continuing Open Repair of Ruptured Abdominal Aortic Aneurysm

BACKGROUNDnMortality after open repair of ruptured abdominal aortic aneurysms (RAAAs) remains high. The purpose of this study is to present the results of open RAAA treatment observing 2 different 10-year periods in a single high-volume center and to consider the possibilities of result improvement in the future.nnnMETHODSnRetrospective analysis of 729 RAAA patients who were treated through 1991-2001 (229 patients, Group A) and 2002-2011 (500 patients, Group B) was performed. Variables significantly associated with mortality were defined and analyzed.nnnRESULTSnOverall 30-day mortality in Group A was 53.7% (123/229 patients) with intraoperative mortality of 13.5% (31/229 patients), while in Group B it was 37.4% (187/500 patients) with intraoperative mortality of 12.4% (62/500 patients). Overall 30-day mortality was significantly lower in Group B (Pxa0=xa00.012). There was no difference regarding intraoperative mortality (Pxa0=xa00.797). Preoperative severe hemodynamic instability (Pxa0<xa00.01, Pxa0<xa00.001), cardiac arrest (Pxa0<xa00.01, Pxa0<xa00.001), consciousness deterioration (Pxa0<xa00.05, Pxa0<xa00.001), renal malfunction (Pxa0<xa00.01, Pxa0<xa00.001), and significant anemia (Pxa0<xa00.01, Pxa0<xa00.001) were associated with increased mortality in both A and B groups, respectively. Aortic cross-clamping level in Group A was predominantly infrarenal (68%) while in Group B it was mostly supraceliac (53%) (Pxa0<xa00.001). Cross-clamping time, duration of surgery, and type of aortic reconstruction had no influence on survival in Group B (Pxa0>xa00.05). Intraoperative hemodynamic instability (Pxa0<xa00.01, Pxa0<xa00.001), significant bleeding (Pxa0<xa00.05, Pxa0<xa00.01), and low urine output (Pxa0<xa00.05, Pxa0<xa00.001) remained parameters that favored lethal outcome in both A and B groups, respectively. Cell saving was used only in Group B. The multivariate logistic regression applied on the complete sample of patients presented several significant predictors of lethal outcome: congestive heart failure on admission (odds ratio [OR] 1.954, 95% confidence interval [CI] 1.103-3.460), intraperitoneal rupture (OR 3.009, 95% CI 1.771-5.423), aortofemoral reconstruction (OR 1.928, 95% CI 1.044-3.563), and total operative time (OR 1.005, 95% CI 1.001-1.010). Postoperative multisystem organ failure (Pxa0<xa00.01, Pxa0<xa00.001), respiratory (Pxa0<xa00.01, Pxa0<xa00.001) and renal (Pxa0<xa00.05, Pxa0<xa00.001) failure, postoperative bleeding (Pxa0<xa00.05), and cerebrovascular incidents (Pxa0<xa00.05, Pxa0<xa00.01) significantly increased mortality in both A and B groups.nnnCONCLUSIONSnAlthough unselective, aggressive surgical approach in RAAA performed by teams experienced in open repair can improve patients survival. Short admission/surgery time, supraceliac aortic cross-clamping, and the use of intraoperative cell saving are recommended.