Browsing by Author "Despotovic, Aleksa (57000516000)"

Introduction: Surveillance of antimicrobial resistance is essential in establishing treatment guidelines for urinary tract infections. The aim of this pilot study was to analyse resistance rates of pathogens, across different demographics and determine whether adjustments in empiric therapy should be considered for different age and gender groups. Methodology: A 5-year retrospective study included 256 patients hospitalised, under the initial diagnosis of Fever of Unknown Origin who were then subsequently diagnosed with a urinary tract infection at the Clinic for Infectious and Tropical Diseases, Clinical Centre of Serbia. Patients were evaluated using demographic, clinical, and antimicrobial resistance data with appropriate statistical analysis including ANOVA significance testing, univariate, and multivariate analysis. Results: Resistance rates were above the threshold of 20% for the majority of the antimicrobials tested, the only exception being carbapenems. Amikacin, cefepime, and norfloxacin were agents that could be effectively used as empiric therapy in younger adults with resistance rates of 4.2, 8.0, and 10.0%, respectively. Moderate resistance rates of 17.4% for amikacin and 19.1% for cefepime were observed in the age group 35-64 years. High resistance rates were observed for all antimicrobials among patients 65 years and over. Among male patients, resistance rates to most antimicrobials were high. In female patients, amikacin and cefepime had resistance rates less than 20%. Younger age presented as a negative risk factor for infection by a multi-drug resistant pathogen. Conclusion: Age and gender demonstrated to be significant factors for determining proper empiric therapy; large-scale studies from Serbia are needed to solidify these findings. © 2016 Zec et al.

Introduction: Surveillance of antimicrobial resistance is essential in establishing treatment guidelines for urinary tract infections. The aim of this pilot study was to analyse resistance rates of pathogens, across different demographics and determine whether adjustments in empiric therapy should be considered for different age and gender groups. Methodology: A 5-year retrospective study included 256 patients hospitalised, under the initial diagnosis of Fever of Unknown Origin who were then subsequently diagnosed with a urinary tract infection at the Clinic for Infectious and Tropical Diseases, Clinical Centre of Serbia. Patients were evaluated using demographic, clinical, and antimicrobial resistance data with appropriate statistical analysis including ANOVA significance testing, univariate, and multivariate analysis. Results: Resistance rates were above the threshold of 20% for the majority of the antimicrobials tested, the only exception being carbapenems. Amikacin, cefepime, and norfloxacin were agents that could be effectively used as empiric therapy in younger adults with resistance rates of 4.2, 8.0, and 10.0%, respectively. Moderate resistance rates of 17.4% for amikacin and 19.1% for cefepime were observed in the age group 35-64 years. High resistance rates were observed for all antimicrobials among patients 65 years and over. Among male patients, resistance rates to most antimicrobials were high. In female patients, amikacin and cefepime had resistance rates less than 20%. Younger age presented as a negative risk factor for infection by a multi-drug resistant pathogen. Conclusion: Age and gender demonstrated to be significant factors for determining proper empiric therapy; large-scale studies from Serbia are needed to solidify these findings. © 2016 Zec et al.

Background: Research involves the systematic collection and analysis of data to enhance understanding of a particular phenomenon. Participation in medical research is crucial for advancing healthcare practices. However, there has been limited focus on understanding the factors that motivate medical students to engage in research. Additionally, in the era of e-learning, the easy accessibility of online resources has contributed to a widespread ‘copy-paste culture’ among digital-native students, which is recognized in academia as plagiarism. Existing studies suggest that a contributing factor to the increasing prevalence of plagiarism is students’ limited understanding of this act. The purpose of this study was to assess medical students’ attitudes toward research and plagiarism, and to evaluate the psychometric properties of the Attitudes Toward Research (ATR) and Attitudes Toward Plagiarism (ATP) questionnaires. Methods: This was a multicenter study conducted among medical undergraduate and postgraduate students attending the three medical universities who were involved in research. Students’ attitudes toward research and plagiarism were assessed using the ATR and ATP questionnaires. The research instruments underwent translation and cultural adaptation in accordance with internationally accepted methodology. The psychometric properties of the ATR and ATP, including validity and reliability, were assessed. Confirmatory factor analysis was used to test the model’s fit to the data. Results: The ATR and ATP questionnaires were completed by 793 medical students who were involved in research (647 undergraduates and 146 PhD students). Cronbach’s alpha coefficients of 0.917 and 0.822 indicated excellent and good scale reliability for the ATR and ATP questionnaires, respectively. The five-and three- factor structures of ATR and ATP have been validated with maximum likelihood confirmatory analysis, and the results demonstrated an adequate level of model fit (TLI = 0.930, CFI = 0.942 and TLI = 0.924, CFI = 0.943, respectively). Medical students showed a high degree of positive attitudes toward research and favorable scores across all three domains of attitudes toward plagiarism. In multivariate regression models, age was found to be positively associated with favorable attitudes of research usefulness, positive attitudes, relevance to life subscales and total ATR scale (p < 0.001), while PhD study level was related to research anxiety (p < 0.001) and favorable attitudes across all three ATP domains (p < 0.001). Conclusion: Medical students who were involved in research showed a high degree of favorable attitudes toward research and plagiarism. Adjusting medical school curricula to include research courses would broaden the students’ interest in scientific research and maximize their impact on the full preservation of research ethics and integrity. © The Author(s) 2024.

Background: Research involves the systematic collection and analysis of data to enhance understanding of a particular phenomenon. Participation in medical research is crucial for advancing healthcare practices. However, there has been limited focus on understanding the factors that motivate medical students to engage in research. Additionally, in the era of e-learning, the easy accessibility of online resources has contributed to a widespread ‘copy-paste culture’ among digital-native students, which is recognized in academia as plagiarism. Existing studies suggest that a contributing factor to the increasing prevalence of plagiarism is students’ limited understanding of this act. The purpose of this study was to assess medical students’ attitudes toward research and plagiarism, and to evaluate the psychometric properties of the Attitudes Toward Research (ATR) and Attitudes Toward Plagiarism (ATP) questionnaires. Methods: This was a multicenter study conducted among medical undergraduate and postgraduate students attending the three medical universities who were involved in research. Students’ attitudes toward research and plagiarism were assessed using the ATR and ATP questionnaires. The research instruments underwent translation and cultural adaptation in accordance with internationally accepted methodology. The psychometric properties of the ATR and ATP, including validity and reliability, were assessed. Confirmatory factor analysis was used to test the model’s fit to the data. Results: The ATR and ATP questionnaires were completed by 793 medical students who were involved in research (647 undergraduates and 146 PhD students). Cronbach’s alpha coefficients of 0.917 and 0.822 indicated excellent and good scale reliability for the ATR and ATP questionnaires, respectively. The five-and three- factor structures of ATR and ATP have been validated with maximum likelihood confirmatory analysis, and the results demonstrated an adequate level of model fit (TLI = 0.930, CFI = 0.942 and TLI = 0.924, CFI = 0.943, respectively). Medical students showed a high degree of positive attitudes toward research and favorable scores across all three domains of attitudes toward plagiarism. In multivariate regression models, age was found to be positively associated with favorable attitudes of research usefulness, positive attitudes, relevance to life subscales and total ATR scale (p < 0.001), while PhD study level was related to research anxiety (p < 0.001) and favorable attitudes across all three ATP domains (p < 0.001). Conclusion: Medical students who were involved in research showed a high degree of favorable attitudes toward research and plagiarism. Adjusting medical school curricula to include research courses would broaden the students’ interest in scientific research and maximize their impact on the full preservation of research ethics and integrity. © The Author(s) 2024.

Aims: Cardiovascular diseases (CVDs) are among the leading causes of death worldwide. Predictive scores providing personalized risk of developing CVD are increasingly used in clinical practice. Most scores, however, utilize a homogenous set of features and require the presence of a physician. The aim was to develop a new risk model (DiCAVA) using statistical and machine learning techniques that could be applied in a remote setting. A secondary goal was to identify new patient-centric variables that could be incorporated into CVD risk assessments. Methods and results: Across 466052 participants, Cox proportional hazards (CPH) and DeepSurv models were trained using 608 variables derived from the UK Biobank to investigate the 10-year risk of developing a CVD. Data-driven feature selection reduced the number of features to 47, after which reduced models were trained. Both models were compared to the Framingham score. The reduced CPH model achieved a c-index of 0.7443, whereas DeepSurv achieved a c-index of 0.7446. Both CPH and DeepSurv were superior in determining the CVD risk compared to Framingham score. Minimal difference was observed when cholesterol and blood pressure were excluded from the models (CPH: 0.741, DeepSurv: 0.739). The models show very good calibration and discrimination on the test data. Conclusion: We developed a cardiovascular risk model that has very good predictive capacity and encompasses new variables. The score could be incorporated into clinical practice and utilized in a remote setting, without the need of including cholesterol. Future studies will focus on external validation across heterogeneous samples. © 2021 The Author(s). Published by Oxford University Press on behalf of the European Society of Cardiology.

Introduction: The relationship between Systemic lupus erythematosus (SLE) and Epstein-Barr virus (EBV) infection has been suggested for decades, but the underlying mechanism of the EBV influence on SLE development remains to be elucidated. Methods: The goals of this research, which included 103 SLE patients and 99 controls, were to investigate the association of the parameters of EBV infection and SLE, to explore whether pooled demographic, clinical and EBV markers achieve a more significant effect on SLE development than each of them individually, and to evaluate EBV nuclear antigen 1 (EBNA1) and latent membrane protein 1 (LMP1) gene polymorphisms in isolates from SLE patients. Results: Comprehensive results related to serological, molecular and sequence markers of EBV infection in SLE patients demonstrated even 24 times higher possibility of having SLE if there is the presence of anti-EBV-EA(D) (early antigen) IgG antibodies (OR=24.086 95%CI OR=2.86-216.07, p=0.004). There was the same distribution of glucocorticoids (p=0.130), antimalarials (p=0.213), and immunosuppressives (p=0.712) in anti-EBV-EA(D) IgG positive and negative SLE patients. Further, higher anti-EBV-EA(D) IgG antibodies titers were identified as independent factors associated with lymphopenia, hematological SLE manifestation (OR=1.041, 95%CI OR=1.01-1.08, p=0.025, while a higher titer of anti-CA (viral capsid antigen) IgG antibodies (OR=1.015, 95%CI OR=1.01-1.03, p=0.019) and positive RF (rheumatoid factors) (OR=4.871, 95%CI OR=1.52-15.61, p=0.008) were identified as independent factors associated with alopecia within SLE. Finally, novel data on EBV EBNA1 and LMP1 gene polymorphisms in lupus are reported. Conclusion: The results support further investigation targeting EBV as a prognostic marker and therapeutic goal for lupus. Copyright © 2023 Banko, Cirkovic, Miskovic, Jeremic, Grk, Basaric, Lazarevic, Raskovic, Despotovic and Miljanovic.

Introduction: The relationship between Systemic lupus erythematosus (SLE) and Epstein-Barr virus (EBV) infection has been suggested for decades, but the underlying mechanism of the EBV influence on SLE development remains to be elucidated. Methods: The goals of this research, which included 103 SLE patients and 99 controls, were to investigate the association of the parameters of EBV infection and SLE, to explore whether pooled demographic, clinical and EBV markers achieve a more significant effect on SLE development than each of them individually, and to evaluate EBV nuclear antigen 1 (EBNA1) and latent membrane protein 1 (LMP1) gene polymorphisms in isolates from SLE patients. Results: Comprehensive results related to serological, molecular and sequence markers of EBV infection in SLE patients demonstrated even 24 times higher possibility of having SLE if there is the presence of anti-EBV-EA(D) (early antigen) IgG antibodies (OR=24.086 95%CI OR=2.86-216.07, p=0.004). There was the same distribution of glucocorticoids (p=0.130), antimalarials (p=0.213), and immunosuppressives (p=0.712) in anti-EBV-EA(D) IgG positive and negative SLE patients. Further, higher anti-EBV-EA(D) IgG antibodies titers were identified as independent factors associated with lymphopenia, hematological SLE manifestation (OR=1.041, 95%CI OR=1.01-1.08, p=0.025, while a higher titer of anti-CA (viral capsid antigen) IgG antibodies (OR=1.015, 95%CI OR=1.01-1.03, p=0.019) and positive RF (rheumatoid factors) (OR=4.871, 95%CI OR=1.52-15.61, p=0.008) were identified as independent factors associated with alopecia within SLE. Finally, novel data on EBV EBNA1 and LMP1 gene polymorphisms in lupus are reported. Conclusion: The results support further investigation targeting EBV as a prognostic marker and therapeutic goal for lupus. Copyright © 2023 Banko, Cirkovic, Miskovic, Jeremic, Grk, Basaric, Lazarevic, Raskovic, Despotovic and Miljanovic.

Background: Acquisition of Hospital-acquired infections (HAIs) in intensive care units (ICUs) predispose patients to higher mortality rates and additional adverse events. Serbian adult ICUs are rarely investigated for HAIs. The aim of this study was to look into HAIs in an adult ICU and identify risk factors for acquisition of HAIs and mortality. Methods: This retrospective study included 355 patients hospitalized over a 2-year period. Patient characteristics, antimicrobial resistance patterns, and risk factors of acquisition and predictors of mortality in patients who had a HAI were examined. Results: HAIs were diagnosed in 32.7% of patients. Resistance rates > 50% were observed in all antimicrobials except for tigecycline (14%), colistin (9%), and linezolid (0%). Predictors of HAI acquisition were underlying viral CNS infections and invasive devices—urinary and central venous catheters, and nasogastric tubes. Diabetes mellitus and intubation (odds ratio 2.5 and 6.7, P = .042 and <.001) were identified as predictors for increased mortality in patients who had a HAI. Conclusions: Prevalence of HAIs and resistance rates are high compared to ICUs in other European countries. Risk factors for both acquisition of HAI and mortality were identified. Large-scale studies are necessary to look at HAIs in adult ICUs in Serbia. © 2020 Association for Professionals in Infection Control and Epidemiology, Inc. This is an open access article under the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Although the connection between Epstein–Barr virus (EBV) and rheumatoid arthritis (RA) has been studied for over 40 years, many questions still need clarification. The study aimed to analyze the possible association between anti-EBV antibody titers, EBV DNA viremia, EBV infection status and EBNA1 (Epstein–Barr nuclear antigen 1—EBNA1) variants and clinical parameters of RA patients. This prospective cohort study included 133 RA patients and 50 healthy controls. Active/recent EBV infection was more prevalent in RA patients than in controls (42% vs. 16%, p < 0.001). RA patients had higher titers of anti-EBV-CA-IgM (capsid antigen—CA) and anti-EBV-EA(D)-IgG (early antigen—EA) antibodies than controls (p = 0.003 and p = 0.023, respectively). Lower levels of anti-EBNA1-IgG and anti-EBV-CA-IgG were observed in RA patients who received methotrexate (anti-EBNA1 IgG p < 0.001; anti-EBV-CA IgG p < 0.001). Based on amino acid residue on position 487, two EBNA1 prototypes were detected: P-Thr and P-Ala. Patients with active/recent EBV infection had a five times more chance of having RA and a nearly six times more chance of getting RA. Also, EBV active/recent infection is twice more likely in newly diagnosed than in methotrexate-treated patients. Further studies are needed to clarify “who is the chicken and who is the egg” in this EBV–RA relationship. © 2023 by the authors.

Although the connection between Epstein–Barr virus (EBV) and rheumatoid arthritis (RA) has been studied for over 40 years, many questions still need clarification. The study aimed to analyze the possible association between anti-EBV antibody titers, EBV DNA viremia, EBV infection status and EBNA1 (Epstein–Barr nuclear antigen 1—EBNA1) variants and clinical parameters of RA patients. This prospective cohort study included 133 RA patients and 50 healthy controls. Active/recent EBV infection was more prevalent in RA patients than in controls (42% vs. 16%, p < 0.001). RA patients had higher titers of anti-EBV-CA-IgM (capsid antigen—CA) and anti-EBV-EA(D)-IgG (early antigen—EA) antibodies than controls (p = 0.003 and p = 0.023, respectively). Lower levels of anti-EBNA1-IgG and anti-EBV-CA-IgG were observed in RA patients who received methotrexate (anti-EBNA1 IgG p < 0.001; anti-EBV-CA IgG p < 0.001). Based on amino acid residue on position 487, two EBNA1 prototypes were detected: P-Thr and P-Ala. Patients with active/recent EBV infection had a five times more chance of having RA and a nearly six times more chance of getting RA. Also, EBV active/recent infection is twice more likely in newly diagnosed than in methotrexate-treated patients. Further studies are needed to clarify “who is the chicken and who is the egg” in this EBV–RA relationship. © 2023 by the authors.

Development of lymphoproliferative disorders (LPDs) is one of the well-known life-threatening complications in rheumatoid arthritis (RA) patients. However, there is a lack of definitive conclusions regarding the role of Epstein-Barr virus (EBV) activity in RA initiation and progression, especially in promoting LPDs. A systematic review and meta-analysis of studies that reported an EBV positive result in RA-LPD patients and controls were conducted. Studies published before 27 July 2021 were identified through PubMed, Web of Science, and SCOPUS. A total of 79 articles were included in the systematic review. The prevalence of EBV positive result among RA-LPD patients was 54% (OR = 1.54, 95% CI = 1.45–1.64). There was a statistically significant association between EBV presence and LPD susceptibility in RA patients in comparison with all controls (OR = 1.88, 95% CI = 1.29–2.73) and in comparison with LPD patients only (OR = 1.92, 95% CI = 1.15–3.19). This association was not shown in comparison with patients with autoimmune diseases other than RA who developed LPD (OR = 0.79, 95% CI = 0.30–2.09). This meta-analysis confirmed a high prevalence of EBV in the RA-LPD population. Furthermore, it provides evidence for the association between EBV presence and LPD susceptibility in RA patients, but not in those with other autoimmune diseases who developed LPD. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Development of lymphoproliferative disorders (LPDs) is one of the well-known life-threatening complications in rheumatoid arthritis (RA) patients. However, there is a lack of definitive conclusions regarding the role of Epstein-Barr virus (EBV) activity in RA initiation and progression, especially in promoting LPDs. A systematic review and meta-analysis of studies that reported an EBV positive result in RA-LPD patients and controls were conducted. Studies published before 27 July 2021 were identified through PubMed, Web of Science, and SCOPUS. A total of 79 articles were included in the systematic review. The prevalence of EBV positive result among RA-LPD patients was 54% (OR = 1.54, 95% CI = 1.45–1.64). There was a statistically significant association between EBV presence and LPD susceptibility in RA patients in comparison with all controls (OR = 1.88, 95% CI = 1.29–2.73) and in comparison with LPD patients only (OR = 1.92, 95% CI = 1.15–3.19). This association was not shown in comparison with patients with autoimmune diseases other than RA who developed LPD (OR = 0.79, 95% CI = 0.30–2.09). This meta-analysis confirmed a high prevalence of EBV in the RA-LPD population. Furthermore, it provides evidence for the association between EBV presence and LPD susceptibility in RA patients, but not in those with other autoimmune diseases who developed LPD. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Hospital-acquired infections (HAIs) are a global public health concern. As the COVID-19 pandemic continues, its contribution to mortality and antimicrobial resistance (AMR) grows, particularly in intensive care units (ICUs). A two-year retrospective study from April 2019–April 2021 was conducted in an adult ICU at the Hospital for Infectious and Tropical Diseases, Belgrade, Serbia to assess causative agents of HAIs and AMR rates, with the COVID-19 pandemic ensuing halfway through the study. Resistance rates >80% were observed for the majority of tested antimicrobials. In COVID-19 patients, Acinetobacter spp. was the dominant cause of HAIs and more frequently isolated than in non-COVID-19 patients. (67 vs. 18, p = 0.001). Also, resistance was higher for imipenem (56.8% vs. 24.5%, p < 0.001), meropenem (61.1% vs. 24.3%, p < 0.001) and ciprofloxacin (59.5% vs. 36.9%, p = 0.04). AMR rates were aggregated with findings from our previous study to identify resistance trends and establish empiric treatment recommendations. The increased presence of Acinetobacter spp. and a positive trend in Klebsiella spp. resistance to fluoroquinolones (R2 = 0.980, p = 0.01) and carbapenems (R2 = 0.963, p = 0.02) could have contributed to alarming resistance rates across bloodstream infections (BSIs), pneumonia (PN), and urinary tract infections (UTIs). Exceptions were vancomycin (16.0%) and linezolid (2.6%) in BSIs; tigecycline (14.3%) and colistin (0%) in PNs; and colistin (12.0%) and linezolid (0%) in UTIs. COVID-19 has changed the landscape of HAIs in our ICUs. Approval of new drugs and rigorous surveillance is urgently needed. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Hospital-acquired infections (HAIs) are a global public health concern. As the COVID-19 pandemic continues, its contribution to mortality and antimicrobial resistance (AMR) grows, particularly in intensive care units (ICUs). A two-year retrospective study from April 2019–April 2021 was conducted in an adult ICU at the Hospital for Infectious and Tropical Diseases, Belgrade, Serbia to assess causative agents of HAIs and AMR rates, with the COVID-19 pandemic ensuing halfway through the study. Resistance rates >80% were observed for the majority of tested antimicrobials. In COVID-19 patients, Acinetobacter spp. was the dominant cause of HAIs and more frequently isolated than in non-COVID-19 patients. (67 vs. 18, p = 0.001). Also, resistance was higher for imipenem (56.8% vs. 24.5%, p < 0.001), meropenem (61.1% vs. 24.3%, p < 0.001) and ciprofloxacin (59.5% vs. 36.9%, p = 0.04). AMR rates were aggregated with findings from our previous study to identify resistance trends and establish empiric treatment recommendations. The increased presence of Acinetobacter spp. and a positive trend in Klebsiella spp. resistance to fluoroquinolones (R2 = 0.980, p = 0.01) and carbapenems (R2 = 0.963, p = 0.02) could have contributed to alarming resistance rates across bloodstream infections (BSIs), pneumonia (PN), and urinary tract infections (UTIs). Exceptions were vancomycin (16.0%) and linezolid (2.6%) in BSIs; tigecycline (14.3%) and colistin (0%) in PNs; and colistin (12.0%) and linezolid (0%) in UTIs. COVID-19 has changed the landscape of HAIs in our ICUs. Approval of new drugs and rigorous surveillance is urgently needed. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.