Browsing by Author "Lalić, Nebojša (13702597500)"

Introduction/Objective Continuing Medical Education (CME) is a crucial element to keep the level of professionalism in the three key fields of medical education: pre-clinical, clinical, and public health. The profile of CME in Serbia has been analyzed for the 2011–2017 period. Methods Between 2011 and 2017, 11,557 courses of CME have been submitted for accreditation, de-scribed by 26 variables. Due to the predominance of nominal data, we employed a principal component analysis (PCA) using the nonlinear iterative partial least squares algorithm (PCA/PLS) to arrange the 16 variables with complete information in such a way that most influential factors could be displayed and ranked. The analysis was done with TIBCO Statistical Software. Results The Faculty of Medicine of Belgrade takes the top position among the medical faculties in Serbia with 569 courses or 47.9% (n = 1187; 2011–2017), whereas non-educational institutions with 86.2% of all courses (n = 11,514) are the most dominant providers. Clinical topics dominate the thematic spectrum with 59.7%. Between 2012 and 2017, the total number of courses offered diminished by 16.9%. A PCA of 16 potential determinants of CME reveals that the most relevant ones are duration, credit points, price, and number of lecturers. Conclusion For the last decade, a standstill or even a regression in the development can be observed. Especially the faculties of medicine in Serbia, as well as other major providers, should reconsider the entire structure of their administrative organization and initiate innovative development. © 2021, Serbia Medical Society. All rights reserved.

Dipeptidyl peptidase-4 (DPP-4)inhibitors are a class of glucose-lowering agent for type 2 diabetes (T2D)that are commonly used in clinical practice. With the recent disclosure of data from the CARMELINA cardiovascular outcomes trial (CVOT), which investigated linagliptin, CV and renal outcomes data are now available for four agents in the DPP-4 inhibitor class that are approved in most markets. To consider how the CARMELINA study may be interpreted, and the relevance for our clinical practice, we convened as an expert group of diabetes specialists from the Central and Eastern Europe region to discuss the new disclosures. Our discussions revealed a general confidence in safety across the class that is further supported by CARMELINA. However, we also concluded that there are important differences in the available evidence level between agents in the setting of heart failure and data on renal outcomes. Here, we noted the clinical relevance to our practice of the study population in CARMELINA, which is unique among CVOTs in including a majority of patients with chronic kidney disease (CKD). Given the risk for future development of renal impairment that is associated with T2D even in patients without current overt CKD, we believe that the CARMELINA study provides important new insights that are clinically relevant for a broad range of patients. Finally, we discuss how these insights can be integrated into the approach to the pharmacotherapeutic management of hyperglycaemia that is recommended in newly updated guidelines. © 2019

Dipeptidyl peptidase-4 (DPP-4)inhibitors are a class of glucose-lowering agent for type 2 diabetes (T2D)that are commonly used in clinical practice. With the recent disclosure of data from the CARMELINA cardiovascular outcomes trial (CVOT), which investigated linagliptin, CV and renal outcomes data are now available for four agents in the DPP-4 inhibitor class that are approved in most markets. To consider how the CARMELINA study may be interpreted, and the relevance for our clinical practice, we convened as an expert group of diabetes specialists from the Central and Eastern Europe region to discuss the new disclosures. Our discussions revealed a general confidence in safety across the class that is further supported by CARMELINA. However, we also concluded that there are important differences in the available evidence level between agents in the setting of heart failure and data on renal outcomes. Here, we noted the clinical relevance to our practice of the study population in CARMELINA, which is unique among CVOTs in including a majority of patients with chronic kidney disease (CKD). Given the risk for future development of renal impairment that is associated with T2D even in patients without current overt CKD, we believe that the CARMELINA study provides important new insights that are clinically relevant for a broad range of patients. Finally, we discuss how these insights can be integrated into the approach to the pharmacotherapeutic management of hyperglycaemia that is recommended in newly updated guidelines. © 2019

Background/Aim. The hypercoagulable state and inflammation state in diabetics has been widely studied by previous researchers, but there is a lack of research about a possible impact of exercise training on this relationship. The aim of this study was to assess and compare correlation between the coagulation and inflammation status in patients with type 2 diabetes mellitus taking into account the gender differences as well as an impact of the 8-week exercise training on the correlation coefficient and parameters of the inflammation and coagulation state. Methods. A total of 60 patients in stable clinical condition and well-regulated diabetic status passed through all phases of the study. The exercise training included the exercise program as interval training with estimated intensity uphill to 75% of a maximal heart rate in particular individual, 5 times a week for 8 weeks, and walking for 30 minutes with a speed of 5 km/h, 5 times a week for 8 weeks. Further fibrinolytic, coagulation and inflammatory parameters were analyzed before and after the study: D-dimer, von Willebrand factor (vWF), fibrinogen, high sensitivity CRP (hs-CRP), leukocytes, thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT) and coagulation factors: FII, FV, FVII and FX. Results. Our research showed a statistically significant reduction in the mean vWF levels after intervention both at the males (p < 0.001) and females (p < 0.001). According to a correlation analysis between hs-CRP and fibrinogen, there was a positive correlation as baseline both at the males (p < 0.05, r = 0.492) and females (p < 0.01, r = 0.516) which became weaker in the males (p < 0.01, r = 0.449) and disappeared in the females (p < 0.05, r = 0.059) after intervention. The correlation which existed as baseline in the males between D-dimer and either hs-CRP (p < 0.01, r = 0.633) or fibrinogen (p < 0.01, r = 0.673) as well as the correlation between hs-CRP and FII (p < 0.01, r = 0.728), FV (p < 0.05, r = 0.366), FVII (p < 0.05, r = 0.373) coagulation as well as between D-dimer and FII (p < 0.01, r = 0.851), FVII (p < 0.05, r = 0.367)was absent in the females. Our research demonstrated a weakening correlations in the males after intervention between D-dimer and hs-CRP (p < 0.05, r = 0.378), between hs-CRP and FII (p < 0.01, r = 0.501), FV (p < 0.05, r = 0.298), FVII (p < 0.05, r = 0.351) as well as between D-dimer and FII (p < 0.01, r = 0.759), and FVII (p < 0.05, r = 0.296). The increase of the FX values (p < 0.05) in the females after intervention suggested the possible antiinflammatory effect of exercise training. Conclusion. According to previous research, the higher levels of vWF was associated with a risk of cardiovascular disease in people with type 2 diabetes mellitus and vWF may be a risk factor unique to these populations. We demonstrated that the 8-week exercise training can significantly reduce the value of vWF in the males and females, suggesting a potential beneficial effect on the endothelial function parameters. Our research demonstrated a stronger correlation between the coagulation and inflammation parameters as baseline in the males than in the females with type 2 diabetes mellitus. According to our results, the 8-week exercise training lead to a weakening of the strength of correlation between the coagulation and inflammation parameters in the males and complete disappearance of this correlation in the females, suggesting a unique effect of exercise training that should be explored in future research. © 2019, Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved.

Introduction: This study investigates the cost-effectiveness of insulin degludec versus insulin glargine U100 in patients with type 1 and type 2 diabetes mellitus in Serbia. Methods: A cost-utility analysis, implementing a simple short-term model, was used to compare treatment costs and outcomes with degludec versus glargine U100 in patients with type 1 (T1DM) and type 2 diabetes (T2DM). Cost-effectiveness was analysed in a 1-year setting, based on data from clinical trials. Costs were estimated from the healthcare payer perspective, the Serbian Health Insurance Fund (RFZO). The outcome measure was the incremental cost-effectiveness ratio (ICER) or cost per quality-adjusted life-year (QALY) gained. Results: Degludec is highly cost-effective compared with glargine U100 for people with T1DM and T2DM in Serbia. The ICERs are estimated at 417,586 RSD/QALY gained in T1DM, 558,811 RSD/QALY gained in T2DM on basal oral therapy (T2DMBOT) and 1,200,141 RSD/QALY gained in T2DM on basal-bolus therapy (T2DMB/B). All ICERs fall below the commonly accepted thresholds for cost-effectiveness in Serbia (1,785,642 RSD/QALY gained). In all three patient groups, insulin costs are higher with degludec than with glargine U100, but these costs are partially offset by savings from a lower daily insulin dose in T1DM and T2DMBOT, a reduction in hypoglycaemic events in all three patient groups and reduced costs of SMBG testing in the T2DM groups with degludec versus glargine U100. Conclusion: Degludec is a cost-effective alternative to glargine U100 for patients with T1DM and T2DM in Serbia. Degludec may particularly benefit those suffering from hypoglycaemia or where the patient would benefit from the option of flexible dosing. Funding: Novo Nordisk. © 2018, The Author(s).

The association between type 2 diabetes mellitus (T2DM) and heart failure (HF) has been firmly established; however, the entity of diabetic myocardial disorder (previously called diabetic cardiomyopathy) remains a matter of debate. Diabetic myocardial disorder was originally described as the occurrence of myocardial structural/functional abnormalities associated with T2DM in the absence of coronary heart disease, hypertension and/or obesity. However, supporting evidence has been derived from experimental and small clinical studies. Only a minority of T2DM patients are recognized as having this condition in the absence of contributing factors, thereby limiting its clinical utility. Therefore, this concept is increasingly being viewed along the evolving HF trajectory, where patients with T2DM and asymptomatic structural/functional cardiac abnormalities could be considered as having pre-HF. The importance of recognizing this stage has gained interest due to the potential for current treatments to halt or delay the progression to overt HF in some patients. This document is an expert consensus statement of the Heart Failure Association of the ESC and the ESC Working Group on Myocardial & Pericardial Diseases. It summarizes contemporary understanding of the association between T2DM and HF and discuses current knowledge and uncertainties about diabetic myocardial disorder that deserve future research. It also proposes a new definition, whereby diabetic myocardial disorder is defined as systolic and/or diastolic myocardial dysfunction in the presence of diabetes. Diabetes is rarely exclusively responsible for myocardial dysfunction, but usually acts in association with obesity, arterial hypertension, chronic kidney disease and/or coronary artery disease, causing additive myocardial impairment. © 2024 European Society of Cardiology.

In both pediatric and adult populations with type 1 diabetes (T1D), technologies such as continuous subcutaneous insulin infusion (CSII), continuous glucose monitoring (CGM), or sensor-augmented pumps (SAP) can consistently improve glycemic control [measured as glycated hemoglobin (HbA1c) and time in range (TIR)] while reducing the risk of hypoglycemia. Use of technologies can thereby improve quality of life and reduce the burden of diabetes management compared with self-injection of multiple daily insulin doses (MDI). Novel hybrid closed-loop (HCL) systems represent the latest treatment modality for T1D, combining modern glucose sensors and insulin pumps with a linked control algorithm to offer automated insulin delivery in response to blood glucose levels and trends. HCL systems have been associated with increased TIR, improved HbA1c, and fewer hypoglycemic events compared with CSII, SAP, and MDI, thereby potentially improving quality of life for people with diabetes (PwD) while reducing the costs of treating short- and long-term diabetes-related complications. However, many barriers to their use and regional inequalities remain in Central and Eastern Europe (CEE). Published data suggest that access to diabetes technologies is hindered by lack of funding, underdeveloped health technology assessment (HTA) bodies and guidelines, unfamiliarity with novel therapies, and inadequacies in healthcare system capacities. To optimize the use of diabetes technologies in CEE, an international meeting comprising experts in the field of diabetes was held to map the current regional access, to present the current national reimbursement guidelines, and to recommend solutions to overcome uptake barriers. Recommendations included regional and national development of HTA bodies, efficient allocation of resources, and structured education programs for healthcare professionals and PwD. The responsibility of the healthcare community to ensure that all individuals with T1D gain access to modern technologies in a timely and economically responsible manner, thereby improving health outcomes, was emphasized, particularly for interventions that are cost-effective. © 2021, The Author(s).

Background: The predictive value of preoperative neutrophil-to-lymphocyte ratio (NLR) in patients with cholecystitis has not been established. The aim of this study was to investigate preoperative NLR in patients with cholecystitis and to identify a relevant NLR value that discriminates between simple and severe cholecystitis. Methods: This study included 136 patients who under went laparoscopic cholecystectomy due to cholecystitis. The Receiver Operating Characteristic (ROC) analysis was performed to identify the most useful NLR cut-off value in relation to the severity of cholecystitis. The patients were di vided into two groups according to the cut-off NLR value: high NLR group (≥4.18, n=23) and low NLR group (<4.18, n=113). Severe cholecystitis was defined as a state which includes inflammation, empyema, gangrene, perforation of gallbladder, adhesions or difficulty in dissecting Calot's triangle. Results: In the high NLR group, severe cholecystitis (p<0.0001) and higher C-reactive protein level (CRP) and white blood cells count (WBC) (p<0.0001) were significantly more frequent. There was no difference in homeostatic model assessment-insulin resistance index (HOMA-IR) between both groups before the operation (p<0.634). The incidence of severe cholecystitis was 16.9%. The NLR of 4.18 could predict severe cholecystitis with 78.3% sensitivity and 74.3% specificity. Spearman's correlation revealed significant association between the preoperative NLR and HOMA-IR on day 1, (r=0.254, p=0.030) and between preoperative NLR and CRP on day 1 (ρ=0.355; p<0.0001). Conclusions: NLR ≥4.18 was significantly associated with severe cholecystitis. The preoperative NLR in patients under going cholecystectomy due to cholecystitis could be a useful surrogate marker of severe cholecystitis. © 2017 Dušan Micić et al.

Background: The predictive value of preoperative neutrophil-to-lymphocyte ratio (NLR) in patients with cholecystitis has not been established. The aim of this study was to investigate preoperative NLR in patients with cholecystitis and to identify a relevant NLR value that discriminates between simple and severe cholecystitis. Methods: This study included 136 patients who under went laparoscopic cholecystectomy due to cholecystitis. The Receiver Operating Characteristic (ROC) analysis was performed to identify the most useful NLR cut-off value in relation to the severity of cholecystitis. The patients were di vided into two groups according to the cut-off NLR value: high NLR group (≥4.18, n=23) and low NLR group (<4.18, n=113). Severe cholecystitis was defined as a state which includes inflammation, empyema, gangrene, perforation of gallbladder, adhesions or difficulty in dissecting Calot's triangle. Results: In the high NLR group, severe cholecystitis (p<0.0001) and higher C-reactive protein level (CRP) and white blood cells count (WBC) (p<0.0001) were significantly more frequent. There was no difference in homeostatic model assessment-insulin resistance index (HOMA-IR) between both groups before the operation (p<0.634). The incidence of severe cholecystitis was 16.9%. The NLR of 4.18 could predict severe cholecystitis with 78.3% sensitivity and 74.3% specificity. Spearman's correlation revealed significant association between the preoperative NLR and HOMA-IR on day 1, (r=0.254, p=0.030) and between preoperative NLR and CRP on day 1 (ρ=0.355; p<0.0001). Conclusions: NLR ≥4.18 was significantly associated with severe cholecystitis. The preoperative NLR in patients under going cholecystectomy due to cholecystitis could be a useful surrogate marker of severe cholecystitis. © 2017 Dušan Micić et al.

The 7th Cardiovascular Outcome Trial (CVOT) Summit on Cardiovascular, Renal, and Glycemic Outcomes, was held virtually on November 18–19, 2021. Pursuing the tradition of the previous summits, this reference congress served as a platform for in-depth discussion and exchange on recently completed CVOTs. This year’s focus was placed on the outcomes of EMPEROR-Preserved, FIGARO-DKD, AMPLITUDE-O, SURPASS 1–5, and STEP 1–5. Trial implications for diabetes and obesity management and the impact on new treatment algorithms were highlighted for endocrinologists, diabetologists, cardiologists, nephrologists, and general practitioners. Discussions evolved from outcome trials using SGLT2 inhibitors as therapy for heart failure, to CVOTs with nonsteroidal mineralocorticoid receptor antagonists and GLP-1 receptor agonists. Furthermore, trials for glycemic and overweight/obesity management, challenges in diabetes management in COVID-19, and novel guidelines and treatment strategies were discussed. Trial registration The 8th Cardiovascular Outcome Trial Summit will be held virtually on November 10–11, 2022 (http://www.cvot.org). © 2022, The Author(s).

Introduction The metabolic syndrome and its influence on coronary artery disease development and progression remains in focus of international research debates, while insulin resistance, which represents its core, is the key component of hypertension, dyslipidaemias, glucose intolerance and obesity. Objective The aim of this study was to establish relationship between basal glucose and insulin levels, insulin sensitivity and lipid panel and the degree of coronary atherosclerosis in non-diabetic patients. Methods The coronary angiograms were evaluated for the presence of significant stenosis, insulin sensitivity was assessed using the intravenous glucose tolerance test with a minimal model according to Bergman, while baseline glucose (G0), insulin (I0) and lipid panel measurements (TC, HDL, LDL, TG) were taken after a 12-hour fasting. Results The protocol encompassed 40 patients (19 men and 21 women) treated at the Institute for Cardiovascular Diseases of the Clinical Centre of Serbia, Belgrade. All were non-diabetics who were divided into 3 groups based on their angios: Group A (6 patients, 15%, with no significant stenosis), Group B (18 patients, 45%, with a single-vessel disease) and Group C (16 patients, 40%, with multi-vessel disease). Presence of lower insulin sensitivity, higher I0 and TC in the group of patients with a more severe degree of coronary atherosclerosis (insulin sensitivity: F=4.279, p=0.023, A vs. C p=0.012, B vs. C p=0.038; I0: F=3.461 p=0.042, A vs. B p=0.045, A vs. C p=0.013; TC: F=2.572, p=0.09), while no significant difference was found for G0, LDL, HDL and TG. Conclusion Baseline insulinaemia, more precisely, fasting hyperinsulinaemia could be a good predictor of significant coronary atherosclerosis in non-diabetic patients, which enables a more elegant cardiometabolic risk assessment in the setting of everyday clinical practice.

Cardiovascular disease (CVD) is the most significant prognostic factor in individuals with type 2 diabetes (T2D). However, a significant number of individuals may develop CVD that does not present with the classic angina-related or heart failure symptoms. In these cases, CVD may seem to be 'silent' or 'asymptomatic', but may be more accurately characterised as unrecognised diabetic cardiac impairment. An initial step to raise awareness of unrecognised CVD in individuals with T2D would be to reach a consensus regarding the terminology used to describe this phenomenon. By standardising the terminologies, and agreeing on the implementation of an efficient screening program, it is anticipated that patients will receive an earlier diagnosis and appropriate and timely treatment. Given the availability of anti-diabetic medications that have been shown to concomitantly reduce CV risk and mortality, it is imperative to improve early identification and initiate treatment as soon as possible in order to enable as many patients with T2D as possible to benefit. © 2018 The Author(s).