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Publikacije (344)

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Z. Lazic, I. Stanković, B. Milenković, B. Zvezdin, S. Hromis, S. Janković, V. Ćupurdija

Background Establishing a regional/national/international registry of patients suffering from chronic obstructive pulmonary disease (COPD) is essential for both research and healthcare, because it enables collection of comprehensive real-life data from a large number of individuals. Objective The aim of this study was to describe characteristics of COPD patients from the Serbian patient registry, and to investigate actual differences of those characteristics among the COPD phenotypes. Methods The Serbian registry of patients with COPD was established in 2018 at University of Kragujevac, Faculty of Medical Sciences, based on an online platform. Entry in the Registry was allowed for patients who were diagnosed with COPD according to the following criteria: symptoms of dyspnea, chronic cough or sputum production, history of risk factors for COPD and any degree of persistent airflow limitation diagnosed at spirometry. Results In the Serbian COPD registry B and D GOLD group were dominant, while among the COPD phenotypes, the most prevalent were non-exacerbators (49.4%) and then frequent exacerbators without chronic bronchitis (29.6%). The frequent exacerbator with chronic bronchitis phenotype was associated with low levels of bronchopulmonary function and absolute predominance of GOLD D group. Anxiety, depression, insomnia, hypertension and chronic heart failure were the most prevalent in the frequent exacerbator with chronic bronchitis phenotype; patients with this phenotype were also treated more frequently than other patients with a triple combination of the most effective inhaled anti-obstructive drugs: long-acting muscarinic antagonists, long-acting beta 2 agonists and corticosteroids. Conclusion In conclusion, the data from the Serbian registry are in line with those from other national registries, showing that frequent exacerbators with chronic bronchitis have worse bronchopulmonary function, more severe signs and symptoms, and more comorbidities (especially anxiety and depression) than other phenotypes. Other studies also confirmed worse quality of life and worse prognosis of the AE-CB phenotype, stressing importance of both preventive and appropriate therapeutic measures against chronic bronchitis.

R. Suša, V. Ćupurdija, Ljiljana Novkovic, Miloš Ratinac, S. Janković, Danijela Đoković, J. Jovanović, Katarina Pantić et al.

Background and Objectives: This paper aims to show whether obstructive sleep apnea (OSA) severity increases the level of systemic inflammation markers regardless of body mass index (BMI) and body composition. Materials and Methods: In total, 128 patients with OSA were included in the study. Examinees were divided into two groups: one with mild OSA (apnea–hypopnea index (AHI) < 15) and one with moderate and severe OSA (AHI ≥ 15). Nutritional status was assessed using body mass index, body composition by dual X-ray absorptiometry. Systemic inflammation was assessed on the basis of plasma concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and serum level of C-reactive protein (CRP). Results: We found elevated mean values of the evaluated systemic inflammation markers (CRP, TNF-α, IL-6) in a group with AHI ≥ 15, although there was no statistical significance. Our research found a significant positive correlation with BMI (r = 0.633, p < 0.001), as well as with body fat percentage (r = 0.450, p = 0.024) and serum CRP values. Significant correlation was found between the plasma IL-6 concentration and body fat percentage (FM%) (r = 0.579, p = 0.003) and lean body mass (r = −0.501, p = 0.013). Multivariate regression analysis did not show any independent predictor (parameters of OSA, nutritional status, body composition) of the systemic inflammation markers. Conclusions: Neither one tested parameter (nutritional status and body composition) of the severity of OSA was identified as an independent prognostic factor for the severity of systemic inflammation in patients with OSA.

S. Janković, Biljana Popovska-Jovičić, R. Pavlović, Radica Živković-Zarić

Introduction: Drug rash with eosinophilia and systemic symptoms (DRESS syndrome) is a rare, severe, systemic, drug-induced hypersensitivity syndrome, the most frequently associated with anticonvulsants. Case Report: A 35-years-old woman with a history of depression and hypothyroidism developed fever 39.5°C, enlarged, painful neck and axillary lymph nodes, slight facial edema around the mouth, confluent maculopapular rash, and laboratory signs of hepatocellular injury, leukocytosis and lymphopenia, but with normal eosinophil count. The syndrome was evident two weeks after starting carbamazepine, and gradually decreased after withdrawal of this drug and introduction of corticosteroid therapy. Conclusion: If a patient is taking carbamazepine and develops skin rash as well as fever and swollen lymph nodes, the physician should always check for internal organ damage and possible DRESS syndrome.

S. Janković, M. Kostić, J. Milovanović

Introduction: Key problems when transferring results of pharmacoeconomic studies between countries are: relative infrequency of observational design, utilization of unreliable estimates of input parameters in many of modelling studies, not reporting variability of the study outputs (e.g. ICER, net monetary benefit) in a publication, and large differences in costs of healthcare services and drugs from country to country. Aim: The aim of this study was to estimate Incremental Cost-effectiveness Ratio (ICER) of denosumab vs. alendronate for treatment of osteoporosis in postmenopausal women in Serbia, using results of published pharmacoeconomic studies in United States of America (USA) and Japan. Material and Methods: The estimate of the ICER was made through the following steps: (1) scaling the ICER of the published studies to Serbian healthcare milieu using unit costs in Serbia, USA and Japan; (2) defining prior distribution of the ICER using adjusted results of the earlier published study; (3) defining sampling distribution of the ICER using adjusted results of the next published study; (4) estimating posterior distribution of the ICER and calculating the most probable values the ICER with Bayesian statistics. Results: The ICER of the prior distribution was 572,787.00 RSD, with 99% confidence interval from 1,116.00 to 998,051.00 RSD, and that of the sampling distribution 706,057.00 RSD, with 99% confidence interval from 1,122.00 to 999,308.00 RSD. The most probable ICER value from the posterior distribution was 752,912.00 RSD, with 99% confidence interval from 667,631.00 to 771,552.07 RSD. The estimated ICER was below one Gross Domestic Product (GDP) of Serbia per capita (the 2019 value: 780,063.60 RSD). Conclusions: Denosumab should be considered cost-effective in Serbia if one to three GDPs/capita/Quality Adjusted Life Year (QALY) gained is taken as the upper limit of willingness to pay by Serbian Health Insurance Fund.

D. Aleksić, Pavle Z. Petković, Miloš N. Milosavljević, S. Stefanović, S. Janković

Introduction: The clinical significance of potential drug-drug interactions (pDDIs), especially in the intensive care unit (ICU) manifested mostly as adverse drug reactions. Aim: The goal of this research was to conduct a focus group, in which the participants were decisionmakers in acute ischemic stroke patient treatment. Also, the aim was to reach a consensus, due to the Delphi process, between neurologists and clinical pharmacologists regarding this highly vulnerable group of patients. Material and Methods: In this academic research, so-called applied focus group (the goal was to reach practical decisions) and clinical focus group (determining motives, predeterminations, bias, prejudice and analyzing the behavior leading to a certain outcome) was done. Results: Continuing medical education of neurologists is needed regarding pDDIs and the use of an online pDDIs checker. Certain groups of patients with AIS are at particular risk of exposure to pDDIs. Certain drug groups are more likely to interact with other drugs. Conclusions: Defining medical recommendations/guidelines on evidence base medicine about pDDIs in patients with AIS would significantly contribute to reducing their frequency in this vulnerable patient population.

M. Kostić, Radica Živković-Zarić, S. Janković

Bacground/Aim. Treatment of neurological diseases usually requires polypharmacy, and it is crucial to detect potential drug-drug interactions (DDIs) and recognize risk factors on time, as consequences of DDIs could be serious. The aim of the study was to analyze risk factors for the occurrence and the number of potential DDIs among patients in a general neurological ward. Methods. This study was conducted with 144 inpatients in a general-care neurological department of a tertiary care hospital. The effects of risk factors for potential DDIs were evaluated by multiple linear regression. The study had retrospective cohort de-sign. Frequencies of various types of potential DDIs (according to severity) were discovered by Medscape, Epocrates and Micromedex online interaction checkers. Results. The number of prescribed drugs, age of a patient, value of the Charlson comorbidity index and prescription of an antidepressant increase risk of potential DDIs in a general neurology ward. On the other hand, being paralyzed, number of prescribers for a single patient, being bedridden for at least one day of hospitalization decreased the number of potential DDIs per patient. Number of prescribed drugs per patient [odds ratio (OR) = 1.466 ? 0.250; p = 0.000) and age (OR = 1.027 ? 0.026; p = 0.041)] increased, and number of prescribers per patient (OR = 0.056 ? 0.028; p = 0.016), especially if the patients were paralyzed (OR = 0.214 ? 0.294; p = 0.007), decreased the risk of contraindicated, serious, ?use alternative? or major potential DDIs. Antidepressants increased the risk of absolute number of all monitor/modify potential DDIs (OR = 1.257 ? 0.726; p = 0.035). Conclusion. Frequency of potential DDIs among neurological patients is considerable and influenced to the largest extent by advanced age, comorbidities, total number of pre-scribed drugs per patient and concomitant use of antidepressants.

D. Aleksić, S. Stefanović, Miloš N. Milosavljević, J. Milosavljević, S. Janković

Introduction: Patients with Parkinson's disease are exposed to higher number of drugs on average than other elderly persons. Levodopa, of the mainstay of Parkinson's disease therapy, is frequently interacting with numerous drugs. Aim: The aim of this study was to identify predictors of potential drug-drug interactions (pDDIs) in hospitalized patients suffering from Parkinson's disease (PD). Material and Methods: This was a academic retrospective cross-sectional study in PD patients hospitalized at the Clinic of Neurology, Clinical Center Kragujevac. Medical records of hospitalized patients during the period 1.1.2017 - 31.12.2019 were analysed. The pDDIs were identified by means of Micromedex andLexi-Interact online softwares, and multivariate regression methods were used to reveal potential predictors of number of pDDIs per patient. Results: Micromedex detected 160 different pDDIs in 77.8% of 72 patients with PD. The most frequent pDDIs were those that involved aspirin (with bisoprolol, sertraline and perindopril). Predictors of pDDIs in general was total number of drugs, while use of antidepressants presented a significant risk factor for major pDDIs. Lexi-Interact revealed 310 pDDIs in 98.6% of patients. The three most common pDDIs were with levodopa (bisoprolol, clonazepam, perindopril). Total number of drugs, number of co-morbidities, hospitalization at the neurodegenerative ward, and use of antipsychotics were identified as the relevant predictors of pDDIs. Lexi-interact software detected significantly more pDDIs than Micromedex (p<0.001). Conclusion: Neurologists should pay special attention when deciding whether to administer new drug to a PD patient with multiple comorbidities, hospitalized in a neurodegenerative ward and/or taking antidepressant or antipsychotic drugs.

I. Masic, A. Kurjak, S. Janković, O. Sinanović, D. Donev, Benjamin, Djulbegovic, Kenan et al.

It is very well known that science is world activity and that there is no good and bad work in the field of scientific research. Nowadays scientific productivity of the individuals, learned societies on regional or state level are measurable parameters. In most of the systems it does include the number of original scientifi papers, quality of journals measured by impact factor and scientific citation index (1-4). There are also additional measurable parameters but for the purpose of this meeting we will avoid discussion about them. New field of scientometrics using the help of impartial and ruthless machines (computers) do help very significantly in evaluation of scientific productivity anywhere in the world. Unfortunately, there are many misused conclusions and interpretation on the data offered by computers. It is clear that some vital important changes are urgently needed. Today’s conference should use rare opportunity having together experts in the field to discuss the problems visible now. This author intends to discuss facts and doubts in writing review articles and chapters in the book (5). Some important flexibility in citation, in particular self citation, should be analyzed. An illustrative examples from author’s own experience will be shown and discussed at the meeting.

I. Masic, S. Janković, A. Kurjak, D. Donev, M. Zildžić, O. Sinanović, I. Hozo, S. Miličević et al.

Background: Enormous number of medical journals published around the globe requires standardization of editing practice. Objective: The aim of this article was to enlist main principles of editing biomedical scientific journals adopted at annual meeting of Academy of Medical Sciences of Bosnia & Herzegovina (AMSB&H). Methods: The evidence for writing this Guideline was systematically searched for during September 2020 in the PUBMED and GOOGLE SCHOLAR databases. The inclusion criteria were: original studies, systematic reviews, invited expert opinions, guidelines and editorials. The exclusion criteria were narrative reviews and uninvited opinion articles. The retrieved evidence was analyzed by members of the AMSB&H, then discussed at 2020 annual meeting of the AMSB&H and adopted by nominal group technique. Results: In total 14 recommendations were made, based on A to C class of evidence. The editors should educate potential authors and instruct them how to structure their manuscript, how to write every segment of the manuscript, and take care about correct use of statistical tests. Plagiarism detection softwares should be used regularly, and statistical and technical editing should be rigorous and thorough. International standards of reporting specific types of studies should be followed, and principles of ethical and responsible behavior of editors, reviewers and authors should be published on the journal’s web site. The editors should insist on registration of clinical studies before submission, and check whether non-essential personal information is removed from the articles; when essential personal information has to be included, an article should not be published without signed informed consent by the patient to whom these information relate. Conclusions: Principles of editing biomedical scientific journals recommended in this guideline should serve as one of the means of improving medical journals’ quality.

I. Masic, S. Janković, A. Kurjak, D. Donev, M. Zildžić, O. Sinanović, I. Hozo, S. Miličević et al.

Background: From 2013 the World Medical Association’s Declaration of Helsinki explicitly requires pre-registration of a study involving human subjects. The registration gives a chance for improvement of design and avoidance of bias. Objective: The aim of this article was to describe process of bearing decision to create regional registry of clinical studies for Balkan countries. Methods: After finding relevant studies about research registries and designing the concept and structure of future regional registry an article was published in IJBH journal. The article was than used as basis for discussion at 2020 meeting of Academy of Medical Sciences of Bosnia and Herzegovina (AMSBH), and final decision was made by the Academy to create the research registry. Results: Regional registry of clinical studies will be under the auspices of AMSBH and web-based, with the option of online registration of new studies. The data required to be entered in the moment of registration relate to key elements of research plan: topic, variables, sample, type of the study and the study population. After applying for registration of a clinical study, the authors will soon receive the review made by the AMSBH expert committee. The application could be accepted, rejected or returned for major or minor revision. After an application is accepted, it will be deposited in the searchable database and given the registration number. Conclusion: The AMSBH’s decision to create the regional registry of clinical studies will satisfy needs of researchers from Balkan countries in the first place, who share cultural and lingual similarities. It will also help with increasing standards of clinical research in the region.

M. Folic, Z. Djordjevic, Nevena Folic, M. Radojevic, S. Janković

Pseudomonas aeruginosa (PA) is a globally recognized cause of healthcare-associated infections (HAIs). The aim of our cross-sectional study, conducted in a Serbian tertiary care hospital, was to investigate clinical characteristics of HAIs caused by the PA, the prevalence of various drug-resistant phenotypes of this pathogen, and risk factors for their occurrence. Prolonged ICU stay and previous carbapenem administration were independent risk factors for HAIs caused by carbapenem-resistant PA, while HAIs caused by multidrug-resistant PA were more frequent in patients with prolonged stay in an ICU, who were previously hospitalized at another department and previously treated with aminoglycosides, fluoroquinolones or glycopeptides. The prolonged ICU stay was the only significant risk factor for HAIs caused by extensively drug-resistant PA. To decrease the incidence of HAIs caused by drug-resistant PA, a multifaceted approach is necessary, including staff education, antibiotic stewardship, improving hygiene, shortening hospitalization, and minimizing exposure to invasive medical procedures/devices.

S. Janković, Radica S Živković Zarić, M. Stojadinovic, Z. Lazic, I. Čekerevac, R. Suša

OBJECTIVE The goal of our study was to discover and analyze possible risk factors for and possible protective factors against the occurrence of potential drug-drug interactions (pDDIs) in a hospitalized patient with community-acquired pneumonia. MATERIALS AND METHODS The central outcome was the incidence of pDDIs in patients with community-acquired pneumonia checked by Lexicomp and Micromedex interaction checkers. RESULTS The most severe pDDIs (Consider therapy modification D/Avoid combination X/Major/Contraindicated) were found in 19 (20%) and 54 (58%) patients, according to Lexicomp and Micromedex, respectively. Patients with community-acquired pneumonia who were older, smokers, and with more prescribed drugs by more than a few independent prescribers had a higher risk to experience pDDIs. Possible protective factors were longer length of hospitalization, transfer from the Emergency Department, antiarrhythmic drugs as well as an anticoagulant therapy. CONCLUSION In conclusion, community-acquired pneumonia patients with the above-mentioned factors should have their treatment more deeply monitored for pDDIs.

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