Browsing by Author "Rančić, Nemanja (54941042300)"

[No abstract available]

Introduction Consumption of alcohol may be an important causative factor in traffic accidents, particularly in categories of drivers and pedestrians. Objective Analysis of frequency and other important medicolegal characteristics of drunken state of motor vehicles drivers. Methods We analyzed autopsies performed at the Institute of Forensic Medicine Belgrade during 2008 and 2009. Data were obtained from autopsy protocols, results of toxicological examinations, and police reports about circumstances of traffic accidents. Results Out of all 84 fatally injured drivers, drunken state was proved in 31 (36.9%). The majority of them were males (30% or 97%), while only one female driver was under the influence of alcohol. The most often drunken drivers were in the third life decade (10% or 32.2%). In most cases the injured alcoholised drivers died immediately after the accident (83.8%). In most of them blood alcohol concentration (BAC) was higher than 2‰ (58.1%), most frequently (12) BAC varied between 2.1‰ and 2.5‰, and the highest determined BAC was 3.85‰. The majority of accidents occurred between midnight and 6 a.m. (54.8%), mostly during working days (77.4%). The most frequent ways of the occurrence of traffic accidents were driving by turning away from the road and striking from behind another vehicle on the road. Conclusion The obtained results point out the important role of the drunken state of the drivers of motor vehicles as a causative factor in traffic accidents in our population. The potentially effective preventive measure could be absolute prohibition of alcohol consumption for all drivers.

Objectives: Many countries around the world have recognized the need for using an electronic health record (EHR) system. However, there is limited literature that could serve as a guide during a lengthy and challenging process of planning, development, and implementation of the e-Health system. Since the EHR system was recently introduced in Serbia, the purpose of this communication is to describe our experience and lessons learned along the way. Methods: The key personnel involved in the implementation of the EHR system in Serbia that began in 2015 conducted in 2019 a retrospective narrative review of the process and early outcomes. Results: An incremental approach in the planning, development, and implementation of the nationwide EHR system was taken. The process was split into phases with the gradual introduction of different regions of the country. The gradual shift from the existing to a new workflow for the prospective users was also implemented. The significant milestones were the achievement of quick legislative changes, the hiring of a professional team of experts in the field, the provision of timely and appropriate information and training to prospective users, the close collaboration between the implementation team and the Ministry of Health and mutual understanding of the aims and expectations, and the flexibility in accepting the evolving nature of the process, goals, and the system model. Conclusions: A successful implementation of the nationwide EHR system is feasible providing careful planning, the assembly of a multi-disciplinary team, the use of a stepwise approach, the early and continued involvement of the intended users, and the willingness to make adjustments along the way. The end-result sets the stage for the reform of the health care system itself. © 2022, Dr. Mladen Stojanovic University Hospital. All rights reserved.

Itraconazole is a triazole antifungal agent with highly variable pharmacokinetics, with not yet fully identified factors as the source of this variability. Our study aimed to examine the influence of body mass index, gender, and age on the first dose pharmacokinetics of itraconazole in healthy subjects, using pharmacokinetic modeling, non-compartmental versus compartmental ones. A total of 114 itraconazole and hydroxy-itraconazole sets of plasma concentrations of healthy subjects of both genders, determined using a validated liquid chromatographic method with mass spectrometric detection (LC-MS), were obtained for pharmacokinetic analyses performed by the computer program Kinetica 5®. Genetic polymorphism in CYP3A4, CYP3A5, CYP1A1, CYP2C9, and CYP2C19 was analyzed using PCR-based methods. Multiple linear regression analysis indicated that gender had a significant effect on AUC as the most important pharmacokinetics endpoint, whereas body mass index and age did not show such an influence. Therefore, further analysis considered gender and indicated that both geometric mean values of itraconazole and hydroxy-itraconazole plasma concentrations in men were prominently higher than those in women. A significant reduction of the geometric mean values of Cmax and AUC and increment of Vd in females compared with males were obtained. Analyzed genotypes and gender differences in drug pharmacokinetics could not be related. Non-compartmental and one-compartmental models complemented each other, whereas the application of the two-compartmental model showed a significant correlation with the analysis of one compartment. They indicated a significant influence of gender on itraconazole pharmacokinetics after administration of the single oral dose of the drug, given under fed conditions. Women were less exposed to itraconazole and hydroxy-itraconazole than men due to poorer absorption of itraconazole, its more intense pre-systemic metabolism, and higher distribution of both drug and its metabolite. Copyright © 2022 Miljković, Rančić, Kovačević, Cikota-Aleksić, Skadrić, Jaćević, Mikov and Dragojević-Simić.

Itraconazole is a triazole antifungal agent with highly variable pharmacokinetics, with not yet fully identified factors as the source of this variability. Our study aimed to examine the influence of body mass index, gender, and age on the first dose pharmacokinetics of itraconazole in healthy subjects, using pharmacokinetic modeling, non-compartmental versus compartmental ones. A total of 114 itraconazole and hydroxy-itraconazole sets of plasma concentrations of healthy subjects of both genders, determined using a validated liquid chromatographic method with mass spectrometric detection (LC-MS), were obtained for pharmacokinetic analyses performed by the computer program Kinetica 5®. Genetic polymorphism in CYP3A4, CYP3A5, CYP1A1, CYP2C9, and CYP2C19 was analyzed using PCR-based methods. Multiple linear regression analysis indicated that gender had a significant effect on AUC as the most important pharmacokinetics endpoint, whereas body mass index and age did not show such an influence. Therefore, further analysis considered gender and indicated that both geometric mean values of itraconazole and hydroxy-itraconazole plasma concentrations in men were prominently higher than those in women. A significant reduction of the geometric mean values of Cmax and AUC and increment of Vd in females compared with males were obtained. Analyzed genotypes and gender differences in drug pharmacokinetics could not be related. Non-compartmental and one-compartmental models complemented each other, whereas the application of the two-compartmental model showed a significant correlation with the analysis of one compartment. They indicated a significant influence of gender on itraconazole pharmacokinetics after administration of the single oral dose of the drug, given under fed conditions. Women were less exposed to itraconazole and hydroxy-itraconazole than men due to poorer absorption of itraconazole, its more intense pre-systemic metabolism, and higher distribution of both drug and its metabolite. Copyright © 2022 Miljković, Rančić, Kovačević, Cikota-Aleksić, Skadrić, Jaćević, Mikov and Dragojević-Simić.

Background/Aim. During the homicidal act, a victim usually tries to defend himself/herself, and due to these attempts he/she could sustain so-called defense injuries, mostly localized on the arms. The aim of this research was to analyze important medicolegal characteristics of defense injuries, particularly regarding their importance in forensic expertise of homicides. Methods. We analyzed autopsies of all homicidal cases with defense injuries in Belgrade during a three-year period. Results. Defensive injuries were registered in 71 victims of murder. The majority (67.61%) of victims with defense injuries were males. About 25% of victims were aged from 21 to 30 years. The majority (60) of victims were not under influence of alcohol. Homicides were mostly (90.14%) performed by mechanical weapons. The highest frequency of defense injuries was noticed in the victims with multiple homicidal injuries localized on the front side of the body. In a half (50.7%) of the cases they were present on both arms of the victim, mostly on the dorsal side of hands and forearms. Bruises were the most frequent form of defense injuries (36.61% out of 71 cases), while incisions, abrasions, gunshot injuries and stab wounds were less common. Conclusion. Determination of defense injuries and their medicolegal characteristics enables collecting of facts that are important for legal estimation of homicide, as well as for adequate sentence at the end of the court procedure. © 2017, Institut za Vojnomedicinske Naucne Informacije/Documentaciju. All rights reserved.

Introduction. Pulmonary arteriovenous malformation (PAVM) is pathological communication between pulmonary artery and pulmonary vein, in way that it shunts normal alveolar capillary membrane resulting in inadequate blood oxygenation in this part of the lung parenchyma Modern therapy of PAVMs includes surgical treatment or endovascular embolization. Case report. A 30-year-old female patient had signs of parestesia and weakness of the extremities on the left side of her body. On physical examination there was only cyanotic discoloration of her lips and clubbing fingers. On the chest x-ray, in the right hemithorax, in the inferior region of the lung, there was relatively homogeneous and well defined shadow, intensity of the soft tissue, which was about 35 mm. A multislice computed tomography pulmonary angiography was performed and showed, in lung parenchyma on both sides, many PAVMs, of which the largest (35 mm) was in inferior right region of the lung on crossing between apical and posterior basal lung segment with 7 mm diameter feeding artery and 9 mm diameter draining vein. The selective pulmonary angiography was performed by Seldingers technique. Through sheath, we placed a plug with a diameter of 10 mm. The plug was expanded and a complete occlusion of the final part of the feeding branch of this PAVM was achieved (confirmed by control angiography). In that way, the PAVM was fully shut off from the circulation. In 3 months follow-up, the patient was feeling well, without any recorded complication. Conclusion. Endovascular embolization is recommended as therapy of the first choice for all of PAVMs that have feeding artery greater than 2 mm. Endovascular embolization has high success rate with minimal complications. © 2021 Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved.

Background/Aim. The incidence of nodular thyroid disease increases significantly with age as well as the incidence and aggressiveness of thyroid cancers. The aim of the study was to determine whether thyroid surgery for geriatric patients is safe in a short hospital stay surgery setting. Methods. In this retrospective study, medical histories of all operated geriatric patients (65 years and older), in whom a total thyroidectomy (TT) or hemithyroidectomy (HT) was performed from January 2012 to December 2018, were analyzed. A total of 976 patients were operated on for thyroid diseases in the mentioned period, out of which 247 geriatric patients fulfilled the inclusion criteria. Patients with thyroid reoperations and simultaneous neck lymph node dissections were excluded from the study. The geriatric patients were divided into two groups: the HT group (33 patients) and the TT group (214 patients). Each of these two geriatric groups, HT and TT, had two additional paired control groups. Control group I consisted of younger subjects from 20–44 years, and control group II included middle-aged subjects from 45–64 years. Results. All three TT groups – geriatric, control I, and control II, had 214 patients each, and all three HT groups had 33 patients each. In all three HT groups, the average hospital stay was 24 hrs, while in the TT geriatric group, 150 (70.1%) of 214 patients spent 24 hrs at the hospital. In the geriatric population, the incidence of neck swelling and increased drainage output were higher compared to both control groups, and thus the need for longer hospitalizations. When the age was compared, it was shown that subjects with each subsequent year of intervention had a 22% lower chance of developing complications, and regarding the pathohistological finding, benign thyroid hyperplasia was less likely to develop complications compared to malignant hyperplasia. Conclusion. According to the study, TT can be safely performed within the concept of a short hospital stay in patients under 65 years, while in the elderly, hospitalization days may be extended due to more frequent surgical and nonsurgical complications. Speaking of HT, the short hospital stay is safe for all age groups. © 2023 Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved.

Background/Aim. Bronchial asthma is a disease that is characterized by the variability of the clinical picture, physical and functional status and the existence of bronchial hypersensitivity and hyperreactivity with varying degrees. Bronchial responsiveness and sensitivity are tested in patients with clinically suspected existence of asthma and normal spirometry test. The aim of the study was to analyze the patients with atopic asthma and study test results of skin sensitization to inhaled allergens, nonspecific bronchial hyperreactivity and specific hyperreactivity estimated by bronchial provocation tests with inhalant allergens. Methods. The prospective study at the Pulmonology Clinic of the Military Medical Academy in Belgrade Serbia, during 2014, included 70 male subjects aged 18–30 years, who had perennial asthma symptoms. All subjects were nonsmokers, with normal spirometry findings, with normal radiological chest findings and with no symptoms of respiratory infection over the past two months. All respondents were tested with skin prick tests with inhalant allergens and nonspecific bronchial provocation test with histamine. On the basis of histamine test, subjects were divided into two groups: the group I, in which there was a slight degree of hypersensitivity [provocation concentration of histamine causing a 20% fall in forced expiratory volume – PC20 = 6.09 ± 1.1 mg/mL], and the group II with negative histamine test (PC20 = 14.58 ± 6.34 mg/mL). Specific bronchial provocation test was performed in all patients, and the selection of the allergens was carried out based on the results of testing of skin hypersensitivity. Results. Results of skin sensitization show the highest incidence of mites Dermatophagoides pterronissinus (83.3% group I and 85.0% group II) followed by grass pollen (53.3% group I and 52.0% group II), and house dust (33.3% group I and 50.0% group II). There were no statistically significant differences in allergens between groups (p > 0.05). In both groups, spirometry findings were within normal values [forced vital capacity – FVC and forced expiratory volume 1 – FEV1 > 80% predictive value], but statistically significant difference was found in FEV1 between groups (p < 0.05). Specific bronchial provocation tests with solutions of inhaled allergens in both groups caused a significant decline in FEV1 (≥ 20%) in all patients individually. No statistically significant differences were found neither between groups, nor between individual allergens (average decline in FEV1: Group I 32.9 ± 2.4% and group II 31.5 ± 2.2%). Conclusion. There is no relationship between the degree of specific and non-specific bronchial hyperreactivity in patients with allergic asthma. © 2017, Institut za Vojnomedicinske Naucne Informacije/Documentaciju. All rights reserved.

Background/Aim. Polymorphisms of genes which encode transporter P-glycoprotein and most important enzymes for tacrolimus pharmacokinetics can have significant influence reflecting on blood concentrations of this drug. The aim of this study was to examine the distribution of polymorphisms of CYP3A5, CYP3A4 and ABCB1 genes in patients subjected to renal transplantation, for the first time in our transplantation center. Methods. The research was designed as a prospective cross-sectional study which included 211 patients subjected to renal transplantation in the Centre for Solid Organ Transplantation of the university tertiary health care hospital, Military Medical Academy, Belgrade, Serbia. Patients of both genders, 22−69-year-old, Caucasians, subjected to immunosuppressive regimen, including tacrolimus, were recruited for the study. CYP3A5 6986A>G (the *3 or *1, rs776746), CYP3A4 - 392A>G (the *1 or *1B, rs2740574) and ABCB1 3435C>T (rs1045642) genotypes were determined by TaqMan® SNP genotyping assays. Results. Most of our patients (94.8%) had functional CYP3A4 enzyme, while 87.7% of all the patients had diminished CYP3A5 enzymatic activity. On the other hand, about one third of them, 31.3%, had functional ABCB1 transporter. Conclusion. A total of 84.8% of our patients were found to express both the CYP3А5*3*3 genotype (associated with diminished CYP3А5 enzymatic activity) and CYP3А4*1*1/*1*1B (associated with functional CYP3А4 enzymatic activity), while out of all the patients with diminished CYP3A5 enzymatic activity, 68.7% had diminished activity of ABCB1 transporter. However, further studies are necessary in order to show the influence of these genetic polymorphisms on tacrolimus blood concentrations in patients after renal transplantation. © 2016, Institut za Vojnomedicinske Naucne Informacije/Documentaciju. All rights reserved.

Background/Aim. Tacrolimus concentration-dose ratio as a potential therapeutic drug monitoring strategy was suggested to be used for the patients subjected to renal trans-plantation. The aim of this study was examining the relationship between tacrolimus concentration-dose ratio, suggested to be used as a therapeutic drug monitoring strategy and the polymorphisms of genes encoding the most important enzymes, such as CYP3A5 and CYP3A4, as well as the transporter P-glycoprotein, for its metabolism and elimination. Methods. The study was designed as a prospective case series study, in which the unit of monitoring was the outpatient examination of 54 patients subjected to renal transplantation. Genotyping was performed by 7500 Real-Time PCR System by assessing allelic discrimination based on TaqMan® methodology. Results. Patients (n = 13) who were treated with less than 2 mg of tacrolimus/day (0.024 ± 0.006 mg/kg/day) had the tacrolimus concentration-dose ratio larger than 150 ng/mL/mg/kg. In this group, 84.62% patients had CYP3А5 *3*3 allele. All of these patients had CYP3А4 *1*1/*1*1B allele. Regarding ABCB1 C3435T gene, 30.77% of patients had the TT gene variant, while 69.23% of our patients had CC and CT gene variants. Conclusion. Tacrolimus concentration-dose ratio greater than 150 ng/mL/mg/kg is cut-off value in patients subjected to renal transplantation which might point to patients who are poor CYP3A5 metabolizers and/or with dysfunctional P-glycoprotein. © 2018, Institut za Vojnomedicinske Naucne Informacije/Documentaciju. All rights reserved.

The COVID-19 pandemic prompted rapid vaccine development and deployment worldwide. Despite widespread vaccination efforts, understanding the effectiveness of vaccines in hospitalized patients remains a critical concern. This retrospective cohort study, conducted at a tertiary healthcare centre in Serbia, tracked patients hospitalized during different waves of COVID-19 variants—Alpha, Delta, and Omicron. Data collection included demographics, comorbidities, symptoms, and vaccination status. Among 3593 patients, those with prior exposure to COVID-19 cases or hospital treatment showed higher positivity rates. Symptom prevalence varied across waves, with coughs persisting. Patients without chronic diseases were more frequent among those testing negative. Vaccine effectiveness varied, with Sinopharm demonstrating a 45.6% effectiveness initially and Pfizer-BioNTech showing an effectiveness of up to 74.8% within 0–84 days after the second dose. Mixed-dose strategies, notably Sinopharm as a primary dose followed by a Pfizer-BioNTech booster, suggested increased protection. Despite substantial vaccination availability, a significant portion of hospitalized patients remained unvaccinated. This study underscores the dynamic nature of vaccine effectiveness and advocates for booster strategies to address evolving challenges in combating COVID-19, particularly in hospitalized patients. © 2024 by the authors.

The COVID-19 pandemic prompted rapid vaccine development and deployment worldwide. Despite widespread vaccination efforts, understanding the effectiveness of vaccines in hospitalized patients remains a critical concern. This retrospective cohort study, conducted at a tertiary healthcare centre in Serbia, tracked patients hospitalized during different waves of COVID-19 variants—Alpha, Delta, and Omicron. Data collection included demographics, comorbidities, symptoms, and vaccination status. Among 3593 patients, those with prior exposure to COVID-19 cases or hospital treatment showed higher positivity rates. Symptom prevalence varied across waves, with coughs persisting. Patients without chronic diseases were more frequent among those testing negative. Vaccine effectiveness varied, with Sinopharm demonstrating a 45.6% effectiveness initially and Pfizer-BioNTech showing an effectiveness of up to 74.8% within 0–84 days after the second dose. Mixed-dose strategies, notably Sinopharm as a primary dose followed by a Pfizer-BioNTech booster, suggested increased protection. Despite substantial vaccination availability, a significant portion of hospitalized patients remained unvaccinated. This study underscores the dynamic nature of vaccine effectiveness and advocates for booster strategies to address evolving challenges in combating COVID-19, particularly in hospitalized patients. © 2024 by the authors.