Advancing HER2-low breast cancer management: enhancing diagnosis and treatment strategies.

BACKGROUND: Recent evidence brought by novel anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugates is leading to significant changes in HER2-negative breast cancer (BC) best practices. A new targetable category termed 'HER2-low' has been identified in tumors previously classified as 'HER2-negative'. Daily practice in pathology and medical oncology is expected to align to current recommendations, but patient access to novel anticancer drugs across geographies might be impeded due to local challenges. MATERIALS AND METHODS: An expert meeting involving ten regional pathology and oncology opinion leaders experienced in BC management in four Central and Eastern Europe (CEE) countries (Bulgaria, Croatia, Serbia, Slovenia) was held. Herein we summarized the current situation of HER2-low metastatic BC (mBC), local challenges, and action plans to prevent delays in patient access to testing and treatment based on expert opinion. RESULTS: Gaps and differences at multiple levels were identified across the four countries. These included variability in the local HER2-low epidemiology data, certification of pathology laboratories and quality control, and reimbursement conditions of testing and anticancer drugs for HER2-negative mBC. While clinical decisions were aligned to international guidelines in use, optimal access to testing and innovative treatment was restricted due to significant delays in reimbursement or limitative reimbursement conditions. CONCLUSIONS: Preventing delays in HER2-low mBC patient access to diagnosis and novel treatments is crucial to optimize outcomes. Multidisciplinary joint efforts and pro-active discussions between clinicians and decision makers are needed to improve care of HER2-low mBC patients in CEE countries.

The association of empathy and the work-family conflict in doctors of dental medicine.

OBJECTIVES: Work-family conflict is a growing problem worldwide, because of changing work-family demographic trends and the spread of technology. Empathy, as the ability to understand and share the feelings of other people, is the essential component of emotional intelligence that plays a crucial role in healthcare settings. This study aimed to assess the level of emotional empathy and investigate its relationship with work-family role conflicts among dental medicine doctors.  Materials and methods: In this study participated 589 doctors of dental medicine from Croatia, Serbia, Bosnia and Herzegovina. The questionnaire included general and demographic data, the Emotional Empathy Scale questionnaire and the Work and Family Role Conflict Assessment Scale questionnaire.  Results: The research results indicate no significant association between empathy and conflict between work and family roles (R = 0.032, p = 0.435). Women have achieved significantly higher scores in Emotional Empathy Scale (p ≤ 0.001), while there was no difference in Work and Family Role Conflict Assessment Scale according to gender (p = 0.194). A difference in emotional empathy was observed depending on where the respondents were employed (p = 0.045) and depending on the specialisation of the dental medicine (p = 0.021).  Conclusion: Female doctors of dental medicine demonstrated higher emotional empathy while the work-family role conflict is experienced equally by both genders.

Molnupiravir's real-world effectiveness in COVID-19 outpatients at high risk of severe disease: a single-center study.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic started in March 2020. Since then, there has been an urgent need for effective therapeutic methods to manage the disease. We aimed to assess the effectiveness of molnupiravir in reducing the need for hospitalization in at-risk, non-hospitalized COVID-19 patients. METHODOLOGY: This was a single-center, non-randomized, observational retrospective study of non-hospitalized patients with confirmed COVID-19, treated at the Clinic for Infectious and Tropical Diseases, University Clinical Center in Belgrade, Serbia. RESULTS: The study was conducted between 15 December 2021 and 15 February 2022 and included 320 patients. Of these, 165 (51.6%) received treatment with molnupiravir. The study and control groups were similar in gender and age distribution. The study group had a higher proportion of vaccination (75.2% vs. 51%, p < 0.001). There was no statistically significant difference in presence of comorbidity within the groups. Majority of the patients who received molnupiravir did not require hospitalization; and this was statistically significant in comparison to control group (92.7 vs. 24.5%, p < 0.001). Oxygen supplementation was less frequently required in the study group compared to the control group (0.6% vs. 31%, p < 0.001). During the follow-up period of 12.12 ± 3.5 days, significantly less patients from the study group were admitted to the intensive care unit (p < 0.001). Molnupiravir significantly reduced the risk of hospitalization by 97.9% (HR 0.021; 95% CI 0.005-0.089; p < 0.001). CONCLUSIONS: Molnupiravir is an effective therapy in preventing the development of severe forms of COVID-19 and hospitalization.

Health-related quality of life in different stages of breast cancer in Serbia.

OBJECTIVE: Breast cancer is the most commonly diagnosed malignant tumor worldwide, and Serbia ranks first in Europe in standardized breast cancer mortality rate. The aim of this research is to estimate health-related quality of life (HRQoL) and work productivity among patients in different stages of breast cancer in Serbia. SUBJECTS AND METHODS: A total of 175 breast cancer patients attending the breast cancer outpatient clinic at the Oncology Institute of Vojvodina between March 2022 and February 2023 were included in the study. Patients were divided into three mutually exclusive groups: (1) First year after primary breast cancer (Group P), (2) Second and following years after primary breast cancer or recurrence (Group S) and (3) Metastatic disease (Group M). The EQ-5D-3L self-classifier was used to estimate the HRQoL, using the EQ-5D-3L index value and visual analog scale (VAS) score. RESULTS: Мean EQ-5D-3L index value was 0.777 for Group P, and 0.768 for Group S. Patients with metastatic disease reported the lowest EQ-5D index value of 0.646 (p < 0.05). Pain/discomfort, as well as anxiety/depression, were the main drivers of the reduction in HRQoL. Patients in Group M also reported the lowest VAS score of 65.4. Furthermore, the highest percentage of women who sought leave or cited breast cancer as the reason for their early retirement were patients with metastatic disease. CONCLUSIONS: HRQoL was most impaired in Group M, and patients with metastatic disease were more likely to take sick leave or retire early due to breast cancer. Delaying or preventing metastatic recurrence could significantly benefit patients' productivity and HRQoL.

High risk of burnout syndrome and associated factors in medical students: A cross-sectional analytical study.

INTRODUCTION: Although research on burnout syndrome in medical students has increased in recent years, results are inconsistent about which factors are associated with a high risk for burnout syndrome. The aim of this study was to assess the prevalence of high risk of burnout syndrome and to identify factors associated with burnout in medical students in preclinical and clinical training. METHOD: A cross-sectional study was conducted at the University of Kragujevac, Serbia. The Maslach Burnout Inventory Student Survey and an epidemiological questionnaire on basic socio-demographic and academic characteristics were used. Statistical evaluation was performed through logistic regression analysis, using Odds Ratio (OR) and 95% Confidence Interval (CI). RESULTS: Among medical students, no statistically significant differences were found in the prevalence of high risk of burnout syndrome in preclinical (14.8%) and clinical grade (15.1%), p > 0.05. High risk for burnout syndrome in preclinical study years was independently associated with the female sex (adjusted OR = 0.41, 95%CI = 0.19-0.91, p = 0.028), and cigarette smoking (adjusted OR = 2.47, 95%CI = 1.05-5.78, p = 0.038). The high risk of burnout syndrome was associated with sedatives use (adjusted OR = 4.03, 95%CI = 1.27-12.73; p = 0.018) only in clinical years medical students. The frequency of alcohol consumption was correlated with the high risk of burnout syndrome in medical students in both preclinical and clinical training, but without statistical significance (both p for trend < 0.1). CONCLUSION: There was a significant prevalence of burnout among medical students, with some modifiable associated factors revealed.

Evaluation of reliability and validity of the Serbian Aphasia Screening Test.

PURPOSE: A rise in strokes worldwide means that the number of people affected by aphasia is increasing. Early and accurate diagnosis of aphasia is crucial for recovery. Presently, there are no dedicated screening tests tailored for evaluating aphasia in Serbian-speaking individuals. This paper presents and describes the psychometric properties of the Serbian Aphasia Screening Test (SAST), a novel aphasia screening tool designed specifically for Serbian speakers. This initiative fills the gap in aphasia assessment tools for the Serbian population, providing a comprehensive and culturally sensitive approach to the evaluation of language disorders. METHOD: Data using the SAST were collected from 240 participants: 120 Serbian speakers with aphasia after stroke compared to 120 neurotypical individuals. The assessment included the following subtests: conversation, verbal automatized sequences, auditory comprehension, visual confrontation naming, responsive naming, repetition of words, repetition of sentences, oral word reading, oral sentence reading, reading comprehension, and writing. The main objectives were to ascertain the psychometric qualities of the SAST, including inter-rater reliability of scoring, test-retest reliability, reliability of the individual subtests, overall test reliability, and inter-correlations among subtests. Additionally, the study evaluated the discriminatory capability of the SAST in distinguishing between individuals with aphasia and neurotypical controls, as well as between individuals with different types of aphasia. RESULTS: The findings revealed that the SAST has excellent inter-rater reliability, test-retest reliability, and internal consistency. There were statistically significant differences between individuals with aphasia and neurotypical controls on all SAST subtests. Furthermore, the study identified significant differences in language profiles among participants with different types of aphasia. The significant correlations between scores on the SAST and on the Boston Diagnostic Aphasia Examination (BDAE) suggest good convergent validity of the SAST. CONCLUSIONS: The results underscore the robust psychometric properties of this novel screening assessment (SAST) and its ability to effectively discriminate between diverse linguistic abilities within different aphasia syndromes in Serbian speaking individuals.

Women's trust in the healthcare system in Serbia: Validation of the Women's Trust and Confidence in Healthcare System scale.

BACKGROUND: Women's role as patients is associated with power relationships embedded in society. Although trust in the health care system is a general prerequisite for positive health outcomes, practices regarding women's agency in healthcare systems in Southeastern Europe reinforce women's passivity. Most of the current psychological measures of trust have been constructed and validated in "WEIRD" (samples that are drawn from populations that are White, Educated, Industrialized, Rich, and Democratic) countries, thus having a limited application in other social contexts. OBJECTIVES: We aimed to construct an instrument for assessing women's trust in healthcare systems to describe the structure of trust: Women's Trust and Confidence in the Healthcare System scale. DESIGN: Two independent samples (N1 = 329; N2 = 333) of adult women in Serbia voluntarily completed an online questionnaire. The questionnaire comprised 20 trust-related items which were selected from an extensive collection of women's experiences in the healthcare system and evaluated by experts on a 5-point Likert-type scale. METHODS: We used exploratory factor analysis of the Women's Trust and Confidence in the Healthcare System scale to analyze the structure of trust in the first sample data set and validated it with the second sample using confirmatory factor analysis. We tested concurrent validity by exploring how women's trust in the healthcare system predicts health-related behaviors (multigroup structural equation modeling). All analyses were conducted using R statistical software. RESULTS: The Women's Trust and Confidence in the Healthcare System scale (Cronbach's alpha = 0.86) indicated a three-factor structure of trust in the healthcare system: trust in healthcare professionals, distrust in the public healthcare system, and confidence in healthcare system. This was validated using an independent sample. Interpersonal trust positively predicted women's desirable health behaviors, while trust in the system had a negative impact. CONCLUSION: The Women's Trust and Confidence in the Healthcare System scale captures women's trust in a paternalistic healthcare system, is reliable, and has a stable three-factor structure. The study's findings reveal the relationship between women's trust and health-related behavior: in paternalistic environments, trust reinforces women's passivity.

Geographic variation of mutagenic exposures in kidney cancer genomes.

International differences in the incidence of many cancer types indicate the existence of carcinogen exposures that have not yet been identified by conventional epidemiology make a substantial contribution to cancer burden1. In clear cell renal cell carcinoma, obesity, hypertension and tobacco smoking are risk factors, but they do not explain the geographical variation in its incidence2. Underlying causes can be inferred by sequencing the genomes of cancers from populations with different incidence rates and detecting differences in patterns of somatic mutations. Here we sequenced 962 clear cell renal cell carcinomas from 11 countries with varying incidence. The somatic mutation profiles differed between countries. In Romania, Serbia and Thailand, mutational signatures characteristic of aristolochic acid compounds were present in most cases, but these were rare elsewhere. In Japan, a mutational signature of unknown cause was found in more than 70% of cases but in less than 2% elsewhere. A further mutational signature of unknown cause was ubiquitous but exhibited higher mutation loads in countries with higher incidence rates of kidney cancer. Known signatures of tobacco smoking correlated with tobacco consumption, but no signature was associated with obesity or hypertension, suggesting that non-mutagenic mechanisms of action underlie these risk factors. The results of this study indicate the existence of multiple, geographically variable, mutagenic exposures that potentially affect tens of millions of people and illustrate the opportunities for new insights into cancer causation through large-scale global cancer genomics.

Quantitative determination of selected elements in infant baby formulae and baby food cereals commercially available in Serbia using the ICP OES method.

The aim of this paper was the quantitative determination of some macro and trace elements, especially potentially toxic elements in the samples of infant baby formulae and baby food cereals commercially available in Serbia using the inductively coupled plasma optical emission spectrometry (ICP OES) method. Among the macro elements, K is the most abundant in all infant formulae samples, followed by Ca, P, Na and Mg. On the other hand, the analysis of food cereals showed that P is presents in the highest contents, followed by K, Ca, Na, and Mg. Potentially toxic elements As, Pb, Hg, and Cd were not detected in any sample of infant formulae, while Cd was detected and quantified in cereal foods. Also, the calculated values of Estimated Tolerable Weekly Intake (ETWI) as well as the Estimated Tolerable Monthly Intake (ETMI) were lower than recommended values for a tolerable weekly intake (TWI) and provisional tolerable monthly intake (PTMI).

Factors Associated with Length of Hospitalization in Patients with Diabetes and Mild COVID-19: Experiences from a Tertiary University Center in Serbia.

Background and Objectives: During the COVID-19 pandemic, there was an increased number of hospitalized COVID-19-positive patients suffering from type 2 diabetes mellitus (T2DM). The objective of this research study was to explore factors associated with the length of hospitalization of patients with T2DM and the mild form of COVID-19. Material and Methods: This retrospective cohort study involved all patients who tested positive for COVID-19 and those who were treated in the dedicated COVID-19 department of the University Clinical Center (UCC) in Nis between 10 September 2021 and 31 December 2021. Upon admission, patients underwent blood tests for biochemical analysis, including blood count, kidney and liver function parameters (C-reactive protein (CRP), creatinine kinase, and D-dimer), and glycemia and HbA1c assessments. Additionally, all patients underwent lung radiography. Univariate and multivariate regression analyses were employed to assess the impact of specific factors on the length of hospitalization among patients with T2DM. Results: Out of a total of 549 treated COVID-19-positive patients, 124 (21.0%) had T2DM, while 470 (79.0%) did not have diabetes. Among patients with T2DM, men were significantly younger than women (60.6 ± 16.8 vs. 64.2 ± 15.3, p < 0.01). The average hospitalization length of patients with diabetes was 20.2 ± 9.6 (5 to 54 days), and it was significantly longer than for patients without diabetes, at 15.0 ± 3.4, which ranged from 3 days to 39 (t-test ≈ 5.86, p < 0.05). According to the results of the univariate regression analysis, each year of age is associated with an increase in the length of hospital stay of 0.06 days (95% CI: 0.024 to 0.128, p = 0.004). Patients who received oxygen therapy were treated for 2.8 days longer than those who did not receive oxygen treatment (95% CI: 0.687 to 4988, p = 0.010), and each one-unit increase in CRP level was associated with a 0.02-day reduction in the length of hospitalization (95% CI: 0.004 to 0.029, p = 0.008). Based on the results of the multivariate regression analysis, each year of age is associated with an increase in the length of hospitalization by 0.07 days (95% CI: 0.022 to 0.110, p = 0.003). Patients who received oxygen therapy were treated for 3.2 days longer than those who did not receive oxygen therapy (95% CI: 0.653 to 5726, p = 0.014), and each unit increase in CRP level was associated with a 0.02-day reduction in the length of hospitalization (95% CI: 0.005 to 0.028, p = 0.004). Conclusions: Based on the presented results, COVID-19-positive patients with diabetes had, on average, longer hospitalizations than COVID-19 patients without diabetes. The hospital treatment of patients with T2DM and a milder form of COVID-19 was associated with older age, the use of oxygen therapy, and elevated CRP values. Patients who received oxygen therapy were treated approximately 3 days longer than those who did not receive this therapy.

Demographic and Socioeconomic Predictors of Prehypertension and Hypertension in the Adult Population: Serbian National Health Survey.

Background and Objectives: Prehypertension and hypertension are the most common cardiovascular disorders worldwide and are increasingly considered one of the most serious public health problems, particularly in developing countries. The objective of this study was to determine the frequency and demographic and socioeconomic predictors of prehypertension and hypertension in the adults in Serbia, and to examine the relationship between prehypertension and hypertension and health behavior determinants (smoking, alcohol use, physical activity) and individual aspects of health (a health self-assessment, multimorbidity, BMI, depressive symptoms). Materials and Methods: The research is part of the fourth National Population Health Survey conducted in 2019, which was conducted by the Republic Institute of Statistics, in cooperation with the Institute of Public Health of Serbia and the Ministry of Health of the Republic of Serbia. As a research instrument, questionnaires were used in accordance with the methodology of the European Health Survey. For the purposes of this research, data on the adult population aged 20 and over were used. Results: Women are at a reduced risk for both prehypertension (OR = 0.328) and hypertension (OR = 0.349) by nearly 70%. Similarly, those aged below 60 years have a lower risk for prehypertension and those younger than 40 years have a lower risk for hypertension (OR = 0.995), whereas people with a lower education have a 4.3 times higher risk of prehypertension (OR = 4.323) and a 1.6 times higher risk of hypertension (OR = 1.614). The poor have a 1.4 times higher risk of prehypertension (OR = 1.413) and a 1 times higher risk of hypertension (OR = 1.035). People with multimorbidity have a 1.2 times higher risk of both prehypertension (OR = 1.218) and a 4.8 times higher risk of hypertension (OR = 4.867). Conclusions: Male gender, lower education, poverty, age and the presence of multimorbidity are significant predictors of prehypertension and hypertension in the Serbian adult population, so preventive strategies should be aimed at these sensitive population groups.

Serbian Version of the eHealth Literacy Questionnaire (eHLQ): Translation, Cultural Adaptation, and Validation Study Among Primary Health Care Users.

BACKGROUND: As digital health services are increasingly developing and becoming more interactive in Serbia, a comprehensive instrument for measuring eHealth literacy (EHL) is needed. OBJECTIVE: This study aimed to translate, culturally adapt, and investigate the psychometric properties of the Serbian version of the eHealth Literacy Questionnaire (eHLQ); to evaluate EHL in the population of primary health care (PHC) users in Serbia; and to explore factors associated with their EHL. METHODS: The validation study was conducted in 8 PHC centers in the territory of the Macva district in Western Serbia. A stratified sampling method was used to obtain a representative sample. The Translation Integrity Procedure was followed to adapt the questionnaire to the Serbian language. The psychometric properties of the Serbian version of the eHLQ were analyzed through the examination of factorial structure, internal consistency, and test-retest reliability. Descriptive statistics were calculated to determine participant characteristics. Differences between groups were tested by the 2-tailed Students t test and ANOVA. Univariable and multivariable linear regression analyses were used to determine factors related to EHL. RESULTS: A total of 475 PHC users were enrolled. The mean age was 51.0 (SD 17.3; range 19-94) years, and most participants were female (328/475, 69.1%). Confirmatory factor analysis validated the 7-factor structure of the questionnaire. Values for incremental fit index (0.96) and comparative fit index (0.95) were above the cutoff of ≥0.95. The root mean square error of approximation value of 0.05 was below the suggested value of ≤0.06. Cronbach α of the entire scale was 0.95, indicating excellent scale reliability, with Cronbach α ranging from 0.81 to 0.90 for domains. The intraclass correlation coefficient ranged from 0.63 to 0.82, indicating moderate to good test-retest reliability. The highest EHL mean scores were obtained for the understanding of health concepts and language (mean 2.86, SD 0.32) and feel safe and in control (mean 2.89, SD 0.33) domains. Statistically significant differences (all P<.05) for all 7 eHLQ scores were observed for age, education, perceived material status, perceived health status, searching for health information on the internet, and occupation (except domain 4). In multivariable regression models, searching for health information on the internet and being aged younger than 65 years were associated with higher values of all domain scores except the domain feel safe and in control for variable age. CONCLUSIONS: This study demonstrates that the Serbian version of the eHLQ can be a useful tool in the measurement of EHL and in the planning of digital health interventions at the population and individual level due to its strong psychometric properties in the Serbian context.

Factors contributing to variability in metformin concentration in polycystic ovary syndrome.

AIM: To investigate the factors affecting metformin concentrations after chronic administration in patients with polycystic ovary syndrome (PCOS), focusing on the pharmacokinetic variability and its implications for personalized therapy. METHODS: This study enrolled 53 PCOS patients undergoing long-term metformin treatment at the Clinic for Gynecology and Obstetrics in Nis, Serbia, from February to December 2019. Pharmacokinetic parameters were measured from blood samples, and metformin concentrations were determined with validated analytical techniques. RESULTS: There was a significant variability in metformin concentrations among PCOS patients, with body mass index (BMI) identified as a major influencing factor. Higher BMI was associated with lower plasma metformin levels, a finding suggesting an altered pharmacokinetic profile in obese patients. CONCLUSIONS: This study highlights the critical role of BMI in influencing metformin pharmacokinetics in PCOS patients and underscores the need for personalized treatment strategies in patients with PCOS.

Immediate and long-term effects of COVID-19 on antibiotic dispensing: increasing use of Watch antibiotics.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic affected antibiotic usage worldwide. However, there is limited data from Serbia. Dispensing of oral antibiotics in Serbian pharmacies was analyzed to calculate monthly and yearly changes between 2018-2021, and to explore immediate and long-term effects of COVID-19 on antibiotic dispensing during this period. METHODOLOGY: The number of antibiotic packages dispensed from pharmacies during the study period was analyzed with a Chi-square test to assess the average change in annual dispensing, and an interrupted time-series analysis was used to evaluate the impact of the pandemic on antibiotic dispensing. The data from 2018-2021 were retrieved from the database of a large community pharmacy chain in Serbia. RESULTS: The average number of antibiotic packages dispensed per day and per pharmacy was higher in 2021 compared to 2018 by one package. However, the dispensing of macrolides increased significantly; 17.7% (2018) vs. 22.5% (2021) (p < 0.05). In general, an increase in antibiotic dispensing was detected during COVID-19 for total antibiotics (16.4%), Watch antibiotics (44.8%), third-generation cephalosporins (80.4%), macrolides (45.5%) and azithromycin (83.7%). However, the immediate effect of COVID-19 was a decrease in the dispensing of Watch antibiotics, penicillin, and third-generation cephalosporins (p < 0.05); and a notable long-term COVID-19 effect was an increase in the dispensing of azithromycin (p < 0.05). CONCLUSIONS: In spite of a relatively stable trend of total antibiotic dispensing before and during COVID-19 pandemic, the use of Watch antibiotics, third-generation cephalosporins, and macrolides (particularly azithromycin) showed an increasing trend in dispensing that should be optimized.

Perceptions on support, challenges and needs among parents and caregivers of children with developmental disabilities in Croatia, North Macedonia and Serbia: a cross-sectional study.

BACKGROUND: Parents/caregivers of children with developmental disabilities (CDD) have a wide range of support needs and there are various interventions available. Support, challenges, and needs among parents/caregivers of CDD likely vary in different geographical settings. This study aimed to analyze the perceptions of support, challenges, and needs among parents/caregivers of CDD in Croatia, North Macedonia, and Serbia. METHODS: We conducted a cross-sectional study in March-April 2023 within the Erasmus + SynergyEd project. The eligible participants were parents and caregivers of CDD in Croatia, North Macedonia, and Serbia, who filled out a modified Caregiver Needs Survey online. RESULTS: Among 953 participants, 542 (57%) were from Croatia, 205 (21%) were from North Macedonia and 206 (22%) were from Serbia. The most common diagnosis of participants' children was autism spectrum disorder (26%). The child most often received the first diagnosis at the median of 2 years, diagnosed by a team of professionals. More than half (58%) of children attended preschool and public school, while 22% did not attend any schooling. Additional support from the state/city/county was received by 66% of CDD. Most participants declared not participating in association/organization for family support. Participants mostly (68%) used experts who work with the child as a source of information about their child's condition, followed by the Internet (53%). In the last 12 months, 60% of participants had difficulties with the availability of services in their area or problems getting appointments. The biggest problem in getting support was ensuring the child's basic rights were protected. Participants stated that ensuring greater rights for CDD was the greatest need for their families. CONCLUSION: Parents/caregivers of CDD in Croatia, North Macedonia, and Serbia faced multiple challenges, but most of them were satisfied with the services provided to their children. Future efforts to develop policies and services related to CDD should consider the opinions of their parents/caregivers and disparities in access to services.

GSTM1 and GSTP1 Polymorphisms Affect Outcome in Colorectal Adenocarcinoma.

Background and Objectives: Despite improvements in screening programs, a large number of patients with colorectal cancer (CRC) are diagnosed in an advanced disease stage. Previous investigations imply that glutathione transferases (GSTs) might be associated with the development and progression of CRC. Moreover, the detoxification mechanism of oxaliplatin, which represents the first line of treatment for advanced CRC, is mediated via certain GSTs. The aim of this study was to evaluate the significance of certain GST genetic variants on CRC prognosis and the efficacy of oxaliplatin-based treatment. Materials and Methods: This prospective study included 523 patients diagnosed with CRC in the period between 2014 and 2016, at the Digestive Surgery Clinic, University Clinical Center of Serbia, Belgrade. Patients were followed for a median of 43.47 ± 17.01 months (minimum 1-63 months). Additionally, 109 patients with advanced disease, after surgical treatment, received FOLFOX6 treatment as a first-line therapy between 2014 and 2020. The Kaplan-Meier method was used to analyze cumulative survival, and the Cox proportional hazard regression model was used to study the effects of different GST genotypes on overall survival. Results: Individuals with the GSTM1-null genotype and the GSTP1 IleVal+ValVal (variant) genotype had significantly shorter survival when compared to referent genotypes (GSTM1-active and GSTP1 IleIle) (log-rank: p = 0.001). Moreover, individuals with the GSTM1-null genotype who received 5-FU-based treatment had statistically significantly shorter survival when compared to individuals with the GSTM1-active genotype (log-rank: p = 0.05). Conclusions: Both GSTM1-null and GSTP1 IleVal+ValVal (variant) genotypes are associated with significantly shorter survival in CRC patients. What is more, the GSTM1-null genotype is associated with shorter survival in patients receiving FOLOFOX6 treatment.

Health policy developments in the Western Balkan Countries 2000-19: towards European Health and Health Care Policies.

BACKGROUND: Albania, Bosnia and Herzegovina, Kosovo, Montenegro, North Macedonia and Serbia have committed to becoming European Union (EU) member states. This, among others, implies that candidate/potential candidate states adopt legally authorized EU policies, including health. The study aims to identify the main country-specific health policy areas critical to the EU accession health policy dimension and present the change in associated selected health indicators from 2000 to 2019. METHODS: The study draws on published reports and analyses of official statistics over time and cross-country. Health care policy adherence to the European Commission's recommended country-specific health actions was classified into five health policy areas: financing, payment, organization, regulation and persuasion. Key health policy areas for Western Balkan countries (WBCs) were identified. Health progress or lack thereof in catching up to the EU15 population health, health expenditure and the number of health professionals are measured. RESULTS: The European Commission prioritized financing and regulation for all WBCs in the five policy areas. Nine of the 18 analyzed selected health indicators showed divergence, and the other nine converged towards the EU15 averages. WBCs continue to face diverse public health challenges in improving life expectancy at birth, death rates caused by circulatory system diseases, malignant neoplasms, traffic accidents, psychoactive substance use, tuberculosis incidence, tobacco smoking prevalence and public-sector health expenditure. CONCLUSIONS: By 2019, there is limited evidence of WBCs catching up to the average EU15 health levels and health care policies. Closer attention towards EU health and health care policies would be favourable.

Structure of Aspergillus flavus populations associated with maize in Greece, Spain, and Serbia: Implications for aflatoxin biocontrol on a regional scale.

Aspergillus flavus is the most frequently identified producer of aflatoxins. Non-aflatoxigenic members of the A. flavus L strains are used in various continents as active ingredients of bioprotectants directed at preventing aflatoxin contamination by competitive displacement of aflatoxin producers. The current research examined the genetic diversity of A. flavus L strain across southern Europe to gain insights into the population structure and evolution of this species and to evaluate the prevalence of genotypes closely related to MUCL54911, the active ingredient of AF-X1. A total of 2173L strain isolates recovered from maize collected across Greece, Spain, and Serbia in 2020 and 2021 were subjected to simple sequence repeat (SSR) genotyping. The analysis revealed high diversity within and among countries and dozens of haplotypes shared. Linkage disequilibrium analysis indicated asexual reproduction and clonal evolution of A. flavus L strain resident in Europe. Moreover, haplotypes closely related to MUCL54911 were found to belong to the same vegetative compatibility group (VCG) IT006 and were relatively common in all three countries. The results indicate that IT006 is endemic to southern Europe and may be utilized as an aflatoxin mitigation tool for maize across the region without concern for potential adverse impacts associated with the introduction of an exotic microorganism.

Influence of honey bee (Apis mellifera) breeding on wing venation in Serbia and neighbouring countries.

In order to improve the productivity of honey bees (Apis mellifera), some of their traits are selected by breeding. On one hand, breeding is mainly based on the natural geographical variation of this species; on the other hand, mass production and distribution of artificially selected queens can significantly affect the natural geographic variation of honey bees. In this study, we have compared honey bee wings originating from breeding and non-breeding populations in Serbia. In the comparison, we have also used data from a large area of south-eastern Europe. The wings were measured using the 19 landmarks indicated on the wing images. The coordinates were analysed using the methodology of geometric morphometrics. We found that honey bees obtained from honey bee queen breeder differed in wing venation from surrounding populations, which are under natural selection. Therefore, we argue against including populations under artificial selection in the analysis of the natural geographical variation of honey bees. In our analysis of non-breeding samples, we found that in south-eastern Europe there is continuous variation in wing venation and no clear boundaries between A. m. carnica, A. m. cecropia, and A. m. macedonica.

Time Is Life: Golden Ten Minutes on Scene-EuReCa_Serbia 2014-2023.

Background and Objectives: This study analyzed the frequency of factors influencing the course and outcomes of out-of-hospital cardiac arrest (OHCA) in Serbia and the prediction of pre-hospital outcomes and survival. Materials and Methods: Data were collected during the period from 1 October 2014, to 31 September 2023, according to the protocol of the EuReCa_One study (clinical trial ID number NCT02236819). Results: Overall 9303 OHCA events were registered with a median age of 71 (IQR 61-81) years and 59.7% of them being males. The annual OHCA incidence was 85.60 ± 20.73/100,000. Within all bystander-witnessed cases, bystander-initiated cardiopulmonary resuscitation in 15.3%. Within the resuscitation-initiated group, return-of-spontaneous circulation (ROSC) on scene (any ROSC) was present in 1037/4053 cases (25.6%) and ROSC on admission to the nearest hospital in 792/4053 cases (19.5%), while 201/4053 patients survived to hospital discharge (5.0%). Predictive potential on pre-hospital outcomes was shown by several factors. Also, of all patients having any ROSC, 89.2% were admitted to the hospital alive. The probability of any ROSC dropped below 50% after 17 min passed after the emergency call and 10 min after the EMS scene arrival. These time intervals were significantly associated with survival to hospital discharge (p < 0.001). Five-minute time intervals between both emergency calls and any ROSC and EMS scene arrival and any ROSC also had a significant predictive potential for survival to hospital discharge (p < 0.001, HR 1.573, 95% CI 1.303-1.899 and p = 0.017, HR 1.184, 95% CI 1.030-1.361, respectively). Conclusions: A 10-min time on scene to any ROSC is a crucial time-related factor for achieving any ROSC, and indirectly admission ROSC and survival to hospital discharge, and represents a golden time interval spent on scene in the management of OHCA patients. A similar effect has a time interval of 17 min from an emergency call. Further investigations should be focused on factors influencing these time intervals, especially time spent on scene.