Patients In Serbia Research Articles

Validation of the Fatigue Impact Scale in Multiple Sclerosis Patients in Serbia.

Fatigue is one of the most frequent complaints of patients with multiple sclerosis (MS). The Fatigue Impact Scale (FIS), one of the 30 available fatigue questionnaires, is commonly applied because it evaluates multidimensional aspects of fatigue. The chief objectives of this study were to validate FIS and evaluate the psychometric properties of MS patients in Serbia. One hundred and twenty-one (121) MS patients and one hundred and twenty-two (122) age-, gender- and education-matched healthy control (HC) subjects completed the FIS and the Beck Depression Inventory. Internal consistency of the FIS subscales was determined using Cronbach's Alpha Coefficient. Test/retest reliability with an intra-class correlation coefficient (ICC) for each FIS subscale was performed. The total FIS score and subscale scores showed statistically significant differences between the MS patients and the HC subjects in both FIS sessions. Cronbach's Alpha was 0.966. All ICCs were statistically significant (p < 0.05). The Serbian version of this instrument may be useful as a clinical measure for fatigue and functionality in patients with MS.

Whole exome sequencing in Serbian patients with hereditary spastic paraplegia.

Hereditary spastic paraplegia (HSP) is a group of neurodegenerative diseases with a high genetic and clinical heterogeneity. Numerous HSP patients remain genetically undiagnosed despite screening for known genetic causes of HSP. Therefore, identification of novel variants and genes is needed. Our previous study analyzed 74 adult Serbian HSP patients from 65 families using panel of the 13 most common HSP genes in combination with a copy number variation analysis. Conclusive genetic findings were established in 23 patients from 19 families (29%). In the present study, nine patients from nine families previously negative on the HSP gene panel were selected for the whole exome sequencing (WES). Further, 44 newly diagnosed adult HSP patients from 44 families were sent to WES directly, since many studies showed WES may be used as the first step in HSP diagnosis. WES analysis of cohort 1 revealed a likely genetic cause in five (56%) of nine HSP families, including variants inthe ETHE1,ZFYVE26,RNF170,CAPN1, and WASHC5 genes. In cohort 2, possible causative variants were found in seven (16%) of 44 patients (later updated to 27% when other diagnosis were excluded), comprising six different genes:SPAST,SPG11,WASCH5,KIF1A, KIF5A,and ABCD1. These results expand the genetic spectrum of HSP patients in Serbia and the region with implications for molecular genetic diagnosis and future causative therapies. Wide HSP panel can be the first step in diagnosis, alongside with the copy number variation (CNV) analysis, while WES should be performed after.

Diabetes management, dietary supplements use and the effect of coronavirus pandemic on diabetes patients in Serbia: a cross-sectional study

Objectives Diabetes mellitus (DM) is a significant public health challenge in Serbia, mirroring the situation in other European middle-income countries. The aims of this study were to examine the disease-related characteristics and management of diabetes, as well as the prevalence of use of dietary supplements (DS) among diabetes patients in Serbia, and to analyze the effects of the coronavirus pandemic on DM patients in Serbia. Methods The study was carried out as an online, observational, cross-sectional study involving 422 adult diabetes type 1 (DM1) and type 2 (DM2) patients residing in Serbia. Results DM1 patients were more likely than DM2 patients to self-control glucose levels (p < 0.001). Almost one-third of DM2 patients (31.4%) did not know their HbA1c value. Polypharmacy has been reported by 9.7% of DM1 patients and 23.5% of DM2 patients. During the coronavirus pandemic increased anxiety levels for one-third of respondents was noticed. The prevalence of DS use among DM patients was very high (95.3%), with vitamin C, zinc, vitamin D and magnesium being the most commonly used. Women were more likely to use vitamin D (p = 0.001) and magnesium DS (p = 0.005) than men. Most patients (76.9%) faced limited access to healthcare services during the coronavirus pandemic with, sometimes, detrimental consequences. A significant portion of respondents (41.2%) consulted a pharmacist more often in 2021 than in previous years. Conclusions Special caution is needed regarding the potential interactions of DS with chronic therapy. To enhance diabetes care, Serbia needs more accessible mental health support, improved diabetes education, expanded CGM availability, and carefully planned emergency healthcare measures for chronic patients.

The Role of Resilience in the Relationship between Sociodemographic, Clinical Characteristics, and Social Support among Breast Cancer Patients in Serbia.

The management of breast cancer treatments within the limitations of family, social, and professional life is emotionally burdening and negatively affects physical, psychological, and social well-being, reducing the overall quality of life of patients and their families. This cross-sectional descriptive-analytical study was conducted from March to August 2023 at the "Dr. Radivoj Simonović" General Hospital in Sombor. A total of 236 breast cancer patients participated in this study. The research was conducted using the following instruments: a questionnaire on sociodemographic and clinical characteristics of patients, the Berlin Social-Support Scales-for assessing social support-and the Connor-Davidson Resilience Scale-for assessing resilience. This study aimed to determine the predictors and levels of social support and resilience of breast cancer patients. We also wanted to examine whether resilience is a mediator between patients' sociodemographic and clinical characteristics and levels of social support. The total average value of social support was 3.51 ± 0.63, while on the resilience scale, the respondents achieved a total average score of 52.2 ± 9.63. Perceived and actually received social support of breast cancer patients were positively correlated with resilience [p < 0.01], while no statistically significant correlations were found for the need for support and satisfaction. The sets of predictors can significantly predict their effects on all types of perceived social support (emotional social support: 9%; perceived instrumental social support: 9%) and all types of received social support (actually received emotional social support: 8%; actually received instrumental social support: 7%; actually received informational social support: 8%). There is a potential mediating role of resilience in relation to sociodemographic factors, clinical characteristics, and the need for support. This study confirms that a strong connection exists between social support and resilience. However, the analysis did not confirm the mediating role of resilience between the sociodemographic and clinical characteristics on the one hand and social support on the other.

Untargeted Lipidomics Study of Bipolar Disorder Patients in Serbia.

The Lipidomic profiles of serum samples from patients with bipolar disorder (BD) and healthy controls (C) were explored and compared. The sample cohort included 31 BD patients and 31 control individuals. An untargeted lipidomics study applying liquid chromatography (LC) coupled with high-resolution mass spectrometry (HRMS) was conducted to achieve the lipid profiles. Multivariate statistical analyses (principal component analysis and partial least squares discriminant analysis) were performed, and fifty-six differential lipids were confirmed in BD and controls. Our results pointed to alterations in lipid metabolism, including pathways of glycerophospholipids, sphingolipids, glycerolipids, and sterol lipids, in BD patient sera. This study emphasized the role of lipid pathways in BD, and comprehensive research using the LC-HRMS platform is necessary for future application in the diagnosis and improvement of BD treatments.

Pharmacotherapy literacy level and predictors of low literacy among diabetes mellitus type 2 patients in Serbia

BackgroundPharmacotherapy literacy (PTHL) is a specific ability to safely access, appraise and understand the available information concerning medication and to calculate and act accordingly. The concept of PTHL is mostly unknown for the majority of diabetes mellitus type 2 (DMT2) patients in Serbia. With diabetes being one of the major public health problems in Serbia with a prevalence of 9.1%, this two-study research aims at constructing performance-based instrument and estimating the prevalence of PTHL levels and identification of predictors of low PTHL scores in patients with DMT2.MethodsMultistage study was performed to adapt the existing performance–based instrument (PTHL-SR) into specific questionnaire for DMT2 population (PTHL-DM instrument). PTHL levels were assessed through cross-sectional study categorising patients into groups of low, medium, and high PTHL levels. We considered 19 predictors for low PTHL scores, from sociodemographic characteristics, health behaviours and health characteristics, access to health-related information and empowerment-related indicators. Univariate and multivariate logistic regression analyses were used to determine independent predictors of low PTHL.ResultsThe final 15-item PTHL-DM instrument proved to have satisfactory reliability (KR20 = 0.475) and internal reliability [ICC for the whole instrument was 0.97 with 95% confidence intervals (0.95–0.99)]. Positive correlation (rho = 0.69) between PTHL-DM score (15 questions) and the total PTHL-SR score (14 questions) was also observed.It was demonstrated that the majority of 350 patients had low PTHL (62%), and only 5% high PTHL level. Mean score on PTHL-DM was 7.8 ± 2.3. Probability of low PTHL increased among smokers, patients with low interest in health and those who estimated their health as bad. Patients who used pharmacists as sourse of information were less likely to be pharmacotherapy illiterate. Combined therapy with insulin and Oral Hypoglycemic Agents was associated with higher PTHL.ConclusionsOur data indicate that specific PTHL-DM tool is objective, valid, and reliable. It was found that low level of PTHL prevailed among DMT2 patients. Medication literacy is influenced by age, residence, education, and family status. Patients with better health literacy also reported better health behaviours. Different patient empowerment programs and approaches aimed at raising PTHL would be essential to improve self-management and control of this widespread chronic disease in Serbia.

Reconstruction of Moderately and Severely Atrophic Scalp-A Multicentric Experience in Surgical Treatment of Patients Irradiated for Tinea Capitis in Childhood and Surgical Algorithm.

Background and Objectives: Before the introduction of griseofluvin, the use of X-ray radiation was the treatment of choice for tinea capitis. More than half a century later various types of tumors have been found to be associated with childhood irradiation due to tinea capitis, most commonly cancers of the head and neck, as well as brain tumors. The often unusually aggressive and recurrent nature of these tumors necessitates the need for repeated surgeries, while the atrophic skin with an impaired vascular supply due to radiation often poses an additional challenge for defect reconstruction. We present our experience in the surgical treatment of such patients. Materials and Methods: This is a retrospective cohort study. In this study, 37 patients treated for acquired defects of the scalp with a history of irradiation therapy due to tinea capitis in childhood were included in this study, 24 male and 13 female patients. The mean age at the first appointment was 60.6 ± 7.8, with the youngest included patient being 46 and the oldest being 75 years old. Patients' characteristics, surgical treatment, and complications were analyzed and a reconstructive algorithm was developed. Results: Local flaps were used for reconstruction in 34 patients, direct sutures were used in 10 patients and 20 patients received split-thickness skin grafts for coverage of both primary and secondary defects for reconstruction of flap donor sites. One regional flap and one dermal substitute covered by an autologous skin graft were also used for reconstruction. Complications occurred in 43.2% of patients and were significantly associated with the presence of comorbidities (p = 0.001), aseptic bone necrosis (p = 0.001), as well as skin atrophy in frontal, occipital, and parietal region (p = 0.001, p = 0.042 and p = 0.001, respectively). A significant correlation between major complications and moderate skin atrophy was found only in the parietal region (p = 0.026). Conclusions: Unfortunately, many protocols developed for scalp reconstruction are not applicable in the setting of severe or diffuse scalp skin atrophy associated with high tumor recurrence rate and radiation-induced vascular impairment, such as in tinea capitis patients in Serbia. An algorithm has been developed based on the authors' experience in managing these patients.

COVID-19 and Cutaneous Squamous Cell Carcinoma-Impact of the Pandemic on Unequal Access to Healthcare.

Most skin tumors are not fatal, but if not treated in a timely manner, they can lead to significant morbidity. Due to the COVID-19 pandemic and in order to create more capacities for the treatment of COVID-19-positive patients as well as to contain the spread of the virus, the healthcare system was reorganized worldwide, leading to decreased access to preventive screening programs. The aim of this study was to evaluate the impact of the pandemic on healthcare accessibility to cutaneous squamous cell carcinoma patients in Serbia. This retrospective study was conducted at the Clinic for Burns, Plastic, and Reconstructive Surgery, University Clinical Center of Serbia in Belgrade. Patient demographics and pathohistological findings of tumors of patients living in and outside the capital in the period before, during, and after the pandemic were compared. The two groups did not show any differences regarding the largest tumor diameter prior and during the pandemic; however, this difference became extremely noticeable after the pandemic (15 mm vs. 27 mm; p < 0.001). While cSCCs are commonly slow-growing tumors, the impact of the COVID-19 pandemic is not negligible. This study found a population at a significant risk of cSCC metastasis, with additional evidence likely to emerge in the upcoming years.

Predictors of Non-Adherence to Medications in Hypertensive Patients.

Elevated blood pressure (BP) is one of the leading causes for developing major cardiovascular events and still represents a major public health challenge worldwide. We aimed to provide data on predictors of poor adherence to medication in hypertensive patients in Serbia. Observational, analytical study was undertaken at a group of 388 patients who refilled their medications in the Pharmacy Institution, "Apoteka Kragujevac", Kragujevac, Serbia between Jan and Mar 2019. Afterward, we conducted a case-control study to evaluate the influence of the variables associated with the adherence. We used a self-developed questionnaire and SF-36 to assess the influence of the quality of life on medication adherence. Results revealed four independent predictors of non-adherence: increased number of medications, living in a city, forgetfulness of the dosing regimen and low energy. The odds of non-adherence were the highest among the participants living in the city and the low energy was the only factor inversely associated with the level of non-adherence. Many factors were associated with the non-adherence to medication. Further studies are needed to find the most appropriate protocol to promote adherence. The four risk factors (increased number of medications, living in a city, forgetfulness of the dosing regimen and low energy) are associated with non-adherence in adult hypertensive patients.

Cross-Cultural Adaptation and Validation of the Serbian Version of the Brief Assessment of Cognition in Schizophrenia Scale.

The Brief Assessment of Cognition in Schizophrenia (BACS) scale was developed for the assessment of cognitive function in patients with schizophrenia. The objective of this study was to cross-culturally adapt and validate the BACS in to the Serbian language. The study was conducted at the Laza Lazarevic Clinic for Mental Disorders and the Clinic for Psychiatry of the University Clinical Center of Serbia from March 2021 to January 2022. The study enrolled 61 inpatients diagnosed with schizophrenia and 61 healthy controls matched for age and sex. Compared with the healthy control group, the schizophrenia patient group had worse cognitive function in all dimensions measured using BACS (p < 0.001 for all measures). The mean standardized composite BACS score was z = -2.46, and symbol coding (z = -2.54) was the most deficient function. Principal component analysis suggests a two-factor structure, where the first factor consisted of loading the measures of verbal and working memory, attention, speed of information processing, and executive function, while the second factor regarded the loading of motor speed. Cronbach's alpha coefficient demonstrated an excellent level of internal consistency (0.798). These outcomes suggest that the Serbian BACS neurocognitive battery's psychometric properties are satisfactory, with good overall discriminant validity and high internal consistency. The Serbian BACS appears to be a quick and reliable neuropsychological instrument for evaluating global cognition in schizophrenia patients in Serbia.

Assessment of Cancer Patients' Mental Health during the Coronavirus Pandemic in Serbia.

This study aimed to determine the impact of the COVID-19 pandemic on the mental health of cancer patients in Serbia. Data were collected between April-May 2021 using an online questionnaire, which estimated depression, anxiety, and stress in a sample of 221 cancer patients. The Depression, Anxiety, and Stress Assessment Scale (DASS-21) was used to assess the cancer patients' affective status. The T test of independent samples and the one-way analysis of variance (ANOVA), as well as multiple linear regression analysis, have been used as well. The results showed that moderate to extremely severe depression, anxiety, and stress symptoms were present in 33.9%, 21.2%, and 26.7% of patients, respectively. Older patients and those who assessed their socioeconomic and health status as better were less anxious, depressed, and stressed. The study shows that the patients who have stated that medical help has been available significantly differ from those patients who have not had available medical help, meaning that they have shown lower scores on the scales of depression and stress. When it comes to the availability of medical help during the pandemic, statistically significant differences among patients on the scale of anxiety have not been proven. It has been determined that statistically important differences exist between patients who have needed psychological help and those who have not needed it when it comes to the results on all of the three subscales. The patients who have expressed the need for psychological help have higher levels of depression, anxiety, and stress. The patients who have not had available psychological help have higher levels of depression, anxiety, and stress when compared to the patients who have had available psychological help.

Comparative genomics and molecular epidemiology of colistin-resistant Acinetobacter baumannii

This study aimed to investigate the prevalence and resistance mechanisms of colistin-resistant Acinetobacter baumannii (ColRAB) isolates in Serbia, assess their genetic relatedness to other circulating A. baumannii isolates in the neighbouring European countries, and analyse the global genomic epidemiology of ColRAB isolates. A total of 784 isolates of A. baumannii were recovered from hospitalised patients in Serbia between 2018 and 2021. The antimicrobial susceptibility testing was performed using disk diffusion and broth microdilution. All ColRAB isolates were subjected to DNA isolation and whole-genome sequencing (WGS). Overall, 3.94 % (n = 30) isolates were confirmed as ColRAB. Results of mutational and transcriptional analysis of genes associated with colistin resistance indicate the central role of the two-component regulating system, PmrAB, and increased expression of the pmrC gene in ColRAB. Most of the isolates (n = 29, 96.6 %) belonged to international clone II, with the most common sequence type being STPas2 (n = 23, 76.6 %). Based on the WGS analysis, ColRAB isolates belonging to the same ST isolated in various countries were grouped into the same clusters, indicating the global dissemination of several high-risk clonal lineages. Phylogenomic analysis of ColRAB isolates, together with all previously published A. baumannii genomes from South-Eastern European countries, showed that colistin resistance arose independently in several clonal lineages. Comparative genomic analysis revealed multiple genes with various roles (transcriptional regulation, transmembrane transport, outer membrane assembly, etc.), which might be associated with colistin resistance in A. baumannii. The obtained findings serve as the basis for further studies, contributing to a better understanding of colistin resistance mechanisms in A. baumannii.

Impact of the COVID-19 Pandemic on Melanoma Diagnosis: Increased Breslow Thickness in Primary Melanomas—A Single Center Experience

Early melanoma diagnosis plays a key role in ensuring best prognosis with good survival rates. The ongoing global COVID-19 pandemic has greatly impacted global and national healthcare systems, thus making it a real challenge. The aim of this study was to evaluate the impact of the pandemic on diagnostic delay in melanoma patients in Serbia. In this retrospective study, we included patients treated at the university hospital in Serbia's capitol over a period of five years and three months. We compared the prepandemic (01/JAN/17-14/MAR/20) and pandemic periods (15/MAR/20-31/MAR/22) by evaluating patient demographic data, melanoma subtype, Breslow thickness, Clark level, ulceration status, mitotic index rate and pT staging. We observed a significant reduction in the number of diagnosed patients (86.3 vs. 13.7%; p = 0.036), with melanomas having an increased median Breslow thickness (1.80 vs. 3.00; p = 0.010), a higher percentage of Clark IV-V level lesions (44.0% vs. 63.0%; p = 0.009), an increase in median mitotic index rate (2 vs. 5; p < 0.001) and a trend of increase in lesions thicker than 2 mm (37.8% vs. 53.7%; p = 0.026). We believe that this study can be a useful scenario guide for future similar events, highlighting the importance of preventive measures and timely diagnosis for the best patient outcomes.

Diagnosis and treatment of adult asthma patients in Serbia: a 2022 experts group position statement

ABSTRACT Introduction Asthma is the most common non-communicable chronic lung condition across all ages. Epidemiological data indicate that many asthma patients in Serbia remain undiagnosed and untreated. The implementation of recent global advances in asthma management is limited due to the lack of a systematic approach, drug availability and regulatory affairs. In addition, the global coronavirus disease pandemic has posed a significant challenge, particularly in resource-limited settings. Areas covered In this paper, we propose an algorithm for treating adult asthma patients in Serbia. We performed PubMed database search on published asthma clinical trials and guidelines from 1 January 2015 to 10 March 2020. The consensus process incorporated a modified Delphi method that included two rounds of e-mail questionnaires and three rounds of national asthma expert meetings. We focus on 1) objective diagnosis of asthma, 2) the implementation of up-to-date therapeutic options, and 3) the identification and referral of severe asthma patients to newly established severe asthma centers. Expert opinion Regional specificities and variations in healthcare systems require the adaptation of evidence-based knowledge. Practical, clinically oriented algorithms designed to overcome local barriers in healthcare delivery may facilitate timely and adequate asthma diagnosis and the local implementation of current advances in asthma management.

953P EGFR mutation testing from pleural effusions of advanced lung adenocarcinoma patients in Serbia

In Serbia, EGFR mutation testing is performed from liquid biopsy of lung cancer patients only by qPCR. The aim of this study was to evaluate the efficacy of this approach in pleural effusions of patients at diagnosis and after progression on EGFR-TKIs. Mutation testing was performed from blood and pleural effusions of advanced lung adenocarcinoma patients (stage IIIB or IV, ECOG performance status 0, 1, 2) using the Cobas® EGFR Mutation Test. In the period from 2016-2021, 124 patients were tested at baseline (53 % males, 47 % females, age range 37-83 years, median 61), and 104 after progression on first-line EGFR-TKIs (41 % males, 59 % females, age range 34-81 years, median 60). At diagnosis, 9 mutated samples were detected (7.3 %) with a turnaround time of 2 working days, and a 99.2 % testing success rate. At progression, an accordance rate of only 67 % with the initial driver mutation was observed from blood. The T790M mutation was detected in 34 patients (49 % of the mutated samples, 33% of total) which rendered them eligible for third-generation EGFR-TKIs. In the same period, only 6 samples (4.8 %) of pleural effusions were sent to our Laboratory along with blood, all from patients at progression. The testing was performed with a turnaround time of 2 working days, a 100 % testing success rate, and an accordance rate of 100 % with the initial driver mutation. In 3 samples (50 %), the T790M mutation was detected while the corresponding blood sample showed only the presence of the driver mutation. EGFR mutation testing from pleural effusion has proven valuable as an alternative liquid biopsy sample to blood, for detecting the T790M acquired resistance mutation in patients who progressed on first-line EGFR-TKIs in Serbia.

Cross-Cultural Adaptation and Validation of the Functional, Communicative and Critical Health Literacy Instrument (FCCHL-SR) for Diabetic Patients in Serbia.

Thoroughly validated instruments can provide a more accurate and reliable picture of how the instrument works and of the level of health literacy in people with type 2 diabetes mellitus (T2DM). The present work aimed at cross-cultural adaptation and validation of the Functional, Communicative and Critical Health Literacy Instrument (FCCHL) in patients with T2DM in Serbia. After translation and back-translation, views from an expert group, one cognitive interview study (n = 10) and one survey study (n = 130) were conducted among samples of diabetic patients. Item analysis, internal consistency, content validity, confirmatory factor analysis (CFA) and reliability testing were performed. When all 14 items were analyzed, loading factors were above 0.55, but without adequate model fit. After removing two items with the lowest loadings FHL1 and IHL2 the fit indexes indicated a reasonable normed χ2 (SB scaled χ2/df = 1.90). CFI was 0.916 with SRMR = 0.0676 and RMSEA = 0.0831. To determine internal consistency, Cronbach’s alpha coefficient was 0.796 for the whole FCCHL-SR12. With only minor modifications compared to the English version, the 12-item FCCHL instrument is valid and reliable and can be used to measure health literacy among Serbian diabetic patients. However, future research on a larger population in Serbia is necessary for measuring the levels of HL and their relationship with other determinants in this country.

Knowledge and barriers to early detection of breast cancer among female primary care patients in Serbia.

Breast cancer is the leading cause of cancer mortality among women in Serbia and accounts for 22.8% of total cancer mortality in 2018. This study assessed the knowledge and barriers to early detection of breast cancer in women. In March 2019, at the Primary Healthcare Centre Kikinda, Serbia, a 22-item questionnaire was distributed to a series of patients (N = 403, response rate 91.8%) to assess the odds ratio (OR) and 95% confidence interval (CI) between variables explaining knowledge of breast cancer symptoms and risk factors and barriers to screening, and four types of early detection of breast cancer. The majority of patients (85.4%) know that a lump in a breast is a common symptom of breast cancer and that a family history of breast cancer is a risk factor (80.1%); 63.8% of respondents aged ≥ 30 years self-examined their breasts in the past month, 39.1% of patients aged ≥ 40 years had clinical, while 34.4% had ultrasound breast examination in the past year, and 51.1% of patients aged ≥ 50 years had mammography once in the past two years. Patients aged ≥ 40 years retired and those with a positive family history were 84% and 63% less likely not to undergo a clinical breast examination in the past year. Participants over 40 years of age who reported a lack of funds were 2.46 times more likely to miss a clinical breast examination than those who did not have that barrier. Among participants aged 50-69 years, the likelihood of not receiving the mammography increases by 2.82 with an increase in wealth status and it was 65% lower for those who lack information about the available treatment. Women under the age of 50 rarely practice breast cancer screening. Study findings can be used to improve breast cancer screening at the primary level.

Health care access of thyroid disease patients in Serbia during the COVID-19 pandemic.

PurposeThe aim of this study was to assess the impact of repurposing health care facilities in response to COVID-19 on the access of patients with thyroid disease to health care.MethodsThis study consisted of a web-based survey. The survey was anonymous and consisted of forty questions.ResultsThis survey included 206 respondents. 91.3% of the respondents had health insurance through the Republic Fund of Health Insurance, 9.7% had private or both health insurances, and 3.4% did not have any health insurance. A significant proportion of respondents (60.4%) had to switch from public to private health care to reach a physician and 73.8% had to switch from public to private laboratories. For the 91.9%, this was perceived as a financial burden. Before the pandemic, 83.1% of respondents reported regular follow-up by physicians, which decreased to 44.9% during the pandemic (p < 0.01). 76.3% of the respondents regarded that their thyroid disease was managed optimally before the pandemic, while this figure declined to only 48% during the pandemic (p < 0.01).ConclusionsThe COVID-19 pandemic disrupted the medical care of thyroid patients in Serbia. For the patients treated in the public health care system, access to general practice was hindered, while access to specialist care was disrupted. It led to a switch from public to private health care, which was perceived as a financial burden for almost all the respondents. However, private health care proved to be an important safety net when the public system was overwhelmed.

The pharmacogenomics of vincristine-induced peripheral neuropathy in pediatric acute lymphoblastic leukemia patients in Serbia - a single center experience

Introduction/Objective. Vincristine (VCR) is one of the key drugs in current treatment protocols for pediatric acute lymphoblastic leukemia (ALL). By destabilizing microtubules, VCR arrests cells in metaphase, inducing apoptosis of malignant cells. VCR also causes axonal degradation and impairment of axonal transport, which leads to VCR-induced peripheral neuropathy (VIPN). This study aimed to investigate the association of five variants in pharmacogenes involved in VCR metabolism with VIPN in Serbian ALL children. We also wanted to discover candidate pharmacogenomic markers of VIPN in Serbian population. Methods. PCR and sequencing-based methodology was used to detect variants in CYP3?5, CEP72, ACTG1, MIR3117, and MIR4481 genes. Statistical analyses were performed for investigating their association with VIPN in 56 pediatric ALL patients. Population VCR pharmacogenomics analysis of 17 pharmacogenes from in-house next-generation sequencing data was also done. Data on allele frequency distribution for the European population were extracted from public databases. Results. During the treatment, 17.86% of patients developed VIPN. Association analyses have shown that none of the genetic variants contributed to the occurrence of VIPN in our study. Population pharmacogenomics study did not reveal valid candidate pharmacovariants for VIPN. Our results suggested that pre-emptive pharmacogenetic testing for VCR is not applicable presently. Conclusion. More comprehensive approaches are needed to identify the panel of genes that could explain the VIPN development after VCR administration in ALL patients. Utilizing better designed genome-wide association studies and more robust artificial intelligence-based tools would provide a panel of pharmacogenes for pre-emptive tests of VIPN to individualize therapy for ALL in children.

Clinical and genetic characteristics of patients with congenital hyperinsulinism in 21 non-consanguineous families from Serbia.

Persistent hypoglycaemia in newborns and infants is most commonly caused by congenital hyperinsulinism (CHI). Most CHI studies report outcomes in children from both consanguineous and non-consanguineous families which can affect the phenotype-genotype analysis. The aim of this study was to analyze characteristics of patients with CHI in 21 non-consanguineous families from Serbia. This retrospective cohort study included a total of 21 patients with CHI treated in the Mother and Child Healthcare Institute of Serbia during the past 20 years. The prevalence of macrosomia at birth was very low in our cohort (4.8%). Median age at presentation was 6 days, with seizures as the presenting symptom in 76% of patients. Only four patients (19%) were diazoxide unresponsive, and eventually underwent pancreatectomy. Genetic testing was performed in 15 patients and genetic diagnosis was confirmed in 60%, with all patients being heterozygous for detected mutations. The ABCC8 gene mutations were detected in 55.6%, GLUD1 in three patients (33.3%) with HIHA syndrome and one patient had HNF4A gene mutation and unusual prolonged hyperglycaemia lasting 6 days after diazoxide cessation. Neurodevelopmental deficits persisted in 33% of patients.Conclusion: This is the first study regarding CHI patients in Serbia. It suggests that in countries with low consanguinity rate, majority of CHI patients are diazoxide responsive. The most common mutations were heterozygous ABCC8, followed by GLUD1 and HNF4A mutations, suggesting the potential benefit of population-tailored genetic analysis approach, targeting the mutations causing CHI via dominant inheritance model in regions with low consanguinity rates. What is Known: • Persistent hypoglycaemia during infancy and early childhood is most commonly caused by congenital hyperinsulinism (CHI). • Consanguinity is a very important factor regarding the genetics and phenotype of CHI, increasing the risk of autosomal recessive genetic disorders, including the severe, diazoxide-unresponsive forms caused by recessive inactivating mutations in ABCC8 and KCNJ11. What is New: • Results of the present study which included CHI patients from 21 non-consanguineous families suggest that in countries with low consanguinity rates, majority of CHI patients can be diazoxide responsive, with most common mutations being heterozygous ABCC8, followed by GLUD1 and HNF4A mutations. • Unusually prolonged hyperglycaemic reaction to diazoxide treatment in a patient with HNF4A mutation was also described in the present study.