Detection of Del/Dup Inside SHOX/PAR1 Region in Children and Young Adults with Idiopathic Short Stature

Short stature is a common growth disorder defined as a body height two standard deviations (SD) or more below the mean for a given age, gender, and population. A large part of the cases remains unexplained and is referred to as having idiopathic short stature (ISS). One of the leading genetic causes of short stature is variants of short stature homeobox-containing gene (SHOX) and is considered to be responsible for 2–15% of ISS. We aimed to analyse the regulatory and coding region of SHOX in Slovenian children and young adults with ISS and to investigate the pathogenicity of detected variants. Our cohort included 75 children and young adults with ISS. Multiplex ligation-dependent probe amplification (MLPA) was performed in all participants for the detection of larger copy number variations (CNVs). Sanger sequencing was undertaken for the detection of point variants, small deletions, and insertions. A total of one deletion and two duplications were discovered using the MLPA technique. Only one of these four variants was identified as disease-causing and occurred in one individual, which represents 1.3% of the cohort. With Sanger sequencing, two variants were discovered, but none of them appeared to have a pathogenic effect on height. According to the results, in the Slovenian population of children and young adults with ISS, SHOX deficiency is less frequent than expected considering existing data from other populations.

Prevalence and incidence of frailty among community-dwelling older adults in Slovenia

Introduction Frailty is recognized as one of the most important global health challenges as the population is aging. The aim of this study was to evaluate prevalence and incidence of frailty, and associated factors, among the population of older adults in Slovenia compared to other European countries. Methods The prevalence and 4-year incidence of frailty among older adults (≥65 years) were evaluated using data from the Survey of Health, Ageing and Retirement in Europe (SHARE). Frailty was defined by the SHARE operationalization of Frailty phenotype. Multiple logistic regression model was used to explore factors associated with frailty. Results Age-standardized prevalence (95% CI) of frailty and pre-frailty in Slovenia were 14.9% (13.3-16.5) and 42.5% (39.8-45.2), respectively. Factors (OR, 95% CI) associated with increased frailty in Slovenia included age (7584 years: 5.03 (3.08-8.22); ≥85 years 21.7 (10.6-44.7) vs. 65-74 years), self-rated health (fair: 4.58 (2.75-7.61), poor: 54.6 (28.1-105.9) vs. excellent/very good/good), number of chronic diseases (1.20 (1.03-1.40)), and polypharmacy (yes: 3.25 (1.93-5.48) vs. no). Female gender and lower education were significantly associated with pre-frailty, but not frailty, in the adjusted model. Independently of these characteristics, age-standardized prevalence of frailty varied among geographical regions. Age-standardized 4-year incidence of frailty and pre-frailty in Slovenia were 6.6% (3.0-10.1) and 40.2% (32.7-47.6), respectively. Conclusion Among the Slovenian population of older adults aged 65 years and older, the age-standardized prevalence of frailty is 15% and 4-year incidence of frailty is 7%. Regional differences in Slovenia show the lowest prevalence in central Slovenian regions and the highest in northeastern Slovenian regions.

Identification of women at risk for hereditary breast and ovarian cancer in a sample of 1000 Slovenian women: a comparison of guidelines

Background An important number of breast and ovarian cancer cases is due to a strong genetic predisposition. The main tool for identifying individuals at risk is recognizing a suggestive family history of cancer. We present a prospective study on applying three selected clinical guidelines to a cohort of 1000 Slovenian women to determine the prevalence of at-risk women according to each of the guidelines and analyze the differences amongst the guidelines. Methods Personal and family history of cancer was collected for 1000 Slovenian women. Guidelines by three organizations: National Comprehensive Cancer Network (NCCN), American College of Medical Genetics in cooperation with National Society of Genetic Counselors (ACMG/NSGC), and Society of Gynecologic Oncology (SGO) were applied to the cohort. The number of women identified, the characteristics of the high-risk population, and the agreement between the guidelines were explored. Results NCCN guidelines identify 13.2% of women, ACMG/NSGC guidelines identify 7.1% of women, and SGO guidelines identify 7.0% of women from the Slovenian population, while 6.2% of women are identified by all three guidelines as having high-risk for hereditary breast and ovarian cancer. Conclusions We identified 13.7% of women from the Slovenian population as being at an increased risk for breast and ovarian cancer based on their personal and family history of cancer using all of the guidelines. There are important differences between the guidelines. NCCN guidelines are the most inclusive, identifying nearly twice the amount of women as high-risk for hereditary breast and ovarian cancer as compared to the AGMG/NSCG and SGO guidelines in the Slovenian population.

KRAS, NRAS and BRAF mutational status and first line treatment patterns in Slovenian population with metastatic colorectal carcinoma: Five year results.

e15546 Background: A phase IV non-interventional study was performed from 2013 till 2018 including 650 patients with primary aim to assess KRAS, NRAS and BRAF mutational status in Slovenian population with metastatic colorectal carcinoma (mCRC) suitable for first-line treatment. The evaluation of decisions for first-line treatment regarding the biomarkers status and assessing the possible impact of the time period of the biomarker status analysis report on the treatment decision were also incorporated in the analysis. The molecular analyses for KRAS and NRAS gene mutations were performed on exons 2, 3 and 4, and for BRAF gene mutations on exon 15. The first line systemic treatment options for RAS (KRAS/NRAS) wild type (wt) and mutated type (mt) mCRC subjects were as follows: chemotherapy - Fluoropyrimidine based systemic therapy combined with oxaliplatin and/or irinotecan with/without VEGF inhibitor bevacizumab and for RAS wt subjects, with/without EGFR inhibitors, cetuximab or panitumumab. Methods: To indicate the degree of certainty of KRAS, NRAS and BRAF status frequency as being wild type or mutant type 95% confidence interval was calculated. Results: The KRAS/NRAS/BRAF mutation rates were as follows - The distribution of subjects with KRAS mutated and wild-type tumors, was almost equal, 48.8% and 47.9% respectively. Eighty nine percent of the subjects had NRAS wild type tumours and 86.1% had BRAF wild type tumours. The most frequently used treatment regardless the biomarkers status and in accordance with the treatment guidelines was bevacizumab based combination therapy (53.1%). The EGFR inhibitor (cetuximab or panitumumab) based combination therapy was used in one third of mCRC subjects (30.9%), all with mCRC RAS wt. The time period from the initial presentation of the patient until the biomarker status analysis report was two weeks. Conclusions: With this study, we have proven that the distribution of the mutations in exons 2-4 of KRAS and NRAS genes and exon 15 in the BRAF gene in the Slovenian population with metastatic colorectal cancer matches historical data. Based on this, we conclude that the treatment decision in Slovenian population with metastatic colorectal carcinoma should be in the accordance with international treatment guidelines and on evidence based medicine. The molecular analysis performed at the Institute of Oncology Ljubljana was providing necessary biomarkers status report in an acceptable time that didn’t affect the treatment decision or delay the needed cancer treatment.

POS0796 SURVIVAL OF GIANT CELL ARTERITIS PATIENTS IN SLOVENIA

Background:Recent meta-analysis reported no difference in the long-term mortality of GCA patients at a population level, but an increased mortality in hospital-based cohorts1.Objectives:The aim of our study was to evaluate for the first time the survival of GCA patients in Slovenia.Methods:We included patients with clinical diagnosis of GCA supported by histology or imaging diagnosed between September 2011 and December 2019 and prospectively followed at our secondary/tertiary rheumatology center. To evaluate mortality the censor date of 24. June 2020 was used. Kaplan–Meier analysis was used to analyze mortality. Standardized mortality ratio (SMR) was calculated using data of age matched Slovenian population as the reference.Results:Between September 2011 and December 2019 we identified 309 new GCA patients (203 (65.7%) females, median (IQR) age 74.9 (67.7–80.1.7), range 53.7 to 97.5 years). Patients were followed (until death or censor date) of a median (IQR) 33.3 (17.5-60.8) months. Until the censor date 51 (16.5%) GCA patients died (24 females, 27 males). We found no significant sex related differences in the net survival estimates during the first five years of follow up (p=0.68). Figure 1 shows the survival curve of GCA patients and general population as a comparator according to Kaplan–Meier analysis. In the first year following GCA diagnosis the mortality rate was 1.9 times higher compared to general Slovenian population (95% CI 1.19 - 2.88, p=0.03). For patients who survived the first year after diagnosis the mortality was comparable to the general population (Table 1).Figure 1.Survival curve according to Kaplan–Meier analysis in GCATable 1.Standardized mortality ratios of patients who survived the first year after diagnosing GCA (ie. were followed at least one year) compared to the general populationYearsof FUObserved deathsExpected deathsSMR (95%CI)P-value2119.71.14 (0.57-2.03)0.75331416.50.85 (0.46-1.43)0.62642121.60.97 (0.60-1.49)0.98752525.01.00 (0.65-1.48)0.92162627.60.94 (0.61-1.38)0.831Legend: FU follow up; SMR Standardized mortality ratios; CI confidence intervalConclusion:GCA patients had an increased risk of death in the first year from the GCA diagnosis.References:[1]Hill CL, et al. Semin Arthritis Rheum. 2017;46(4):513-9.Disclosure of Interests:None declared

Factors Affecting Attitudes towards COVID-19 Vaccination: An Online Survey in Slovenia

While the problem of vaccine hesitancy is not new, it has become more pronounced with the new COVID-19 vaccines and represents an obstacle to resolving the crisis. Even people who would usually trust vaccines and experts now prefer to wait for more information. A cross-sectional online survey was conducted in Slovenia in December 2020 to find out the attitudes of the population regarding COVID-19 vaccination and the factors that affect these attitudes. Based on 12,042 fully completed questionnaires, we find that higher intention to get vaccinated is associated with men, older respondents, physicians and medical students, respondents who got the influenza vaccination, those who knew someone who had gotten hospitalised or died from COVID-19 and those who have more trust in experts, institutions and vaccines. Nurses and technicians were less likely to get vaccinated. In answers to an open question, sceptics were split into those doubting the quality due to the rapid development of the vaccine and those that reported personal experiences with side effects of prior vaccinations. Although the Slovenian population is diverse in its attitudes towards vaccination, the results are comparable to those found in other countries. However, there are potential limitations to the generalizability of the findings that should be addressed in future studies.

Dietary Intake of trans Fatty Acids in the Slovenian Population

Consumption of trans fatty acids (TFAs) has been unequivocally linked to several adverse health effects, with the increased risk of cardiovascular disease being one of the most well understood. To reduce TFA-related morbidity and mortality, several countries have imposed voluntary or mandatory measures to minimize the content of industrial TFAs (iTFAs) in the food supply. In 2018, Slovenia introduced a ban on iTFAs on top of preceding voluntary calls to industry to reduce its use of partially hydrogenated oils (PHOs) as the main source of iTFAs. To investigate the consumption of TFAs, data available from the nationally representative dietary survey SI.Menu were analyzed. The survey consisted of two 24-h non-consecutive day recalls from 1248 study participants from three age groups (10–17, 18–64, 65–74 years old), combined with socio-demographic, socio-economic, and lifestyle parameters. The analyses demonstrated that, on average, TFAs accounted for 0.38–0.50% of total energy intake (TEI). However, 13% of adolescents, 29.4% of adults, and 41.8% of the elderly population still consumed more than 0.50% TEI with TFAs. The main sources of TFAs in the diet were naturally present TFAs from butter, meat dishes, and meat products, regardless of the age group. Results indicate that following the reformulation activities, the major sources of TFAs in the diets of the Slovenian population now represent foods which are natural sources of TFAs.

EQ-5D-5L Slovenian population norms

Background The study aims to present Slovenian EQ-5D-5L population norms for different age and gender subgroups that can be used as reference values in future studies concerning health status. The secondary aim is to compare those norms with population norms from some other countries in Europe and elsewhere. Methods The cross-sectional survey was conducted between November 2019 and February 2020 via online panel. 1071 adults aged 18+ were included in the survey. The general population was sampled using quota sampling in terms of age, gender, and NUTS2 region. In the study, the EQ-5D-5L Slovenian online version was used. Descriptive statistics was used to present health status by age groups and genders for the EQ-5D-5L descriptive system, EQ VAS and the EQ-5D-5L index score. The latter was derived from Slovenian EQ-3D-3L tariff, transformed to five levels using the crosswalk methodology. Results The mean EQ VAS score in the Slovenian population was 79.9, mean utility index was 0.808. 28.2% of the population did not have problems on any dimension and 3.9% of the population had problems on all dimensions. Persons residing in Western Slovenia had, on average, 0.016 higher utility score, compared to Eastern Slovenia. Effect of gender was not significant. Age was negatively associated with both utility index and EQ VAS score. Education was positively correlated to health status. Problems on dimensions were generally increasing with age, except for anxiety/depression dimension, where youngest group (ages 18–29) reported more anxiety/depression compared to older counterparts. Self-reported anxiety/depression was more pronounced in women. Conclusions Similarly to other countries, the health generally deteriorates with age, except for the anxiety/depression dimension where the share of respondents reporting no problems was lowest in the youngest age group. The open question for the future remains, whether population norms from this online sample differ significantly from the actual EQ-5D-5L health status data of the Slovenian general population.

Identification of Women at Risk for Hereditary Breast and Ovarian Cancer in A Sample of 1000 Slovenian Women: A Comparison of Guidelines

Background: An important number of breast and ovarian cancer cases is due to a strong genetic predisposition. The main tool for identifying individuals at risk is recognizing a suggestive family history of cancer. We present a prospective study on applying three selected clinical guidelines to a cohort of 1000 Slovenian women to determine the prevalence of at-risk women according to each of the guidelines and analyze the differences amongst the guidelines.Methods: Personal and family history of cancer was collected for 1000 Slovenian women. Guidelines by three organizations: National Comprehensive Cancer Network (NCCN), American College of Medical Genetics in cooperation with National Society of Genetic Counselors (ACMG/NSGC), and Society of Gynecologic Oncology (SGO) were applied to the cohort. The number of women identified, the characteristics of the high-risk population, and the agreement between the guidelines were explored. Results: NCCN guidelines identify 16.7 % of women, ACMG/NSGC guidelines identify 7.1 % of women, and SGO guidelines identify 7.0 % of women from the Slovenian population, while 6.2 % of women are identified by all three guidelines as having high-risk for hereditary breast and ovarian cancer.Conclusions: We identified 17.4 % of women from the Slovenian population as being at an increased risk for breast and ovarian cancer based on their personal and family history of cancer using all of the guidelines. There are important differences between the guidelines. NCCN guidelines are the most inclusive, identifying more than twice the amount of women as high-risk for hereditary breast and ovarian cancer as compared to the AGMG/NSCG and SGO guidelines in the Slovenian population.

Multidestination travel of the Slovenian population

This paper focuses on the multidestination travel of the Slovenian population. It presents the results of a questionnaire survey that aimed to gain insight into some relevant characteristics of the travel behaviour of the Slovenian population and its links to factors that were found in previous research to be related to the incidence of multidestination travel. A destination was defined within this research as any location where an overnight stop is made. Single-destination trips prevailed. Still, a considerable percentage of respondents’ most recent trips had been multidestination trips. The greater part of them was directed to just one country within which they visited several overnight destinations. The results indicate that duration of trip, distance of destination from tourists’ residential location, familiarity of destination, travel-group size and tourists’ activities are associated with the likelihood of multidestination travel.