Deregulation in adult IgA vasculitis skin as the basis for the discovery of novel serum biomarkers.

INTRODUCTION: Immunoglobulin A vasculitis (IgAV) in adults has a variable disease course, with patients often developing gastrointestinal and renal involvement and thus contributing to higher mortality. Due to understudied molecular mechanisms in IgAV currently used biomarkers for IgAV visceral involvement are largely lacking. Our aim was to search for potential serum biomarkers based on the skin transcriptomic signature. METHODS: RNA sequencing analysis was conducted on skin biopsies collected from 6 treatment-naïve patients (3 skin only and 3 renal involvement) and 3 healthy controls (HC) to get insight into deregulated processes at the transcriptomic level. 15 analytes were selected and measured based on the transcriptome analysis (adiponectin, lipopolysaccharide binding protein (LBP), matrix metalloproteinase-1 (MMP1), C-C motif chemokine ligand (CCL) 19, kallikrein-5, CCL3, leptin, C-X-C motif chemokine ligand (CXCL) 5, osteopontin, interleukin (IL)-15, CXCL10, angiopoietin-like 4 (ANGPTL4), SERPIN A12/vaspin, IL-18 and fatty acid-binding protein 4 (FABP4)) in sera of 59 IgAV and 22 HC. Machine learning was used to assess the ability of the analytes to predict IgAV and its organ involvement. RESULTS: Based on the gene expression levels in the skin, we were able to differentiate between IgAV patients and HC using principal component analysis (PCA) and a sample-to-sample distance matrix. Differential expression analysis revealed 49 differentially expressed genes (DEGs) in all IgAV patient's vs. HC. Patients with renal involvement had more DEGs than patients with skin involvement only (507 vs. 46 DEGs) as compared to HC, suggesting different skin signatures. Major dysregulated processes in patients with renal involvement were lipid metabolism, acute inflammatory response, and extracellular matrix (ECM)-related processes. 11 of 15 analytes selected based on affected processes in IgAV skin (osteopontin, LBP, ANGPTL4, IL-15, FABP4, CCL19, kallikrein-5, CCL3, leptin, IL-18 and MMP1) were significantly higher (p-adj < 0.05) in IgAV serum as compared to HC. Prediction models utilizing measured analytes showed high potential for predicting adult IgAV. CONCLUSION: Skin transcriptomic data revealed deregulations in lipid metabolism and acute inflammatory response, reflected also in serum analyte measurements. LBP, among others, could serve as a potential biomarker of renal complications, while adiponectin and CXCL10 could indicate gastrointestinal involvement.

Breast cancer risk prediction using Tyrer-Cuzick algorithm with an 18-SNPs polygenic risk score in a European population with below-average breast cancer incidence.

GOALS: To determine whether an 18 single nucleotide polymorphisms (SNPs) polygenic risk score (PRS18) improves breast cancer (BC) risk prediction for women at above-average risk of BC, aged 40-49, in a Central European population with BC incidence below EU average. METHODS: 502 women aged 40-49 years at the time of BC diagnosis completed a questionnaire on BC risk factors (as per Tyrer-Cuzick algorithm) with data known at age 40 and before BC diagnosis. Blood samples were collected for DNA isolation. 250 DNA samples from healthy women aged 50 served as a control cohort. 18 BC-associated SNPs were genotyped in both groups and PRS18 was calculated. The predictive power of PRS18 to detect BC was evaluated using a ROC curve. 10-year BC risk was calculated using the Tyrer-Cuzick algorithm adapted to the Slovenian incidence rate (S-IBIS): first based on questionnaire-based risk factors and, second, including PRS18. RESULTS: The AUC for PRS18 was 0.613 (95 % CI 0.570-0.657). 83.3 % of women were classified at above-average risk for BC with S-IBIS without PRS18 and 80.7 % when PRS18 was included. CONCLUSION: BC risk prediction models and SNPs panels should not be automatically used in clinical practice in different populations without prior population-based validation. In our population the addition of an 18SNPs PRS to questionnaire-based risk factors in the Tyrer-Cuzick algorithm in general did not improve BC risk stratification, however, some improvements were observed at higher BC risk scores and could be valuable in distinguishing women at intermediate and high risk of BC.

Fall Risk in Adult Family Practice Non-Attenders: A Cross-Sectional Study from Slovenia.

Introduction: Not much is known about the fall risk among the adult population of those who rarely visit doctors. We wanted to determine the prevalence of increased fall risk in a population of family practice non-attenders and the factors associated with it. Methods: We included participants from family medicine practices in this cross-sectional study. To be included in the study, the participants had to be adults living in the community (home-dwelling people) who had not visited their chosen family physician in the last five years (non-attenders). The identification of the eligible persons was done through a search of electronic medical records, which yield 2,025 non-attenders. Community nurses collected data in the participants' homes. The outcome measure was increased fall risk as assessed by the Morse fall scale: increased risk (≥25) vs. no risk. Results: The sample consisted of 1,945 patients (96.0% response rate) with a mean age of 60.4 years (range 20.5 to 99.7 years). An increased fall risk was determined in 482 or 24.8% (95% CI: [22.9, 26.8]) of the patients. The multivariate model showed a significant association of increased fall risk with higher age (p<0.001), lower systolic blood pressure (p=0.047), poor family function (p=0.016), increased risk of malnutrition (p=0.013), higher number of chronic diseases (p=0.027), higher pain intensity (p<0.001), lower self-assessment of current health (p=0.002), and higher dependence in daily activities (p<0.001). Conclusion: Non-attenders may have an increased risk of falling which depends on their health status and age. The inclusion of community nurses in primary healthcare teams could be of use not only to identify the non-attenders' health needs, but also to better manage their health, especially the factors that were identified to be associated with greater fall risk.

Bias-reduced estimators of conditional odds ratios in matched case-control studies with unmatched confounding.

We study bias-reduced estimators of exponentially transformed parameters in general linear models (GLMs) and show how they can be used to obtain bias-reduced conditional (or unconditional) odds ratios in matched case-control studies. Two options are considered and compared: the explicit approach and the implicit approach. The implicit approach is based on the modified score function where bias-reduced estimates are obtained by using iterative procedures to solve the modified score equations. The explicit approach is shown to be a one-step approximation of this iterative procedure. To apply these approaches for the conditional analysis of matched case-control studies, with potentially unmatched confounding and with several exposures, we utilize the relation between the conditional likelihood and the likelihood of the unconditional logit binomial GLM for matched pairs and Cox partial likelihood for matched sets with appropriately setup data. The properties of the estimators are evaluated by using a large Monte Carlo simulation study and an illustration of a real dataset is shown. Researchers reporting the results on the exponentiated scale should use bias-reduced estimators since otherwise the effects can be under or overestimated, where the magnitude of the bias is especially large in studies with smaller sample sizes.

European fitness landscape for children and adolescents: updated reference values, fitness maps and country rankings based on nearly 8 million test results from 34 countries gathered by the FitBack network.

OBJECTIVES: (1) To develop reference values for health-related fitness in European children and adolescents aged 6-18 years that are the foundation for the web-based, open-access and multilanguage fitness platform (FitBack); (2) to provide comparisons across European countries. METHODS: This study builds on a previous large fitness reference study in European youth by (1) widening the age demographic, (2) identifying the most recent and representative country-level data and (3) including national data from existing fitness surveillance and monitoring systems. We used the Assessing Levels of PHysical Activity and fitness at population level (ALPHA) test battery as it comprises tests with the highest test-retest reliability, criterion/construct validity and health-related predictive validity: the 20 m shuttle run (cardiorespiratory fitness); handgrip strength and standing long jump (muscular strength); and body height, body mass, body mass index and waist circumference (anthropometry). Percentile values were obtained using the generalised additive models for location, scale and shape method. RESULTS: A total of 7 966 693 test results from 34 countries (106 datasets) were used to develop sex-specific and age-specific percentile values. In addition, country-level rankings based on mean percentiles are provided for each fitness test, as well as an overall fitness ranking. Finally, an interactive fitness platform, including individual and group reporting and European fitness maps, is provided and freely available online (www.fitbackeurope.eu). CONCLUSION: This study discusses the major implications of fitness assessment in youth from health, educational and sport perspectives, and how the FitBack reference values and interactive web-based platform contribute to it. Fitness testing can be conducted in school and/or sport settings, and the interpreted results be integrated in the healthcare systems across Europe.

Centile Reference Curves of the SLOfit Physical Fitness Tests for School-Aged Children and Adolescents.

ABSTRACT: Blagus, R, Jurak, G, Starc, G, and Leskosek, B. Centile reference curves of the SLOfit physical fitness tests for school-aged children and adolescents. J Strength Cond Res 37(2): 328-336, 2023-The study provides sex- and age-specific centile norms of Slovenian children and youth. Physical fitness was assessed using the SLOfit test battery on population data, including 185,222 children, aged 6-19 years, measured in April and May 2018. Centile curves for both sexes and 12 test items were constructed using the generalized additive models for location, scale, and shape (GAMLSS). Boys generally achieved higher scores in most of the physical fitness tests, except in stand and reach, but this was not consistent throughout childhood and adolescence, nor did it pertain to the entire range of performance. Girls outperformed boys in the arm-plate tapping test throughout childhood; the poorest performing girls outperformed the poorest performing boys in the 600-m run, 60-m dash, backward obstacle course, and standing broad jump. The shapes and trends of physical fitness curves adequately reflect the effects of growth and development on boys' and girls' physical performance. Comparing the existing reference fitness curves showed that Slovenian children and adolescents display higher fitness levels than their peers from other countries. This study provides the most up-to-date sex- and age-specific reference fitness centile curves of Slovenian children, which can be used as benchmark values for health and fitness monitoring and surveillance systems.

Treatment of erythema migrans with doxycycline for 7 days versus 14 days in Slovenia: a randomised open-label non-inferiority trial.

BACKGROUND: Lyme borreliosis is the most prevalent vector-borne disease in Europe and the USA. Doxycycline for 10 days is the primary treatment recommendation for erythema migrans. To reduce potentially harmful antibiotic overuse by identifying shorter effective treatments, we aimed to assess whether oral doxycycline for 7 days is non-inferior to 14 days in adults with solitary erythema migrans. METHODS: In this randomised open-label non-inferiority trial, we enrolled patients with a solitary erythema at the University Medical Centre in Ljubljana, Slovenia. Patients were excluded if they were pregnant or lactating, immunosuppressed, allergic to doxycycline, or had received antibiotics with anti-borrelial activity within 10 days preceding enrolment or had additional manifestations of Lyme borreliosis Adults were randomly allocated 1:1 to receive oral doxycycline 100 mg twice a day for 7 days or 14 days. The primary efficacy endpoint was the difference in proportion of patients with treatment failure, defined as persistent erythema, new objective signs of Lyme borreliosis, or borrelial isolation on skin re-biopsy at 2 months, in a per-protocol analysis (the population that completed the assigned doxycycline regimen according to the study protocol and did not receive any other antibiotics with anti-borrelial activity until the 2-month visit). The non-inferiority margin was 6 percentage points. Safety was assessed in all randomly assigned patients who followed the study protocol and were evaluable at the 14-day visit. This study is registered with ClinicalTrials.gov, NCT03153267. FINDINGS: Between July 3, 2017, and Oct 2, 2018, we enrolled 300 patients (150 per group: median age 56 years [IQR 47-65]; 126 [45%] of 300 male; skin culture positive 72 [30%] of 239 assessed). 295 patients completed antibiotic therapy as per protocol and 294 (98%) patients were evaluable 2 months post-enrolment. Five (3%) of 147 patients from the 7-day group versus 3 (2%) of 147 patients from the 14-day group (one patient did not attend the 2-month visit and was unreachable by telephone) had treatment failure manifesting as persistence of erythema (difference 1·4 percentage points; upper limit of one-sided 95% CI 5·2 percentage points; p=0·64). No patients developed new objective manifestations of Lyme borreliosis during follow-up or had positive repeat skin biopsies. Two (1%) of 150 patients in the 7-day and one (1%) of 150 patients in the 14-day group discontinued therapy due to adverse events. INTERPRETATION: Our data support 7 days of oral doxycycline for adult European patients with solitary erythema migrans, permitting less antibiotic exposure than current guideline-driven therapy. FUNDING: Slovenian Research Agency and the University Medical Centre Ljubljana.

Wild Carnivore Survey of Echinococcus Species in Slovenia.

Wild carnivores are definitive hosts and potential reservoirs for the tapeworm Echinococcus sp. which can cause cystic and alveolar echinococcosis. Both are considered neglected and important food-borne pandemics. This study is the first to molecularly test Slovenian wild carnivores for Echinococcus species that can cause disease in humans. Fecal samples from 210 red foxes (Vulpes vulpes), 42 wolves (Canis lupus), 39 golden jackals (Canis aureus), 18 martens (Marten sp.), 2 Eurasian lynx (Lynx lynx), 2 European badger (Meles meles), and 1 Eurasian otter (Lutra lutra) were examined for Echinococcus granulosus sensu lato (EGsl: E. granulosus sensu stricto, E. canadensis) and E. multilocularis (EM) using real-time PCR. Red foxes (29.1%) and golden jackals (18%) were positive for EM. All animals examined were negative for EGsl. Univariate analysis showed no significant differences in EM prevalence with respect to animal species (red fox vs., golden jackal) (p = 0.22), age (p = 0.12), and sex (p = 0.18). Prevalence of EM was associated with the region (p < 0.001), with regions in central and southern Slovenia having higher EM prevalence and risk of infection. Due to the increase in population and expansion of habitat, the golden jackal may soon become as important definitive host for EM as the red fox.

SLOfit Lifelong: A model for leveraging citizen science to promote and maintain physical fitness and physical literacy across the lifespan.

SLOfit Lifelong is a public health initiative which was created to upgrade a well-established, national physical fitness surveillance system for Slovenian schoolchildren that has been collecting annual fitness and health data for over three decades. The ultimate objective of creating SLOfit Lifelong was to build a modern societal infrastructure with the capacity and ability to detect future causal associations between childhood physical fitness trends and future health outcomes based on the lifelong surveillance of one's own fitness status. By instilling citizens with an ambition to test, understand, and follow-up their own physical fitness and health status (including related health risk factors), this initiative provides the technical support and expert feedback needed to engender greater individual control over understanding (and thus modulating), one's own physical fitness status as they progress into older adulthood. This perspective paper details the extensive approach taken to devise appropriate fitness test batteries for adults and older adults which can also relate to the student version of the original SLOfit test database, including establishing criterion health risk zones and a public approach to establish this national, citizen-driven health feedback framework. Through its sophisticated online web applications, social media, print media, and outreach workshops, SLOfit Lifelong provides the expert support for public health engagement by fostering positive lifelong physical literacy experiences an individual can enjoy across their aging journey.

Ringing the bell for quality P.E.: What are the realities of remote physical education?

BACKGROUND: To date, few data on the quality and quantity of online physical education (P.E.) during the COVID-19 pandemic have been published. We assessed activity in online classes and reported allocated curriculum time for P.E. in a multi-national sample of European children (6-18 years). METHODS: Data from two online surveys were analysed. A total of 8395 children were included in the first round (May-June 2020) and 24 302 in the second round (January-February 2021). RESULTS: Activity levels during P.E. classes were low in spring 2020, particularly among the youngest children and in certain countries. 27.9% of students did not do any online P.E. and 15.7% were hardly ever very active. Only 18.4% were always very active and 14.9% reported being very active quite often. In winter 2020, we observed a large variability in the allocated curriculum time for P.E. In many countries, this was lower than the compulsory requirements. Only 65.7% of respondents had the same number of P.E. lessons than before pandemic, while 23.8% had less P.E., and 6.8% claimed to have no P.E. lessons. Rates for no P.E. were especially high among secondary school students, and in large cities and megapolises. CONCLUSIONS: During the COVID-19 pandemic, European children were provided much less P.E. in quantity and quality than before the pandemic. Countermeasures are needed to ensure that these changes do not become permanent. Particular attention is needed in large cities and megapolises. The critical role of P.E. for students' health and development must be strengthened in the school system.

Secular trends in physical fitness of Slovenian boys and girls aged 7 to 15 years from 1989 to 2019: a population-based study.

Using the population-based data we aim to estimate the general population trends of multiple components of physical fitness of children, identify critical structural changes in these trends, and evaluate the potential changes in differences in the test scores between the children. During the entire study period, 1989-2019, median body mass index and triceps skinfold increased in both genders and all age groups. Muscular fitness, in general, showed negative trends, with some exceptions: during the post-2010 period, children were mostly experiencing the improvement of isometric strength of the upper body. The neuromuscular components of physical fitness showed positive trends, especially in girls. Cardiorespiratory fitness has been declining in all age groups until the last decade, with the largest decreases occurring before 2000. In the last decade, the trends reversed. The flexibility indicator revealed the largest differences between boys and girls, with boys mainly experiencing negative and girls mostly positive trends. The variability of the test scores mostly increased during the study period. This increasing variance suggests that-despite generally favourable trends in the last decade-children in Slovenia have been facing increasing inequalities in their development, which can potentially lead to future inequalities in health.

An investigation of penalization and data augmentation to improve convergence of generalized estimating equations for clustered binary outcomes.

BACKGROUND: In binary logistic regression data are 'separable' if there exists a linear combination of explanatory variables which perfectly predicts the observed outcome, leading to non-existence of some of the maximum likelihood coefficient estimates. A popular solution to obtain finite estimates even with separable data is Firth's logistic regression (FL), which was originally proposed to reduce the bias in coefficient estimates. The question of convergence becomes more involved when analyzing clustered data as frequently encountered in clinical research, e.g. data collected in several study centers or when individuals contribute multiple observations, using marginal logistic regression models fitted by generalized estimating equations (GEE). From our experience we suspect that separable data are a sufficient, but not a necessary condition for non-convergence of GEE. Thus, we expect that generalizations of approaches that can handle separable uncorrelated data may reduce but not fully remove the non-convergence issues of GEE. METHODS: We investigate one recently proposed and two new extensions of FL to GEE. With 'penalized GEE' the GEE are treated as score equations, i.e. as derivatives of a log-likelihood set to zero, which are then modified as in FL. We introduce two approaches motivated by the equivalence of FL and maximum likelihood estimation with iteratively augmented data. Specifically, we consider fully iterated and single-step versions of this 'augmented GEE' approach. We compare the three approaches with respect to convergence behavior, practical applicability and performance using simulated data and a real data example. RESULTS: Our simulations indicate that all three extensions of FL to GEE substantially improve convergence compared to ordinary GEE, while showing a similar or even better performance in terms of accuracy of coefficient estimates and predictions. Penalized GEE often slightly outperforms the augmented GEE approaches, but this comes at the cost of a higher burden of implementation. CONCLUSIONS: When fitting marginal logistic regression models using GEE on sparse data we recommend to apply penalized GEE if one has access to a suitable software implementation and single-step augmented GEE otherwise.

Effectiveness of Ultrasound-Guided Canal Adductor Blockade for Chronic Pain and Functioning in Knee Osteoarthritis: A Prospective Longitudinal Observational Study.

METHODS: Seventy-seven patients with chronic knee osteoarthritis pain received ultrasound-guided ACB with 14 ml 0.25% levobupivacaine and 100 mcg clonidine. At baseline and 1 month after the blockade, we assessed maximal and minimal pain intensity in the knee using a numeric rating scale (NRS) and the Knee Injury and Osteoarthritis Outcome Score (KOOS). The range of motion in extension and flexion (ROMext and ROMflex) and quadriceps muscle strength of both knees (QS), Timed Up and Go Test (TUG), and 30-Second Chair Stand Test (30CST) results were determined at baseline, 1 hour, 1 week, and 1 month after the blockade. RESULTS: ACB with levobupivacaine and clonidine appeared to decrease pain severity (NRSmax 8.13 to 4.2, p < 0.001 and NRSmin 3.32 to 1.40, p < 0.001). Similarly, knee ROMext decreased from 3.90 preintervention to 2.89 postintervention at 1 month, p < 0.001; ROMflex decreased from 5.70 to 3.29, p < 0.001; TUG time decreased from 3.22 to 2.93, <0.001; QS increased from 18.43 to 22.77, p < 0.001; CST increased from 8.23 to 10.74, p < 0.001. The KOOS for pain (36.40 to 58.34), symptoms (52.55 to 64.32), activities of daily living functions (ADLs, 36.36 to 60.77), and quality of life (QoL, 17.87 to 30.97) also increased, all p < 0.001. CONCLUSION: ACB appeared to decrease pain and increase ambulation. If our preliminary results are reproducible in a planned randomized controlled trial, ACB could be a useful adjunctive pain therapy in patients with disabling pain due to knee OA.

Effect of intrabronchial administration of autologous adipose-derived mesenchymal stem cells on severe equine asthma.

BACKGROUND: Severe equine asthma (SEA) is a common chronic respiratory disease and a significant health and well-being problem in horses. Current therapeutic strategies improve pulmonary function and clinical signs in some horses, but in the long-term, return to full athletic function appears to be rare. The aim of this study was to assess the safety and the effect of intrabronchial administration of adipose-derived mesenchymal stem cells (AD-MSC) on pulmonary inflammatory and clinical parameters in horses with SEA. METHODS: This was a randomized controlled trial. Twenty adult horses diagnosed with SEA were randomly divided into two groups (n = 10), and treated either with a single intrabronchial application of autologous AD-MSC or oral dexamethasone for three weeks. A targeted clinical examination with determination of clinical score, maximal change in pleural pressure during the breathing cycle, and an endoscopic examination of the airways were performed at baseline and three weeks after treatment. Bronchoalveolar lavage fluid was analyzed cytologically, and IL-1ß, IL-4, IL-8, IL-17, TNFα and IFNγ mRNA and protein concentrations were measured at baseline and three weeks. The horses were then monitored over one year for recurrence of SEA. A non-inferiority analysis and a linear mixed-effects model were performed to assess differences between treatments. RESULTS: The non-inferiority of AD-MSC treatment was not established. However, AD-MSC administration significantly ameliorated the clinical score (P = 0.01), decreased the expression of IL-17 mRNA (P = 0.05) and IL-1ß (P ≤ 0.001), IL-4 (P ≤ 0.001), TNFα (P = 0.02) protein levels, and had a positive long-term effect on SEA-associated clinical signs (P = 0.02). CONCLUSIONS: Intrabronchial administration of AD-MSC had limited short-term anti-inflammatory effects but improved the clinical signs of SEA at one year.

Are we underestimating the impact of COVID-19 on children's physical activity in Europe?-a study of 24 302 children.

This repeat cross-sectional study investigated the impact of lockdown in Europe in Winter (January and February 2021) on children's and adolescent's physical activity (PA) and recreational screen time (RST), and compared PA to the lockdown in Spring 2020. An online survey was administered (n = 24 302; 6-18 years; 51.7% boys) in nine countries. PA and RST were assessed by 7-day recall. In total, 9.3% of children (95% confidence interval: 6.9-11.7) met WHO PA recommendation, which was half of the proportion observed in Spring 2020 [19.0% (18.2-19.9)]. Sixty percent exceeded the RST recommendations. This suggests that winter lockdown could have a more negative impact on PA than in spring.

Individualised screening of diabetic foot: creation of a prediction model based on penalised regression and assessment of theoretical efficacy.

AIMS/HYPOTHESIS: A large proportion of people with diabetes do not receive proper foot screening due to insufficiencies in healthcare systems. Introducing an effective risk prediction model into the screening protocol would potentially reduce the required screening frequency for those considered at low risk for diabetic foot complications. The main aim of the study was to investigate the value of individualised risk assignment for foot complications for optimisation of screening. METHODS: From 2015 to 2020, 11,878 routine follow-up foot investigations were performed in the tertiary diabetes clinic. From these, 4282 screening investigations with complete data containing all of 18 designated variables collected at regular clinical and foot screening visits were selected for the study sample. Penalised logistic regression models for the prediction of loss of protective sensation (LOPS) and loss of peripheral pulses (LPP) were developed and evaluated. RESULTS: Using leave-one-out cross validation (LOOCV), the penalised regression model showed an AUC of 0.84 (95% CI 0.82, 0.85) for prediction of LOPS and 0.80 (95% CI 0.78, 0.83) for prediction of LPP. Calibration analysis (based on LOOCV) presented consistent recall of probabilities, with a Brier score of 0.08 (intercept 0.01 [95% CI -0.09, 0.12], slope 1.00 [95% CI 0.92, 1.09]) for LOPS and a Brier score of 0.05 (intercept 0.01 [95% CI -0.12, 0.14], slope 1.09 [95% CI 0.95, 1.22]) for LPP. In a hypothetical follow-up period of 2 years, the regular screening interval was increased from 1 year to 2 years for individuals at low risk. In individuals with an International Working Group on the Diabetic Foot (IWGDF) risk 0, we could show a 40.5% reduction in the absolute number of screening examinations (3614 instead of 6074 screenings) when a 10% risk cut-off was used and a 26.5% reduction (4463 instead of 6074 screenings) when the risk cut-off was set to 5%. CONCLUSIONS/INTERPRETATION: Enhancement of the protocol for diabetic foot screening by inclusion of a prediction model allows differentiation of individuals with diabetes based on the likelihood of complications. This could potentially reduce the number of screenings needed in those considered at low risk of diabetic foot complications. The proposed model requires further refinement and external validation, but it shows the potential for improving compliance with screening guidelines.

Physical activity, screen time and the COVID-19 school closures in Europe - An observational study in 10 countries.

To date, few data on how the COVID-19 pandemic and restrictions affected children's physical activity in Europe have been published. This study examined the prevalence and correlates of physical activity and screen time from a large sample of European children during the COVID-19 pandemic to inform strategies and provide adequate mitigation measures. An online survey was conducted using convenience sampling from 15 May to 22 June, 2020. Parents were eligible if they resided in one of the survey countries and their children aged 6-18 years. 8395 children were included (median age [IQR], 13 [10-15] years; 47% boys; 57.6% urban residents; 15.5% in self-isolation). Approximately two-thirds followed structured routines (66.4% [95%CI, 65.4-67.4]), and more than half were active during online P.E. (56.6% [95%CI, 55.5-57.6]). 19.0% (95%CI, 18.2-19.9) met the WHO Global physical activity recommendation. Total screen time in excess of 2 h/day was highly prevalent (weekdays: 69.5% [95%CI, 68.5-70.5]; weekend: 63.8% [95%CI, 62.7-64.8]). Playing outdoors more than 2 h/day, following a daily routine and being active in online P.E. increased the odds of healthy levels of physical activity and screen time, particularly in mildly affected countries. In severely affected countries, online P.E. contributed most to meet screen time recommendation, whereas outdoor play was most important for adequate physical activity. Promoting safe and responsible outdoor activities, safeguarding P.E. lessons during distance learning and setting pre-planned, consistent daily routines are important in helping children maintain healthy active lifestyle in pandemic situation. These factors should be prioritised by policymakers, schools and parents. HighlightsTo our knowledge, our data provide the first multi-national estimates on physical activity and total screen time in European children roughly two months after COVID-19 was declared a global pandemic.Only 1 in 5 children met the WHO Global physical activity recommendations.Under pandemic conditions, parents should set pre-planned, consistent daily routines and integrate at least 2-hours outdoor activities into the daily schedule, preferable on each day. Schools should make P.E. lessons a priority. Decision makers should mandate online P.E. be delivered by schools during distance learning. Closing outdoor facilities for PA should be considered only as the last resort during lockdowns.

Association between statin use and clinical course, microbiologic characteristics, and long-term outcome of early Lyme borreliosis. A post hoc analysis of prospective clinical trials of adult patients with erythema migrans.

BACKGROUND: Statins were shown to inhibit borrelial growth in vitro and promote clearance of spirochetes in a murine model of Lyme borreliosis (LB). We investigated the impact of statin use in patients with early LB. METHODS: In this post-hoc analysis, the association between statin use and clinical and microbiologic characteristics was investigated in 1520 adult patients with early LB manifesting as erythema migrans (EM), enrolled prospectively in several clinical trials between June 2006 and October 2019 at a single-center university hospital. Patients were assessed at enrollment and followed for 12 months. RESULTS: Statin users were older than patients not using statins, but statin use was not associated with Borrelia seropositivity rate, Borrelia skin culture positivity rate, or disease severity as assessed by erythema size or the presence of LB-associated symptoms. The time to resolution of EM was comparable in both groups. The odds for incomplete recovery decreased with time from enrollment, were higher in women, in patients with multiple EM, and in those reporting LB-associated symptoms at enrollment, but were unaffected by statin use. CONCLUSION: Statin use was not associated with clinical and microbiologic characteristics or long-term outcome in early LB.

High Seroprevalence of Toxoplasma gondii in Slovenian Wild Boars (Sus scrofa).

Toxoplasma gondii is a zoonotic parasite of great public health concern. Wild boars could be considered an emerging source of toxoplasmosis in humans due to the popularity of venison and their increasing population. The aim of this study was to determine the seroprevalence of T. gondii in the Slovenian wild boar population and evaluate risk factors for human infection. Of 353 samples, 62% were positive for T. gondii using ELISA tests. This is the highest T. gondii seroprevalence reported to date in wild boar worldwide. The increase in prevalence with increasing age (p = 0.003) and weight (p = 0.002) were statistically significant, whereas gender was not (p = 0.781). Odds for being T. gondii-positive increased with age with the largest difference being between 2-3-year-old and 1-2-year-old animals (OR = 2.66, 95%CI: 1.03-6.85). Animals weighing 20-40 kg had a higher risk than animals weighing 0-20 kg (OR = 2.74, 95%CI: 1.21-6.20), whereas a further increase in the weight was not associated with increasing the odds. Due to the high Toxoplasma prevalence, the study concluded that the risk of exposure to T. gondii from handling raw or undercooked wild boar meat is high. Surveillance protocols should be established at the national level together with increased awareness within the hunting community.