School Well-Being and Academic Performance of Children With Juvenile Idiopathic Arthritis: A National Register-Based Study.

OBJECTIVE: We aimed to investigate how school well-being (SWB) and academic performance of children with juvenile idiopathic arthritis (JIA) compare to their peers on a national level using the Danish national registers. Further, we investigated the potential influence of socioeconomic status (SES). METHODS: A population-wide, register-based, cross-sectional study was performed. We compared the results of children with and without JIA in the Danish National Well-Being Questionnaire (DNWQ), the National Danish School Testing (NDST), and their ninth grade (aged approximately 16 yrs) final school marks in Danish and mathematics. The results were analyzed using adjusted ordinal logistic regression (SWB) and linear regression (tests and marks). RESULTS: In separate cohorts, we included a total of 505,340 children answering the DNWQ, 812,461 children with NDST results, and the ninth-grade final marks of 581,804 children. Of these children, 1042, 1541, and 1410, respectively, fulfilled the criteria of JIA. Children with JIA reported SWB comparable to their peers, except for the question "Do you perform well in school?" (odds ratio 0.89, 95% CI 0.81-0.99). In the NDST, the children with JIA in general did just as well as their peers. We found no differences in the ninth-grade final marks in either Danish or mathematics. Stratifying the analyses on SES showed no significant differences in the associations. CONCLUSION: Overall, children with JIA report SWB comparable to that of children without JIA and perform equally well in school as children without JIA.

Assessing Competencies, Needs, and Satisfaction With the Transition From Pediatric to Adult Health Care in Rheumatology: Development and Validation of the Transition-KompAZ.

OBJECTIVE: The aim of this study was to develop and psychometrically validate a self-report instrument to assess (1) competencies, (2) needs, and (3) satisfaction among youth transitioning from pediatric to adult rheumatology. METHODS: The Transition-KompAZ was developed in several steps with conceptual and psychometric analyses. To test its psychometric properties, the instrument was administered to adolescents and young adults (AYAs; 16-25 years) with inflammatory rheumatic diseases before (group 1) or after (group 2) transfer to adult rheumatology. A 2-factor, higher-order confirmatory factor analysis (CFA) model was applied to test the hypothesized factor structure. Internal consistency was estimated using the approach of Raykov with the factor loadings and error variances estimated in the CFA. Spearman rank correlation coefficients were used to assess construct validity. RESULTS: The Transition-KompAZ includes the following modules: (1) competencies in transition (knowledge, self-management), (2) needs (healthcare services, information), and (3) satisfaction (general, transitional care). A total of 173 AYAs (group 1: n = 86; group 2: n = 87) from 12 rheumatology sites completed the Transition-KompAZ. It showed good model fit (comparative fit index > 0.9; Tucker-Lewis index > 0.9; weighted root mean square residual < 0.9) with good internal consistency. The instrument demonstrated moderate-to-good construct validity and good test-retest reliability. CONCLUSION: The Transition-KompAZ appears to be a reliable tool for assessing important dimensions of transition. It may support a structured and individualized transition, as well as the evaluation of transition services. However, further studies are required to assess its predictive value in terms of transfer readiness and successful transition.

Mental comorbidities in adolescents and young adults with juvenile idiopathic arthritis: an analysis of German nationwide health insurance data.

BACKGROUND: Studies on prevalence rates of mental comorbidities in patients with juvenile idiopathic arthritis (JIA) have reported varying results and provided limited information on related drugs. The purpose of this study was to determine the prevalence of selected mental health diagnoses and the range of associated drug prescriptions among adolescents and young adults (AYA) with JIA compared with general population controls. FINDINGS: Nationwide statutory health insurance data of the years 2020 and 2021 were used. Individuals aged 12 to 20 years with an ICD-10-GM diagnosis of JIA in ≥ 2quarters, treated with disease-modifying antirheumatic drugs and/or glucocorticoids were included. The frequency of selected mental health diagnoses (depression, anxiety, emotional and adjustment disorders) was determined and compared with age- and sex-matched controls. Antirheumatic, psychopharmacologic, psychiatric, and psychotherapeutic therapies were identified by Anatomical Therapeutic Chemical (ATC) codes and specialty numbers. Based on data from 628 AYA with JIA and 6270 controls, 15.3% vs. 8.2% had a diagnosed mental health condition, with 68% vs. 65% receiving related drugs and/or psychotherapy. In both groups, depression diagnosis became more common in older teenagers, whereas emotional disorders declined. Females with and without JIA were more likely to have a mental health diagnosis than males. Among AYA with any psychiatric diagnosis, 5.2% (JIA) vs. 7.0% (controls) received psycholeptics, and 25% vs. 27.3% psychoanaleptics. CONCLUSIONS: Selected mental health conditions among 12-20-year-old JIA patients are diagnosed more frequently compared to general population. They tend to occur more frequently among females and later in childhood. They are treated similarly among AYA regardless of the presence of JIA.

Optimized Treatment of Interleukin (IL-1)-Mediated Autoinflammatory Diseases: Impact of Disease Activity-Based Treatment Adjustments.

Background: Effective control of disease activity in Interleukin-1 autoinflammatory diseases (IL-1 AID) is crucial to prevent damage. The aim was to longitudinally analyze the impact of protocolized disease activity-based treatment adjustments in a real-life cohort. Methods: A single-center study of consecutive children with IL-1 AID followed between January 2016 and December 2019 was performed. Demographics, phenotypes, genotypes, inflammatory markers, physician (PGA), and patient/parent (PPGA) global assessment were captured. Disease activity and treatment changes were assessed. The impact of distinct parameters on disease activity trajectories was analyzed. Results: A total of 56 children were included, median follow-up was 2.1 years reflecting 361 visits. Familial Mediterranean Fever was the most common IL-1 AID. At the first visit, 68% of the patients had moderate/severe disease activity. Disease activity-based treatment adjustments were required in 28/56 children (50%). At last follow-up, 79% had a well-controlled disease. Both PGA and PPGA decreased significantly over time (p < 0.001; p < 0.017, respectively), however, both differed statistically at last visit (p < 0.001). Only PGA showed a significant estimated mean decrease across all IL-1 AID over time. Conclusions: Disease activity-based treatment adjustments can effectively refine treat-to-target strategies, enable personalized precision health approaches, and improve outcomes in children with IL-1 AID.

Varicose vein surgery after acute isolated superficial vein thrombosis in daily practice: INSIGHTS-SVT study.

OBJECTIVE: The aim of this study was to assess the utilization of surgical interventions in patients diagnosed with superficial vein thrombosis (SVT) and its potential association with the occurrence of venous thromboembolism (VTE) and bleeding events. METHODS: INSIGHTS-SVT, a prospective, non-interventional, multicenter study in Germany, investigated the management and outcomes of patients with acute SVT who received conservative and/or invasive treatments at the discretion of the treating physician. RESULTS: Among the 872 patients with 12-month data, 657 had medical therapy only, and 215 patients underwent vascular surgery (70 within 3 months of SVT diagnosis, 136 between months 4 and 12, and nine had an intervention in both periods). The most commonly performed procedures included endovenous thermal ablation, ligation of the saphenofemoral or saphenopopliteal junction, and vein stripping. The primary outcome of symptomatic VTE was observed in 5.8% of conservatively treated patients and 6.3% of those who underwent surgical intervention. Additionally, the secondary outcome of recurrent or extended SVT was documented in 4.7% of conservatively treated patients and 5.3% of invasively treated patients. Bleeding events occurred in 1.4% of conservatively treated patients and 2.1% of surgically treated patients. These differences were statistically not significant. Furthermore, our analysis indicated a potential protective effect associated with surgical treatments, such as ligation of the saphenofemoral or saphenopopliteal junction, stripping and endovenous thermal ablation, concerning the endpoint of VTE for patients when applied after 3 months from the index SVT event. CONCLUSIONS: In line with previous research, our study suggests that surgical interventions are not frequently employed in the management of SVT, although they may be warranted in select cases. Nevertheless, additional research is essential to gain a deeper understanding of the indications, criteria, and benefit of surgical interventions in the treatment of SVT.

Risk perception, well-being, depression and anxiety in children and adolescents with rheumatic diseases during the COVID-19 pandemic - results from the prospective multicenter KICK-COVID study in Germany.

OBJECTIVE: To investigate the psychosocial burden in children and adolescents with juvenile rheumatic diseases during the COVID-19 pandemic. METHODS: As part of the multicentre observational KICK-COVID study linked to the National Pediatric Rheumatology Database, adolescents < 21 years and parents of children < 12 years with rheumatic diseases answered questions on perceptions of health risk (PHR) due to SARS-CoV2, stress, well-being (WHO-5) and symptoms of depression (PHQ-9) and anxiety (GAD-7). Data were collected at routine visits from June to December 2021 and assessed for association with demographic and clinical parameters, treatment and patient-reported outcomes by multivariable regression analyses. RESULTS: Data from 1356 individuals (69% female, 50% adolescents) were included. Median PHR on a numeric rating scale (NRS, 0-10) was 4 (IQR 2-6), median perceived stress was 3 (IQR 1-6). Adolescents reported a worse well-being with a significantly lower median WHO-5-score (60, IQR 40-76) than parents reported for their children < 12 years (80, IQR 68-84). Moderate to severe symptoms of depression and anxiety were reported by 14.3% and 12.3% of the adolescents, respectively. PHR was significantly higher in patients with systemic lupus erythematosus, methotrexate or biologic disease-modifying anti-rheumatic drug therapy than in patients without these characteristics, whereas lower WHO-5 or higher PHQ-9 or GAD-7 scores were only associated with poorer patient-reported health status and physical functioning. CONCLUSION: The perception of health risk due to SARS-CoV2 infection was not paralleled by an impairment of mental health, which were, however, significantly correlated with self-rated health status and functional capacity, highlighting the importance of patient-reported outcome assessment. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), no. DRKS00027974. Registered on 27th of January 2022.

Level and correlates of physical activity among children and adolescents with juvenile idiopathic arthritis compared to controls: results from a German nationwide prospective observational cohort study.

BACKGROUND: Physical active lifestyles are essential throughout growth and maturation and may offer potential preventive and therapeutic benefit in patients with juvenile idiopathic arthritis (JIA). Insufficient physical activity (PA), in contrast, can lead to aggravation of disease-related symptoms. This study aimed to i) examine PA levels in children and adolescents with JIA compared to general population controls and ii) investigate correlates of pronounced physical inactivity in order to identify risk groups for sedentary behaviour. METHODS: Data from children and adolescents with JIA and population controls aged 3 to 17 years documented in the National Pediatric Rheumatologic Database (NPRD) and the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) were used. Self-reported PA was collected from parents/guardians of children up to 11 years of age or adolescents 12 years of age and older. To compare PA-related data, age- and sex-specific pairwise analyses were conducted considering NPRD/KiGGS participants' data from 2017. Correlates of physical inactivity among patients were identified using a linear regression model. RESULTS: Data of 6,297 matched-pairs (mean age 11.2 ± 4.2 years, female 67%, patients' disease duration 4.5 ± 3.7 years, persistent oligoarthritis 43%) were available for evaluation. Almost 36% of patients aged 3-17 years (vs. 20% of controls) achieved the WHO recommended amount of PA, while PA steadily decreased with age (18% of patients aged ≥ 12 years) and varied between JIA categories. Female adolescents and patients with enthesitis-related arthritis were least likely to achieve the minimum recommended level of PA. Physical inactivity was associated with female sex, higher age at disease onset, longer disease duration, more functional disability (C-HAQ) and higher disease activity (cJADAS-10). CONCLUSIONS: Depending on JIA category, children and adolescents with JIA were similarly or even more likely to achieve the WHO recommended minimum level of PA compared to general population controls. However, since a large proportion of young JIA patients appear to be insufficiently physically active, engagement in targeted efforts to promote PA is urgently needed.

Cholesterol crystals at the culprit lesion in patients with acute coronary syndrome are associated with worse cardiovascular outcomes at two years follow up - results from the translational OPTICO-ACS study program.

BACKGROUND: Cholesterol crystals (CCs) represent a feature of advanced atherosclerotic plaque and may be assessed by optical coherence tomography (OCT). Their impact on cardiovascular outcomes in patients presenting with acute coronary syndromes (ACS) is yet unknown. METHODS: The culprit lesion (CL) of 346 ACS-patients undergoing preintervention OCT imaging were screened for the presence of CCs and divided into two groups accordingly. The primary end-point was the rate of major adverse cardiac events plus (MACE+) consisting of cardiac death, myocardial infarction, target vessel revascularization and re-hospitalization due to unstable or progressive angina at two years. RESULTS: Among 346 patients, 57.2% presented with CCs at the CL. Patients with CCs exhibited a higher prevalence of ruptured fibrous caps (RFC-ACS) (79.8% vs. 56.8%; p < 0.001) and other high-risk features such as thin cap fibroatheroma (80.8% vs. 64.9%; p = 0.001), presence of macrophages (99.0% vs. 85.1%; p < 0.001) as well as a greater maximum lipid arc (294.0° vs. 259.3°; p < 0.001) at the CL as compared to patients without CCs. MACE+ at two years follow-up occurred more often in CC-patients (29.2% vs. 16.1%; p = 0.006) as compared to patients without CCs at the culprit site. Multivariable cox regression analysis identified CCs as independent predictor of MACE+ (HR 1.705; 1.025-2.838 CI, p = 0.040). CONCLUSIONS: CCs were associated with conventional high-risk plaque features and associated with increased MACE+-rates at two years follow up. The identification of CCs might be useful as prognostic marker in patients with ACS and assist "precision prevention" in the future.

Uncovering the hidden socioeconomic impact of juvenile idiopathic arthritis and paving the way for other rare childhood diseases: an international, cross-disciplinary, patient-centered approach (PAVE Consortium).

BACKGROUND: Juvenile idiopathic arthritis (JIA) refers to a heterogeneous group of rheumatic conditions in children. Novel drugs have greatly improved disease outcomes; however, outcomes are impacted by limited awareness of the importance of early diagnosis and adequate treatment, and by differences in access across health systems. As a result, patients with JIA continue to be at risk for short- and long-term morbidity, as well as impacts on virtually all aspects of life of the child and family. MAIN BODY: Literature on the socioeconomic burden of JIA is largely focused on healthcare costs, and the impact of JIA on patients, families, and communities is not well understood. High quality evidence on the impact of JIA is needed to ensure that patients are receiving necessary support, timely diagnostics, and adequate treatment, and to inform decision making and resource allocation. This commentary introduces the European Joint Programme on Rare Diseases: Producing an Arthritis Value Framework with Economic Evidence: Paving the Way for Rare Childhood Diseases (PAVE) project, which will co-develop a patient-informed value framework to measure the impact of JIA on individuals and on society. With a patient-centered approach, fundamental to PAVE is the involvement of three patient advocacy organizations from Canada, Israel, and Europe, as active research partners co-designing all project phases and ensuring robust patient and family engagement. The framework will build on the findings of projects from six countries: Canada, Germany, Switzerland, Spain, Israel, and Belgium, exploring costs, outcomes (health, well-being), and unmet needs (uveitis, mental health, equity). CONCLUSION: This unique international collaboration will combine evidence on costs (from family to societal), outcomes (clinical, patient and family outcomes), and unmet needs, to co-design and build a framework with patients and families to capture the full impact of JIA. The framework will support the development of high-quality evidence, encompassing economic and clinical considerations, unmet needs, and patient perspectives, to inform equitable resource allocation, health system planning, and quality of care better aligned with the needs of children with JIA, their families, and communities. Knowledge gained from this novel approach may pave the way forward to be applied more broadly to other rare childhood diseases.

Anxiety and depression symptoms in adolescents and young adults with juvenile idiopathic arthritis: results of an outpatient screening.

BACKGROUND: Previous studies have shown that growing up with rheumatic conditions can fuel dissatisfaction and psychological distress, which in turn affects disease self-management and treatment adherence. Primary objective of this study was to estimate the prevalence of anxiety and depression symptoms in adolescents and young adults (AYA) with juvenile idiopathic arthritis (JIA) and to identify correlates of conspicuous screening results. METHODS: Initiated as part of the COACH multicenter observational study, outpatients aged 12 to 21 years participating in the National Pediatric Rheumatological Database (NPRD) were prospectively screened for mental health using the Patient Health Questionnaire-9 (PHQ-9) and the Generalised Anxiety Disorder Scale-7 (GAD-7). RESULTS: Data from 1,150 adolescents with JIA (mean age 15.6 ± 2.2 years; mean disease duration 7.2 ± 4.9 years, 69% female, 43% oligoarthritis, 26% polyarthritis) were analysed. Overall, 32.7% (n = 316) of AYA showed conspicuous screening results, of whom 30.4% reported clinically relevant suicidal or self-harm thoughts. About 19% of screened patients showed moderate to severe depressive or anxious symptoms. AYA with conspicuous screening results were older (15.8 vs. 15.2 years; p < 0.0001), more often female (81% vs. 64%; p < 0.0001) and more often overweight (25% vs. 17%; p = 0.006). They had higher disease activity (physician global assessment on NRS 0-10; 1.7 vs. 1.2; p < 0.0001), more functional limitations (CHAQ; 0.44 vs. 0.14; <0.0001) and rated their health status worse (NRS 0-10; 3.5 vs. 1.8; p < 0.0001) than AYA with inconspicuous screening results. Females (OR 2.33 [CI 1.53-3.56]; p < 0.0001), older age (OR 1.09 [CI 1.01-1.18]; p = 0.026), patients with more functional limitations (OR 3.36 [CI 1.98-5.72]; p < 0.0001), and patients with worse subjective health status (OR 1.17 [CI 1.07-1.27]; p < 0.0001) were more likely to have a conspicuous screening result. Regular sports participation was associated with a lower likelihood of conspicuous screening result (OR 0.69 [CI 0.49-0.98]; p = 0.039). CONCLUSIONS: A large-scale outpatient screening of AYA with JIA in Germany shows a high prevalence of anxiety and depression symptoms. The need for routine screening for early detection of mental health problems became apparent.

Medida de troponina en circulación mediante un ensayo sensible para la evaluación del riesgo cardiovascular en prevención primaria / Circulating troponin as measured by a sensitive assay for cardiovascular risk assessment in primary prevention / Medição da troponina circulante por um teste sensível para a avaliação de risco cardiovascular na prevenção primária

Background: Measuring circulating cardiac troponin using novel sensitive assays has revealed that even minute elevations are associated with increased mortality in patients with coronary artery disease or even in the general population. Less well defined, however, is the incremental value of measuring circulating cardiac troponin I (cTnI) by a sensitive assay for risk assessment in primary prevention. Methods: We measured circulating concentrations of cTnI, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hsCRP) in 5388 individuals free of known cardiovascular disease recruited into the DETECT study, a prospective longitudinal population-based cohort study. We determined the prognostic implications for incident major adverse cardio­vascular events (MACE) during 5 years of follow-up. Results: Circulating cTnI was detectable in 19% of the subjects. Increased cTnI concentrations were associated with established risk factors for atherosclerosis and demonstrated a graded relationship with all-cause mortality and incident MACE during 5-year follow-up. A single measurement of cTnI significantly improved risk prediction over established risk factors, and also added prognostic information, when adjusted for serum concentrations of NT-proBNP and hsCRP. Conclusions: Minute increases in cTnI are associated with increased mortality and incident MACE in a large primary prevention cohort and, thus, identify contributors to cardiovascular risk not fully captured by traditional risk factor assessment.

Antecedentes: La medición de troponina cardíaca en circulación mediante nuevos ensayos sensibles ha revelado que incluso mínimas elevaciones se asocian con mayor mortalidad en pacientes con enfermedad arterial coronaria, o incluso en la población general. Sin embargo, menos conocido es el valor incremental o agregado de la medición de la troponina I cardiaca (cTnI) circulante mediante un ensayo sensible para la evaluación del riesgo en prevención primaria. Métodos: Se midieron las concentraciones circulantes de cTnI, de pro- péptido natriurético tipo B N-terminal (NT-proBNP), y de proteína C reactiva de alta sensibilidad (PCRus), en 5388 personas sin enfermedad cardiovascular conocida reclutadas en el estudio DETECT, un estudio prospectivo longitudinal de cohorte de base poblacional. Se determinaron las implicancias pronósticas en la incidencia de eventos adversos cardiovasculares mayores (MACE) durante 5 años de seguimiento. Resultados: La cTnI se detectó en el 19% de los sujetos. El aumento de las concentraciones de cTnI se asoció con factores de riesgo establecidos para la aterosclerosis y demostró una relación gradual con la mortalidad por todas las causas y la incidencia de MACE durante los 5 años de seguimiento. Una sola medición de cTnI mejoró significativamente la predicción del riesgo por encima de los factores de riesgo establecidos, y también agregó información pronóstica cuando se ajustó por la concentración sérica de NT-proBNP y PCRus. Conclusiones: Mínimos incrementos de cTnI se asociaron con mayor mortalidad e incidencia de MACE en una gran cohorte de prevención primaria y, por tanto, la identificación de sujetos con riesgo cardiovascular no siempre son detectados completamente por la evaluación de factores de riesgo tradicionales.