[Protocols in pediatric rheumatology (PROKIND): treat-to-target in polyarticular juvenile idiopathic arthritis]. / Protokolle in der Kinderrheumatologie (PROKIND): Treat-to-Target bei polyartikulärer juveniler idiopathischer Arthritis.

BACKGROUND: The aims of the PROKIND protocols are improvement and harmonization of the diagnostics, monitoring, treatment decision and prognosis. MATERIAL AND METHODS: This article reports the results of a prospective treat-to-target observational study of patients with polyarticular juvenile idiopathic arthritis (JIA) during the first year of treatment. Disease activity was assessed with the 10-joint juvenile arthritis disease activity score (JADAS-10), functional limitation with the childhood health assessment questionnaire disability index (CHAQ-DI) and with information on overall well-being, on pain, on fatigue and on global estimation of disease activity. RESULTS: Overall, 129 patients with polyarticular JIA (rheumatoid factor, RF, positive (+) polyarthritis n = 22, RF negative (-) polyarthritis n = 133 from 23 pediatric rheumatology institutions in Germany and Austria were recruited. Patients with initial treatment with methotrexate formed cohort 1, patients with additional repeated intravenous corticosteroid pulse therapy formed cohort 2 and patients with concomitant intra-articular corticosteroid administration in at least 5 joints formed cohort 3. The mean JADAS10 showed a decrease in disease activity from 16.4 ± 6.1 to 2.8 ± 3.6 and the decrease in the CHAQ-DI from 1.0 ± 0.8 to 0.3 ± 0.5 showed the improvement in functional capacity. Similarly, improvements in quality of life, pain and fatigue were demonstrable. A JADAS inactive disease was achieved by 18.1% at month 3, 47.7% at month 6 and 66.7% at month 12. In cohort 1 a JADAS remission was achieved by 72.4%, by 50% in cohort 2 and by 69.2% in cohort 3. An escalation to treatment with biologics was necessary in 38% of patients in cohort 1, 60% in cohort 2 and 46% in cohort 3. CONCLUSION: Using a treat-to-target approach a dramatic improvement in disease activity, functional capacity and quality of life in polyarticular JIA could be achieved. Even after 12 months an inactive disease was achieved in the majority of cases.

Performance of commercial SARS-CoV-2 wild-type and Omicron BA.1 antibody assays compared with pseudovirus neutralization tests.

BACKGROUND: Commercially available ELISA-based antibody tests are used to approximate vaccination success against SARS-CoV-2 in at-risk patients, but it is unclear whether they correlate with neutralization of the Omicron variant. METHODS: 269 serum samples of a cohort of 44 non-immunosuppressed participants and 65 MTX-treated rheumatic patients taken before and after COVID-19 booster vaccinations were measured using COVID-19 antibody testing systems with wild-type and Omicron BA.1 antigens developed by three different manufacturers (surrogate virus neutralization test cPass, and binding antibody tests QuantiVac and SeraSpot), as well as with a pseudovirus neutralization test (pVNT). The pVNT was considered the gold standard for determining the presence and level of anti-SARS-CoV-2 antibodies. RESULTS: All three wild-type ELISAs showed excellent test performance compared with wild-type neutralization in pVNT. However, out of 56 samples without Omicron BA.1 neutralization in pVNT, 71.4% showed positive results in at least one and 28.6% in all three wild-type ELISAs at the manufacturer-defined cut-offs. Omicron ELISAs showed either decreased specificity (57.1% and 55.4% for binding ELISAs) or sensitivity (51.2% in cPass) compared to Omicron neutralization in pVNT. The proportion of any false positive results among all samples decreased from 26.5% before to 3.2% after booster vaccination, however binding antibody test specificities remained below 70%. CONCLUSIONS: We found a poorer test performance of new Omicron antibody test systems compared to wild-type tests in detecting neutralizing antibodies against the corresponding SARS-CoV-2 variants. Decisions for booster vaccination or passive immunization of at-risk patients should not be based solely on antibody test results.

Manifestation and staging of arthropathy in cystic fibrosis. Defining different stages of cystic fibrosis arthropathy using ultrasound imaging and clinical scoring.

BACKGROUND: The true prevalence of cystic fibrosis arthropathy (CFA) remains unclear and may be significantly higher than previously reported. In recent studies, joint symptoms have been reported in up to 30% of adults with CF. This underlines the importance of CFA as a rising and clinically relevant co-morbidity. A clear definition of CFA is yet missing and its pathogenesis remains unclear. We investigated the clinical manifestation of CFA particularly via ultrasound (US) examination to define and implement a staging for clinical assessment. METHODS: In a prospective cohort study between March 2018 and February 2020 a total of 98 consecutively recruited, adult cystic fibrosis (CF) patients underwent joint-US examination according to a newly developed ultrasound score (US-CFA). A clinical assessment including rheumatological scores (DAS28, HAQ) has been conducted as well as a specially designed questionnaire. Investigation on clinical and microbiological data, as well as a comprehensive laboratory analysis, were carried out. Cluster analysis has been performed to detect patterns defining different CFA stages based on disease activity. RESULTS: US imaging has shown a considerable incidence of mild to moderate effusion as sign of joint inflammation/(teno-)synovitis. K-means clustering was used to distinguish 3 different stages of CFA based on the intensity of the detected effusion. These stages showed a significant association with disease activity (DAS28, p = 0.0004) as well as with patient-reported symptoms such as total weeks of CFA per year (p = 0.004), acute CFA (p = 0.015), chronic CFA (p = 0.016), disease burden (p = 0.04). Based on the US-CFA, 16% of patients suffered from severe CFA (II), 51% from intermediate CFA (I) and 33% did not present detectable arthritis. Positive serology for Chlamydophilia pneumoniae (IgA, IgG) and Chlamydia trachomatis (IgA, IgG) significantly correlated with the US-CFA. CONCLUSIONS: The results of this study show that a definition and categorization for the clinical manifestation of CFA can be described through US examination, which is able to detect disease activity concordant with the DAS28 as a validated clinical score on arthritis. Defining these stages will lead to a better understanding of the clinical phenotype of the disease and will optimize diagnosis, therapy and research on CFA in the future.

Monitoring of patients with rheumatoid arthritis by indocyanine green (ICG)-enhanced fluorescence optical imaging treated with anti-TNFα therapy.

BACKGROUND: Fluorescence optical imaging (FOI) enables visualisation of inflammation in both hands in rheumatoid arthritis (RA). OBJECTIVE: To investigate the usefulness of FOI in treatment monitoring under anti-TNFα therapy with certolizumab pegol (CZP) in patients with RA in comparison to clinical and laboratory outcome parameters. METHODS: CZP-naïve patients with RA were eligible for this open-label study with an observational period of 52 weeks. Disease activity was monitored by the clinical score DAS28, tender/swollen joint count (TJC-28/SJC-28) and laboratory outcomes for systemic inflammation (CRP and ESR). FOI results were analysed in three different phases (P1-3) and PrimaVistaMode (PVM) by the FOI activity score (FOIAS). RESULTS: Twenty-eight RA patients (median age 52.5 years, 26 females, thirteen with a history of other biologic therapy) were included. DAS28 (CRP) decreased from moderate disease activity at baseline (median 4.6, IQR 1.8) to low disease activity at week (w)52 (median 2.7, IQR 2.1; p < 0.001). Statistically significant decreases could also be demonstrated for SJC-28 and TJC-28. CRP/ESR were reduced numerically from baseline to w52. FOIAS in P1 (early phase) showed a continuous decrease of enhancement during the course of treatment period: from baseline (median 1.5, IQR 9.3) over w6 (median 1.0, IQR 3.0; p = 0.069), w12 (median 0.5, IQR 3.0; p = 0.171), w24 (n = 27, median 0.0, IQR 3.0; p = 0.004), until w52 (n = 18, median 0.0, IQR 2.8; p = 0.091), which could not be presented for FOIAS in P2, P3 and PVM. CONCLUSION: FOI in P1 appears to be a valuable tool for fast and easy monitoring of treatment response to certolizumab in a clinical setting.

Detection of subclinical skin manifestation in patients with psoriasis and psoriatic arthritis by fluorescence optical imaging.

OBJECTIVES: To investigate the frequency of subclinical skin inflammation in both hands by fluorescence optical imaging (FOI) in patients with psoriasis/psoriatic arthritis (Pso/PsA) vs. rheumatoid arthritis (RA) and healthy individuals, and to correlate these findings with cardiovascular (CV) risk factors. PATIENTS AND METHODS: The FOI scans were analyzed retrospectively to detect clinically invisible skin enhancement (0-3 scale) in both hands without relationship to underlying joints or blood vessels. We further characterized the FOI patterns and sorted the scans into groups based on the assumed diagnosis (Pso/PsA, RA, and healthy controls), which was compared with the physician's diagnosis. Furthermore, the associations between CV risk factors and imaging findings were investigated by regression analyses. RESULTS: We included FOI scans of patients with Pso/PsA (n = 80), RA (n = 78), and healthy controls (n = 25). Subclinical skin enhancement on the back of their hands was more common in Pso/PsA (72.5%) than in RA patients (20.5%) and healthy individuals (28.0%) (p < 0.001). Based on the FOI pattern, the majority of patients with Pso/PsA (72.5%), RA (76.9%), and healthy controls (68.0%) were classified correctly using the physician-based diagnosis as reference (overall agreement of 74%, kappa = 0.57). No CV risk factors except body weight (kg) were associated with subclinical skin enhancement (OR 1.04, 95% CI 1.02-1.06; p < 0.001). CONCLUSION: Subclinical subdermal skin inflammation was common in Pso/PsA patients using FOI. Based on the FOI pattern, most patients with Pso/PsA and were classified with the correct diagnosis. We demonstrated an important influence of the body weight on our FOI results. FOI may be a helpful novel tool to study microcirculation in rheumatic diseases with skin involvement.

Temporomandibular joint involvement in patients with juvenile idiopathic arthritis: a retrospective chart review.

OBJECTIVE: To study the proportion of patients with temporomandibular joint (TMJ) involvement among patients with juvenile idiopathic arthritis (JIA), as well as associated clinical characteristics and signs/symptoms. METHOD: We performed a retrospective chart review on consecutive patients followed in the Hamburg Centre for Paediatric and Adolescent Rheumatology Eilbek between January 2010 and July 2012. TMJ involvement was diagnosed based on clinical examination; a subgroup of patients was also assessed by magnetic resonance imaging (MRI). RESULTS: The study included 2413 patients with JIA (52.1% girls, mean age at JIA onset 9.5 years). The most frequent JIA category was oligoarthritis (46.6%), followed by enthesitis-related arthritis (ERA; 38.1%). TMJ involvement was diagnosed in 843/2413 patients (34.9%) (677 MRI-confirmed, four not MRI-confirmed, no MRI examination in 162). Female gender (p = 0.017), higher number of additional joints with active arthritis (p < 0.001), anti-nuclear antibody (ANA) positivity (p = 0.005), higher age (p = 0.020), and oligoarthritis (persistent and extended; p = 0.043) were significantly associated with TMJ involvement. Human leucocyte antigen-B27-positive patients were less likely to have TMJ involvement (p = 0.023). Pain on palpation and pain while chewing were statistically significantly associated with TMJ involvement (p = 0.008 and p = 0.020, respectively). CONCLUSIONS: Based on our findings, to identify TMJ involvement special attention should be paid to JIA patients with female gender, ANA positivity, and oligoarthritis, as well as those with a higher number of additional joints with active arthritis; and regular examinations of the TMJ should be performed.

The first composite score predicting Digital Ulcers in systemic sclerosis patients using Clinical data, Imaging and Patient history-CIP-DUS.

BACKGROUND: Digital ulcers (DU) present a challenging complication in systemic sclerosis (SSc). The aim of this study was to combine clinical characteristics and imaging methods to a composite score for the prediction of DU in SSc patients. METHODS: Seventy-nine SSc patients received clinical examination, their patient history was taken and nailfold capillaroscopy (NC), colour Doppler ultrasonography (CDUS) and fluorescence optical imaging (FOI) of the hands were performed at baseline. Newly developed DU over a period of approximately 12 months were registered. We used criteria with area under the curve (AUC) of at least 0.6 in regard to the development of these new DU to create the score (CIP-DUS, clinical features, imaging, patient history-digital ulcer score). RESULTS: Twenty-nine percent of all SSc patients developed new DU during follow-up (48.1% diffuse, 18.4% limited SSc). Based on the cross-validated (cv) AUC, a weight (cvAUC > 0.6 and ≤ 0.65: 1; cvAUC > 0.65 and ≤ 0.7: 2; cvAUC > 0.7: 3) was assigned to each selected parameter. The performance of the final CIP-DUS was assessed with and without the CDUS/FOI component. For the scleroderma patterns in NC, three points were appointed to late, two to active and one point to early capillaroscopy pattern according to Cutolo et al. The CIP-DUS including the CDUS and FOI parameters resulted in a good diagnostic performance (AUC after cross-validation: 0.83, 95%CI 0.74 to 0.92) and was well calibrated (chi-square = 12.3, p = 0.58). The cut-off associated with the maximum of sensitivity and specificity was estimated at ≥ 10 points resulting in a sensitivity of 100% and specificity of 74% for new DU during follow-up. Excluding CDUS and FOI parameters leads to a non-statistically significant lower performance (AUC after cross-validation: 0.81, 95%CI 0.72 to 0.91). However, including CDUS and FOI resulted in a better classification of patients in respect to the outcome new DU in follow-up due to significantly better reclassification performance (NRI = 62.1, p = 0.001) and discrimination improvement (IDI = 9.7, p = 0.01). CONCLUSION: A new score was introduced with the aim to predict digital ulcers. If applied correctly and with the new imaging techniques proposed, all patients at risk of digital ulcers throughout 12 months could be identified.

Quality of life in a German cohort of Parkinson's patients assessed with three different measures.

BACKGROUND: Parkinson's disease (PD) is characterized by severe motor and non-motor symptoms reducing patients' quality of life (QoL). Instruments have been well established for QoL assessments in PD, including the EuroQol (EQ-5D), the Parkinson's disease questionnaire (PDQ-39), or rather uncommon, like the WHOQOL-100. So far, the impact of variables has been investigated for each of these measures separately in different study populations, limiting the comparability of the results. Thus, this study compared the EQ-5D, PDQ-39, and the WHOQOL-100 (with its short-form WHOQOL-BREF) in the same study population. METHODS: Seventy-five PD outpatients were assessed in a prospective study, including disease severity according to Hoehn and Yahr stage (HY) and Unified Parkinson Disease Rating Scale (UPDRS). The Geriatric Depression Scale (GDS-15) screened for depression. RESULTS: Decreased QoL was found with all three instruments. In multivariate models, sex and treatment complications had an impact on QoL according to all three measures, while duration of PD and HY was not associated with QoL in any of them. Depression was relevant for the WHOQOL-100/WHOQOL-BREF and the PDQ-39, but not for the EQ-5D. The total variances explained by the WHOQOL-100, WHOQOL-BREF, PDQ-39, and the EQ-5D were 0.27, 0.34, 0.70, and 0.50, respectively. CONCLUSIONS: The associations between clinical aspects of PD and QoL vary substantially among all three measures. Importantly, depression as a frequent comorbidity in PD is underestimated by the EQ-5D, but not by the PDQ-39 and the WHOQOL-100/WHOQOL-BREF. In turn, motor impairments are underestimated by the latter and associated strongest with QoL in the EQ-5D.

IL-6 blockade in systemic juvenile idiopathic arthritis - achievement of inactive disease and remission (data from the German AID-registry).

BACKGROUND: Systemic juvenile idiopathic arthritis (sJIA) is a complex disease with an autoinflammatory component of unknown etiology related to the innate immune system. A major role in the pathogenesis has been ascribed to proinflammatory cytokines like interleukin-6 (IL-6), and effective drugs inhibiting their signaling are being developed. This study evaluates sJIA patients treated with the IL-6 inhibitor tocilizumab (TCZ) concerning clinical response rate, disease course and adverse effects in a real-life clinical setting. METHODS: In 2009 a clinical and research consortium was established, including an online registry for autoinflammatory diseases (AID) ( https://aid-register.de ). Data for this retrospective TCZ study were documented by 13 centers. RESULTS: From 7/2009 to 4/2014, 200 patients with sJIA were recorded in the AID-registry. Out of these, 46 (19 m, 27 f, age 1-18 years) received therapy with TCZ. Long term treatment (median 23 months) has been documented in 24/46 patients who were evaluated according to Wallace criteria (active disease 6/24, inactive disease 5/24, remission 13/24 cases). Under observation co-medication were used in 40/46 cases. Adverse events were reported in 11/46 patients. The clinical response rate (no clinical manifestation, no increased inflammation parameters) within the first 12 weeks of treatment was calculated to be 35%. CONCLUSION: Out of 200 sJIA children reported in the German AID-registry, 46 were treated with TCZ, showing a clinical response rate of 35% during the first 12 weeks, and inactive disease and/or remission under medication in 75% after one year. Adverse events were seen in 24% and severe adverse events in 4%. TRIAL REGISTRATION: The AID-Registry is funded by the BMBF (01GM08104, 01GM1112D, 01GM1512D).

Temporal change in prevalence and complications of uveitis associated with juvenile idiopathic arthritis:data from a cross-sectional analysis of a prospective nationwide study.

OBJECTIVES: To analyse the nationwide prevalence of uveitis in JIA and its complications over a whole decade. METHODS: We conducted a prospective, observational and cross-sectional study including all JIA patients from a National Paediatric Rheumatological Database (NPRD) with a uveitis add-on module in Germany (2002-2013). Temporal changes in uveitis prevalence, related secondary complications and anti-inflammatory medication were evaluated. RESULTS: A total of 60 centres including 18,555 JIA patients (mean 3,863 patients/year, SD=837) were documented in the NPRD between 2002 and 2013. The mean age of the patients was 11.4 ± 4.6 years, their mean disease duration 4.4 ± 3.7 years. Among them, 66.9% were female and 51.7% ANA positive. Patients' mean age at arthritis onset was 6.9 ± 4.5 years. Treatment rates with synthetic and biological DMARDs increased during the observation period (sDMARD: 39.8% to 47.2%, bDMARD: 3.3% to 21.8%). Uveitis prevalence decreased significantly from 2002 to 2013 (13.0% to 11.6%, OR = 0.98, p=0.015). The prevalence of secondary uveitis complications also decreased significantly between 2002 and 2013 (33.6% to 23.9%, OR=0.94, p<0.001). Among the complications, the most common ones were posterior synechiae, cataract and band keratopathy. A significant increase in achieving uveitis inactivity was observed at 30.6% in 2002 and 65.3% in 2013 (OR=1.15, p<0.001). CONCLUSIONS: Uveitis prevalence and complications significantly decreased between 2002 and 2013. This may be associated with a more frequent use of DMARDs.

Prevalence of overweight in children and adolescents with juvenile idiopathic arthritis.

OBJECTIVES: To assess the prevalence of overweight in patients with juvenile idiopathic arthritis (JIA) between 2003 and 2012 and to determine correlates of overweight relevant to the change in the overweight rate. METHOD: Annual overweight prevalence was determined in the National Paediatric Rheumatological Database (NPRD) between 2003 and 2012. The prevalence of overweight in JIA was compared to representative data from Germany in 2005. RESULTS: The median age of JIA patients was 11.5 years and the mean disease duration 4 years. Almost 50% of JIA patients had persistent oligoarthritis, followed by rheumatoid factor (RF)-negative polyarthritis (14%). The overweight prevalence decreased significantly from 14.2% in 2003 to 8.3% in 2012 [odds ratio (OR) 0.92, 95% confidence interval (CI) 0.89-0.95]. Higher levels of physical activity and less frequent treatment with high-dose glucocorticoids (GCs) were associated with decreasing overweight rates. Systemic JIA had the highest decrease in the overweight rate over time. Patients with JIA had an overweight rate comparable to that of children and adolescents in the general population. However, systemic JIA and enthesitis-related arthritis were more likely to be associated with overweight. The use of high-dose GCs, lower functional limitations, and a lower level (or lack) of participation in school sports were significant predictors of overweight in multivariable analyses. CONCLUSIONS: The prevalence of overweight in JIA was comparable to the general population and decreased significantly over time. The decrease was associated with higher functional ability and JIA patients should be encouraged to be more physically active. The role of an elevated body mass index (BMI) in the long-term outcome of JIA needs to be addressed in future studies.

[Current news from the BIKER register]. / Aktuelles aus dem BIKER-Register.

Innovative developments in the pharmacotherapy of juvenile idiopathic arthritis and especially biologics allow the formulation of new therapeutic targets, such as the rapid induction of remission with shortening of the period of active disease and therefore preventing damage and disability. These new therapies also represent a challenge to the monitoring of drug safety, the pharmacovigilance. For this purpose the Society for Paediatric and Adolescent Rheumatology has set up an early register to record achievements in treatment improvement and in addition to independently assess information on drug safety, acute tolerance and long-term safety.

[Therapy of juvenile idiopathic arthritis in early adulthood with biologics: transition from pediatric to adult care]. / Biologikatherapie der juvenilen idiopathische Arthritis im jungen Erwachsenenalter: Übergang von der pädiatrischen in die Erwachsenenversorgung.

BACKGROUND: The majority of patients with juvenile idiopathic arthritis (JIA) need specialized care when they enter adulthood. An increasing number of these patients take biologic disease modifying antirheumatic drugs (DMARDs) at the time of transition. The biologic register BiKeR provides information about the health status and healthcare situation of JIA patients during childhood and adolescence and with their entrance into adulthood these patients are systematically transferred to JuMBO, the follow-up register for young adults with JIA treated with biologics and nonbiologic DMARDs. OBJECTIVE: The aim of this study was to investigate the healthcare situation of patients with JIA during transition from pediatric to adult care. METHODS: The current analyses included patients who were successfully transferred from the BiKeR to JuMBO registers. The DMARD treatment and patient-reported outcome (i.e. disease activity, pain and functional ability) were assessed at the last documentation in BikeR and at the first as well as the last documentation in JuMBO. RESULTS: During the transition period 1 in 10 JIA patients stopped DMARD therapy and 1 in 20 patients did not visit a physician for adults. Three-quarters of the adult JIA patients included in JuMBO (N = 811) reached adult rheumatology care. Adult rheumatologists usually continued therapy with biologics in these patients. Every second patient was still being treated with etanercept, 5 years after the start of the first treatment with biologics. Adult rheumatologists changed the biologic substance in every fourth patient, mainly because of treatment failure. In comparison to patients in regular adult rheumatology care, those who did not remain in specialized care had a higher discontinuation rate of biologics. Moreover, patients with sporadic use of medical care had a significantly poorer health status than those with a regular use of medical care at least every 6 months. CONCLUSION: The data show that there is a need for improving healthcare during the period of transition from pediatric to adult rheumatology.

IGF-I levels and depressive disorders: results from the Study of Health in Pomerania (SHIP).

In vitro and in vivo models revealed that the somatotropic system exerts central effects on the central nervous system. Disturbances to this system such as in the case of growth hormone deficiency or growth hormone excess, are associated with a wide range of psychiatric disorders. Nonetheless, there is no epidemiological data available regarding the influence of growth hormone and its mediator, insulin-like growth factor I (IGF-I), on depressive disorders. The objective of this study was to investigate whether endogenous IGF-I levels may predict depression in humans. We included 4079 adult subjects from the Study of Health in Pomerania (SHIP), a population-based study with a 5-year follow-up period. The main predictor was the baseline IGF-I value categorized in three levels as <10th percentile, between the 10th and the 90th percentile (the reference group) and >90th percentile. The outcome measure was the incidence of depressive disorders according to the Composite International Diagnostic-Screener (CID-S). After adjustment for potential confounding variables, females with IGF-I levels below the 10th percentile had a higher incidence of depressive disorders during follow-up (OR 2.70 95% CI 1.38-5.28, p=0.004) compared to females within the reference group (10th-90th percentile). Among males, those with IGF-I levels above the 90th percentile had a higher risk of depressive disorder (OR 3.26 95% CI 1.52-6.98, p=0.002) than those within the 10th-90th percentile. In conclusion we can demonstrate that low IGF-I levels in females and high IGF-I levels in males predict the development of depressive disorders in this general adult population sample.

Dimensional anxiety scales for DSM-5: sensitivity to clinical severity.

PURPOSE: Psychometric properties and clinical sensitivity of brief self-rated dimensional scales to supplement categorical diagnoses of anxiety disorders in the DSM-5 were recently demonstrated in a German treatment seeking sample of adults. The present study aims to demonstrate sensitivity of these scales to clinical severity levels. METHODS: The dimensional scales were administered to 102 adults at a university outpatient clinic for psychotherapy. Diagnostic status was assessed using the Munich-Composite International Diagnostic Interview. To establish a wide range of clinical severity, we considered subthreshold (n=83) and threshold anxiety disorders (n=49, including Social Phobia, Specific Phobia, Agoraphobia, Panic Disorder, and Generalized Anxiety Disorder). RESULTS: Individuals with either subthreshold or threshold anxiety disorder scored higher on all dimensional scales relative to individuals without anxiety. In addition, individuals with a threshold anxiety disorder scored higher on the dimensional scales than individuals with a subthreshold anxiety disorder (except for specific phobia). Disorder-related impairment ratings, global functioning assessments and number of panic attacks were associated with higher scores on dimensional scales. Findings were largely unaffected by the number of anxiety disorders and comorbid depressive disorders. CONCLUSION: The self-rated dimensional anxiety scales demonstrated sensitivity to clinical severity, and a cut-off based on additional assessment of impairment and distress may assist in the discrimination between subthreshold and threshold anxiety disorders. Findings suggest further research in various populations to test the utility of the scales for use in DSM-5.

[Biologics register JuMBO. Long-term safety of biologic therapy of juvenile idiopathic arthritis]. / Biologikaregister JuMBO. Langzeitsicherheit von Biologikatherapie bei juveniler idiopathischer Arthritis.

In recent years the treatment of juvenile idiopathic arthritis (JIA) has changed dramatically. Nowadays one out of three children with polyarticular JIA is treated with a biologic drug; however, knowledge about the long-term safety of biologics is still limited. Information on drug safety is collected in the JIA biologic register (BiKeR) and the follow-up register juvenile arthritis methotrexate/biologics long-term observation (JuMBO). The latter currently includes information on more than 700 young adults most of whom were treated with etanercept and prospectively followed for more than 5 years. Preliminary data on the long-term safety of etanercept for JIA are therefore available. Over an observation period of 1,800 etanercept exposure-years, events of particular interest, such as malignancies, serious infections and new onset immune-mediated diseases have been recorded which occurred at rates of 0.1, 1.1 and 0.9/100 patient-years, respectively. Overall, new safety risks were not detected during long-term etanercept exposure. Moreover, JuMBO has also provided information on the long-term outcome of JIA and initial evidence suggests that JIA outcome, especially in functional aspects has improved in the biologic era. Data from BiKeR and JuMBO contribute to the risk-benefit assessment of biologic drugs which have been implemented in the routine treatment of JIA.

[The prevalence of Parkinson's disease, associated dementia, and depression in Dresden]. / Die epidemiologie des idiopathischen Parkinson-syndroms und assoziierter demenz und depression in Dresden.

BACKGROUND: Parkinson's disease (PD) is frequently compounded by dementia and depression. Yet local total estimates on the prevalence of PD with dementia/depression are still lacking. These are socioeconomically important, especially for the eastern federal states in Germany due to the demographic structures. METHODS: We conducted a two-staged total estimation in the area of Dresden. First, all local office-based neurologists, hospitals and retirement homes were asked to list their patients/residents with PD on a single study day. Then a random sample of patients/home residents was neuropsycholoigcally examined, including the Mini-mental-state exam and the Montgomery-Asberg Depression rating scale. Dementia was diagnosed according to DSM-IV criteria. RESULTS: Overall, 886 PD cases (95 % CI: 809 - 926) were estimated, of which 252 (95 % CI: 226 - 279) suffered from dementia and 216 (95 % CI: 191 - 242) from depression. Dementia rates increased by age with 13.8 % (≤ 65 years) to 40.2 % (≥ 76 years). Depression rates ranged from 23.3 % to 28.0 %. Overall, 20.6 % of all ambulatory treated PD patients and 85.7 % of all home residents with PD had dementia. CONCLUSION: The prevalence of PD in Dresden dovetails with previous reported estimates. Dementia and depression are frequent complications in outpatients as well as home residents with PD.

[Characteristics and management of idiopathic pulmonary fibrosis: INSIGHTS-IPF registry]. / Charakteristika und Versorgung der idiopathischen Lungenfibrose. Rationale für das INSIGHTS-IPF-Register.

Idiopathic pulmonary fibrosis (IPF), a manifestation of chronic progressive fibrosing interstitial pneumonia, is with a prevalence of 2-29 cases per 100,000 individuals a rare disease. Current treatment options are limited, and the mean survival time of the newly diagnosed (mostly elderly) patients is only about 2-3 years. As in Europe data are limited on the characteristics and management of such patients, INSIGHTS-IPF was initiated as a new registry that documents incident and prevalent patients with confirmed IPF diagnosis prospectively. Detailed data on patient characteristics, diagnostics, management, clinical outcomes, quality of life and resource utilization are recorded. It is planned to document 500 patients in 30 centers. The registry will contribute to the optimization of the management of IPF patients in the long term.

Omalizumab versus 'usual care': results from a naturalistic longitudinal study in routine care.

BACKGROUND: It is unclear how far the superior efficacy of omalizumab, established in randomized controlled clinical trials of patients with severe allergic asthma (SAA), translates into routine practice and when compared to matched controls. METHODS: New-onset omalizumab-treated (OT) patients with SAA (n = 53) were compared to a matched control group of usual-care (UC) patients (n = 53). Treatment and procedures were naturalistic. Subsequent to a baseline assessment, patients were followed up over at least 6 months with at least two follow-up assessments. Primary clinical outcomes were the number of asthma attacks, persistence of asthma symptoms and degree of control [asthma control test (ACT), Global Initiative for Asthma]. Secondary outcome criteria were quality of life (Euro-Qol 5D) and number of medications. For each outcome we compared within-group effects from baseline to 6-month follow-up as well as between-group effects. RESULTS: OT patients showed significant improvements in number [effect size (ES) = 0.03] and frequency (ES = 0.04) of asthma attacks as well as asthma control (ES = 0.09), whereas controls revealed no significant improvements in these measures. Further improvements in the OT group were found for 'perceived control always' (ACT, p = 0.006), no impairment (ACT, p = 0.02), reduction of sickness days (p = 0.002) and number of medications needed (p = 0.001). CONCLUSIONS: Substantial beneficial effects of omalizumab, similar to those observed in controlled trials and after marketing studies, were confirmed, particularly with regard to the reduction of asthma attacks, persistence of symptoms, asthma control and reduction of concomitant asthma medications. This study provides a tougher test and generalizable evidence for the effectiveness of omalizumab in routine care.