Krankheitslast der juvenilen idiopathischen Arthritis

Die juvenile idiopathische Arthritis ist eine chronische Erkrankung mit Beginn im Kindes- und Jugendalter. Bei mehr als 50% der Patienten persistiert die JIA bis in das Erwachsenenalter. Vor diesem Hintergrund sind die Kontrolle der Entzündung der Gelenke bzw. der Krankheitsaktivität, das Erreichen einer Remission, Verhinderung von Gelenkschäden und langfristiger Behinderungen, sowie das Erreichen der bestmöglichen Lebensqualität die wichtigsten Therapieziele bei der Behandlung der JIA. Die Krankheitslast der JIA hat sich in den letzten Jahren deutlich verringert. Die Versorgungssituation der Patienten, ein schnellerer Zugang zu spezialisierten multidisziplinären Behandlungszentren, der Einzug von konsentierten Therapieempfehlungen und deren Umsetzung in der Routineversorgung, sowie der breite Einsatz von konventionellen DMARDs und die Einführung der Biologika in der Behandlung der JIA haben einen entscheidenden Anteil an dieser Entwicklung. Das Therapieziel einer inaktiven Erkrankung wird heutzutage bei bis zu 75% der Patienten erreicht, wobei die Raten zwischen den Studien stark variieren, abhängig von der Definition der inaktiven Erkrankung, der Kohorte, der Erkrankungsdauer und dem Beobachtungszeitraum. Das Erreichen einer optimalen Lebensqualität für den Patienten gewinnt neben anderen vom Patienten berichteten Parametern als Therapieziel zunehmend an Bedeutung, da die JIA alle Bereiche des Lebens des Kindes und seiner Familie beeinflusst. Bisherige Studien zeigen weiterhin im Mittel eine signifikant niedrigere Lebensqualität der JIA Patienten im Vergleich zu gesunden Kontrollen. Es gibt aber auch Hinweise, dass Patienten mit einer inaktiven JIA in ihrer Lebensqualität das Niveau einer gesunden Kontrollkohorte erreichen können. Daten aus dem Biologika Register JuMBO zeigten, dass sich die Lebensqualität der Patienten seit der Einführung der biologischen Medikamente kontinuierlich verbesserte. Der Grad der Funktionseinschränkung ist ein wesentlicher Einflussfaktor für die subjektiv erreichte Lebensqualität. In der Kinderkerndokumentation (2000 bis 2015) kann man eine stetige Zunahme des Anteiles der Patienten ohne Funktionseinschränkungen beobachten. Dieser Trend wird begleitet von der immer früheren und intensiveren Therapie mit csDMARDs und bDMARDs in diesem Patientenkollektiv. Mit dem Blick auf die potentiell lange Exposition der schwerer betroffenen JIA Patienten mit csDMARDs und bDMARDs rückt die Therapiesicherheit und damit vor allem auch die fatalen Outcomes einer malignen Erkrankung oder die Mortalität in den Blick. Der derzeitige Kenntnisstand bezüglich des Zusammenhanges zwischen dem Auftreten von malignen Erkrankungen und einer DMARD Therapie lässt keinen endgültigen Schluss zu. Die Beurteilung des Malignomrisikos bei JIA Patienten gestaltet sich aus mehreren Gründen als schwierig. Gründe sind das seltene Auftreten maligner Erkrankungen im Kindes- und Jugendalter, die möglicherweise lange Latenzzeit nach Exposition bis zum Auftritt und das Zuordnungsproblem bei Exposition mit mehreren immunsupprimierenden Substanzen im Krankheitsverlauf. Allgemein akzeptiert ist das 3-fach erhöhte Malignomrisiko bei JIA Patienten im Vergleich zur Allgemeinbevölkerung. Die Therapie mit MTX, Etanercept und Adalimumab scheint das Malignomrisiko nur marginal zu erhöhen. Die Mortalität bei JIA-Patienten ist in den letzten 30 Jahren deutlich zurückgegangen. Im Vergleich zur Allgemeinbevölkerung ist die Mortalitätsrate bei Patienten mit einer JIA aber weiterhin erhöht. Die geschätzte Letalität bei Kindern und Jugendlichen mit einer JIA lag bei 4% vor 1980 und 0,4% im Jahr 2016. Die langfristige Beobachtung der JIA Patienten in Registern wie BiKeR und JuMBO ist eine wichtige Aufgabe der Kinder und Jugendrheumatologie, um die Sicherheit der eingesetzten Substanzen im Hinblick auf das Auftreten von seltenen Erkrankungen und Erkrankungen mit einer langen Latenzzeit beurteilen zu können

Inadequate medical treatment of patients with coronary artery disease by primary care physicians in Germany

Aims: The DETECT study was performed to obtain representative data about the frequency, distribution, and treatment of patients with coronary artery disease (CAD) in the primary care setting in Germany. Methods and results: The DETECT study was a cross–sectional clinical– epidemiological survey of a nationally representative sample of 3795 primary care offices and 55 518 patients. Overall, 12.4% of patients were diagnosed with CAD. Stable angina pectoris and myocardial infarction were the most frequent (4.2%) subgroups, followed by status post (s/p) percutaneous coronary interventions (PCI, 3.0%) and s/p coronary bypass surgery (2.2%). Patients with CAD were prescribed AT1 receptor antagonists (in 19.4% of cases), beta blockers (57.2%), ACE inhibitors (49.9%), antiplatelet agents (52.7%), statins (43.0%), and long–term nitrates (24.5%). When comparing all CAD patients with social health care insurance to those who had private insurance, private patients had significantly higher rates of revascularisation procedures and use of preventive medications. Conclusion: Great potential remains for improving secondary prevention in primary care in Germany to reduce the risk of further coronary or vascular events, especially in patients with social health care insurance

Changes in the prevalence, treatment and control of hypertension in Germany? : a clinical-epidemiological study of 50.000 primary care patients

INTRODUCTION: Medical societies have developed guidelines for the detection, treatment and control of hypertension (HTN). Our analysis assessed the extent to which such guidelines were implemented in Germany in 2003 and 2001. METHODS: Using standardized clinical diagnostic and treatment appraisal forms, blood pressure levels and patient questionnaires for 55,518 participants from the cross-sectional Targets and Essential Data for Commitment of Treatment (DETECT) study (2003) were analyzed. Physician's diagnosis of hypertension (HTN(doc)) was defined as coding hypertension in the clinical appraisal questionnaire. Alternative definitions used were physician's diagnosis or the patient's self-reported diagnosis of hypertension (HTN(doc,pat)), physician's or patient's self-reported diagnosis or a BP measurement with a systolic BP≥140 mmHg and/or a diastolic BP≥90 (HTN(doc,pat,bp)) and diagnosis according to the National Health and Nutrition Examination Survey (HTN(NHANES)). The results were compared with the similar German HYDRA study to examine whether changes had occurred in diagnosis, treatment and adequate blood pressure control (BP below 140/90 mmHg) since 2001. Factors associated with pharmacotherapy and control were determined. RESULTS: The overall prevalence rate for hypertension was 35.5% according to HTN(doc) and 56.0% according to NHANES criteria. Among those defined by NHANES criteria, treatment and control rates were 56.0% and 20.3% in 2003, and these rates had improved from 55.3% and 18.0% in 2001. Significant predictors of receiving antihypertensive medication were: increasing age, female sex, obesity, previous myocardial infarction and the prevalence of comorbid conditions such as coronary heart disease (CHD), hyperlipidemia and diabetes mellitus (DM). Significant positive predictors of adequate blood pressure control were CHD and antihypertensive medication. Inadequate control was associated with increasing age, male sex and obesity. CONCLUSIONS: Rates of treated and controlled hypertension according to NHANES criteria in DETECT remained low between 2001 and 2003, although there was some minor improvement

Depression als komorbide Störung in der primärärztlichen Versorgung

Auf der Grundlage der DETECT-Studie wird die querschnittliche Assoziation depressiver Störungen mit einem weiten Spektrum körperlicher Erkrankungen in einer bundesweit repräsentativen Stichprobe von 51.000 Patienten aus der primärärztlichen Versorgung in Deutschland sowie der Zusammenhang mit gesundheitsbezogener Lebensqualität und Arbeitsunfähigkeit untersucht. Das Vorliegen einer Depression wurde über den Depression Screening Questionnaire (DSQ) mit seinem ICD-10 Algorithmus ermittelt. Bei einer Gesamt-Querschnittsprävalenz depressiver Störungen von 7,5 % ergaben sich erhöhte Depressionsraten und signifikante Assoziationen für nahezu alle untersuchten Krankheitsgruppen. (1) Ko- und Multimorbidität somatischer als auch somatischer mit depressiven Störungen sind die Regel: „Reine“ (nicht komorbide) Depressionen sind ebenso wie reine somatische Erkrankungen die Ausnahme. (2) Das Depressionsrisiko steigt stetig mit der Anzahl komorbider Krankheiten. (3) Besonders ausgeprägte Assoziationen ergaben sich für schwergradige Herzinsuffizienzen (OR: 5,8), diabetische Folgekomplikationen (OR: 1,7–2,0), koronare Herzerkrankungen (KHK) (OR: 1,7), zerebrale Insulte (OR: 2,5) sowie muskuloskelettäre Erkrankungen (OR: 1,5). Demgegenüber waren z. B. die Raten bei Hyperlipidämie (OR: 1,1) nur leicht erhöht. (4) Komorbide Depression und steigende Multimorbidität waren mit stetig zunehmenden Arbeitsunfähigkeits- raten und absinkender gesundheitsbezogener Lebensqualität assoziiert. Angesichts der quantitativen Bedeutung der Depression sowie des mit Multimorbidität drastisch ansteigenden Depressionsrisikos und der damit verbundenen hohen direkten und indirekten Krankheitslast für das Gesundheitssystem und die Gesellschaft ist das hohe Ausmaß der Unterschätzung von Depression in der Routineversorgung besorgniserregend.As part of the DETECT study, a nationwide representative clinical-epidemiological study, the frequency and associated problems of comorbid depression with a wide range of somatic illnesses were studied in N = 51,000 primary care patients. Further the association with health related quality of life and disability is examined. Depression was assessed with the Depression Screening Questionnaire (DSQ) with an ICD-10 algorithm. Results: (1) 7.5 % of all primary care patients met criteria for ICD-10 depressive disorders. (2) Depression risk was increased whenever any somatic disorder was present and increased in a dose-response relationship by number of comorbid conditions. (3) Elevation of depression risk was fairly independent of type of diagnosis, although associations with coronary heart disease (OR: 1.7), diabetic complications (OR: 1.7– 2.0), stroke (OR: 2.5) and pain-related chronic disorders (OR: 1.5) were particularly pronounced. Moderate associations were found for hyperlipidaemia (OR: 1.1). (4) Associated with the increasing number of comorbid conditions, patients with comorbid depression had increasingly more disability days and lower health related quality of life. It is concluded that the degree to which the frequency and the deleterious effects of comorbid depression is underestimated and unrecognized is alarming. The use of comorbidity indices might improve recognition

Mapping the EQ-5D index by UPDRS and PDQ-8 in patients with Parkinson’s disease

Background: Clinical studies employ the Unified Parkinson’s Disease Rating Scale (UPDRS) to measure the severity of Parkinson’s disease. Evaluations often fail to consider the health-related quality of life (HrQoL) or apply disease-specific instruments. Health-economic studies normally use estimates of utilities to calculate quality-adjusted life years. We aimed to develop an estimation algorithm for EuroQol- 5 dimensions (EQ-5D)-based utilities from the clinical UPDRS or disease-specific HrQoL data in the absence of original utilities estimates. Methods: Linear and fractional polynomial regression analyses were performed with data from a study of Parkinson’s disease patients (n=138) to predict the EQ-5D index values from UPDRS and Parkinson’s disease questionnaire eight dimensions (PDQ-8) data. German and European weights were used to calculate the EQ-5D index. The models were compared by R2, the root mean square error (RMS), the Bayesian information criterion, and Pregibon’s link test. Three independent data sets validated the models. Results: The regression analyses resulted in a single best prediction model (R2: 0.713 and 0.684, RMS: 0.139 and 13.78 for indices with German and European weights, respectively) consisting of UPDRS subscores II, III, IVa-c as predictors. When the PDQ-8 items were utilised as independent variables, the model resulted in an R2 of 0.60 and 0.67. The independent data confirmed the prediction models. Conclusion: The best results were obtained from a model consisting of UPDRS subscores II, III, IVa-c. Although a good model fit was observed, primary EQ-5D data are always preferable. Further validation of the prediction algorithm within large, independent studies is necessary prior to its generalised use

Predictors of graft survival at diagnosis of antibody‐mediated renal allograft rejection: a retrospective single‐center cohort study

Antibody-mediated rejection (ABMR) is a major cause of graft loss in renal transplantation. We assessed the predictive value of clinical, pathological, and immunological parameters at diagnosis for graft survival. We investigated 54 consecutive patients with biopsy-proven ABMR. Patients were treated according to our current standard regimen followed by triple maintenance immunosuppression. Patient characteristics, renal function, and HLA antibody status at diagnosis, baseline biopsy results, and immunosuppressive treatment were recorded. The risk of graft loss at 24 months after diagnosis and the eGFR slope were assessed. Multivariate analysis showed that eGFR at diagnosis and chronic glomerulopathy independently predict graft loss (HR 0.94; P = 0.018 and HR 1.57; P = 0.045) and eGFR slope (beta 0.46; P < 0.001). Cyclophosphamide treatment (6x 15 mg/m²) plus high-dose intravenous immunoglobulins (IVIG) (1.5 g/kg) was superior compared with single-dose rituximab (1x 500 mg) plus low-dose IVIG (30 g) (HR 0.10; P = 0.008 and beta 10.70; P = 0.017) and one cycle of bortezomib (4x 1.3 mg/m(2)) plus low-dose IVIG (HR 0.16; P = 0.049 and beta 11.21; P = 0.010) regarding the risk of graft loss and the eGFR slope. In conclusion, renal function at diagnosis and histopathological signs of chronic ABMR seem to predict graft survival independent of the applied treatment regimen. Stepwise modifications of the treatment regimen may help to improve outcome

Comparison of treatment response, remission rate and drug adherence in polyarticular juvenile idiopathic arthritis patients treated with etanercept, adalimumab or tocilizumab

Background Treatment response, remission rates and compliance in patients with polyarticular juvenile idiopathic arthritis (polyJIA) treated with adalimumab, etanercept, or tocilizumab were analyzed in clinical practice. Methods Data collected in the German BIKER registry were analyzed in patients with polyJIA who started treatment with approved biologics, adalimumab, etanercept or tocilizumab, from 2011 to 2015. Baseline patient characteristics, treatment response, safety and drug survival were compared. Results Two hundred thirty- six patient started adalimumab, 419 etanercept and 74 tocilizumab, with differences in baseline patient characteristics. Baseline Juvenile Disease Activity Score (JADAS)10 (mean ± SD) in the adalimumab/etanercept/tocilizumab cohorts was 12.1+/−7.6, 13.8 ± 7.1 and 15.1 ± 7.4, respectively (adalimumab vs etanercept, p = 0.01), and Childhood Health Assessment Questionnaire (CHAQ)-disability index scores was 0.43 ± 0.58, 0.59 ± 0.6 and 0.63 ± 0.55, respectively (adalimumab vs etanercept, p < 0.001). Uveitis history was more frequent in the adalimumab cohort (OR 5.73; p < 0.001). Balanced patients’ samples were obtained by a generalized propensity score to adjust for baseline differences. Pediatric ACR30/50/70/90 criterion improvement after 3 months treatment was achieved by 68%/60%/42%/24% in the etanercept cohort, 67%/59%/43%/27% in the adalimumab cohort and 61%/52%/35%/26% in the tocilizumab cohort. At 24 months, JADAS minimal disease activity was achieved in 52.4%/61.3%/52.4% and JADAS remission in 27.9%/34.8%/27.9% patients in the adalimumab/etanercept/tocilizumab cohorts, respectively. Etanercept was used in 95.5% of patients as a first biologic, adalimumab in 50.8% and tocilizumab in 20.2%. There were no important differences in efficacy between first-line and second-line use of biologics. In total 60.4%/49.4%/31.1% patients discontinued adalimumab/etanercept/tocilizumab, respectively (HR for adalimumab 1.67; p < 0.001; HR for tocilizumab 0.35; p = 0.001). Drug survival rates did not differ significantly in patients on biologic monotherapy compared with combination therapy with methotrexate. Over 4 years observation under etanercept/adalimumab/tocilizumab, 996/386/103 adverse events, and 148/119/26 serious adverse events, respectively, were reported. Conclusions In clinical practice, etanercept is most frequently used as first-line biologic. Adalimumab/etanercept/tocilizumab showed comparable efficacy toward polyJIA. Overall, tolerance was acceptable. Interestingly, compliance was highest with tocilizumab and lowest with adalimumab. This study provides the first indication for the comparison of different biologic agents in polyarticular JIA based on observational study data with all their weaknesses and demonstrates the need for well-controlled head-to-head studies for confirmation

Psychoneuroendocrine evaluation of an acceptance and commitment based stress management training

Acceptance and Commitment Therapy (ACT), a behavioral therapy that targets psychological flexibility (PF), has been shown to be efficacious across a wide range of problems, including chronic work-related stress and perceived stress. ACT's effect on the multiple levels of the acute stress response (i.e., subjective and biological) is less well understood. The aim of the current study was to test whether ACT, by working toward PF, would reduce both the endocrine and subjective evaluations of participants' acute stress response.; Participants (n = 35) were randomized to an ACT condition or waitlist (WL). Participants in the ACT condition received a two-day ACT workshop on how to flexibly deal with stress. All participants completed a standardized laboratory stress test.; The ACT and WL groups did not differ on main comparisons of the endocrine response (i.e., cortisol) or subjective evaluation. Baseline levels of PF moderated some outcomes. Avoidant participants had a stronger endocrine stress reaction if they received the ACT intervention.; The control condition was a WL and not an active intervention comparison.; ACT is not useful in reducing the acute stress response and may even be iatrogenic, at least during tasks with little real-world impact for their personal values

Red Blood Cell Contamination of the Final Cell Product Impairs the Efficacy of Autologous Bone Marrow Mononuclear Cell Therapy

ObjectivesThe aim of this study was to identify an association between the quality and functional activity of bone marrow-derived progenitor cells (BMCs) used for cardiovascular regenerative therapies and contractile recovery in patients with acute myocardial infarction included in the placebo-controlled REPAIR-AMI (Reinfusion of Enriched Progenitor cells And Infarct Remodeling in Acute Myocardial Infarction) trial.BackgroundIsolation procedures of autologous BMCs might affect cell functionality and therapeutic efficacy.MethodsQuality of cell isolation was assessed by measuring the total number of isolated BMCs, CD34+ and CD133+ cells, their colony-forming unit (CFU) and invasion capacity, cell viability, and contamination of the final BMC preparation with thrombocytes and red blood cells (RBCs).ResultsThe number of RBCs contaminating the final cell product significantly correlated with reduced recovery of left ventricular ejection fraction 4 months after BMC therapy (p = 0.007). Higher numbers of RBCs in the BMC preparation were associated with reduced BMC viability (r = −0.23, p = 0.001), CFU capacity (r = −0.16, p = 0.03), and invasion capacity (r = −0.27, p < 0.001). To assess a causal role for RBC contamination, we coincubated isolated BMCs with RBCs for 24 h in vitro. The addition of RBCs dose-dependently abrogated migratory capacity (p = 0.003) and reduced CFU capacity (p < 0.05) of isolated BMCs. Neovascularization capacity was significantly impaired after infusion of BMCs contaminated with RBCs, compared with BMCs alone (p < 0.05). Mechanistically, the addition of RBCs was associated with a profound reduction in mitochondrial membrane potential of BMCs.ConclusionsContaminating RBCs affects the functionality of isolated BMCs and determines the extent of left ventricular ejection fraction recovery after intracoronary BMC infusion in patients with acute myocardial infarction. These results suggest a bioactivity response relationship very much like a dose–response relationship in drug trials. (Reinfusion of Enriched Progenitor cells and Infarct Remodeling in Acute Myocardial Infarction [REPAIR-AMI]; NCT00279175