Healthcare utilization and unmet needs of patients with antisynthetase syndrome: An international patient survey.

Antisynthease syndrome (ASSD) is a rare, complex and understudied autoimmune disease. Internet-based studies can overcome barriers of traditional on-site research and are therefore very appealing for rare diseases. The aim of this study was to investigate patient-reported symptoms, diagnostic delay, symptoms, medical care, health status, working status, disease knowledge and willingness to participate in research of ASSD patients by conducting an international web-based survey. The multilingual questionnaire was created by an international group of rheumatologists and patients and distributed online. 236 participants from 22 countries completed the survey. 184/236 (78.0%) were female, mean age (SD) was 49.6 years (11.3) and most common antisynthetase antibody was Jo-1 (169/236, 71.6%). 79/236 (33.5%) reported to work full-time. Median diagnostic delay was one year. The most common symptom at disease onset was fatigue 159/236 (67.4%), followed by myalgia 130/236 (55.1%). The complete triad of myositis, arthritis and lung involvement verified by a clinician was present in 42/236 (17.8%) at disease onset and in 88/236 (37.3%) during the disease course. 36/236 (15.3%) reported to have been diagnosed with fibromyalgia and 40/236 (16.3%) with depression. The most reported immunosuppressive treatments were oral corticosteroids 179/236 (75.9%), followed by rituximab 85/236 (36.0%). 73/236 (30.9%) had received physiotherapy treatment. 71/236 (30.1%) reported to know useful online information sources related to ASSD. 223/236 (94.5%) were willing to share health data for research purposes once a year. Our results reiterate that internet-based research is invaluable for cooperating with patients to foster knowledge in rare diseases.

Peripartal pain perception and pain therapy: introduction and validation of a questionnaire as a quality instrument.

BACKGROUND: Labor pain is difficult to measure. The aim of this proof-of-concept study is to implement and test a questionnaire assessing pain sensation during and after vaginal deliveries. Its key aspect is a highly standardized survey of patient-reported outcome (PRO) by staff not involved in routine care. METHODS: Between January and November 2015 339 women were assessed 24-48 h after spontaneous or operative-vaginal delivery of a singleton. German language skills were a prerequisite to participate. The test-retest reliability was calculated in 38 women 24-36 and 48-72 h postpartum between July and October 2017. Primiparae after spontaneous delivery and multiparae with no history of operative deliveries were compared in a subgroup analysis. RESULTS: Maximum labor pain and post-partum pain were reported a median of 9 [8-10] and 4 [3-6]. Higher ratings were associated with younger age, higher gestational ages, infant's biometrics, and the duration of laboring. Only regional analgesia tended to reduce pain perception (NRS 8 vs. 9). Higher-degree injuries were associated with less pain postpartum. The questionnaire proved to be reliable in most aspects (Cronbach's α > 0.6 for 19/21 questions) and showed an acceptable content and criterion validity (Cohen correlation > ± 0.3, interrelation between items). CONCLUSION: Labor is a very painful experience, irrespective of previous obstetric history. Ratings indicate inadequateness of treatment except for patients receiving preventive postoperative pain management. Systematic postpartum pain assessment, hence, is still a pending issue. Adjustments will be made concerning language skills and specific questions on effectiveness of analgesia otherwise good reliability and validity of the questionnaire were proven.

Intravenous gold-induced autologous serum injection therapy (Go ACT®) as a new treatment for seasonal pollen-based allergies.

OBJECTIVE: This prospective case study investigated the new therapeutic paradigm of autologous gold-induced immunotherapy (Go ACT®) in the treatment of pollen-based allergies. The safety and clinical efficacy of Go ACT® were investigated by assessing patients in the first pollen season following treatment with Go ACT®. PATIENTS AND METHODS: In this prospective case study, patients were enrolled who had a proven pollen allergy and had been previously unsuccessfully treated with standard medication. Clinical improvement following Go ACT® treatment was analyzed using symptom scores, ARIA classification and symptom control. The data generated in the case study were compared to the data from the previous pre-treatment pollen season. RESULTS: 16 patients were included in this study. The treatment was well tolerated by all patients. On completion of the study all of the patients rated the tolerability of the treatment as either good or very good. Local reactions to the treatment were not seen. No Serious Adverse Events (SAEs) occurred. The symptom scores decreased significantly from the 2016 pollen season to the 2017 pollen season in patients who received Go ACT® treatment. Analysis of the ARIA classification showed that 81.0% of patients had persistent, moderate-to-severe rhinitis before treatment.  Following treatment 7.1% of patients had persistent, moderate-to-severe rhinitis. A total of 62.4% of patients in the study achieved symptom control. A total of 38.8% of patients required no symptomatic medication after Go ACT® treatment. The rhino-conjunctivitis score was significantly lower after the treatment. CONCLUSIONS: This study has shown that Go ACT® treatment is safe, effective, well-tolerated and accepted by patients suffering from pollen allergy. The results of the symptom scores, RCAT, ARIA classification show that Go ACT® treatment elicits immediate beneficial effects during the pollen season under treatment and for the season following treatment.

[Myofasciitis under nivolumab treatment]. / Myofasziitis unter Nivolumab-Therapie.

We report the case of a 73-year-old female patient with malignant melanoma who developed rapidly progressive dermatosclerosis of the arms and legs as well as myalgia and flexion contractures during treatment with the immune checkpoint inhibitor nivolumab. The diagnosis of a myofasciitis was confirmed by imaging and biopsy. Following consultation with the treating dermato-oncologists nivolumab treatment was paused and treatment with methotrexate and prednisolone was initiated. Immune checkpoint inhibitors can induce a variety of immune-mediated side effects and can also imitate symptoms of rheumatological diseases. The occurrence of myofasciitis under immune checkpoint inhibition has been reported in the literature only in a few cases. Further oncological and rheumatological treatment management should be carried out in close interdisciplinary coordination.

[Pericarditis is inflammation of the pericardium, which rheumatologists should know]. / Perikarditis im Rahmen rheumatologischer Erkrankungen ­ Was der Rheumatologe wissen sollte.

Pericarditis is the term for inflammatory involvement of the pericardium, which can be associated with pericardial effusion and myocardial involvement (perimyocarditis). Pericarditis can be present in the context of systemic inflammatory rheumatic diseases but can also constitute a distinct disease entity. Idiopathic recurrent pericarditis (IRP) describes relapsing conditions of pericarditis with an unknown cause, which show essential common features with autoinflammatory diseases. This article gives an overview of the frequency of pericarditis in systemic rheumatic diseases. Moreover, the clinical manifestations and pathophysiology of IRP are discussed. Finally, the therapeutic algorithms for acute and idiopathic pericarditis are explained.

Real-world evaluation of adverse pregnancy outcomes in women with gestational diabetes mellitus in the German health care system.

AIMS: This study aims to estimate the incidence of adverse pregnancy outcomes in women with gestational diabetes mellitus (GDM) in Germany. METHODS: Pregnant women were identified from a health claims database for the year of 2016. Three groups were defined: general population without GDM, women with GDM without treatment and women with GDM and insulin treatment. Operationalisation of outcomes was aligned with the hyperglycaemia and adverse pregnancy outcomes (HAPO) study. RESULTS: The cohort consisted of 58,297 mother-child pairs. Of those, 7245 had a GDM diagnosis and 1407 had a GDM diagnosis with a prescription of insulin. Adverse pregnancy outcomes were higher in both GDM groups compared to the control group. Birthweight (OR 2.08 [95% CI 1.50-2.90]), primary caesarean section (OR 1.70 [95% CI 1.48-1.95]), intensive neonatal care (OR 1.25 [95% CI 1.04-1.50]), preeclampsia (OR 1.51 [95% CI 1.23-1.85]), and clinical neonatal hypoglycaemia (OR 5.32 [95% CI 4.27-6.62]) were higher in the GDM+insulin group in comparison to a control group after adjustment for potential confounders. CONCLUSION: Most of the adverse pregnancy outcomes were moderately higher in both identified GDM groups in comparison to women without GDM. Women receiving insulin treatment are at an increased risk of most of the defined adverse pregnancy outcomes.

Lifetime radiation risk of stochastic effects - prospective evaluation for space flight or medicine.

The concept of lifetime radiation risk of stochastic detrimental health outcomes is important in contemporary radiation protection, being used either to calculate detriment-weighted effective dose or to express risks following radiation accidents or medical uses of radiation. The conventionally applied time-integrated risks of radiation exposure are computed using average values of current population and health statistical data that need to be projected far into the future. By definition, the lifetime attributable risk (AR) is an approximation to more general lifetime risk quantities and is only valid for exposures under 1 Gy. The more general quantities, such as excess lifetime risk (ELR) and risk of exposure-induced cancer, are free of dose range constraints, but rely on assumptions concerning the unknown total radiation effect on demographic and health statistical data, and are more computationally complex than AR. Consideration of highly uncertain competing risks for other radiation-attributed outcomes are required in appropriate assessments of time-integrated risks of specific outcomes following high-dose (>1 Gy) exposures, causing non-linear dose responses in the resulting ELR estimate.Being based on the current population and health statistical data, the conventionally applied time-integrated risks of radiation exposure are: (i) not well suited for projections many years into the future because of the large uncertainties in future secular trends in the population-specific disease rates; and (ii) not optimal for application to atypical groups of exposed persons not well represented by the general population. Specifically, medical patients are atypical in this respect because their prospective risks depend strongly on the original diagnosis, the treatment modality, general cure rates, individual radiation sensitivity, and genetic predisposition. Another situation challenging the application of conventional risk quantities is a projection of occupational radiation risks associated with space flight, both due to higher radiation doses and astronauts' generally excellent health condition due to pre-selection, training, and intensive medical screening.An alternative quantity, named 'radiation-attributed decrease of survival' (RADS), known in past general statistical literature as 'cumulative risk', is recommended here for applications in space and medicine to represent the cumulative radiation risk conditional on survival until a certain age. RADS is only based on the radiation-attributed hazard rendering an insensitivity to competing risks or projections of current population statistics far into the future. Therefore, RADS is highly suitable for assessing semi-personalised radiation risks after radiation exposures from space missions or medical applications of radiation.

[Auricular chondritis as first symptom of ANCA-associated vasculitis]. / Aurikuläre Chondritis als Erstsymptom einer ANCA-assoziierten Vaskulitis.

Auricular chondritis frequently occurs in relapsing polychondritis. In addition to the primary form of the disease up to 30% of cases of chondritis can be secondary, e.g. due to autoimmune diseases. We describe the case of a 62-year-old male patient with auricular chondritis as the first symptom of granulomatosis with polyangiitis. Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis should always be considered in the differential diagnostics of relapsing polychondritis and antibody testing should be performed accordingly.

[Recurrence of septic arthritis of the wrist by Pseudomonas aeruginosa due to colonization of a central venous indwelling catheter]. / Rezidiv einer septischen Arthritis des Handgelenks durch Pseudomonas aeruginosa bei Besiedelung eines zentralvenösen Verweilkatheters.

A diabetic patient, wearer of a port and with a history of gonarthritis due to Pseudomonas aeruginosa presented with subacute arthritis of a wrist. After a protracted interval P. aeruginosa was detected by microbial culture from the explanted port and the affected joint. This case shows that in patients with unclear arthritis of the wrist, a history of septic arthritis with P. aeruginosa and risk factors for hematogenous spread, a recurrent infection should be excluded. The treatment consisted of explantation of the port, débridement with synovectomy of the joint and adequate antibiotic treatment.

[IgG4-Related Orbitopathy as an Important Differential Diagnosis of Advanced Silent Sinus Syndrome. German version]. / IgG4-assoziierte Orbitopathie als wichtige Differenzialdiagnose eines fortgeschrittenen Silent-Sinus-Syndroms.

BACKGROUND: Immunoglobulin (Ig)G4-related disease is classified as an immune-mediated disease. The etiology of this condition has not been explained to date. Manifestations of the disease are diverse, and simultaneous involvement of multiple organs is not unusual. CASE REPORT: We report the case of a patient referred to us after multiple unsuccessful paranasal sinus operations who presented with enophthalmos and a resultant migratory keratitis with a suspected diagnosis of silent sinus syndrome. Preservation of the orbit was no longer feasible. After five years without a definitive diagnosis, we ascertained that this was a case of IgG4-related disease. DISCUSSION: IgG4-related disease represents an important element in the differential diagnosis of chronic advanced diseases of the orbit and paranasal sinuses. The diagnosis should be considered in the case of unclear disease presentations. Typical histological findings include a storiform pattern of fibrosis, vasculopathy, and tissue infiltration by IgG4 plasma cells.

IgG4-related orbitopathy as an important differential diagnosis of advanced silent sinus syndrome.

BACKGROUND: Immunoglobulin (Ig)G4-related disease is classified as an immune-mediated disease. The etiology of this condition has not been explained to date. Manifestations of the disease are diverse, and simultaneous involvement of multiple organs is not unusual. CASE REPORT: We report the case of a patient referred to us after multiple unsuccessful paranasal sinus operations who presented with enophthalmos and a resultant migratory keratitis with a suspected diagnosis of silent sinus syndrome. Preservation of the orbit was no longer feasible. After five years without a definitive diagnosis, we ascertained that this was a case of IgG4-related disease. DISCUSSION: IgG4-related disease represents an important element in the differential diagnosis of chronic advanced diseases of the orbit and paranasal sinuses. The diagnosis should be considered in the case of unclear disease presentations. Typical histological findings include a storiform pattern of fibrosis, vasculopathy, and tissue infiltration by IgG4 plasma cells.

Assessment of excess medical costs for persons with type 2 diabetes according to age groups: an analysis of German health insurance claims data.

AIM: This cross-sectional study used a large nationwide claims data set to assess the excess medical costs of people with type 2 diabetes according to age group in 2015. METHODS: Data from 291 709 people with diabetes and 291 709 age- and sex-matched controls were analysed. Total costs (expressed as 2015 euros) of outpatient and inpatient services, medication, rehabilitation, and the provision of aids and appliances were examined. Overall and age-stratified excess costs of people with diabetes were estimated using gamma regression with a log-link. RESULTS: Overall, the estimated total direct costs of a person with type 2 diabetes are approximately double those of a person without diabetes: €4727 vs. €2196, respectively. Absolute excess costs were approximately the same in all age groups (around €2500), however, relative excess costs of persons with diabetes were much higher in younger (~ 334% for < 50 years) than in older age groups (~ 156% for ≥ 80 years). Regional costs, both absolute and excess, partly differed from the national level. CONCLUSIONS: This study complements and updates previous studies on the excess medical costs of people with diabetes in Germany. The results indicate the importance of preventing the development of type 2 diabetes, especially in younger age groups. Longitudinal and regional studies examining changes in prevalence and the development of excess costs in groups with different types of diabetes, and according to age, would be of interest to validate our findings and better understand the avoidable burden of having diabetes.

Advanced automatic detection of fetal body movements from multichannel magnetocardiographic signals.

OBJECTIVE: Both heart rate (HR) monitoring and detection and description of fetal movements provide essential information of the integrity of in utero development and fetal wellbeing. Our previously described method to identify movements from multichannel magnetocardiographic (MCG) recordings lacks of reliability in some cases. This work is aimed at the improvement of fetal movement detection by means of an advanced signal processing and validation strategy. APPROACH: The previously proposed methodology of fetal body movement detection from MCG recordings using single space angle (SSA), min-max amplitude (MMA) and a measure of the overall signal strength across (RSS) was extended by moving correlation coefficient (MCC). The methodology was developed with respect to the discrimination between active and quiet sleep, validated by testing its coupling with HR accelerations in a total of 137 recordings lasting 30 min from 98 fetuses aged 34-38 weeks of gestation (WGA) of normal pregnancy. MAIN RESULTS: The developed algorithm improves the reliable automatic detection of fetal body movements independent of the fetal sleep states and their changes in the individual MCG recordings. In the fetuses aged 34-38 WGA 94% of 15 × 15 HR accelerations were coupled with detected movements. The visual inspection of the movement graphs of 30 fetuses aged 20-32 WGA supports the transferability of the movement detector to this age. In four subjects MCG-based movement detection and maternal report on percepted fetal movements were consistent. SIGNIFICANCE: The presented methodology allows the parallel automatic acquisition of precise fetal heart rate variability (HRV) indices based on subsequent beat intervals and of fetal body movements from MCG recordings during late 2nd and 3rd trimester. Potential advantages of parallel monitoring of fetal HRV and movements using MCG compared to established ultrasound technology should be investigated in subsequent studies with respect to the identification of fetuses at risk.

Research plans in Europe for radiation health hazard assessment in exploratory space missions.

The European Space Agency (ESA) is currently expanding its efforts in identifying requirements and promoting research towards optimizing radiation protection of astronauts. Space agencies use common limits for tissue (deterministic) effects on the International Space Station. However, the agencies have in place different career radiation exposure limits (for stochastic effects) for astronauts in low-Earth orbit missions. Moreover, no specific limits for interplanetary missions are issued. Harmonization of risk models and dose limits for exploratory-class missions are now operational priorities, in view of the short-term plans for international exploratory-class human missions. The purpose of this paper is to report on the activity of the ESA Topical Team on space radiation research, whose task was to identify the most pertinent research requirements for improved space radiation protection and to develop a European space radiation risk model, to contribute to the efforts to reach international consensus on dose limits for deep space. The Topical Team recommended ESA to promote the development of a space radiation risk model based on European-specific expertise in: transport codes, radiobiological modelling, risk assessment, and uncertainty analysis. The model should provide cancer and non-cancer radiation risks for crews implementing exploratory missions. ESA should then support the International Commission on Radiological Protection to harmonize international models and dose limits in deep space, and guarantee continuous support in Europe for accelerator-based research configured to improve the models and develop risk mitigation strategies.

[Response of dermatomyositis with lung involvement to Janus kinase inhibitor treatment]. / Ansprechen einer Dermatomyositis mit Lungenbeteiligung auf eine Januskinase-Inhibitor-Therapie.

We report on a 32-year-old male patient presenting with anti-MDA-5 and anti-Ro52 antibody positive hypomyopathic dermatomyositis (CADM) with clinically leading interstitial pulmonary involvement. Under several immunosuppressive treatment regimens including high-dose steroids, cyclophosphamide, rituximab, immunoglobulins, plasmapheresis, ciclosporin and mycophenolate mofetil, pulmonary involvement was refractory to progressive. Based on the detection of a clear-cut interferon signature by flow cytometric determination of SIGLEC-1 as an interferon-dependent marker, treatment with the Janus kinase inhibitor tofacitinib was initiated. This resulted in a response to treatment with a significant increase in physical performance, an ameliorated skin condition and computed tomographic (CT) morphologically improved interstitial lung disease with overall good tolerability.

Nonequilibrium Mass Transport in the 1D Fermi-Hubbard Model.

We experimentally and numerically investigate the sudden expansion of fermions in a homogeneous one-dimensional optical lattice. For initial states with an appreciable amount of doublons, we observe a dynamical phase separation between rapidly expanding singlons and slow doublons remaining in the trap center, realizing the key aspect of fermionic quantum distillation in the strongly interacting limit. For initial states without doublons, we find a reduced interaction dependence of the asymptotic expansion speed compared to bosons, which is explained by the interaction energy produced in the quench.

The Global Precipitation Climatology Project (GPCP) Monthly Analysis (New Version 2.3) and a Review of 2017 Global Precipitation.

The new Version 2.3 of the GPCP Monthly analysis is described in terms of changes made to improve the homogeneity of the product, especially after 2002. These changes include corrections to cross calibration of satellite data inputs and updates to the gauge analysis. Over ocean, changes starting in 2003 result in an overall precipitation increase of 1.8% after 2009. Updating the gauge analysis to its final, high quality version increases the global land total by 1.8% for the post-2002 period. These changes correct a small, incorrect dip in the estimated global precipitation over the last decade in the earlier Version 2.2. The GPCP analysis is also used to describe global precipitation for 2017. The general La Nina pattern for 2017 is noted and the evolution from the early 2016 El Nino pattern is described. The 2017 global value is one of the highest for the 19792017 period, exceeded only by 2016 and 1998 (both El Nino years) and reinforces the small positive trend. Results for 2017 also reinforce significant trends in precipitation intensity (on a monthly scale) in the tropics. These results for 2017 indicate the value of the GPCP analysis for climate monitoring in addition to research.

Notch inhibition counteracts Paneth cell death in absence of caspase-8.

Opposing activities of Notch and Wnt signaling regulate mucosal barrier homeostasis and differentiation of intestinal epithelial cells. Specifically, Wnt activity is essential for differentiation of secretory cells including Wnt3-producing Paneth cells, whereas Notch signaling strongly promotes generation of absorptive cells. Loss of caspase-8 in intestinal epithelium (casp8∆int) is associated with fulminant epithelial necroptosis, severe Paneth cell death, secondary intestinal inflammation, and an increase in Notch activity. Here, we found that pharmacological Notch inhibition with dibenzazepine (DBZ) is able to essentially rescue the loss of Paneth cells, deescalate the inflammatory phenotype, and reduce intestinal permeability in casp8∆int mice. The secretory cell metaplasia in DBZ-treated casp8∆int animals is proliferative, indicating for Notch activities partially insensitive to gamma-secretase inhibition in a casp8∆int background. Our data suggest that casp8 acts in the intestinal Notch network.