ObjectiveTo analyse the impact of the COVID-19 pandemic on rheumatic patients’ and rheumatologists’ usage, preferences and perception of digital health applications (DHAs).MethodsA web-based national survey was developed by the Working Group Young Rheumatology of the German Society for Rheumatology and the German League against Rheumatism. The prospective survey was distributed via social media (Twitter, Instagram and Facebook), QR code and email. Descriptive statistics were calculated, and regression analyses were performed to show correlations.ResultsWe analysed the responses of 299 patients and 129 rheumatologists. Most patients (74%) and rheumatologists (76%) believed that DHAs are useful in the management of rheumatic and musculoskeletal diseases (RMDs) and felt confident in their own usage thereof (90%; 86%). 38% of patients and 71% of rheumatologists reported that their attitude had changed positively towards DHAs and that their usage had increased due to COVID-19 (29%; 48%). The majority in both groups agreed on implementing virtual visits for follow-up appointments in stable disease conditions. The most reported advantages of DHAs were usage independent of time and place (76.6%; 77.5%). The main barriers were a lack of information on suitable, available DHAs (58.5%; 41.9%), poor usability (42.1% of patients) and a lack of evidence supporting the effectiveness of DHAs (23.2% of rheumatologists). Only a minority (<10% in both groups) believed that digitalisation has a negative impact on the patient–doctor relationship.ConclusionThe COVID-19 pandemic instigated an increase in patients’ and rheumatologists’ acceptance and usage of DHAs, possibly introducing a permanent paradigm shift in the management of RMDs.

Objective Mepolizumab proved to be an efficacious treatment for eosinophilic granulomatosis with polyangiitis (EGPA) at a dose of 300 mg every 4 weeks in the randomized, controlled MIRRA trial. In a few recently reported studies, successful real‐life experiences with the approved dose for treating severe eosinophilic asthma (100 mg every 4 weeks) were observed. We undertook this study to assess the effectiveness and safety of mepolizumab 100 mg every 4 weeks and 300 mg every 4 weeks in a large European EGPA cohort. Methods We included all patients with EGPA treated with mepolizumab at the recruiting centers in 2015–2020. Treatment response was evaluated from 3 months to 24 months after initiation of mepolizumab. Complete response to treatment was defined as no disease activity (Birmingham Vasculitis Activity Score [BVAS] = 0) and a prednisolone or prednisone dose (or equivalent) of ≤4 mg/day. Respiratory outcomes included asthma and ear, nose, and throat (ENT) exacerbations. Results Two hundred three patients, of whom 191 received a stable dose of mepolizumab (158 received 100 mg every 4 weeks and 33 received 300 mg every 4 weeks) were included. Twenty‐five patients (12.3%) had a complete response to treatment at 3 months. Complete response rates increased to 30.4% and 35.7% at 12 months and 24 months, respectively, and rates were comparable between mepolizumab 100 mg every 4 weeks and 300 mg every 4 weeks. Mepolizumab led to a significant reduction in BVAS score, prednisone dose, and eosinophil counts from 3 months to 24 months, with no significant differences observed between 100 mg every 4 weeks and 300 mg every 4 weeks. Eighty‐two patients (40.4%) experienced asthma exacerbations (57 of 158 [36%] who received 100 mg every 4 weeks; 17 of 33 [52%] who received 300 mg every 4 weeks), and 31 patients (15.3%) experienced ENT exacerbations. Forty‐four patients (21.7%) experienced adverse events (AEs), most of which were nonserious AEs (38 of 44). Conclusion Mepolizumab at both 100 mg every 4 weeks and 300 mg every 4 weeks is effective for the treatment of EGPA. The 2 doses should be compared in the setting of a controlled trial.

The histaminergic neurons in the tuberomamillary nucleus (TMN) of the posterior hypothalamus are involved in the control of arousal. These neurons are sensitive to hypercapnia as has been shown in experiments examining c-Fos expression, a marker for increased neuronal activity. We investigated the mechanisms through which TMN neurons respond to changes in extracellular levels of acid/CO2. Recordings in rat brain slices revealed that acidification within the physiological range (pH from 7.4 to 7.0), as well as ammonium chloride (5 mM), excite histaminergic neurons. This excitation is significantly reduced by antagonists of type I metabotropic glutamate receptors and abolished by benzamil, an antagonist of acid-sensing ion channels (ASICs) and Na+/Ca2+ exchanger, or by ouabain which blocks Na+/K+ ATPase. We detected variable combinations of 4 known types of ASICs in single TMN neurons, and observed activation of ASICs in single dissociated TMN neurons only at pH lower than 7.0. Thus, glutamate, which is known to be released by glial cells and orexinergic neurons, amplifies the acid/CO2-induced activation of TMN neurons. This amplification demands the coordinated function of metabotropic glutamate receptors, Na+/Ca2+ exchanger and Na+/K+ ATPase. We also developed a novel HDC-Cre transgenic reporter mouse line in which histaminergic TMN neurons can be visualized. In contrast to the rat, the mouse histaminergic neurons lacked the pH 7.0-induced excitation and displayed only a minimal response to the mGluR I agonist DHPG (0.5 μM). On the other hand, ammonium-induced excitation was similar in mouse and rat. These results are relevant for the understanding of the neuronal mechanisms controlling acid/CO2-induced arousal in hepatic encephalopathy and obstructive sleep apnoea. Moreover, the new HDC-Cre mouse model will be a useful tool for studying the physiological and pathophysiological roles of the histaminergic system.

Objective Despite increased physician’s awareness and improved diagnostic and serological testing in the recent years, the interval between the initial symptoms and the diagnosis of Systemic lupus erythematosus (SLE) is still very long. Our aim was to study this delay and its association to the outcome of the disease. Methods Information on demographics, onset of first symptoms, first physicians visit and time of diagnosis was assessed by self-reported questionnaires among SLE patients in Germany (LuLa cohort, n = 585) in the year 2012. Disease activity (Systemic Lupus Activity Questionnaire; SLAQ), disease related damage (Brief Index of Lupus Damage; BILD), health related quality of life (Short Form 12) and fatigue (FSS) were chosen as proxies for outcome. Linear regression analysis was used to analyze the association of the delay in diagnosis to the outcome, adjusted for age, disease duration and sex. Results Mean duration between the onset of symptoms and the diagnosis of SLE was 47 months (SD 73). The longer the time to diagnosis, the higher the disease activity (β = 0.199, p < 0.0001), the disease-related damage (β = 0.137, p = 0.002) and fatigue (β 0.145, p = 0.003) and the lower the health-related quality of life (physical β = −0.136, p = 0.004, mental β = −0.143, p = 0.004). Conclusion In systemic lupus erythematosus, longer time to diagnosis was associated with worse outcome. Concepts in care with the intention to shorten the time to diagnosis are needed to improve the long-term outcome of the disease.

Objective Our aim was to study the quality of medical care in patients with systemic lupus erythematosus (SLE) to understand gaps and to analyze the association with outcome of the disease. Methods Information on demographics and medical care was assessed by self-reported questionnaires among SLE patients (LuLa cohort, 2011, n = 580). In total, 21 aspects of medical care were analyzed. Univariate analysis selected 10 predictor variables for further analysis: (1) urine examination and (2) blood test in the previous year, (3) taking antimalarials, (4) taking vitamin D and calcium if the dosage of prednisolone was greater than 7.5 mg/day, counseling regarding (5) lipid metabolism, (6) vaccination, and (7) blood pressure, and treatment of the comorbidities (8) hypertension, (9) osteoporosis and (10) lipid metabolism disorder. The association of these 10 items with the outcome of the disease, assessed in 2015, was analyzed by linear regression analysis, adjusted for age, disease duration and sex. Results On average six of the 10 items were met (±1.7). Receiving more clinical care in 2013 was predictive for low disease activity (SLAQ, p = 0.024, β = –0.104, corr. R2 = 0.048), low progress in disease-related damage (Delta Brief Index of Lupus Questionnaire, p = 0.048, β = –0.132, corr. R2 = 0.036) and high health-related quality of life (SF-12 physical, p = 0.035, β = 0.100, corr. R2 = 0.091) in 2015. Conclusion Our study illustrates a link between the quality of care and the SLE outcome parameters disease activity, disease-related damage and quality of life. Consistent considerations of these care parameters, which are recommended in several management guidelines, could therefore be a good approach to improve the outcome of patients with SLE.

A few decades ago, the therapy goal of patients with systemic lupus erythematosus (SLE) was survival and the prevention of organ failure. Today, clinical remission and low disease activity are believed to be the optimal therapeutic targets. These aims are difficult to reach for many patients, but they still do not address the health-related quality of life (QoL) that is significantly impaired in SLE patients. Even in the state of remission, QoL and fatigue are insufficient controlled. Thus, patient-oriented research is essential to design new strategies for the management of lupus patients. The INTEGRATE project analyses the patients’ and physicians’ perspectives to pave the way to design an innovative therapeutic strategy for lupus and focuses on the multifaceted dimensions of the disease burden. Shared decision making (SDM) could include the patient’s perspective of SLE to treatment strategy and consider QoL and the burden of lupus into the process of therapy decision.

Breathing and vigilance are regulated by pH and CO2 levels in the central nervous system. The hypocretin/orexin (Hcrt/Orx)- and histamine (HA)-containing hypothalamic neurons synergistically control different aspects of the waking state. Acidification inhibits firing of most neurons but these two groups in the caudal hypothalamus are excited by hypercapnia and protons, similar to the chemosensory neurons in the brain stem. Activation of hypothalamic wake-on neurons in response to hypercapnia, seen with the c-Fos assay, is supported by patch-clamp recordings in rodent brain slices: Hcrt/Orx and HA neurons are excited by acidification in the physiological range (pH from 7.4 to 7.0). Multiple molecular mechanisms mediate wake-promoting effects of protons in HA neurons in the tuberomamillary nucleus (TMN): among them are acid-sensing ion channels, Na(+),K(+)-ATPase, group I metabotropic glutamate receptors (mGluRI). HA neurons are remarkably sensitive to the mGluRI agonist DHPG (threshold concentration 0.5 µM) and mGluRI antagonists abolish proton-induced excitation of HA neurons. Hcrt/Orx neurons are excited through block of a potassium conductance and release glutamate with their peptides in TMN. The two hypothalamic nuclei and the serotonergic dorsal raphe cooperate toward CO2/acid-induced arousal. Their interactions and molecular mechanisms of H(+)/CO2-induced activation are relevant for the understanding and treatment of respiratory and metabolic disorders related to sleep-waking such as obstructive sleep apnea and sudden infant death syndrome.

Objective The aim of this study was to identify factors associated with impaired work productivity and impaired daily activities in patients with systemic lupus erythematosus (SLE). Methods The LuLa study is a longitudinal patient-reported study. Beyond sociodemographic data, work productivity, daily activities and fatigue, several other clinical outcome parameters (e.g. mental health–related quality of life and physical functioning, disease activity, damage and pain) were surveyed with validated questionnaires. The effects of confounders on work productivity (WPAI 2) and daily activity domains (WPAI 4) were studied by multivariate regression analysis. Results A total of 585 patients completed the questionnaire of whom 259 were employed and analysed. The median impairment in work productivity (WPAI 2) was 20% (Q1–3 0–40), and the median impairment in daily activities (WPAI 4) was 30% (Q1–3 10–50%). Multivariate regression analysis revealed that fatigue, pain, disease activity and health-related quality of life affected WPAI 2 and 4. Furthermore, we observed distinct synergistic effects of fatigue, disease activity and pain on both work productivity and daily activities: a higher impact of fatigue was associated with the reported extent of pain or disease activity. Conclusion In employed patients with SLE, impaired work productivity and impaired daily activities were frequently reported. Fatigue, pain, disease activity and health-related quality of life demonstrated a detrimental impact, with a synergistic effect of fatigue, disease activity and pain. Hence, both optimized pain management and targeted immunomodulatory therapy are important for preserving active participation in life among patients with fatigue.