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Background: To date, real-life data on non-surgical correction of Dupuytren’s contracture with collagenase clostridium histolyticum injection (CCH, Xiapex) are limited. Methods and results: In an open-label non-interventional study in in Germany (mean age 65.1±9.8 years, 79.3% males), patients were followed up until 1 year after injection. 63 (73.3%) received the injection at the MCP joint, and 23 (26.7%) at the PIP. The mean grade of contracture in the presently treated finger at baseline was for the MCP joint 32.4°±25.1, for the PIP° 29.2±31.5, and for the DIP° 0.5±2.0. At days 30/360 compared to baseline, the degree of contracture of the MCP joint was reduced by 28.2°±24.6/30.8°±25.0, of the PIP by 20.0°±24.7/8.5°±29.6, and of the DIP by 0.01°±1.9/0.7±2.3. Improvement of hand function at day 30/360 was rated by physicians as very good in 69.5/60.9%, as good in 23.2/28.3%, and as poor in 7.3/8.7%, and none in 0.0/2.2%. No serious adverse drug reactions (SADR) occurred. Adverse drug reactions (ADR) were noted within injection in 64 patients (74.4%), mostly contusion/swelling, pain, blood blister or other bleeding at the injection site, or ecchymosis. In an overall assessment, at day 30/360, 73.5%/95.7% of the physicians rated tolerability of CCH in their patients as very good, 22.9%/2.2% as good, and 3.6%/2.2% as moderate. On the EQ-5D Visual Analog Scale the mean score improved from 79.5±17.9 to 83.8±15.8 at day 30, and to 85.4±14.1 at day 360. On the Michigan Hand Questionnaire, the total score was 67.5 points at baseline, at day 30 and 75.2 points at day 360.Conclusions: Overall, treatment with CCH under clinical practice conditions was effective and well tolerated. Quality of life and hand function improved substantially. No unknown safety issues were identified during the study.

RationaleClinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities.MethodsThe Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology-a non-profit international organisation dedicated to consensus methodology in identification of outcome measures-conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF).ResultsA core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed.ConclusionIdentification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field.

Objectives Pulmonary arterial hypertension (PAH) occurs in various connective tissue diseases (CTDs). We sought to assess contemporary treatment patterns and survival of patients with various forms of CTD-PAH. Methods We analysed data from COMPERA, a European pulmonary hypertension registry, to describe treatment strategies and survival in patients with newly diagnosed PAH associated with SSc, SLE, MCTD, UCTD and other types of CTD. All-cause mortality was analysed according to the underlying CTD. For patients with SSc-PAH, we also assessed survival according to initial therapy with endothelin receptor antagonists (ERAs), phosphodiesterase type 5 inhibitors (PDE5is) or a combination of these two drug classes. Results This analysis included 607 patients with CTD-PAH. Survival estimates at 1, 3 and 5 years for SSc-PAH (n  = 390) were 85%, 59% and 42%; for SLE-PAH (n  = 34) they were 97%, 77% and 61%; for MCTD-PAH (n  = 33) they were 97%, 70% and 59%; for UCTD-PAH (n  = 60) they were 88%, 67% and 52%; and for other CTD-PAH (n  = 90) they were 92%, 69% and 55%, respectively. After multivariable adjustment, the survival of patients with SSc-PAH was significantly worse compared with the other conditions (P  = 0.001). In these patients, the survival estimates were significantly better with initial ERA–PDE5i combination therapy than with initial ERA or PDE5i monotherapy (P  = 0.016 and P  = 0.012, respectively). Conclusions Mortality remains high in patients with CTD-PAH, especially for patients with SSc-PAH. However, for patients with SSc-PAH, our results suggest that long-term survival may be improved with initial ERA–PDE5i combination therapy compared with initial monotherapy. [ABSTRACT FROM AUTHOR]

Background: Primary care physicians (PCP) play a key role in the care of people living with dementia. However, the implementation and practicability of the German S3 Dementia Guideline in primary care remain unclear. The main objective of the present study was to evaluate an intervention for improving guideline‐based dementia care in primary care. Design: A two‐arm, 9‐month follow‐up cluster‐randomized controlled trial with two parallel groups. Setting: 28 primary care practices in Berlin and the surrounding area in Germany. Participants: A total of N = 28 PCP, N = 91 people living with dementia, and N = 88 informal caregivers participated in the trial. Intervention: A tablet‐based intervention to improve adherence to the German S3 Dementia Guideline in primary care was compared to a control group (care as usual plus a handbook on dementia). MeasurementsAdherence to dementia guideline (primary outcome) was measured on PCP' (23 items) and informal caregivers' level (19 items) with a self‐developed checklist. Secondary outcomes (quality of life, neuropsychiatric symptoms, activities of daily living, general health status, depression, and caregiver burden) were measured with standardized assessments. Also, post‐hoc per‐protocol analyses were conducted. Results: No differences in guideline adherence between the intervention and the control group were observed. Further, no significant impact of the intervention on secondary outcomes was detected. Conclusion: The DemTab Study did not improve self‐reported guideline adherence in PCP. However, important implementation barriers such as lack of interoperability and low applicability of existing German S3 Dementia Guideline in the primary care setting were identified and are being discussed. Trial registration: The DemTab trial was prospectively registered with the ISRCTN registry (Trial registration number: ISRCTN15854413). Registered 01 April 2019, https://doi.org/10.1186/ISRCTN15854413. [ABSTRACT FROM AUTHOR]

Objectives The prevalence and characteristics of SSc-associated interstitial lung disease (SSc-ILD) vary between geographical regions worldwide. The objectives of this study were to explore the differences in terms of prevalence, phenotype, treatment and prognosis in patients with SSc-ILD from predetermined geographical regions in the EUSTAR database. Material and methods Patients were clustered into seven geographical regions. Clinical characteristics and survival of patients with SSc-ILD were compared among these pre-determined regions. Results For baseline analyses, 9260 SSc patients were included, with 6732 for survival analyses. The prevalence of SSc-ILD in the overall population was 50.2%, ranging from 44.0% in 'Western Europe and Nordic countries' to 67.5% in 'Eastern European, Russia and Baltic countries'. In all regions, anti-topoisomerase antibodies were associated with SSc-ILD. Management also significantly differed; mycophenolate mofetil was prescribed at baseline in 31.6% of patients with SSc-ILD in 'America (North and South)' and 31.7% in 'Middle East' but only 4.3% in 'Asia and Oceania' (P  <0.0001). Patients from 'America (North and South)' and 'Middle East' had the highest survival rate at the end of follow-up (85.8% and 85.2%, respectively). Conclusions Our study highlights key differences among regions in terms of clinical presentation and prognosis of SSc-ILD. This work also demonstrates that the management of SSc-ILD is highly variable among the different regions considered, suggesting that efforts are still needed for the standardization of medical practice in the treatment of this disease. [ABSTRACT FROM AUTHOR]

Objectives To characterize patients with positive anti-topoisomerase I (ATA) in lcSSc. Methods SSc patients enrolled in the EUSTAR cohort with a disease duration of ≤3 years at database entry were considered. We assessed the risk of major organ involvement in the following groups: ATA-lcSSc vs ACA-lcSSc and vs ANA without specificity (ANA)-lcSSc, and ATA-lcSSc vs ATA-dcSSc. Cox regression models with time-dependent covariates were performed with the following outcomes: new-onset interstitial lung disease (ILD), ILD progression [forced vital capacity (FVC) decline ≥10% and ≥5% vs values at ILD diagnosis), primary myocardial involvement (PMI), pulmonary hypertension (PH), any organ involvement and all-cause mortality. Results We included 1252 patients [194 ATA-lcSSc (15.5%)], with 7.7 years (s. d. 3.5) of follow-up. ILD risk was higher in ATA-lcSSc vs ACA- and ANA-lcSSc and similar to ATA-dcSSc, although with less frequent restrictive lung disease. The risk of FVC decline ≥10% (35% of ATA-lcSSc) was lower in ATA-lcSSc than in ATA-dcSSc, whereas FVC decline ≥5% occurs similarly between ATA-lcSSc (58% of patients) and other SSc subsets, including ATA-dcSSc. The risk of PMI was similar in ATA-lcSSc and ANA-lcSSc but lower than in ACA-lcSSc; no difference in PH and mortality risk was observed among lcSSc subsets. The risk of any organ involvement, PMI and PH was lower and the mortality tended to be lower in ATA-lcSSc vs ATA-dcSSc. Conclusion ATA-lcSSc patients have a high risk of ILD, albeit with a lower risk of progression compared with ATA-dcSSc, supporting careful screening for ILD in this subgroup. [ABSTRACT FROM AUTHOR]