Background
The X‐ACT study aimed to examine the effect of omalizumab treatment on quality of life (QoL) in chronic spontaneous urticaria (CSU) patients with angioedema refractory to high doses of ...H1‐antihistamines.
Methods
In X‐ACT, a phase III, double‐blind, placebo‐controlled study, CSU patients (18‐75 years) with ≥4 angioedema episodes during the 6 months before inclusion were randomized (1:1) to receive omalizumab 300 mg or placebo every 4 weeks for 28 weeks. Angioedema‐related QoL, skin‐related QoL impairment, and psychological well‐being were assessed.
Results
Ninety‐one patients were randomized and 68 (omalizumab, n = 35; placebo, n = 33) completed the 28‐week treatment period. At baseline, the mean (SD) total Angioedema QoL (AE‐QoL; 56.2 18.7 and 59.9 19.2) and Dermatology Life Quality Index (DLQI; 14.6 5.7 and 16.6 7.3) score were high in the omalizumab and placebo group, respectively. At Week 4 (after the first treatment), the least squares mean difference in the AE‐QoL and DLQI score between groups was −17.6 (P < .001) and −7.2 (P < .001), respectively. Significant QoL improvements in the omalizumab vs placebo groups continued until Week 28, but returned to placebo levels at the follow‐up visit. The mean (SD) baseline 5‐item World Health Organization Well‐being Index was 10.0 (5.5, omalizumab) and 7.7 (5.3, placebo), which increased above the depression threshold (<13) from Week 4 and throughout with omalizumab but not placebo treatment. Compared to placebo, omalizumab was also associated with decreased fear of suffocation due to angioedema.
Conclusions
Our findings support omalizumab treatment in patients with severe H1‐antihistamine‐refractory CSU with angioedema.
The installation process changes the state of the soil in the vicinity of a pile and therefore influences its load-displacement behaviour during the operational phase following the installation. The ...installation process itself and its effect on the pile behaviour under a subsequent high-cyclic loading are numerically investigated in this work. Two different installation techniques, namely impact driving and jacking, are investigated using a coupled Eulerian-Lagrangian approach in combination with a hypoplastic material model. Either ideally drained or partially drained conditions are assumed. Afterwards the pile response to a high-cyclic loading with up to five million load cycles is studied using a high-cycle accumulation (HCA) model. Compared to a wished-in-place (WIP) pile, the simulations accounting for the installation process showed considerable less permanent pile displacements in case of initially medium dense sand. However, the opposite was observed in case of initially dense sand. Current practice assuming a WIP state as the starting point in numerical simulations seems thus to be conservative for initially medium dense sand but leads to an underestimation of permanent deformations for initially dense sand.
•Coupled Eulerian-Lagrangian (CEL) method considering partially drained conditions for problems with high accelerations.•Simulation of pile installation considering partially drained conditions using the CEL method.•Influence of the installation on the long-term cyclic behaviour using the high-cycle accumulation (HCA) model.
Background: The current EAACI/GA²LEN/EDF guidelines recommend assessing disease activity in chronic urticaria (CU) by using an established and well‐defined symptom score, i.e. the urticaria activity ...score (UAS), which combines daily wheal numbers and pruritus intensity. However, this UAS has never been formally tested for its suitability in assessing CU activity.
Aim: To determine the UAS correlation with quality of life (QoL) in CU patients and to compare the UAS to other symptom scores.
Methods: Chronic urticaria symptoms (wheals, erythema, angioedema, pruritus) were assessed on seven consecutive days in 111 CU patients for their numbers, duration, size, and/or intensity. Quality of life was assessed by using the Dermatology Life Quality Index. Both, urticaria activity and QoL were determined before and after a 3‐week period, in which the patients followed a pseudoallergen‐low diet.
Results: Urticaria activity score values correlated positively, albeit weakly, with QoL impairment in CU patients (r2 = 0.31, P < 0.05). Also, changes in QoL following a pseudoallergen‐low diet were reflected by the changes observed in the UAS (r2 = 0.30, P < 0.05). No significant differences were found comparing the QoL correlation of the UAS and other symptom scores combining up to four CU symptom qualities. Quality of life correlation with UAS values increased with the number of days the UAS was assessed and plateaued starting from the fourth consecutive day.
Conclusions: Our findings back the current guideline recommendations to use the UAS for monitoring disease activity in CU patients. Urticaria activity score mean values of at least four consecutive days should be used.
Earthquake stability assessment of large opencast mine slopes are complex and non-linear problems, often addressed using pseudo-static approaches neglecting material-induced failures and the role of ...pore-fluids. In this study, a numerical approach is used to understand the dynamic response of saturated and partially saturated soils. For this purpose user-defined elements have been implemented in Abaqus/Standard including user-defined material models. The governing equations involving coupled fluid flow and finite deformation processes in partially saturated soils are derived within the framework of the Theory of Porous Media. The stress-strain behavior of granular soils is represented by a hypoplastic constitutive model and for clayey soils the ISA-Clay model is used. The saturation-suction behavior is modeled using the van Genuchten model. To account for the large scale of the finite element model, a scaling procedure of the system of equations is proposed to purge the influence of initial stress. The performance of the user-defined elements is tested by back analysis of a centrifuge test available in the literature. Finally, large-scale fully coupled finite element simulations are performed to study the response of a flooded opencast mine under earthquake loading. The paper illustrates the importance of accounting the pore-fluids as independent phases in the context of seismic analysis of slopes and the influence of simplifications on which the calculation is based are highlighted. The simulations show strong wave diffraction effects for inhomogeneous dump structures, resulting in smaller displacements in near-surface areas of the slope. Further it was found that large areas of the dump show a temporary decrease of effective stress. The initial strong differences in stiffness between the different materials may decrease with time after several seismic events due stress redistributions caused by earthquakes.
•Large-scale FE simulation of an opencast mine with inhomogeneous internal geometry.•Influence of additional compaction measures on the earthquake resistance.•Influence of initial stress on the numerical stability of large-scale FE simulations.•Modification of the System of Equations for large-scale geotechnical simulations.
Plasma concentration–time profiles of talinolol following a single oral dose of 100mg alone (control), with a single dose of quercetin and after short-term treatment with quercetin (mean±SD, n=10).
...Quercetin has been shown to inhibit intestinal P-glycoprotein-mediated drug efflux. A crossover clinical study was performed in 10 healthy volunteers to assess the effect of single-dose and repeated quercetin intake on the pharmacokinetics of talinolol, a substrate of intestinal P-glycoprotein. Unexpectedly, mean area under the plasma concentration–time curve (AUC0–48h) and maximal plasma concentration (cmax) were slightly decreased following concomitant and short-term quercetin administration (3186.0 versus 2468.3 and 2527.7ngh/ml, p>0.05; 309.7 versus 212.0 and 280.6ng/ml, p>0.05). Individual analysis revealed that talinolol AUC0–48h was lowered by 23.9% up to 60.6% in 5 subjects and cmax was decreased by 29.2% up to 78.7% in 7 subjects after quercetin co-administration. These effects were less pronounced following repeated quercetin intake. Overlapping modification of efflux and uptake transport involving carrier proteins of the OATP superfamily as well as site–dependent interaction are possible explanations for these observations. In conclusion, clinically relevant quercetin–drug interaction cannot be ruled out.
Background
The Atopic Dermatitis (AD) TREATgermany registry was initiated by the German Society for Dermatology (DDG) in 2011 to evaluate the ‘real‐life’ situation of health care for patients with ...AD.
Objectives
Interim data analysis on baseline characteristics as well as current and prescribed systemic treatments of the TREATgermany registry patients.
Methods
Patients (≥18 years) with moderate‐to‐severe AD objective (o)SCORAD > 20, or with current or previous anti‐inflammatory systemic treatment for AD within 24 months, were included and are followed up over at least 24 months. To assess clinical signs, the eczema area severity index (EASI, 0–72), the oSCORAD (0–83) and the Investigator Global Assessment (IGA; 6‐point scale) were used. The disease severity was globally scored by the patients Patient Global Assessment (PGA); six‐step Likert scale. Disease symptoms were assessed by the patient‐oriented eczema measure (POEM, 0–28) and numeric rating scales (NRS, 0–10). Health‐related quality of life was measured using the dermatological life quality index (DLQI, 0–30).
Results
A total of 612 patients were recruited across 32 sites between 06/2016 and 01/2019 (mean age: 42.6 ± 14.2 years; mean oSCORAD: 40.8 ± 16.3). The mean POEM score was 16.3 ± 7.5. Pruritus was rated highest among subjective symptoms (NRS: 5.4 ± 2.7). The mean DLQI value was 11.3 ± 7.5. The frequency of arterial hypertension was lower (20.8%) compared with the general population, whilst this was higher for depression (10%). More than 60% of the patients had received systemic glucocorticosteroids, and 36.8% had received cyclosporine A prior to inclusion. Dupilumab was the leading substance documented as either ‘current’ (12.1%) or ‘prescribed’ (31.4%) at baseline.
Conclusions
These ‘real‐life’ data clearly demonstrate the substantial disease burden. Most of TREATgermany patients were already treated with or prescribed dupilumab at baseline. Moreover, current findings indicate the urgent need for further alternative agents in order to achieve a perceptible improvement of quality of life of patients with moderate‐to‐severe AD.
The aim of this multicentre, randomized, double-blind, placebo-controlled, cross-over, phase-II study was to determine the antipruritic effect of aprepitant vs. placebo in 58 patients with ...anti-histamine-refractory chronic pruritus in chronic nodular prurigo. Patients were randomized to receive either first oral aprepitant 80 mg/day or placebo for 4 weeks. Following a 2-week wash-out phase, the patients were crossed-over to receive the other treatment for 4 weeks. Primary efficacy criterion was the intra-individual difference between mean itch intensity (visual analogue scale) at baseline compared with the end of treatment period. Prurigo lesions, pruritus course, quality of life, patient benefits, and safety were secondary parameters. No significant differences were found between aprepitant treatment and placebo for any of the parameters investigated. Under the experimental conditions of the study, aprepitant, 80 mg daily for 4 weeks, did not have an antipruritic effect in patients with chronic prurigo. (DRKS00005594; EudraCT Number: 2013-001601-85).
Background
Comprehensive data on the epidemiology and comorbidities of chronic urticaria (CU) in Germany are either limited, or not contemporary.
Objectives
To investigate the epidemiology of CU, ...overall comorbidities and healthcare resource utilized by patients with CU in Germany, using an anonymized statutory health insurance (SHI) database.
Methods
Anonymized SHI claims research database of the Institute for Applied Health Research, Berlin InGef (01 January 2015–30 September 2018) was used to analyse insured individuals with a confirmed diagnosis of CU (ICD‐10‐GM codes). Twelve‐month diagnosed prevalence and incidence, comorbidities (vs. atopic dermatitis and psoriasis), and healthcare utilization by patients with CU were investigated.
Results
Of 4 693 772 individuals of all ages listed in the database, 3 538 540 were observable during 2017. Overall, 17 524 patients (˜0.5%) were diagnosed with CU; chronic spontaneous urticaria (CSU: 71.2%), chronic inducible urticaria (CIndU: 19.7%), CSU+CIndU (9.1%). Females, vs. males, had higher diagnosed prevalence (0.62% vs. 0.37%) and diagnosed incidence (0.18% vs. 0.11%) of CU among all patients. Patients most frequently visited general practitioners (41.3% of total visits). Hypertensive diseases (43.5%), lipoprotein metabolism disorders (32.1%) and affective disorders (26.0%) were the most frequently reported comorbidities of special interest. Rates of most comorbidities of special interests were similar to atopic dermatitis and psoriasis patients, and all higher vs. overall population. More than half (54.1%) of all CU patients were not prescribed any treatment. Second‐generation H1‐antihistamines were the most commonly prescribed medication for adult (17.9%) and paediatric (27.9%) patients. Patients with CIndU (paediatric, 15.5%; adult, 7.8%) were more often hospitalized versus patients with CSU (paediatric, 9.9%; adult, 4.6%).
Conclusions
In Germany, prevalence of CU along with multiple comorbidities may pose increased burden on the healthcare system. Awareness of adhering to treatment guidelines, and aiming for complete control of urticaria, needs to be driven and may improve outcomes.
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