Current treatment goals are achieved by the majority of patients with atopic dermatitis treated with tralokinumab: results from a multicentric, multinational, retrospective, cohort study.

BACKGROUND: Tralokinumab is a human monoclonal antibody targeting interleukin-13 that is approved for the treatment of moderate-severe atopic dermatitis. Studies analyzing the efficacy and safety of tralokinumab in a real-world setting are scarce. RESEARCH DESIGN AND METHODS: A European, multicentric, real-world, retrospective cohort study was defined to assess the effectiveness and safeness profile of tralokinumab, investigating the achievement of pre-specified treatment goals; and to detect potential differences in terms of effectiveness and safeness across some selected patient subcohorts. RESULTS: A total of 194 adult patients were included in this study. A significant improvement in physician-assessed disease severity was detected at each follow-up visit as compared with baseline and similar trend was observed for patient-reported outcomes and quality of life. No meaningful difference in effectiveness was found when considering patient age (<65 versus ≥65 years), neither dissecting patient cohort in dupilumab-naive vs dupilumab-treated subjects. Among tralokinumab-treated patients, 88% achieved at least one currently identified real-world therapeutic goal at week 16. CONCLUSIONS: This retrospective multicenter study confirmed the effectiveness and safeness of tralokinumab throughout 32 weeks of observation, showing the achievement of therapeutic goals identified in both trial and real-world settings in a large proportion of tralokinumab-treated patients.

Features and predictors of activity limitations and participation restriction 2 years after intensive rehabilitation following first-ever stroke.

BACKGROUND: Although stroke-related disability has been extensively studied, only few studies have investigated Participation restriction in chronic stroke survivors. AIM: To identify features and predictors of Activity limitation and Participation restriction in the chronic phase of a first-ever stroke. DESIGN: Cross-sectional observational study. SETTING: Comprehensive stroke unit with outpatient rehabilitation facility. POPULATION: Subjects submitted to intensive rehabilitation after first-ever stroke, from 1st January 2009 to 31st December 2010. METHODS: Participation was investigated through the Frenchay Activity Index (FAI) and the Functional Status Questionnaire (FSQ) at 2.4±0.5 years after the event. Basic activities of daily living (ADL) and mood were also assessed through the Modified Barthel Index (MBI) and the Beck Depression Inventory (BDI). A retrospective search of the medical records looked for: type/side of brain lesion, stroke clinical syndromes, comorbidities and functional condition at discharge from intensive rehabilitation (upper limb motricity index-ULMI-, Functional Ambulation Category-FAC, MBI, cognitive deficits). RESULTS: Forty-five subjects (17 female, age 70.1±11.5 years) were enrolled. They showed a striking restriction in their Participation, mainly for FAI-outdoor activities (median FAI score was <50% of the theoretical maximum). A poor gait function (FAC) and an impaired mood (BDI) were the only independent predictors of FAI indoor (F=6.1; p=,005; R^2= 64%) and outdoor activities (F=4.1; P=0.01; R^2=48%), respectively. The univariate analysis showed a strong dependence of all FSQ scores from global disability (MBI), motor function impairment (ULMI and FAC) and cognitive deficits. Depression influenced "psychological function" score, whereas gait capacity was the only factor significantly associated with the "work performance" score. The gait function level, achieved after intensive rehabilitation, was extrapolated by the multivariate analysis, as the most powerful independent predictor of the chronic activity limitations, as measured by MBI (F=33.8, P<0.0001, R2=0.539). CONCLUSION: Gait dysfunction is the main factor of Activity limitations and Participation restriction in chronic stroke. Participation is restricted by global disability, depression, older age and dementia. More than 50% variance of Participation measures cannot be explained by the quoted factors. CLINICAL REHABILITATION IMPACT: The study results support the need to integrate the standard rehabilitation approach with vocational rehabilitation in order to reduce Participation restriction.

Hydration of chloride anions in the NanC Porin from Escherichia coli: a comparative study by QM/MM and MD simulations.

Chloride anions permeate the bacterial NanC porin in physiological processes. Here we present a DFT-based QM/MM study of this porin in the presence of these anions. Comparison is made with classical MD simulations on the same system. In both QM/MM and classical approaches, the anions are almost entirely solvated by water molecules. However, the average water-Cl(-) distance is significantly larger in the first approach. Polarization effects of protein groups close to Cl(-) anion are sizeable. These effects might modulate the anion-protein electrostatic interactions, which in turn play a central role for selectivity mechanisms of the channel.