Recommendations for assessing Patient-Reported Outcomes and Health-Related quality of life in clinical trials on allergy: a GA(2)LEN taskforce position paper

The aim of this Global Allergy and Asthma European Network (GA(2)LEN) consensus report is to provide recommendations for patient-reported outcomes (PROs) evaluation in clinical trials for allergic diseases, which constitute a global health problem in terms of physical, psychological economic and social impact. During the last 40 years, PROs have gained large consideration and use in the scientific community, to gain a better understanding of patients' subjective assessment with respect to elements concerning their health condition. They include all health-related reports coming from the patient, without involvement or interpretation by physician or others. PROs assessment should be performed by validated tools (disease-specific tools when available or generic ones) selected taking into account the aim of the study, the expected intervention effects and the determinant and confounding factors or patient-related factors which could influence PROs. Moreover, each tool should be used exclusively in the patient population following the authors' indications without modification and performing a cross-cultural validation if the tool must be used in a language that differs from the original. The result analysis also suggests that the relevance of PROs results in any interventional study should include a pre-post assessment providing information concerning statistical differences within or among groups, rates of response for the PROs and a minimal important difference for the population. The report underlines the importance of further investigation on some topics, such as the quality assessment of existing PROs tools, the definition of inclusion and exclusion criteria and a more extensive evaluation of the correlation between PROs, besides health-related quality of life, and clinical data

1D model of precursors to frictional stick-slip motion allowing for robust comparison with experiments

We study the dynamic behaviour of 1D spring-block models of friction when the external loading is applied from a side, and not on all blocks like in the classical Burridge-Knopoff-like models. Such a change in the loading yields specific difficulties, both from numerical and physical viewpoints. To address some of these difficulties and clarify the precise role of a series of model parameters, we start with the minimalistic model by Maegawa et al. (Tribol. Lett. 38, 313, 2010) which was proposed to reproduce their experiments about precursors to frictional sliding in the stick-slip regime. By successively adding (i) an internal viscosity, (ii) an interfacial stiffness and (iii) an initial tangential force distribution at the interface, we manage to (i) avoid the model's unphysical stress fluctuations, (ii) avoid its unphysical dependence on the spatial resolution and (iii) improve its agreement with the experimental results, respectively. Based on the behaviour of this improved 1D model, we develop an analytical prediction for the length of precursors as a function of the applied tangential load. We also discuss the relationship between the microscopic and macroscopic friction coefficients in the model.Comment: 13 pages, 14 figures, accepted in Tribology Letter

Septicaemia models using Streptococcus pneumoniae and Listeria monocytogenes: understanding the role of complement properdin

Streptococcus pneumoniae and Listeria monocytogenes, pathogens which can cause severe infectious disease in human, were used to infect properdin-deficient and wildtype mice. The aim was to deduce a role for properdin, positive regulator of the alternative pathway of complement activation, by comparing and contrasting the immune response of the two genotypes in vivo. We show that properdin-deficient and wildtype mice mounted antipneumococcal serotype-specific IgM antibodies, which were protective. Properdin-deficient mice, however, had increased survival in the model of streptococcal pneumonia and sepsis. Low activity of the classical pathway of complement and modulation of FcγR2b expression appear to be pathogenically involved. In listeriosis, however, properdin-deficient mice had reduced survival and a dendritic cell population that was impaired in maturation and activity. In vitro analyses of splenocytes and bone marrow-derived myeloid cells support the view that the opposing outcomes of properdin-deficient and wildtype mice in these two infection models is likely to be due to a skewing of macrophage activity to an M2 phenotype in the properdin-deficient mice. The phenotypes observed thus appear to reflect the extent to which M2- or M1-polarised macrophages are involved in the immune responses to S. pneumoniae and L. monocytogenes. We conclude that properdin controls the strength of immune responses by affecting humoral as well as cellular phenotypes during acute bacterial infection and ensuing inflammation

Adaptation and initial results of the Polish version of the GA2LEN Chronic Urticaria Quality Of Life Questionnaire (CU-Q2oL)

Background: Strong negative influence upon the quality of life in chronic urticaria is well proved. Before the GA2LEN Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) was introduced, the quality of life in chronic urticaria had been measured with general or dermatology specific questionnaires. CU-Q2oL was initially developed in Italy and consisted of 23 items divided into 6 quality of life dimensions. Objective: The aim of our study was to adapt the Polish version of CU-Q2oL and to provide initial results from the Polish sample. Methods: To prepare the Polish version forward and back translation was prepared. After cognitive debriefing, we collected a group of 126 chronic urticaria patients who completed Polish CU-Q2oL, Dermatology Life Quality Index (DLQI) and Skindex-29 questionnaire. Disease severity was assessed with Urticaria Activity Score (UAS). We performed the factorial analysis to identify CU-Q2oL subscales in our study, internal consistency and convergent validity assessment as well as factors driving the results. Moreover, we analysed tool's reproducibility and responsiveness. Results: The factor analysis resulted in six subscales of Polish CU-Q2oL version with satisfying face validity: Itching, Swelling/Mental status, Functioning, Sleep, Eating/Limits, Embarrassment. All subscales presented recommended internal consistency and convergent validity. Disease severity was the only factor predicting results of all the subscales. Polish CU-Q2oL version was reproducible and sensitive to change. We noticed the highest quality of life impairment in Itching and Embarrassment subscales whereas Eating/Limits was the least affected. Conclusions: Our study supports reliability, responsiveness and validity of the Polish version of CU-Q2oL - easy in use, non time-consuming instrument to be used in research, clinical management and treatment outcome assessment and is one more step to confirm quality of life impairment in chronic urticaria. © 2011 Japanese Society for Investigative Dermatology