Mepolizumab versus placebo for asthma

Background Mepolizumab is a human monoclonal antibody against interleukin-5 (IL-5), the main cytokine involved in the activation of eosinophils, which in turn causes airway inflammation. Recent studies have suggested these agents may have a role in reducing exacerbations and improving health-related quality of life (HRQoL). There are no recommendations for the use of mepolizumab in adults or children in the recent update of the BTS/SIGN guidelines (BTS/SIGN 2014). Objectives To compare the effects of mepolizumab with placebo on exacerbations and HRQoL in adults and children with chronic asthma. Search methods We searched the Cochrane Airways Group Register (CAGR) of trials, clinical trial registries, manufacturers' websites and the reference lists of included studies. Searches were conducted in November 2013 and updated in November 2014. Selection criteria We included randomised controlled trials comparing mepolizumab versus placebo in adults and children with asthma. Data collection and analysis Two authors independently extracted data and analysed outcomes using a random-effects model. We used standard methods expected by The Cochrane Collaboration. Main results Eight studies on 1707 participants met the inclusion criteria. Only two studies included children (over 12 years of age), but they did not report separate findings for the adolescents. Seven studies involved intravenous mepolizumab alone; one included a subcutaneous arm. There was heterogeneity in the severity and clinical pattern of asthma among the participants in the eight studies, varying from mild to moderate atopic asthma, to persistent asthma and eosinophilic asthma with recurrent exacerbations. Selection bias was a concern in several of the studies included in this review. Four trials compared intravenous mepolizumab to placebo in relation to HRQoL. Two studies measured scores from the Asthma Quality of Life Questionnaire (AQLQ), which showed a non-significant difference between mepolizumab and placebo (mean difference (MD) 0.21, 95% confidence interval (CI) − 0.01 to 0.44; participants = 682), in the direction favouring mepolizumab. The third study used the St. George's Respiratory Questionnaire (SGRQ) and found a significant difference between mepolizumab and placebo (MD 6.40, 95% CI 3.15 to 9.65; participants = 576), which indicated a clinically important benefit favouring mepolizumab. A fourth study noted that there was no significant difference but did not provide any data. The two studies in people with eosinophilic asthma showed a reduction in clinically significant exacerbation rates (Risk Ratio 0.52, 95% CI 0.43 to 0.64; participants = 690). However, an analysis of four studies that were not confined to people with eosinophilic asthma indicated considerable heterogeneity and no significant difference in people with one or more exacerbations between mepolizumab and placebo using a random-effects model (Risk Ratio 0.67, 95% CI 0.34 to 1.31; participants = 468; I2 = 59%).The analysis of serious adverse events indicated a significant difference favouring mepolizumab (Risk ratio 0.49, 95% CI 0.30 to 0.80; participants = 1441; studies = 5; I2 = 0%). It was not possible to combine the results for adverse events, and we deemed the quality of this evidence to be low. A single study compared subcutaneous mepolizumab to placebo in 385 adults with severe eosinophilic asthma and found an improvement in HRQoL scores and a reduction in asthma exacerbations, including exacerbations requiring admission to hospital. Authors' conclusions It is not possible to draw firm conclusions from this review with respect to the role of mepolizumab in patients with asthma. Our confidence in the results of this review are limited by the fact that the intravenous route is not currently licensed for mepolizumab, and the evidence for the currently licenced subcutaneous route is limited to a single study in participants with severe eosinophilic asthma. The currently available studies provide evidence that mepolizumab can lead to an improvement in health-related quality of life scores and reduce asthma exacerbations in people with severe eosinophilic asthma. Further research is needed to clarify which subgroups of patients with asthma could potentially benefit from this treatment. Dosage, ideal dosing regimens and duration of treatment need to be clarified, as the studies included in this review differed in their protocols. There are no studies reporting results from children, so we cannot comment on treatment for this age group. At the present time, larger studies using licenced treatment regimens are required to establish the role of mepolizumab in the treatment of severe asthma

Evaluation of characterization methods of Printer MTF

We explore two recent methods for measuring the Modeling Transfer Function of a printing system. We investigate the dependency on the amplitude when using the sinusoidal patches of the method proposed in and show that for too small amplitudes the measurement of the MTF is not trustworthy. For the method proposed in we discuss the underlying theory and in particular the use of a significance test for a statistical analysis. Finally we compare both methods with respect our application – the processing and printing of photographic images

Compensating Printer Modulation Transfer Function in Spatial and Color Adaptive Rendering Workflows

Experiments have shown that the quality of printed images depends on the capacity of the printing system to accurately re- produce details. We propose to improve the quality by compensat- ing for the Modulation Transfer Function (MTF) of the printing system. The MTF of the printing system is measured using a mod- ified version of the method proposed by Jang and Allebach [1]. Then the MTF is adaptively compensated in the Fourier domain, depending on the frequency and on the local mean value. This compensation is included within our mathematical framework for Spatial and Color Adaptive Gamut Mapping Algorithms. Results of a category judgment experiment show significant improvement as the printed MTF compensated images obtain the best scores

Measurement of printer MTFs

In this paper we compare three existing methods to measure the Modulation Transfer Function (MTF) of a printing system. Although all three methods use very distinct approaches, the MTF values computed for two of these methods strongly agree, lending credibility to these methods. Additionally, we propose an improvement to one of these two methods, initially proposed by Jang & Allebach. We demonstrate that our proposed modification improves the measurement precision and simplicity of implementation. Finally we discuss the pros and cons of the methods depending on the intended usage of the MTF

Compensation of printer MTFs

Preliminary experiments have shown that the quality of printed images depends on the capacity of the printing system to accurately reproduce details.1 We propose to improve the quality of printed images by compensating for the Modulation Transfer Function (MTF) of the printing system. The MTF of the printing system is measured using the method proposed by Jang and Allebach,2 in which test pages consisting of series of patches with different 1D sinusoidal modulations (modified to improve the accuracy of the results3) are printed, scanned and analyzed. Then the MTF is adaptively compensated in the Fourier domain, depending both on frequency and local mean values. Results of a category judgment experiment show significant improvement as the printed MTF compensated images obtain the best scores

Comparison of CD63 Upregulation Induced by NSAIDs on Basophils and Monocytes in Patients with NSAID Hypersensitivity

Background. An in vitro basophil activation test, based on the detection of CD63 upregulation induced by NSAIDs, has been described. Its clinical significance remains controversial. Objectives. In patients with a history of nonallergic NSAID hypersensitivity, stratified according to the severity of the symptoms, to assess with NSAIDs the predictive value of basophil (BAT) and monocyte (MAT) activation tests. Patients/Methods. Sixty patients who had NSAIDs-induced or exacerbated urticaria/angiooedema and 20 controls was included. After incubation with NSAIDs or acetaminophen, leukocytes were analysed for CD63 upregulation. Results. With aspirin, the sensitivity (37%) and specificity (90%) of BAT agree with already published results. In contrast, when patients had had cutaneous and visceral reactions, the frequency of positive BAT 14/22 (64%, P < 0.001) or MAT 10/22 (46%, P < 0.01) were increased. Conclusions. Positive tests were more frequent among patients having a severe hypersensitivity contrasting with the other patients who had results similar to controls

Randomized, double-blind, placebo-controled clinical trial of sublingual immunotherapy in natural rubber latex allergic patients

<p>Abstract</p> <p>Background</p> <p>Natural rubber latex allergy is a common and unsolved health problem. Since the avoidance of exposure is very difficult, immunotherapy is strongly recommended, but before its use in patients, it is essential to prove the efficacy and safety of extracts.</p> <p>The aim of the present randomised, double-blind, placebo-controlled clinical trial was to assess the efficacy and tolerability of latex sublingual immunotherapy in adult patients undergoing permanent latex avoidance.</p> <p>Methods</p> <p>Twenty-eight adult latex-allergic patients (5 males and 23 females), with mean age of 39 years (range 24-57) were randomized to receive a commercial latex-sublingual immunotherapy or placebo during one year, followed by another year of open, active therapy. The following outcomes were measured at baseline and at the end of first and second year of follow-up: skin prick test, gloves-use score, conjunctival challenge test, total and specific IgE, basophil activation test, and adverse reactions monitoring.</p> <p>Results</p> <p>No significant difference in any of the efficacy <it>in vivo </it>variables was observed between active and placebo groups at the end of the placebo-controlled phase, nor when each group was compared with their baseline values at the end of the two year-study. An improvement in the average percentage of basophils activated was observed. During the induction phase, 4 reactions in the active group and 5 in the placebo group were recorded. During the maintenance phase, two patients dropped out due to pruritus and to acute dermatitis respectively.</p> <p>Conclusion</p> <p>Further studies are needed to evaluate latex-sublingual immunotherapy, since efficacy could not be demonstrated in adult patients with avoidance of the allergen.</p> <p>Trial registration number</p> <p><a href="http://www.anzctr.org.au/ACTRN12611000543987.aspx">ACTRN12611000543987</a></p