Prevention of Atopic Dermatitis

Despite advances in atopic dermatitis (AD) treatments, research into AD prevention has been slow. Systematic reviews of prevention strategies promoting exclusive and prolonged breastfeeding, or interventions that reduce ingested or airborne allergens during pregnancy and after birth have generally not shown convincing benefit. Maternal/infant supplements such as Vitamin D have also not shown any benefit with the possible exception of omega-3 fatty acids. Systematic reviews suggest that probiotics could reduce AD incidence by around 20%, although the studies are quite variable and might benefit from individual patient data meta-analysis. Skin barrier enhancement from birth to prevent AD and food allergy has received recent interest, and results from national trials are awaited. It is possible that trying to influence major immunological changes that characterise AD at birth through infant-directed interventions may be too late, and more attention might be directed at fetal programming in utero

Coevolutionary diversification creates nested-modular structure in phage-bacteria interaction networks

This is a post-print of an article published in Interface Focus. Please cite the published article.Phage and their bacterial hosts are the most diverse and abundant biological entities in the oceans, where their interactions have a major impact on marine ecology and ecosystem function. The structure of interaction networks for natural phage-bacteria communities offers insight into their coevolutionary origin. At small phylogenetic scales, observed communities typically show a nested structure, in which both hosts and phage can be ranked by their range of resistance and infectivity respectively. A qualitatively different multiscale structure is seen at larger phylogenetic scales; a natural assemblage sampled from the Atlantic Ocean displays large-scale modularity and local nestedness within each module. Here we show that such “nested-modular” interaction networks can be produced by a simple model of host-phage coevolution in which infection depends on genetic matching. Negative frequency-dependent selection causes diversification of hosts (to escape phage) and phage (to track their evolving hosts). This creates a diverse community of bacteria and phage, maintained by kill-the-winner ecological dynamics. When the resulting communities are visualised as bipartite networks of who-infects-whom, they show the nested-modular structure characteristic of the Atlantic sample. The statistical significance and strength of this observation varies depending on whether the interaction networks take into account the density of the interacting strains, with implications for interpretation of interaction networks constructed by different methods. Our results suggest that the apparently complex community structures associated with marine bacteria and phage may arise from relatively simple coevolutionary origins.University of Exete

FALCON: a software package for analysis of nestedness in bipartite networks

This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.Nestedness is a statistical measure used to interpret bipartite interaction data in several ecological and evolutionary contexts, e.g. biogeography (species-site relationships) and species interactions (plant-pollinator and host-parasite networks). Multiple methods have been used to evaluate nestedness, which differ in how the metrics for nestedness are determined. Furthermore, several different null models have been used to calculate statistical significance of nestedness scores. The profusion of measures and null models, many of which give conflicting results, is problematic for comparison of nestedness across different studies. We developed the FALCON software package to allow easy and efficient comparison of nestedness scores and statistical significances for a given input network, using a selection of the more popular measures and null models from the current literature. FALCON currently includes six measures and five null models for nestedness in binary networks, and two measures and four null models for nestedness in weighted networks. The FALCON software is designed to be efficient and easy to use. FALCON code is offered in three languages (R, MATLAB, Octave) and is designed to be modular and extensible, enabling users to easily expand its functionality by adding further measures and null models. FALCON provides a robust methodology for comparing the strength and significance of nestedness in a given bipartite network using multiple measures and null models. It includes an “adaptive ensemble” method to reduce undersampling of the null distribution when calculating statistical significance. It can work with binary or weighted input networks. FALCON is a response to the proliferation of different nestedness measures and associated null models in the literature. It allows easy and efficient calculation of nestedness scores and statistical significances using different methods, enabling comparison of results from different studies and thereby supporting theoretical study of the causes and implications of nestedness in different biological contexts

Development of a critical appraisal tool to assess the quality of cross-sectional studies (AXIS)

Objectives: The aim of this study was to develop a critical appraisal (CA) tool that addressed study design and reporting quality as well as the risk of bias in cross-sectional studies (CSSs). In addition, the aim was to produce a help document to guide the non-expert user through the tool. Design: An initial scoping review of the published literature and key epidemiological texts was undertaken prior to the formation of a Delphi panel to establish key components for a CA tool for CSSs. A consensus of 80% was required from the Delphi panel for any component to be included in the final tool. Results: An initial list of 39 components was identified through examination of existing resources. An international Delphi panel of 18 medical and veterinary experts was established. After 3 rounds of the Delphi process, the Appraisal tool for Cross-Sectional Studies (AXIS tool) was developed by consensus and consisted of 20 components. A detailed explanatory document was also developed with the tool, giving expanded explanation of each question and providing simple interpretations and examples of the epidemiological concepts being examined in each question to aid non-expert users. Conclusions: CA of the literature is a vital step in evidence synthesis and therefore evidence-based decision-making in a number of different disciplines. The AXIS tool is therefore unique and was developed in a way that it can be used across disciplines to aid the inclusion of CSSs in systematic reviews, guidelines and clinical decision-making

Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a critical appraisal

Aim Blauvelt et al. (The Lancet 2017; 389: 2287-303) aimed to compare the long-term efficacy and safety of dupilumab with medium-potency topical corticosteroids (TCS) versus placebo with TCS in adults with moderate-to-severe atopic dermatitis (AD). Setting and design This multicentre randomised, double-blinded, placebo-controlled trial was conducted in hospitals, clinics and academic institutions across 161 sites in 14 countries. Study exposure Adults with moderate-to-severe AD were randomly assigned (3:1:3) to receive subcutaneous dupilumab 300mg once weekly (qw) plus TCS, dupilumab 300mg every 2 weeks (q2w) plus TCS, or placebo plus TCS until week-52. Primary outcome measures Co-primary efficacy endpoints were patients (%) achieving Investigator's Global Assessment (IGA) 0/1 and 2-points or higher improvement from baseline, and Eczema Area and Severity Index 75% improvement from baseline (EASI-75) at week-16. Results 740 patients were included in the trial: 319 were randomly assigned to dupilumab qw, 106 to dupilumab q2w and 315 to the placebo arm. At week-16, more patients in the dupilumab groups achieved the co-primary endpoints: IGA 0/1 (39% [125 patients] qw dosing, 39% [41 patients] q2w dosing vs 12% [39 patients] receiving placebo; p<0.0001) and EASI-75 (64% [204] and 69% [73] vs 23% [73]; p<0.0001). Whilst no new safety signals were identified, adverse effects (AEs) were noted in 261 (83%) in those receiving dupilumab qw plus TCS, 97 (88%) dupilumab q2w plus TCS and 266 (84%) for placebo plus TCS. Rates of conjunctivitis, injection site reactions and local herpes simplex infections were higher in the dupilumab groups compared with placebo. Conclusions Blauvelt et al. concluded that dupilumab treatment added to TCS improved AD up to week-52 compared with TCS alone, and also demonstrated acceptable safety

Using Semantic Similarity and Text Embedding to Measure the Social Media Echo of Strategic Communications

Online discourse covers a wide range of topics and many actors tailor their content to impact online discussions through carefully crafted messages and targeted campaigns. Yet the scale and diversity of online media content make it difficult to evaluate the impact of a particular message. In this paper, we present a new technique that leverages semantic similarity to quantify the change in the discussion after a particular message has been published. We use a set of press releases from environmental organisations and tweets from the climate change debate to show that our novel approach reveals a heavy-tailed distribution of response in online discourse to strategic communications.Comment: 12 pages, 5 figure

Validation of treatment escalation as a definition of atopic eczema flares.

BACKGROUND: Atopic eczema (AE) is a chronic disease with flares and remissions. Long-term control of AE flares has been identified as a core outcome domain for AE trials. However, it is unclear how flares should be defined and measured. OBJECTIVE: To validate two concepts of AE flares based on daily reports of topical medication use: (i) escalation of treatment and (ii) days of topical anti-inflammatory medication use (topical corticosteroids and/or calcineurin inhibitors). METHODS: Data from two published AE studies (studies A (n=336) and B (n=60)) were analysed separately. Validity and feasibility of flare definitions were assessed using daily global bother (scale 0 to 10) as the reference standard. Intra-class correlations were reported for continuous variables, and odds ratios and area under the receiver operator characteristic (ROC) curve for binary outcome measures. RESULTS: Good agreement was found between both AE flare definitions and change in global bother: area under the ROC curve for treatment escalation of 0.70 and 0.73 in studies A and B respectively, and area under the ROC curve of 0.69 for topical anti-inflammatory medication use (Study A only). Significant positive relationships were found between validated severity scales (POEM, SASSAD, TIS) and the duration of AE flares occurring in the previous week - POEM and SASSAD rose by half a point for each unit increase in number of days in flare. Smaller increases were observed on the TIS scale. Completeness of daily diaries was 95% for Study A and 60% for Study B over 16 weeks). CONCLUSION: Both definitions were good proxy indicators of AE flares. We found no evidence that 'escalation of treatment' was a better measure of AE flares than 'use of topical anti-inflammatory medications'. Capturing disease flares in AE trials through daily recording of medication use is feasible and appears to be a good indicator of long-term control. TRIAL REGISTRATION: Current Controlled Trials ISRCTN71423189 (Study A)