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Contains fulltext : 287316.pdf (Publisher’s version ) (Open Access) BACKGROUND: Chronic inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis (PSO) present major challenges in health care. Thus, biomarkers to identify disease trajectories and response to treatments to improve the lives of affected individuals warrant great research consideration. The requirements that these biomarkers must fulfil for use as practical clinical tools have not yet been adequately investigated. AIM: To identify the core elements of high-quality AD and PSO biomarkers to prepare recommendations for current biomarker research. METHOD: A cross-sectional two-round Delphi survey was conducted from August to October 2019 and October to November 2020. All participants were members of the BIOMAP project, an EU-funded consortium of clinicians, researchers, patient organizations and pharmaceutical industry partners. The first round consisted of three open-ended questions. Responses were qualitatively analysed, and 26 closed statements were developed. For the second round, 'agreement' was assumed when the responses of ≥70% of the participants were ≥5 points on a 7-point Likert scale for each statement. Priority classification was based on mean scores (60th percentile = high). RESULTS: Twenty-one and twenty-six individuals participated in rounds one and two, respectively. From 26 statements that were included in round 2, 18 achieved agreement (8 concerning the performance, 8 for the purpose and 2 on current obstacles). Seven statements were classified as high priority, e.g. those concerning reliability, clinical validity, a high positive predictive value, prediction of the therapeutic response and disease progression. Another seven statements were assigned medium priority, e.g. those about analytical validity, prediction of comorbidities and therapeutic algorithm. Low priority included four statements, like those concerning cost effectiveness and prediction of disease flares. CONCLUSION: The core requirements that experts agreed on being essential for high-quality AD and PSO biomarkers require rapid validation. Biomarkers can therefore be assessed based on these prioritized requirements.

BACKGROUND: Although well described in adults, there are scarce and heterogeneous data on the diagnosis and management of chronic urticaria (CU) in children (0-18 years) throughout Europe. Our aim was to explore country differences and identify the extent to which the EAACI/GA²LEN/EDF/WAO guideline recommendations for pediatric urticaria are implemented. METHODS: The EAACI Task Force for pediatric CU disseminated an online clinical survey among EAACI pediatric section members. Members were asked to answer 35 multiple choice questions on current practices in their respective centers. RESULTS: The survey was sent to 2,773 physicians of whom 358 (13.8%) responded, mainly pediatric allergists (80%) and pediatricians (49.7%), working in 69 countries. For diagnosis, Southern European countries used significantly more routine tests (eg, autoimmune testing, allergological tests, and parasitic investigation) than Northern European countries. Most respondents (60.3%) used a 2(nd) -generation antihistamine as first-line treatment of whom 64.8% updosed as a second line. Omalizumab was used as a second-line treatment by 1.7% and third line by 20.7% of respondents. Most clinicians (65%) follow EAACI/WAO/GA2LEN/EDF guidelines when diagnosing CU, and only 7.3% follow no specific guidelines. Some clinicians prefer to follow national guidelines (18.4%, mainly Northern European) or the AAAAI practice parameter (1.7%). CONCLUSIONS: Even though most members of the Pediatric Section of EAACI are familiar with the EAACI/WAO/GA2LEN/EDF guidelines, a significant number do not follow them. Also, the large variation in diagnosis and treatment strengthens the need to re-evaluate, update, and standardize guidelines on the diagnosis and management of CU in children.

Asthma prevalence in children varies substantially around the world, but the contribution of known risk factors to this international variation is uncertain. The International Study of Asthma and Allergies in Childhood (ISAAC) Phase Two studied 8-12 year old children in 30 centres worldwide with parent-completed symptom and risk factor questionnaires and aeroallergen skin prick testing. We used multilevel logistic regression modelling to investigate the effect of adjustment for individual and ecological risk factors on the between-centre variation in prevalence of recent wheeze. Adjustment for single individual-level risk factors changed the centre-level variation from a reduction of up to 8.4% (and 8.5% for atopy) to an increase of up to 6.8%. Modelling the 11 most influential environmental factors among all children simultaneously, the centre-level variation changed little overall (2.4% increase). Modelling only factors that decreased the variance, the 6 most influential factors (synthetic and feather quilt, mother's smoking, heating stoves, dampness and foam pillows) in combination resulted in a 21% reduction in variance. Ecological (centre-level) risk factors generally explained higher proportions of the variation than did individual risk factors. Single environmental factors and aeroallergen sensitisation measured at the individual (child) level did not explain much of the between-centre variation in wheeze prevalence.

Background Skin barrier dysfunction precedes eczema development. We tested whether daily emollient in the first year can prevent eczema in high-risk children. Methods We conducted a UK, multicentre, pragmatic, 2-arm, parallel-group randomised controlled trial. Term newborns with family history of atopic disease were randomised (1:1) to apply emollient daily (Diprobase cream® or DoubleBase® gel®) for the first year plus standard skin-care advice (emollient group) or standard skin-care advice only (controls). Research nurses assessing outcomes at 2-years were masked to allocation. Primary outcome was eczema at 2 years (UK working party criteria) with analysis as randomised regardless of adherence to allocation and adjusting for stratification variables. Trial registration: ISRCTN21528841. Findings 1394 newborns were randomised between November 2014 and November 2016; 693 emollient and 701 control. Adherence in emollient group was 88% (466/532), 82% (427/519) and 74% (375/506) at 3, 6 and 12 months in those with complete data. At 2 years, eczema was present in 139/598 (23%) children in the emollient group and 150/612 (25%) in controls, adjusted relative risk 0·95, 95% CI 0·78 to 1·16, p=0·61 and adjusted risk difference -1·2%, 95% CI -5·9% to 3·6%. Other eczema definitions supported the primary analysis. Mean number of skin infections per child in year 1 was 0·23 (SD 0·68) in the emollient group versus 0·15 (SD 0·46) in controls; adjusted incidence rate ratio 1·55 95% CI 1·15 to 2·09. Interpretation We found no evidence that daily emollient during the first year of life prevents eczema in high-risk children and some evidence to suggest an increased risk of skin infections. Funding National Institute for Health Research Health Technology Assessment (12/67/12) funded the main trial. Supplementary funding for food allergy assessments was from Goldman Sachs Gives and the Sheffield Children’s Hospital Charity.

Background Recently, we have published an overview of systematic reviews in allergy epidemiology and identified asthma as the most commonly reviewed allergic disease. Building on this work, we aimed to investigate the quality of systematic reviews in asthma using the AMSTAR checklist and to provide a reference for future, more in-depth assessment of the extent of previous knowledge. Methods We included all 307 systematic reviews indexed with asthma, including occupational asthma, and/or wheeze from our previous search in PubMed and EMBASE up to December 2014 for systematic reviews on epidemiological research on allergic diseases. Topics of the included systematic reviews were indexed and we applied the AMSTAR checklist for methodological quality to all. Statistical analyses include description of lower and upper bounds of AMSTAR scores and variation across publication time and topics. Results Of 43 topics catalogued, family history, birth weight, and feeding of formula were only covered once in systematic reviews published from 2011 onwards. Overall, at least one meta-analysis was conducted for all topics except for “social determinants”, “perinatal”, “birth weight”, and “climate”. AMSTAR quality scores were significantly higher in more recently published systematic reviews, in those with meta-analysis, and in Cochrane reviews. There was evidence of variation of quality across topics even, after accounting for these characteristics. Genetic factors in asthma development were often covered by systematic reviews with some evidence of unsubstantiated updates or repetition. Conclusions We present a comprehensive overview with an indexed database of published systematic reviews in asthma epidemiology including quality scores. We highlight some topics including active smoking and pets, which should be considered for future systematic reviews. We propose that our search strategy and database could be a basis for topic-specific overviews of systematic reviews in asthma epidemiology. Electronic supplementary material The online version of this article (doi:10.1186/s13601-017-0146-y) contains supplementary material, which is available to authorized users.

Summary Background Oral propranolol is widely prescribed as first-line treatment for infantile haemangiomas (IHs). Anecdotally, prescribing practice differs widely between centres. Objectives The Propranolol In the Treatment of Complicated Haemangiomas (PITCH) Taskforce was founded to establish patterns of use of propranolol in IHs. Methods Participating centres entered data on all of their patients who had completed treatment with oral propranolol for IHs, using an online data capture tool. Results The study cohort comprised 1097 children from 39 centres in eight European countries. 76·1% were female and 92·8% had a focal IH, with the remainder showing a segmental, multifocal or indeterminate pattern. The main indications for treatment were periocular location (29·3%), risk of cosmetic disfigurement (21·1%) and ulceration and bleeding (20·6%). In total 69·2% of patients were titrated up to a maintenance regimen, which consisted of 2 mg kg−1 per day (85·8%) in the majority of cases. 91·4% of patients had an excellent or good response to treatment. Rebound growth occurred in 14·1% upon stopping, of whom 53·9% were restarted and treatment response was recaptured in 91·6% of cases. While there was no significant difference in the treatment response, comparing a daily maintenance dose of < 2 mg kg−1 vs. 2 mg kg−1 vs. > 2 mg kg−1, the risk of adverse events was significantly higher: odds ratio (OR) 1 vs. adjusted OR 0·70, 95% confidence interval (CI) 0·33–1·50, P = 0·36 vs. OR 2·38, 95% CI 1·04–5·46, P = 0·04, Ptrend < 0·001. Conclusions The PITCH survey summarizes the use of oral propranolol across 39 European centres, in a variety of IH phases, and could be used to inform treatment guidelines and the design of an interventional study.