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Summary: Background: Several studies have identified an association between water hardness and atopic eczema (AE); however, there is a paucity of longitudinal data in early life. Objectives: To examine whether water hardness is associated with an increased risk of AE and skin barrier dysfunction in infants and to assess effect modification by filaggrin (FLG) loss‐of‐function variants. Methods: We performed a longitudinal analysis of data from infants in the Enquiring About Tolerance (EAT) study, who were enrolled at 3 months and followed up until 36 months of age. Results: Of 1303 infants enrolled in the EAT study, 91·3% (n = 1189) attended the final clinic visit and 94·0% (n = 1225) of participants' families completed the 36‐month questionnaire. In total, 761 (58·4%) developed AE by 36 months. There was no overall association between exposure to harder (> 257 mg L−1 CaCO3) vs. softer (≤ 257 mg L−1 CaCO3) water: adjusted hazard ratio (HR) 1·07, 95% confidence interval (CI) 0·92–1·24. However, there was an increased incidence of AE in infants with FLG mutations exposed to hard water (adjusted HR 2·72, 95% CI 2·03–3·66), and statistically significant interactions between hard water plus FLG and both risk of AE (HR 1·80, 95% CI 1·17–2·78) and transepidermal water loss (0·0081 g m−2 h−1 per mg L−1 CaCO3, 95% CI 0·00028–0·016). Conclusions: There is evidence of an interaction between water hardness and FLG mutations in the development of infantile AE. What's already known about this topic? Several cross‐sectional studies have found an association between domestic water hardness exposure and atopic eczema (AE) risk.Loss‐of‐function mutations in the skin barrier gene filaggrin (FLG) are the strongest genetic risk factor for AE. What does this study add? There was no overall association between AE risk and exposure to harder vs. softer domestic water in a large, well‐phenotyped cohort of infants living in England and Wales followed up at 3–36 months of age.However, infants with at least one FLG loss‐of‐function mutation exposed to harder water have a threefold increased risk of developing AE up to age 36 months compared with infants with wild‐type FLG exposed to softer water. Linked Comment: Arents and Leonardi-Bee. Br J Dermatol 2020; 183:203–204. Plain language summary available online [ABSTRACT FROM AUTHOR]

Purpose: To describe secondary care health care resource utilization (HCRU) for children and adolescents with atopic dermatitis (AD)., Patients and Methods: This UK chart review of patients with moderate-to-severe AD was conducted in four National Health Service hospitals. Cohorts were defined by age (children 6-11 years, adolescents 12-17) at first consultation. Eligible patients were selected consecutively, starting with the most recently consulting patient. At least 12 months' data were abstracted from medical records. Data were collected on HCRU, demographics/clinical characteristics, treatment, and patient-reported outcomes., Results: Data were abstracted for 55 patients. Most patients (80%) had severe AD at first referral, a mean (SD) of 3.2 (10.7) patient-reported flare episodes/patient/year-of-observation, and 18.5 (16.7) tests/scans/procedures/patient/year. Mean (SD) observation duration was 3.6 (1.8) years. Patients had tried mean (SD) 7.9 (5.3) treatments/patient/year of observation. Topical corticosteroids (TCS; 24.5% of prescriptions) were most frequently prescribed. Mean (SD) use of emollients/moisturizers, TCS, systemic corticosteroids, and systemic immunosuppressants was 30.9 (21.3), 21.1 (23.4), 1.7 (8.3), and 7.8 (8.2) months. There was a mean (SD) of 5.3 (2.9) consultations/patient/year-of-observation; 116 (10.7%) for flare. Most hospitalizations (87.5%) were for children; the 8/55 (15%) hospitalized patients (mean 2.0 hospitalizations/patient during observation period) spent 6.2 (SD: 5.1) nights in hospital/hospitalization. Earliest mean (SD) Children's Dermatology Life Quality Index score was 15.3 (7.2); latest was 12.9 (7.5)., Conclusion: Children and adolescents with moderate-to-severe AD had a high HCRU burden and small changes in quality of life, indicating that current treatments may provide suboptimal AD control in most cases., (© 2022 Wiley Periodicals LLC.)

Background: Whilst eczema is a common inflammatory skin condition, we lack contemporary estimates of disease incidence and prevalence across the lifespan., Objective: To estimate the incidence and prevalence of eczema in children and adults in England and variation by sociodemographic factors (sex, socio-economic status, ethnicity, and geography)., Methods: We used the Royal College of General Practitioners Research and Surveillance Centre primary care research database of 3.85 million children and adults registered with participating general practitioner practices between 2009 and 2018 inclusive. Eczema incidence was defined as the first-ever diagnosis of eczema recorded in the primary care record, and eczema prevalence was defined as fulfilment of criteria for active eczema (two eczema records appearing in the primary care record within any one-year period)., Results: Eczema incidence was highest in infants younger than 1 year (15.0 per 100 person-years), lowest in adults aged 40-49 (0.35 p/100 person-years), and increased from middle age to a second smaller peak in people 80 years or older (0.79 p/100 person-years). Eczema prevalence was highest in children aged 2 (16.5%) and lowest in adults aged 30-39 (2.8%). Eczema incidence was higher in male infants (<2) and male adults older than 70; for all other ages, incidence was higher in females. Eczema was more common in Asian and black ethnic groups than in people of white ethnicity. Higher socio-economic status was associated with a greater incidence of eczema in infants younger than 2, but the reverse was seen for all other age groups. Both incidence and prevalence of eczema were greater in urban settings and in North-West England., Conclusions and Clinical Relevance: Eczema has a bimodal distribution across the lifespan. We observed differences in incidence and prevalence of eczema by ethnicity, geography, sex, and socio-economic status, which varied in magnitude throughout life., (© 2020 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

Importance: There are no strategies for the prevention of celiac disease (CD). Current guidelines stating that the age at gluten introduction does not affect the prevalence of CD are based on the results from several randomized clinical trials, but the doses of gluten and timing of its introduction varied., Objective: To determine whether early introduction of high-dose gluten lowers the prevalence of CD at age 3 years., Design, Setting, and Participants: The Enquiring About Tolerance (EAT) Study was an open-label randomized clinical trial. A total of 1303 children from the general population in England and Wales were recruited and followed up from November 2, 2009, to July 30, 2012. For the present study, samples were collected from November 1, 2012, to March 31, 2015, and data were analyzed from April 25, 2017, to September 17, 2018., Interventions: Infants were randomized to consume 6 allergenic foods (peanut, sesame, hen's egg, cow's milk, cod fish, and wheat) in addition to breast milk from age 4 months (early introduction group [EIG]) or to avoid allergenic foods and follow UK infant feeding recommendations of exclusive breastfeeding until approximately age 6 months (standard introduction group [SIG])., Main Outcomes and Measures: Evaluation of CD was an a priori secondary end point of the EAT Study, and at age 3 years, all children with available serum samples were tested for antitransglutaminase type 2 antibodies. Children with antibody levels greater than 20 IU/L were referred to independent gastroenterologists for further investigation., Results: Of the 1004 infants included in the analysis, 514 were male (51.2%). The mean (SD) quantity of gluten consumed between ages 4 and 6 months was 0.49 (1.40) g/wk in the SIG and 2.66 (1.85) g/wk in the EIG (P < .001). Mean (SD) weekly gluten consumption ranged from 0.08 (1.00) g/wk at age 4 months to 0.9 (2.05) g/wk at age 6 months in the SIG vs 1.3 (1.54) g/wk at age 4 months to 4.03 (2.40) g/wk at age 6 months in the EIG. Seven of 516 children from the SIG (1.4%) had a diagnosis of CD confirmed vs none of the 488 children in the EIG (P = .02, risk difference between the groups using the bootstrap, 1.4%; 95% CI, 0.6%-2.6%)., Conclusions and Relevance: In this analysis of infants in the EAT Study, the introduction of gluten from age 4 months was associated with reduced CD prevalence. These results suggest that early high-dose consumption of gluten should be considered as a strategy to prevent CD in future studies., Trial Registration: isrctn.org Identifier: ISRCTN14254740.

Introduction: Atopic dermatitis (AD) is one of the most common inflammatory skin conditions in both children and adults. Despite this, contemporary descriptions of the incidence, prevalence and current management of the condition in the UK are lacking., Methods and Analysis: We will perform a series of retrospective studies using a large population-based cohort derived from the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) network database to explore two key research themes: AD epidemiology and AD management.In the epidemiology theme, we will describe the incidence and prevalence of AD in children and adults in England from 2009 to 2018 inclusive. We will stratify findings by age, national Index of Multiple Deprivation (IMD), ethnicity, urban-rural environment and geographic location; and explore independent associations of these features with AD in multivariable models.In the management theme, we will explore healthcare utilisation and treatment in people with AD. Regarding healthcare utilisation, we will evaluate rates of AD-associated primary care visits and specialist dermatology referrals in people with AD. Rates will be stratified by age, gender, socioeconomic IMD quintile and ethnicity. We will describe contemporary treatment by estimating prescribing rates across medication classes used in AD (emollients, topical corticosteroids by potency, topical calcineurin inhibitors, topical antimicrobials, antihistamines, oral corticosteroids and systemic immunomodulatory therapies) overall, and by age and sociodemographic groupings. We will also examine trends in prescribing over the study period. In people first diagnosed with AD during the study period, we will describe differences in treatment escalation by sociodemographic factors using time-to-event analysis., Ethics and Dissemination: The Health Research Authority decision tool classed this a study of 'usual practice', ethics approval was not required. Study approval was granted by the RCGP RSC Study Approval Committee. Results will be disseminated through peer-reviewed publications., Trial Registration Number: NCT03823794., Competing Interests: Competing interests: SdL is director of RCGP RSC, and had received funding for projects from Eli Lilly, AstraZeneca, GSK, Seqirus and Takeda—all through his universities and none related to this study. JD and AM are employees of Momentum Data who were paid consultants to Pfizer in connection with the development of this manuscript. ClF is an employee of Pfizer. CaF is chief investigator of the UK National Institute for Health Research-funded TREAT (ISRCTN15837754) and SOFTER (ClinicalTrials.gov: NCT03270566) trials as well as the UK-Irish Atopic Eczema Systemic Therapy Register (A-STAR; ISRCTN11210918) and a principal investigator in the European Union Horizon 2020-funded BIOMAP Consortium (http://www.biomap-imi.eu/). His department has also received funding from Sanofi-Genzyme., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)