BackgroundEczema is a very common chronic inflammatory skin condition.ObjectivesTo update the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) systematic review of treatments for atopic eczema, published in 2000, and to inform health-care professionals, commissioners and patients about key treatment developments and research gaps.Data sourcesElectronic databases including MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Skin Group Specialised Register, Latin American and Caribbean Health Sciences Literature (LILACS), Allied and Complementary Medicine Database (AMED) and Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched from the end of 2000 to 31 August 2013. Retrieved articles were used to identify further randomised controlled trials (RCTs).Review methodsStudies were filtered according to inclusion criteria and agreed by consensus in cases of uncertainty. Abstracts were excluded and non-English-language papers were screened by international colleagues and data were extracted. Only RCTs of treatments for eczema were included, as other forms of evidence are associated with higher risks of bias. Inclusion criteria for studies included availability of data relevant to the therapeutic management of eczema; mention of randomisation; comparison of two or more treatments; and prospective data collection. Participants of all ages were included. Eczema diagnosis was determined by a clinician or according to published diagnostic criteria. The risk of bias was assessed using the Cochrane Collaboration risk-of-bias tool. We used a standardised approach to summarising the data and the assessment of risk of bias and we made a clear distinction between what the studies found and our own interpretation of study findings.ResultsOf 7198 references screened, 287 new trials were identified spanning 92 treatments. Trial reporting was generally poor (randomisation method: 2% high, 36% low, 62% unclear risk of bias; allocation concealment: 3% high, 15% low, 82% unclear risk of bias; blinding of the intervention: 15% high, 28% low, 57% unclear risk of bias). Only 22 (8%) trials were considered to be at low risk of bias for all three criteria. There was reasonable evidence of benefit for the topical medications tacrolimus, pimecrolimus and various corticosteroids (with tacrolimus superior to pimecrolimus and corticosteroids) for both treatment and flare prevention; oral ciclosporin; oral azathioprine; narrow band ultraviolet B (UVB) light; Atopiclair™ and education. There was reasonable evidence to suggest no clinically useful benefit for twice-daily compared with once-daily topical corticosteroids; corticosteroids containing antibiotics for non-infected eczema; probiotics; evening primrose and borage oil; ion-exchange water softeners; protease inhibitor SRD441 (Serentis Ltd); furfuryl palmitate in emollient; cipamfylline cream; andMycobacterium vaccaevaccine. Additional research evidence is needed for emollients, bath additives, antibacterials, specialist clothing and complementary and alternative therapies. There was no RCT evidence for topical corticosteroid dilution, impregnated bandages, soap avoidance, bathing frequency or allergy testing.LimitationsThe large scope of the review coupled with the heterogeneity of outcomes precluded formal meta-analyses. Our conclusions are still limited by a profusion of small, poorly reported studies.ConclusionsAlthough the evidence base of RCTs has increased considerably since the last NIHR HTA systematic review, the field is still severely hampered by poor design and reporting problems including failure to register trials and declare primary outcomes, small sample size, short follow-up duration and poor reporting of risk of bias. Key areas for further research identified by the review include the optimum use of emollients, bathing frequency, wash products, allergy testing and antiseptic treatments. Perhaps the greatest benefit identified is the use of twice weekly anti-inflammatory treatment to maintain disease remission. More studies need to be conducted in a primary care setting where most people with eczema are seen in the UK. Future studies need to use the same core set of outcomes that capture patient symptoms, clinical signs, quality of life and the chronic nature of the disease.FundingThe National Institute for Health Research Programme Grants for Applied Research programme.

Summary Background Eczema control has been identified as an important outcome by key stakeholders in eczema research (including patients, carers, healthcare professionals and researchers) but no validated instruments for the domain have been identified. Objectives To develop a measurement instrument to capture a patient's perspective of eczema control that is suitable for use in eczema clinical trials. Methods Best practice for the development of a patient‐reported outcome was followed. A mixed‐methods approach was used to develop and refine a conceptual framework, generate, refine and select items and to test the distribution and construct validity of the final scale. The mixed‐methods approach involved expert panel meetings (including patient representatives, healthcare professionals and methodologists), and data collection using a focus group, cognitive interviews and an online survey with people with eczema and caregivers. Multivariable linear regression was used in the item selection process. Results Fourteen expert panel members co‐produced the instrument, with input from people with eczema and caregivers via a focus group (n = 6), cognitive interviews (n = 13) and an online survey (n = 330). The resulting instrument, Recap of atopic eczema (RECAP), is a seven‐item questionnaire that captures eczema control via self or caregiver report. The development process aimed to ensure good content validity and feasibility. Initial testing suggested no floor or ceiling effects and good construct validity. Hypothesized correlation with the Patient‐Oriented Eczema Measure was confirmed [r(258) = 0·83, P < 0·001]. Conclusions RECAP has the potential to improve reporting of eczema control in research and clinical practice. Further exploration of measurement properties is required. Linked Comment: Pattinson and Bundy. Br J Dermatol 2020; 183:418–419. What's already known about this topic? Eczema control has been identified as an important outcome by key stakeholders in eczema research (including patients, carers, healthcare professionals and researchers). Qualitative studies suggest eczema control is a multifaceted and individual experience and no instrument has been identified that captures eczema control in this way. What does this study add? We have developed Recap of atopic eczema (RECAP), a seven‐item questionnaire to capture the experience of eczema control in all ages and eczema severities; there are two versions: a self‐reported version for adults and older children with eczema, and a caregiver‐reported version for younger children with eczema. Designed with input from people with eczema, caregivers and healthcare professionals to ensure good content validity. Initial testing of score distributions and construct validity suggests good measurement properties. What are the clinical implications of the work? The RECAP instrument is appropriate and feasible for measuring eczema control in clinical trials and may also be useful in routine practice.

Objective. To evaluate the validity of the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) for use by rheumatologists via reliability testing, and to extend the validation for dermatologists. Methods. Fourteen subjects with cutaneous lupus erythematosus (CLE; n ‫؍‬ 10), a mimicker skin disease only (a cutaneous lesion that may appear clinically similar to CLE; n ‫؍‬ 1), or both (n ‫؍‬ 3) were rated with the CLASI by academic-based dermatologists (n ‫؍‬ 5) and rheumatologists (n ‫؍‬ 5). Results. The dermatology intraclass correlation coefficient (ICC) was 0.92 for activity and 0.82 for damage; for rheumatology the ICC was 0.83 for activity and 0.86 for damage. For intrarater reliability, the dermatology Spearman's rho was 0.94 for activity and 0.97 for damage; for rheumatology the Spearman's rho was 0.91 for activity and 0.99 for damage. Conclusion. Our data confirm the reliability of the CLASI when used by dermatologists and support the CLASI as a reliable instrument for use by rheumatologists.

. (2016) What is the evidence-base for atopic eczema treatments? A summary of published randomised controlled trials. British Journal of Dermatology . ISSN 1365ISSN -2133 Access from the University of Nottingham repository: http://eprints.nottingham.ac.uk/36094/1/What%20is%20the%20evidence-base%20for %20atopic%20%20eczema%20treatments%20A%20summary%20of%20published %20randomised%20controlled%20trials.pdf Copyright and reuse:The Nottingham ePrints service makes this work by researchers of the University of Nottingham available open access under the following conditions. This article is made available under the University of Nottingham End User licence and may be reused according to the conditions of the licence. For more details see: http://eprints.nottingham.ac.uk/end_user_agreement.pdf A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription. for non-infected AE. Many common treatments lack evidence of efficacy and warrant further evaluation. 65The evidence base for AE is still hampered by poor trial design and reporting. The trials included in this review 66 were used to establish the Global Resource of Eczema Trials (GREAT) Database.

 There is no consensus over how best to measure long-term control of atopic dermatitis in clinical trials  To date, repeated measurement of eczema severity, assessment of flares and use of atopic dermatitis medications have all been used.  Consensus agreement of core outcome sets for atopic dermatitis will improve evidence-based practice.1 Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease. There are no standardised methods for 1 capturing long-term control of AD. 2Objective: To identify how long-term control has been captured in published randomised controlled trials (RCTs). Results 3 will initiate consensus discussions on how best to measure long-term control in the core outcome set for AD. 4Methods: Systematic review of RCTs of AD treatments published between 2000 and 2013, with a follow-up period of ≥3 5 months, at least one outcome measure recorded at ≥3 time-points, full paper available, and published in English. 6Results: 101/ 353 RCTs were eligible. Methods to capture long-term control included: repeated measurement of AD 7 outcomes (92 RCTs; 91%), use of AD medication (29 RCTs; 28.7%); and AD flares/remissions (26 RCTs; 25.7%). 8Repeated measurements of AD outcomes were typically collected 3 to 5 times during a trial, but analysis methods often 9 failed to make best use of the data. Time to first flare was most commonly for trials including flare data (21/52). 10Medication-use was recorded based on quantity, potency and frequency of application. 11

Airway remodelling describes the histopathological changes leading to fixed airway obstruction in patients with asthma and includes extra-cellular matrix (ECM) deposition. Matrix metalloproteinase-1 (MMP-1) is present in remodelled airways but its relationship with ECM proteins and the resulting functional consequences are unknown. We used airway smooth muscle cells (ASM) and bronchial biopsies from control donors and patients with asthma to examine the regulation of MMP-1 by ECM in ASM cells and the effect of MMP-1 on ASM contraction. Collagen-I and tenascin-C induced MMP-1 protein expression, which for tenascin-C, was greater in asthma derived ASM cells. Tenascin-C induced MMP-1 expression was dependent on ERK1/2, JNK and p38 MAPK activation and attenuated by function blocking antibodies against the β1 and β3 integrin subunits. Tenascin-C and MMP-1 were not expressed in normal airways but co-localised in the ASM bundles and reticular basement membrane of patients with asthma. Further, ECM from asthma derived ASM cells stimulated MMP-1 expression to a greater degree than ECM from normal ASM. Bradykinin induced contraction of ASM cells seeded in 3D collagen gels was reduced by the MMP inhibitor ilomastat and by siRNA knockdown of MMP-1. In summary, the induction of MMP-1 in ASM cells by tenascin-C occurs in part via integrin mediated MAPK signalling. MMP-1 and tenascin-C are co-localised in the smooth muscle bundles of patients with asthma where this interaction may contribute to enhanced airway contraction. Our findings suggest that ECM changes in airway remodelling via MMP-1 could contribute to an environment promoting greater airway narrowing in response to broncho-constrictor stimuli and worsening asthma symptoms.

Background Standardized outcome reporting is crucial for trial evidence synthesis and translation of findings into clinical decision‐making. The OMERACT 2.0 Filter and COMET outcome domain taxonomy propose frameworks for consistent reporting of outcomes. There is an absence of a uniform dermatology‐specific reporting strategy that uses precise and consistent outcome definitions. Objectives Our aim was to map efficacy/effectiveness outcomes assessed in dermatological trials to the OMERACT 2.0 Filter as a starting point for developing an outcome taxonomy in dermatology. Methods We critically appraised 10 Cochrane Skin Reviews randomly selected from all 69 Cochrane Skin Reviews published until 01/2015 and the 220 trials included covering a broad spectrum of dermatological conditions and interventions. Efficacy/effectiveness outcomes were mapped to core areas and domains according to the OMERACT 2.0 Filter. The extracted trial outcomes were used for critical appraisal of outcome reporting in dermatology trials and for the preliminary development of a dermatology‐specific outcome taxonomy. Results The allocation of 1086 extracted efficacy/effectiveness outcomes to the OMERACT 2.0 Filter resulted in a hierarchically structured dermatology‐specific outcome classification. In 506 outcomes (47%), the outcome concept to be measured was insufficiently described, hindering meaningful evidence synthesis. Although the core areas assessed in different dermatology trials of the same condition overlap considerably, quantitative evidence synthesis usually failed due to imprecise outcome definitions, non‐comparable outcome measurement instruments, metrics and reporting. Conclusions We present an efficacy/effectiveness outcome classification as a starting point for a dermatology‐specific taxonomy to provide trialists and reviewers with the opportunity to better synthesize and compare evidence.

Summary'Symptoms' is a core outcome domain for atopic eczema (AE) trials, agreed by consensus as part of the Harmonising Outcome Measures for Eczema (HOME) initiative. To standardize and validate the core domain symptoms and symptom instruments for AE trials the HOME roadmap is followed. Its first step is to establish if and how symptoms have been measured in published AE treatment trials. Therefore the Global Resource for Eczema Trials database was used to collect all randomized controlled trials (RCTs) of treatments for AE between January 2000 and April 2014. Study selection and data extraction were performed by three reviewers independently. We identified the use of symptoms in 295 of 378 trials (78%). Symptoms as a primary end point were applied by 147 RCTs (50%). Seventeen different symptoms were measured, but mostly itch and sleep loss. Symptoms were assessed by only 37% of trials by a stand-alone symptom measurement. Overall 63% of RCTs used a composite instrument, and 30 different instruments were identified. The Scoring Atopic Dermatitis (SCORAD) index was the most commonly applied, but only 23% of RCTs reported the SCORAD symptom score separately. This systematic review demonstrates that symptoms, most frequently itch and sleep loss, are commonly reported in AE treatment trials, but are measured using many different instruments. Often symptoms are evaluated as part of a composite instrument, and currently it is not possible to extract symptoms-only data from most published studies. Future trials should report symptom scores to permit meta-analysis of the core outcomes.What's already known about this topic?• There is a high level of variation in outcome domains and instruments used for atopic eczema (AE).• Harmonization of AE instruments is necessary to allow better evidence-based clinical decision making.• The Harmonising Outcome Measures for Eczema (HOME) initiative aims to validate a core outcome set (COS) for AE clinical trials; 'symptoms' is selected as one of the four core outcome domains beside clinical signs, quality of life and long-term control.What does this study add?• Symptoms, most frequently itch and sleep loss, are commonly reported in AE trials, but are often poorly measured using many different instruments and as part of a composite instrument, most commonly the SCORing Atopic Dermatitis (SCORAD) index.• Describing patient-reported symptoms and clinician-reported signs separately will improve trial reporting and facilitate meta-analysis.• Deployment of the COS for AE in future trials is a key requirement in moving forward.