Avoidable research waste in dermatology: what are the solutions?

In the last editorial, I provided examples of research waste in dermatology and suggested that it was due to a system failure rather than just a few "bad apples". Here, I focus on possible solutions, mainly in relation to clinical trials, building on examples from work at the Centre of Evidence-Based Dermatology (CEBD) and other research groups.

Classifying atopic dermatitis: a systematic review of phenotypes and associated characteristics.

Atopic dermatitis is a heterogeneous disease, accompanied by a wide variation in disease presentation and the potential to identify many phenotypes that may be relevant for prognosis and treatment. We aimed to systematically review previously reported phenotypes of atopic dermatitis and any characteristics associated with them. Ovid EMBASE, Ovid MEDLINE and Web of Science were searched from inception till 12 February 2021 for studies attempting to classify atopic dermatitis. Primary outcomes are atopic dermatitis phenotypes and characteristics associated with them in subsequent analyses. A secondary outcome is the methodological approach used to derive them. In total, 8511 records were found. By focussing only on certain clinical phenotypes, 186 studies were eligible for inclusion. The majority of studies were hospital-based (59%, 109/186) and cross-sectional (76%, 141/186). The number of included patients ranged from seven to 526 808. Data-driven approaches to identify phenotypes were only used in a minority of studies (7%, 13/186). Ninety-one studies (49%) investigated a phenotype based on disease severity. A phenotype based on disease trajectory, morphology and eczema herpeticum was investigated in 56 (30%), 22 (12%) and 11 (6%) studies respectively. Thirty-six studies (19%) investigated morphological characteristics in other phenotypes. Investigated associated characteristics differed between studies. In conclusion, we present an overview of phenotype definitions used in literature for severity, trajectory, morphology and eczema herpeticum, including associated characteristics. There is a lack of uniform and consistent use of atopic dermatitis phenotypes across studies.

Interventions for basal cell carcinoma: abridged Cochrane systematic review and GRADE assessments.

BACKGROUND: Basal cell carcinoma (BCC) is the most common cancer affecting white-skinned individuals, and the worldwide incidence is increasing. Although rarely fatal, BCC is associated with significant morbidity and costs. OBJECTIVES: To assess the effects of interventions for primary BCC in immunocompetent adults. METHODS: We updated our searches of the following databases to November 2019: Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and LILACS. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation method. We used standard methodological procedures expected by Cochrane. RESULTS: We included 52 randomized controlled trials with 6990 participants (median age 65 years; range 20-95). Mean study duration was 13 months (range 6 weeks-10 years). Ninety-two per cent (n = 48/52) of studies exclusively included histologically low-risk BCC (nodular and superficial subtypes). The certainty of evidence was predominantly low or moderate for the outcomes of interest. Overall, surgical interventions have the lowest recurrence rates, and there may be slightly fewer recurrences with Mohs micrographic surgery over surgical excision for primary, facial BCC (high-risk histological subtype or located in the 'H-zone' or both) (low-certainty evidence). Nonsurgical treatments, when used for low-risk BCC, are less effective than surgical treatments, but recurrence rates are acceptable and cosmetic outcomes are probably superior. CONCLUSIONS: Surgical interventions have lower recurrence rates and remain the gold standard for high-risk BCC. Of the nonsurgical treatments, topical imiquimod has the best evidence to support its efficacy for low-risk BCC. Priorities for future research include agreement on core outcome measures and studies with longer follow-up.

Recommended core outcome instruments for health-related quality of life, long-term control and itch intensity in atopic eczema trials: results of the HOME VII consensus meeting.

BACKGROUND: The Harmonising Outcome Measures for Eczema (HOME) initiative has established a core outcome set of domains for atopic eczema (AE) clinical trials. Previous consensus meetings have agreed on preferred instruments for clinician-reported signs (Eczema Area and Severity Index, EASI) and patient-reported symptoms (Patient-Oriented Eczema Measure, POEM). This paper reports consensus decisions from the HOME VII meeting. OBJECTIVES: To complete the core outcome set for AE by agreeing on core outcome instruments for the domains of quality of life (QoL), long-term control and itch intensity. METHODS: A face-to-face consensus meeting was held in Tokyo, Japan (8-10 April 2019) including 75 participants (49 healthcare professionals/methodologists, 14 patients, 12 industry representatives) from 16 countries. Consensus decisions were made by presentations of evidence, followed by whole and small group discussions and anonymous voting using predefined consensus rules. RESULTS: It was agreed by consensus that QoL should be measured using the Dermatology Life Quality Index (DLQI) for adults, the Children's Dermatology Life Quality Index (CDLQI) for children and the Infant's Dermatology Quality of Life Index (IDQoL) for infants. For long-term control, the Recap of Atopic Eczema (RECAP) instrument or the Atopic Dermatitis Control Test (ADCT) should be used. Consensus was not reached over the frequency of data collection for long-term control. The peak itch numerical rating scale (NRS)-11 past 24 h was recommended as an additional instrument for the symptom domain in trials of older children and adults. Agreement was reached that all core outcome instruments should be captured at baseline and at the time of primary outcome assessment as a minimum. CONCLUSIONS: For now, the core outcome set for clinical trials in AE is complete. The specified domains and instruments should be used in all new clinical trials and systematic reviews of eczema treatments.

An economic evaluation of the randomized controlled trial of topical corticosteroid and home-based narrowband ultraviolet B for active and limited vitiligo (the HI-Light Vitiligo Trial).

BACKGROUND: Economic evidence for vitiligo treatments is absent. OBJECTIVES: To determine the cost-effectiveness of (i) handheld narrowband ultraviolet B (NB-UVB) and (ii) a combination of topical corticosteroid (TCS) and NB-UVB compared with TCS alone for localized vitiligo. METHODS: Cost-effectiveness analysis alongside a pragmatic, three-arm, placebo-controlled randomized controlled trial with 9 months' treatment. In total 517 adults and children (aged ≥ 5 years) with active vitiligo affecting < 10% of skin were recruited from secondary care and the community and were randomized 1: 1: 1 to receive TCS, NB-UVB or both. Cost per successful treatment (measured on the Vitiligo Noticeability Scale) was estimated. Secondary cost-utility analyses measured quality-adjusted life-years using the EuroQol 5 Dimensions 5 Levels for those aged ≥ 11 years and the Child Health Utility 9D for those aged 5 to < 18 years. The trial was registered with number ISRCTN17160087 on 8 January 2015. RESULTS: The mean ± SD cost per participant was £775 ± 83·7 for NB-UVB, £813 ± 111.4 for combination treatment and £600 ± 96·2 for TCS. In analyses adjusted for age and target patch location, the incremental difference in cost for combination treatment compared with TCS was £211 (95% confidence interval 188-235), corresponding to a risk difference of 10·9% (number needed to treat = 9). The incremental cost was £1932 per successful treatment. The incremental difference in cost for NB-UVB compared with TCS was £173 (95% confidence interval 151-196), with a risk difference of 5·2% (number needed to treat = 19). The incremental cost was £3336 per successful treatment. CONCLUSIONS: Combination treatment, compared with TCS alone, has a lower incremental cost per additional successful treatment than NB-UVB only. Combination treatment would be considered cost-effective if decision makers are willing to pay £1932 per additional treatment success.

Randomized controlled trial of topical corticosteroid and home-based narrowband ultraviolet B for active and limited vitiligo: results of the HI-Light Vitiligo Trial.

BACKGROUND: Evidence for the effectiveness of vitiligo treatments is limited. OBJECTIVES: To determine the effectiveness of (i) handheld narrowband UVB (NB-UVB) and (ii) a combination of potent topical corticosteroid (TCS) and NB-UVB, compared with TCS alone, for localized vitiligo. METHODS: A pragmatic, three-arm, placebo-controlled randomized controlled trial (9-month treatment, 12-month follow-up). Adults and children, recruited from secondary care and the community, aged ≥ 5 years and with active vitiligo affecting < 10% of skin, were randomized 1 : 1 : 1 to receive TCS (mometasone furoate 0·1% ointment + dummy NB-UVB), NB-UVB (NB-UVB + placebo TCS) or a combination (TCS + NB-UVB). TCS was applied once daily on alternating weeks; NB-UVB was administered on alternate days in escalating doses, adjusted for erythema. The primary outcome was treatment success at 9 months at a target patch assessed using the participant-reported Vitiligo Noticeability Scale, with multiple imputation for missing data. The trial was registered with number ISRCTN17160087 on 8 January 2015. RESULTS: In total 517 participants were randomized to TCS (n = 173), NB-UVB (n = 169) and combination (n = 175). Primary outcome data were available for 370 (72%) participants. The proportions with target patch treatment success were 17% (TCS), 22% (NB-UVB) and 27% (combination). Combination treatment was superior to TCS: adjusted between-group difference 10·9% (95% confidence interval 1·0%-20·9%; P = 0·032; number needed to treat = 10). NB-UVB alone was not superior to TCS: adjusted between-group difference 5·2% (95% CI - 4·4% to 14·9%; P = 0·29; number needed to treat = 19). Participants using interventions with ≥ 75% expected adherence were more likely to achieve treatment success, but the effects were lost once treatment stopped. Localized grade 3 or 4 erythema was reported in 62 (12%) participants (including three with dummy light). Skin thinning was reported in 13 (2·5%) participants (including one with placebo ointment). CONCLUSIONS: Combination treatment with home-based handheld NB-UVB plus TCS is likely to be superior to TCS alone for treatment of localized vitiligo. Combination treatment was relatively safe and well tolerated but was successful in only around one-quarter of participants.

Scoping the international impact from four independent national dermatology trials.

BACKGROUND: Research impact describes whether and how research results in wider benefits to society beyond academic publication. Little is known about translation of clinical trial research into dermatological practice. AIM: We scoped international impact from four independently funded clinical trials published by our group over the past 10 years. METHODS: This was a scoping survey of 35 international colleagues from 22 countries followed by a narrative summary of emergent themes. RESULTS: All recipients kindly responded to the survey. At least 20 emergent themes were identified, which broadly included: (i) interest and enthusiasm in the concept of trying to document clinical trial impact; (ii) direct impacts such as adoption of the drug as tested and recommended from the trial results, including more confidence using the drug in slightly different ways for the same condition; (iii) the finding that trial impact was dependent on factors such as drug availability and country-specific disease patterns; and (iv) the educational value of good trial design for journal club discussions and improving future clinical trial designs in dermatology. Our survey suggests that uptake into clinical practice was surprisingly rapid and widespread. CONCLUSION: Clinical trial research is of little use unless findings are translated into clinical practice for patient benefit. Our international scoping survey suggests that independent clinical trials that address important questions identified by the dermatology community have substantial, diverse and far-reaching impacts on dermatological practice.

Dermatological games: Part 2. What has changed 40 years on?

In this two-part report, we review and critically appraise 'Dermatological games' by J. A. Cotterill, a seminal article published in 1981, which attempted to explain the interaction between dermatologists and patients using Berne's game theory. Part 1 described and critically appraised the educational value of Cotterill's original list of games in relation to how they apply to dermatology practice. In Part 2, a list of new 'games' that might be observed in current dermatological practice is introduced. The relevance of Cotterill's paper and an explanation for why his article remains relevant to dermatology practice and training today is scrutinized, in order to stimulate discussion and improve patient care.

Dermatological games: Part 1. Original description and critique.

'Dermatological games' by J. A. Cotterill was a seminal article published in 1981, which attempted to explain the interaction between dermatologists and patients using Berne's game theory. In Part 1 of this series of two reviews, we review Cotterill's original list of games and how they applied to dermatology in the context of when they were written. We then critically appraise Cotterill's article and arguments. Although the article was deliberately provocative, we found Cotterill's arguments to be well-structured and logical, and the 'games' described are well-conceived. Cotterill's candid analysis of doctors' motivations and the potential impact on the patient is refreshing and insightful. It is striking that, 40 years on, many of the original 'games' described remain recognizable in current practice. In Part 2, a list of new 'games' that might be observed in modern dermatological practice is introduced. The relevance of Cotterill's paper and an explanation for why his educational article remains relevant to dermatology practice and training today is scrutinized in order to stimulate discussion, promote education and improve patient care.

Outcome assessment in dermatology clinical trials and cochrane reviews: call for a dermatology-specific outcome taxonomy.

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.

Assessing the effect of clinical trial evidence and anecdote on caregivers' willingness to use corticosteroids: a randomized controlled trial: a critical appraisal.

AIM: Johnson et al. aimed to assess caregivers' willingness to treat childhood atopic dermatitis (AD) with a corticosteroid when presented with clinical trial evidence, anecdote, or both. SETTING AND DESIGN: This prospective parallel group (1: 1; eight groups) randomized control trial (RCT) was carried out with caregivers recruited from a tertiary care dermatology clinic in the USA and an online crowdsourcing platform using caregivers who may not have had a child with AD. STUDY EXPOSURE: Caregivers were randomized to eight groups. The three main groups were given clinical trial evidence, anecdote, or a combination of both. Each of these three groups was further divided and presented with either the term 'medication' or 'topical steroid'. These were compared with the two remaining groups, which included a group told that they would not be informed of a medication's efficacy or safety profile, and a group informed that the medication was recommended by the doctor. OUTCOME: Caregivers were asked about their willingness to treat based on the information they had received using a 10-point Likert scale where 1 was 'not willing' and 10 'completely willing'. RESULTS: A total of 476 caregivers were recruited (80 clinic, 396 online), 48% of whom had a history of a child with AD. Caregivers' willingness to treat was higher in all information assignment groups compared with those not provided with safety information: clinical trial evidence of a 'medication' (P = 0·003; Cohen's d = 0·83) or 'topical steroid' (P = 0·030; d = 0·55), anecdote of a 'medication' (P < 0·0001; d = 1·37) or 'topical steroid' (P < 0·0001; d = 0·85), both clinical trial evidence and anecdote of a 'medication' (P < 0·0001; d = 1·00) or 'topical steroid' (P = 0·000; d = 0·89), and simply the doctor's recommendation (P < 0·0001; d = 0·92). CONCLUSION: Johnson et al. conclude that the provision of anecdotal reassurance may be an effective strategy to improve caregivers' willingness to use topical steroids. COMMENT: Exploring factors that affect caregivers' willingness to adhere to topical corticosteroids is an important area of research. This study was a potentially efficient way of conducting a rapid RCT to explore such factors. The study conclusions are significantly undermined by lack of a registered trial protocol, poor trial reporting, the use of caregivers who did not have experience of AD, the multiplicity and complexity of treatment arms, and the use of an unvalidated primary outcome.

'Efficacy and safety of imiquimod 5% cream for basal cell carcinoma: a meta-analysis of randomized controlled trial': a critical appraisal.

AIM: Jia and He aimed 'to compare the efficacy and safety of imiquimod with other treatments in patients with basal cell carcinoma' (BCC). DESIGN AND INCLUSION CRITERIA: Meta-analysis of studies that included patients with histologically confirmed BCC treated with imiquimod 5% cream compared with all other treatments, including vehicle, excisional surgery, cryosurgery, fluorouracil and methyl aminolaevulinate photodynamic therapy. OUTCOMES: The main outcome measures included histological and composite clearance rates, success rates, complete response rates, tumour-free survival and adverse events. RESULTS: Thirteen studies with a total of 4265 patients were included in the review. Pooled analyses comparing imiquimod with all or any of the listed comparators, including vehicle, demonstrated higher histological clearance rates [risk ratio (RR) 9·28, 95% confidence interval (CI) 5·56-15·5; P < 0·001], higher composite clearance rates (RR 34·2, 95% CI 21·3, 55·1; P = 0·001), no significant difference in success rates (RR 0·98, 95% CI 0·89-1·08; P = 0·73), higher complete response rates (RR 3·15, 95% CI 1·55-6·38; P = 0·001), no significant difference in tumour-free survival (RR 1·15, 95% CI 0·98-1·35; P = 0·088) and increased incidence of adverse events (RR 2·00, 95% CI 1·39-2·88; P < 0·001). CONCLUSIONS: The authors state that 'imiquimod significantly exhibited benefit effect in improving the histological/composite clearance rates' compared with other treatments, and they suggest it could be used as the first-choice treatment for patients with BCC. COMMENT: The main concerns related to the article by Jia and He are that the research question is replicative, it makes little sense to combine all BCC types in a meta-analysis, and it also makes no sense to combine an active treatment against a combination of vehicle and other active treatments. There are also concerns about bias related to the use of the same study data more than once in a meta-analysis. Furthermore, we have identified an example of covert duplicate publication, which further compounds the profusion of misleading systematic reviews.

Direct infant ultraviolet light exposure is associated with eczema and immune development: a critical appraisal.

AIM: Rueter et al. aimed to 'determine the effects of early postnatal vitamin D supplementation on infant eczema and immune development'. SETTING AND DESIGN: This was a double-blind randomized placebo-controlled trial with an additional nonrandomized exploratory analysis on the effects of ultraviolet (UV) exposure led from a hospital setting. STUDY EXPOSURE: Vitamin D (400 iU daily) drops or placebo drops (coconut and palm kernel oil) were allocated randomly to 195 infants born to families with a first-degree relative with atopic disease. Eighty-six of these infants were allocated personal UV dosimeters in a nonrandomized fashion to measure UV light (290-380 nm) exposure until 3 months of age. OUTCOMES: Eczema and wheeze were assessed at 3 and 6 months, and 25 immune function markers were assessed at 6 months of age. Infant vitamin D levels and immune functions were measured at 6 months of age. RESULTS: Although vitamin D levels were significantly greater in infants in the intervention group than in those in the placebo group at 3 and 6 months of age, there was no difference in eczema between groups at either time point (10·0% vs. 6·7% at 3 months and 21·8 vs. 19·3% at 6 months for the vitamin D and placebo groups, respectively). In the subset of infants given a dosimeter, those with eczema had less UV light exposure (median 555 J m-2 ) than infants who did not develop eczema (median 998 J m-2 ). Across the 25 immune functions, UV light exposure was inversely correlated with interleukin-2, granulocyte macrophage colony-stimulating factor and eotaxin production by Toll-like receptor ligands. CONCLUSIONS: Vitamin D supplementation in high-risk infants increased vitamin D levels but did not reduce eczema. Exploratory post-hoc analyses in a nonrandomized subset showed an association between greater direct UV light exposure and reduction of eczema. The authors claim that their 'findings indicate that UV light exposure appears more beneficial than vitamin D supplementation as an allergy prevention strategy in early life'.

Clinical characteristics, symptoms and burden of psoriasis and atopic dermatitis in adults.

BACKGROUND: There is debate as to whether psoriasis and atopic dermatitis (AD) belong to the same disease spectrum. OBJECTIVES: To describe and compare disease characteristics, lifestyle factors and disease burden in adult patients with psoriasis and AD. METHODS: We linked registry data with clinical and patient-reported outcomes from the Danish Skin Cohort, containing 3348 and 3834 adults with dermatologist-verified psoriasis or AD respectively, and 2946 adults from the general population. RESULTS: The participants were predominantly women and middle-aged. Patients with psoriasis mostly reported disease onset throughout adulthood, but with a distinct early incidence peak in those with a positive family history or severe disease. AD predominantly began in childhood, with only a very discrete incidence peak in adulthood. Scalp, extremity, chest and abdomen involvement was common to both diseases. Scalp/hairline, elbows, nails, intergluteal cleft, umbilicus, knees and legs were most frequently affected in patients with psoriasis. In AD, periocular, neck, antecubital fossae, back of the hands, interdigital areas and popliteal fossae were commonly affected. Patients with psoriasis (but not AD) were generally more overweight, obese and physically inactive, and had a positive smoking history, compared with the general population. Patients with both diseases experienced more frequent flares with increasing disease severity. Patients generally displayed uncontrolled disease despite being on systemic therapies. Itch and skin pain were much more severe in patients with AD, whereas joint pain was more common in patients with psoriasis. CONCLUSIONS: We identified important similarities and differences in the clinical characteristics of adults with psoriasis and AD; these should help clinicians to prioritize and improve patient management. What's already known about this topic? Psoriasis and atopic dermatitis in adults are increasingly being compared, and there is discussion as to whether they are part of the same disease spectrum. What does this study add? In this comparative study, patient-reported disease burden was markedly higher in atopic dermatitis than in psoriasis, whereas lifestyle-associated cardiometabolic risk factors were more frequent in psoriasis. In both disease groups, the condition in the majority of patients was uncontrolled even while they were on systemic therapy. The contrasting presentations highlight that these diseases are two distinct and different entities rather than belonging to the same spectrum.

A behaviour change package to prevent hand dermatitis in nurses working in the National Health Service: results of a cluster randomized controlled trial.

BACKGROUND: Occupational hand dermatitis poses a serious risk for nurses. OBJECTIVES: To evaluate the clinical and cost-effectiveness of a complex intervention in reducing the prevalence of hand dermatitis in nurses METHODS: This was a cluster randomized controlled trial conducted at 35 hospital trusts, health boards or universities in the UK. Participants were (i) first-year student nurses with a history of atopic conditions or (ii) intensive care unit (ICU) nurses. Participants at intervention sites received access to a behavioural change programme plus moisturizing creams. Participants at control sites received usual care. The primary outcome was the change of prevalent dermatitis at follow-up (adjusted for baseline dermatitis) in the intervention vs. the control group. Randomization was blinded to everyone bar the trials unit to ensure allocation concealment. The trial was registered on the ISRCTN registry: ISRCTN53303171. RESULTS: Fourteen sites were allocated to the intervention arm and 21 to the control arm. In total 2040 (69·5%) nurses consented to participate and were included in the intention-to-treat analysis. The baseline questionnaire was completed by 1727 (84·7%) participants. Overall, 789 (91·6%) ICU nurses and 938 (84·0%) student nurses returned completed questionnaires. Of these, 994 (57·6%) had photographs taken at baseline and follow-up (12-15 months). When adjusted for baseline prevalence of dermatitis and follow-up interval, the odds ratios (95% confidence intervals) for hand dermatitis at follow-up in the intervention group relative to the controls were 0·72 (0·33-1·55) and 0·62 (0·35-1·10) for student and ICU nurses, respectively. No harms were reported. CONCLUSIONS: There was insufficient evidence to conclude whether our intervention was effective in reducing hand dermatitis in our populations. Linked Comment: Brans. Br J Dermatol 2020; 183:411-412.

What is the evidence for interactions between filaggrin null mutations and environmental exposures in the aetiology of atopic dermatitis? A systematic review.

BACKGROUND: Epidemiological studies indicate that gene-environment interactions play a role in atopic dermatitis (AD). OBJECTIVES: To review the evidence for gene-environment interactions in AD aetiology, focusing on filaggrin (FLG) loss-of-function mutations. METHODS: A systematic search from inception to September 2018 in Embase, MEDLINE and BIOSIS was performed. Search terms included all synonyms for AD and filaggrin/FLG; any genetic or epidemiological study design using any statistical methods were included. Quality assessment using criteria modified from guidance (ROBINS-I and Human Genome Epidemiology Network) for nonrandomized and genetic studies was completed, including consideration of power. Heterogeneity of study design and analyses precluded the use of meta-analysis. RESULTS: Of 1817 papers identified, 12 studies fulfilled the inclusion criteria required and performed formal interaction testing. There was some evidence for FLG-environment interactions in six of the studies (P-value for interaction ≤ 0·05), including early-life cat ownership, older siblings, water hardness, phthalate exposure, higher urinary phthalate metabolite levels (which all increased AD risk additional to FLG null genotype) and prolonged breastfeeding (which decreased AD risk in the context of FLG null genotype). Major limitations of published studies were the low numbers of individuals (ranging from five to 94) with AD and FLG loss-of-function mutations and exposure to specific environmental factors, and variation in exposure definitions. CONCLUSIONS: Evidence on FLG-environment interactions in AD aetiology is limited. However, many of the studies lacked large enough sample sizes to assess these interactions fully. Further research is needed with larger sample sizes and clearly defined exposure assessment. Linked Comment: Park and Seo. Br J Dermatol 2020; 183:411.

Recommended core outcome instruments for health-related quality of life, long-term control and itch intensity in atopic eczema trials: results of the HOME VII consensus meeting.

BACKGROUND: The Harmonising Outcome Measures for Eczema (HOME) initiative has established a core outcome set of domains for atopic eczema clinical trials. Previous consensus meetings have agreed upon preferred instruments for clinician-reported signs (Eczema Area and Severity Index - EASI) and patient-reported symptoms (Patient-Oriented Eczema Measure - POEM). This paper reports consensus decisions from the HOME VII meeting. OBJECTIVE: To complete the core outcome set for atopic eczema by agreeing upon core outcome instruments for the domains of quality of life, long-term control and itch intensity. METHODS: Face-to-face consensus meeting held in Tokyo, Japan (8th to 10th April, 2019) including 74 participants (47 healthcare professionals/methodologists, 14 patients, 13 industry representatives), from 16 countries. Consensus decisions were made by presentations of evidence, followed by whole and small group discussions and anonymous voting using pre-defined consensus rules. RESULTS: It was agreed by consensus that quality of life should be measured using the Dermatology Life Quality Index (DLQI) for adults, the Children's Dermatology Life Quality Index (CDLQI) for children, and the Infant's Dermatology Quality of Life Index (IDQoL) for infants. For long-term control, the Recap of Atopic Eczema (RECAP) instrument or the Atopic Dermatitis Control Test (ADCT) should be used. Consensus was not reached over the frequency of data collection for long-term control. The peak itch numerical rating scale(NRS)-11 past 24 hours was recommended as an additional instrument for the symptom domain in trials of older children and adults. Agreement was reached that all core outcome instruments should be captured at baseline and at the time of primary outcome assessment as a minimum. CONCLUSIONS: For now, the core outcome set for clinical trials in atopic eczema is complete. The specified domains and instruments should be used in all new clinical trials and systematic reviews of eczema treatments.

Strengths and limitations of the United Kingdom Working Party criteria for atopic dermatitis in adults.

BACKGROUND: The United Kingdom Working Party's (UKWP) criteria were developed to improve epidemiological research in atopic dermatitis (AD), but have not been validated in an exclusively adult European population. OBJECTIVE: To validate the UKWP criteria for AD in adults. METHODS: In this cross-sectional study, three independent samples of adult individuals were drawn and interviewed: patients with a hospital diagnosis of AD or plaque psoriasis in adulthood, and general population controls. Various versions of the UKWP criteria for AD were utilized. RESULTS: A total of 3490 (general population), 3834 (AD) and 4016 (psoriasis) adult individuals were enrolled in the study. The best combination of the UKWP criteria leads to a sensitivity of 0.71 and a specificity of 0.96 in the general population. The criteria better captured 'AD ever' compared with 'AD within the past 12 months' and had a higher sensitivity in patients with moderate (87.2-97.7%) or severe (95.8-100%) AD at the time of interview compared with those who where asymptomatic (12.6-36.8%). The UKWP criteria also captured high proportions of psoriasis patients (19.7-47.7%) when applied in a cohort of unique psoriasis patients. CONCLUSIONS: It remains a challenge to accurately diagnose a history of AD in adulthood since symptoms are shared with other skin conditions and AD may have resolved or can be waxing and waning, in turn leading to recall bias. The UKWP criteria performed well in the general population for the purpose of determining the prevalence, but should be used cautiously when studying comorbidity.

A self-report questionnaire to detect hand dermatitis in nurses.

BACKGROUND: Hand dermatitis is highly prevalent among nurses due to their frequent exposure to wet work. Providing cost-effective dermatological health surveillance for this occupational group presents a challenge to health service providers. AIMS: To ascertain the predictive value of nurses' self-assessment of whether they had current hand dermatitis using a screening questionnaire when compared with the assessment made by a dermatologist of the nurses' hand photographs. METHODS: We conducted a cross-sectional study comparing the self-report decision made by student and intensive care nurses using a single hand dermatitis screening question with the clinical assessment of their hand photographs made by dermatologists using a standardized photographic guide. RESULTS: We analysed data collected at study baseline (n = 1599). The results showed that the screening question had a high negative predictive value (91%; 95% CI 89-93), but a low positive predictive value (39%; 95% CI 34-45). It demonstrated acceptable accuracy in distinguishing those with and without the disease (area under the receiver operator curve = 0.7) and had a high specificity (86%; 95% CI 84-88) but a sensitivity of only 52% (95% CI 46-59) in identifying hand dermatitis. CONCLUSIONS: We found that nurses were able to accurately self-assess themselves as not having any signs of hand dermatitis. By contrast, they were less able to accurately self-assess positive cases suggesting under-recognition of early disease. We propose that a questionnaire containing a single hand dermatitis screening question should be considered as a tool for screening out clear cases as part of a workplace health surveillance programme for detecting hand dermatitis.

Magnitude of benefit for topical crisaborole in the treatment of atopic dermatitis in children and adults does not look promising: a critical appraisal.

AIM: To assess the efficacy and safety of crisaborole ointment, a phosphodiesterase 4 inhibitor, for the treatment of mild or moderate atopic dermatitis (AD) in two phase III studies (AD-301 and AD-302). DESIGN AND SETTING: Two identically designed multicentre, double-blind randomized controlled trials were conducted in the U.S.A. Participants were randomized 2 : 1 to receive crisaborole or vehicle treatment. In total 47 and 42 investigational centres were identified for AD-301 and AD-302, respectively. STUDY PARTICIPANTS: Inclusion criteria were identified as age ≥ 2 years, clinical diagnosis of AD (as per the Hanifin and Rajka criteria), ≥ 5% body surface area involvement, and baseline Investigator's Static Global Assessment (ISGA) mild or moderate. Exclusion criteria included previous use of biologics or systemic corticosteroids (within the last 28 days) or a topical calcineurin inhibitor/corticosteroid (within the last 14 days), and active skin infection. EXPOSURES: Participants were instructed to apply the study drug twice daily to all lesions identified at baseline, and all new lesions identified after day 1 (with weekly review of application instructions). Bland emollients were permitted to be used on skin not treated with the study drug. PRIMARY OUTCOME: The primary outcome was defined as ISGA clear or almost clear at day 29, with a 2-grade or more improvement from baseline. OUTCOMES: Secondary outcomes included the proportion of patients with an ISGA score of clear or almost clear at day 29, and time to success in ISGA score. Additional outcomes included pruritus severity and signs of AD (erythema, exudation, excoriation, induration/papulation and lichenification), and were measured on a 4-point scale (none, mild, moderate, severe). Adverse events were also recorded. RESULTS: More participants in the crisaborole-treated group achieved ISGA scores of clear or almost clear with ≥ 2-grade improvement than in the vehicle-treated group (AD-301, 32·8% vs. 25·4%, P = 0·38; AD-302, 31·4% vs. 18·0%, P < 0·001). Greater percentages of clear and almost clear scores were observed in the treatment groups (51·7% vs. 40·6%, P = 0·005; 48·5% vs. 29·7%; P < 0·001), as well as earlier success in ISGA score and improvement in pruritus (P ≤ 0·001). No serious treatment-related adverse events were identified. CONCLUSIONS: Based on the study results, the authors suggest that crisaborole is a safe treatment that improves disease severity, pruritus and clinical signs associated with AD.