Hywel Williams

• DSc, FMedSci
• Managing Director at University of Nottingham

The Harmonizing Outcomes Measurement in Eczema (HOME) initiative developed a core outcome set for atopic dermatitis (AD), but uptake in trials is still limited. An online survey was sent out to corresponding authors of AD interventional randomized clinical trials, to assess their awareness to the HOME COS, evaluate barriers to uptake, and identify...

Objective Methotrexate is first-line treatment for many immune-mediated inflammatory diseases. However, it inhibits vaccine-induced immunity – a major concern for this vulnerable group of patients. We evaluated if a 2-week interruption of methotrexate treatment immediately after COVID-19 booster improved antibody response against spike protein of t...

Background Eczema is a common condition with significant impact on quality of life. The main cause of treatment failure is non-use of prescribed treatments because treatments are time-consuming to apply; they may sting when first applied to inflamed skin; there are concerns about the safety of some treatments; and because people often receive confl...

Background Eczema Care Online (www.EczemaCareOnline.org.uk/) is an online self-management toolkit which includes tailored content for young people (13–25 years) and for parents of children that have eczema (0–12 years). Testing in two randomised controlled trials has shown that it is easy to use, cost effective and offers a sustained improvement in...

Background Randomised controlled trials (RCTs) evaluating new systemic treatments for atopic dermatitis (AD) have increased dramatically over the last decade. These trials often incorporate topical therapies either as permitted concomitant or rescue treatments. Differential use of these topicals post-randomisation introduces potential bias as they...

Background A priority setting partnership for eczema (syn atopic eczema, atopic dermatitis) has identified that bathing frequency is a key area of patient interest. However, there are nolarge, high-quality randomised controlled trials (RCTs) investigating this. The Rapid Eczema Trials project is a novel programme of research that aims to deliver mu...

Background A priority setting partnership for eczema (syn atopic eczema, atopic dermatitis) has identified that bathing frequency is a key area of patient interest. However, there are nolarge, high-quality randomised controlled trials (RCTs) investigating this. The Rapid Eczema Trials project is a novel programme of research that aims to deliver mu...

Objective Eczema is the most burdensome skin condition worldwide and topical anti‐inflammatory treatments are commonly used to control symptoms. The relative effectiveness and safety of different topical anti‐inflammatory treatments is uncertain. Design Network meta‐analysis performed within a Cochrane systematic review to compare and statisticall...

The Eczema Area and Severity Index is an investigator‐assessed instrument reporting clinical signs of atopic dermatitis. The instrument is extensively validated in both adult and paediatric populations and recommended as a core outcome measure to assess clinical signs by the Harmonising Outcome Measures for Eczema initiative in clinical trials and...

Background: Eczema (atopic dermatitis) is the most burdensome skin condition worldwide and cannot currently be prevented or cured. Topical anti-inflammatory treatments are used to control eczema symptoms, but there is uncertainty about the relative effectiveness and safety of different topical anti-inflammatory treatments. Objectives: To compare...

Background Atopic eczema is a common childhood skin problem linked with asthma, food allergy and allergic rhinitis that impairs quality of life. Objectives To determine whether advising parents to apply daily emollients in the first year can prevent eczema and/or other atopic diseases in high-risk children. Design A United Kingdom, multicentre, p...

Background Cow's milk allergy (CMA) overdiagnosis in young children appears to be increasing and has not been well characterised. We used a clinical trial population to characterise CMA overdiagnosis and identify individual‐level and primary care practice‐level risk factors. Methods We analysed data from 1394 children born in England in 2014–2016...

Importance Outcome measurement is an essential component of value-based health care and can aid patient care, quality improvement, and clinical effectiveness evidence generation. The Harmonising Outcome Measures for Eczema Clinical Practice initiative aims to identify a list of validated, feasible, outcome measurement instruments recommended to mea...

Background Autofluorescence (AF) - Raman spectroscopy is a technology that can detect residual basal cell carcinoma (BCC) on the resection margin of fresh surgically excised tissue specimens. The technology does not require tissue fixation, staining, labelling, or sectioning, and provides quantitative diagnosis maps of the surgical margins in 30 mi...

Objective To explore the acceptability of an individualised risk-stratified approach to monitoring for target-organ toxicity in adult patients with immune-mediated inflammatory diseases established on immune-suppressing treatment(s). Methods Adults (≥18 years) taking immune-suppressing treatment(s) for at-least six months, and healthcare professio...

Background Sulfasalazine-induced cytopenia, nephrotoxicity and hepatotoxicity is uncommon during long-term treatment. Some guidelines recommend 3 monthly monitoring blood tests indefinitely during long-term treatment while others recommend stopping monitoring after 1 year. To rationalise monitoring, we developed and validated a prognostic model for...

As well as quantifying the burden of skin disease, epidemiology provides a direct method for assessing the causes of skin diseases. Identification of causes is a necessary step in pursuing the ultimate goal of disease prevention. This chapter covers the importance of thinking in terms of population rather than individuals, and provides a summary of...

Objective To estimate the cost-effectiveness of online behavioral interventions (EczemaCareOnline.org.uk) designed to support eczema self-care management for parents/carers and young people from an NHS perspective. Methods Two within-trial economic evaluations, using regression-based approaches, adjusting for baseline and pre-specified confounder...

An autofluorescence-Raman spectroscopy-based prototype device was developed and utilised to detect basal cell carcinoma on the margins of skin specimens removed via surgery. This lecture will present the clinical integration of the device and results obtained intra-operatively. Full-text article not available; see video presentation

Background: Sulfasalazine induced cytopenia, nephrotoxicity, and hepatotoxicity is uncommon during long-term treatment. Some guidelines recommend three monthly monitoring blood-tests indefinitely while others recommend stopping monitoring after one year. To rationalise monitoring we developed and validated a prognostic model for clinically signific...

Background Autofluorescence (AF)‐Raman spectroscopy is a technology that can detect tumour tissue in surgically excised skin specimens. The technique does not require tissue fixation, staining, labelling or sectioning, and provides quantitative diagnosis maps within 30 min. Objectives To explore the clinical application of AF‐Raman microscopy to d...

Background There is no evidence base supporting the use of six-monthly monitoring blood tests for the early detection of liver, blood, and renal toxicity during established anti-TNF-alpha treatment. Objectives To evaluate the incidence and risk factors of anti-TNF-alpha treatment cessation due to liver, blood, and renal side-effects and, to estima...

Purpose Environmental factors such as bathing may play a role in atopic dermatitis (AD) development. This analysis utilized data from the Community Assessment of Skin Care, Allergies, and Eczema (CASCADE) Trial (NCT03409367), a randomized controlled trial of emollient therapy for AD prevention in the general population, to estimate bathing frequenc...

Background – Research is not often readily taken up in healthcare, which results in research waste. Eczema Care Online (www.EczemaCareOnline.org.uk/) has been shown in randomised controlled trials to be an effective online self-management intervention to improve eczema outcomes. Implementation requires adoption at patient/family, clinician and orga...

Background Patients established on thiopurines (e.g., azathioprine) are recommended to undergo three-monthly blood tests for the early detection of blood, liver, or kidney toxicity. These side-effects are uncommon during long-term treatment. We developed a prognostic model that could be used to inform risk-stratified decisions on frequency of monit...

Background Emollients are recommended for children with eczema (atopic eczema/dermatitis). A lack of head-to-head comparisons of the effectiveness and acceptability of the different types of emollients has resulted in a ‘trial and error’ approach to prescribing. Objective To compare the effectiveness and acceptability of four commonly used types o...

Background Topical corticosteroids (TCS) are a first‐line treatment for eczema, but there are concerns about their safety when used long‐term. Objectives To systematically review adverse effects associated with longer‐term use of TCS for eczema. Methods Randomised controlled trials (RCTs), cohort and case‐control studies reporting adverse effects...

Background: Recent discoveries have led to the suggestion that enhancing skin barrier from birth might prevent eczema and food allergy. Objective: To determine the cost-effectiveness of daily all-over-body application of emollient during the first year of life for preventing atopic eczema in high-risk children at 2 years from a health service pe...

Background: Core outcome sets (COS) are consensus-driven sets of minimum outcomes that should be measured and reported in all clinical trials. COS aim to reduce heterogeneity in outcome measurement and reporting, and selective outcome reporting. Implementing COS into clinical trials is challenging. Guidance to improve COS uptake in dermatology is...

The Harmonising Outcome Measures for Eczema (HOME) initiative established a core outcome set (COS) for atopic eczema (AE) clinical trials in 2019. This set encompasses four core outcome domains and corresponding measurement instruments: clinical signs (EASI), patient-reported symptoms (POEM and NRS 11 point for worst itch over the last 24 h), quali...

Assessing the severity of eczema in clinical research requires face-to-face skin examination by trained staff. Such approaches are resource-intensive for participants and staff, challenging during pandemics, and prone to inter- and intra-observer variation. Computer vision algorithms have been proposed to automate the assessment of eczema severity...

Surgical site infection (SSI) following excision of ulcerated skin cancers is a well-recognized complication; however, the exact risk is unknown and there is no consensus on antibiotic prescribing in this setting. The EXCISE trial (EXamining antibiotics for ulCerated skIn cancer Surgical Excision) aims to address this evidence gap. An online survey...

Our public engagement exercise showed the Fitzpatrick Scale does not adequately represent how members of the public consider their own skin. Descriptions offered by respondents regarding their skin tone were richly varied; some also indicated that structured and embedded inequalities affected the language they used. The patient voice is key to deve...

Objective: To develop and validate a prognostic model to inform risk stratified decisions on frequency of monitoring blood tests during long term methotrexate treatment. Design: Retrospective cohort study. Setting: Electronic health records within the UK's Clinical Practice Research Datalink (CPRD) Gold and CPRD Aurum. Participants: Adults (...

The COVID-19 pandemic has accelerated a rapid expansion of digital Advice and Guidance (A&G) across UK medical and surgical specialties. Dermatology A&G requests have increased by over 400% since the onset of the pandemic in 2020, with rapid expansion of teledermatology A&G services across England. Dermatology A&G is usually carried out asynchronou...

Background: Early-onset atopic dermatitis is a strong risk factor for food allergy, suggesting that early effective treatment may prevent transcutaneous sensitization. Objective: We tested whether enhanced treatment of atopic dermatitis to clinically affected and unaffected skin is more effective in preventing hen's egg allergy than reactive tre...

Background Eczema (atopic dermatitis) is a major global public health issue with high prevalence and morbidity. Our goal was to evaluate eczema prevalence over time, using standardized methodology. Methods The Global Asthma Network (GAN) Phase I study is an international collaborative study arising from the International Study of Asthma and Allerg...

Objective To determine the effectiveness of two online behavioural interventions, one for parents and carers and one for young people, to support eczema self-management. Design Two independent, pragmatic, parallel group, unmasked, randomised controlled trials. Setting 98 general practices in England. Participants Parents and carers of children (...

Background There is a lack of well-conducted randomised controlled trials evaluating the effectiveness of theory-based online interventions for eczema. To address these deficiencies, we previously developed and demonstrated the effectiveness of two online behavioural interventions: Eczema Care Online for parents/carers of children with eczema, and...

Assessing the severity of eczema in clinical research requires face-to-face skin examination by trained staff. Such approaches are resource-intensive for participants and staff, challenging during pandemics, and prone to inter- and intra-observer variation. Computer vision algorithms have been proposed to automate the assessment of eczema severity...

Background The effectiveness of emollients for preventing atopic dermatitis/eczema is controversial. The Barrier Enhancement for Eczema Prevention trial evaluated the effects of daily emollients during the first year of life on atopic dermatitis and atopic conditions to age 5 years. Methods 1394 term infants with a family history of atopic disease...

Background: Eczema and food allergy are common health conditions that usually begin in early childhood and often occur in the same people. They can be associated with an impaired skin barrier in early infancy. It is unclear whether trying to prevent or reverse an impaired skin barrier soon after birth is effective for preventing eczema or food all...

Importance: Measuring outcomes in clinical practice can aid patient care, quality improvement, and real-world evidence generation. The Harmonising Outcome Measures for Eczema (HOME) Clinical Practice initiative is developing a list of validated, feasible instruments to measure atopic eczema in clinical care. Prior work identified symptoms and long...

Objectives To investigate the association between vaccination against Covid-19 and autoimmune rheumatic disease (AIRD) flare. Methods Patients with AIRDs vaccinated against Covid-19 who consulted for disease flare between 01/12/2020 and 31/12/2021 were ascertained in Clinical Practice Research Datalink (Aurum). AIRD flare was defined as consultati...

Abstract is missing (Corrigendum)

Background: There is significant overdiagnosis of milk allergy in young children in some countries, leading to unnecessary use of specialised formula. This guidance, developed by experts without commercial ties to the formula industry, aims to reduce milk allergy overdiagnosis and support carers of children with suspected milk allergy. Methods:...

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To compare the efficacy and safety of topical anti-inflammatory treatments for reducing eczema symptoms or signs or improving eczema-related quality of life in children and adults with eczema, by undertaking a network meta-analysis. To provide a cli...

Background Eczema affects one in five children in the UK. Regular application of emollients is routinely recommended for children with eczema. There are four main emollient types, but no clear evidence of which is best. The current ‘trial and error’ approach to find suitable emollients can be frustrating for parents, children, and clinicians. Aim...

Assessing the severity of atopic dermatitis (AD, or eczema) traditionally relies on a face-to-face assessment by healthcare professionals, and may suffer from inter- and intra-rater variability. With the expanding role of telemedicine, several machine learning algorithms have been proposed to automatically assess AD severity from digital images. Th...

Background To our knowledge, there are no trials comparing emollients commonly used for childhood eczema. We aimed to compare the clinical effectiveness and safety of the four main emollient types: lotions, creams, gels, and ointments. Methods We did a pragmatic, individually randomised, parallel group, phase 4 superiority trial in 77 general prac...

In part 1 of this 2‐part review, conceptual frameworks for defining skin diseases were articulated. In this review, the main approaches that can be used to develop diagnostic criteria for skin disease are summarised, using atopic dermatitis as an example. Different frameworks for defining skin disease for research purposes are articulated, includin...

Objectives: To describe the development of Eczema Care Online (ECO), an online behaviour change intervention for young people with eczema (phase I); and explore and optimise the acceptability of ECO among this target group using think-aloud interviews (phase II). Methods: Theory-based, evidence-based and person-based approaches to intervention d...

Assessing the severity of atopic dermatitis (AD, or eczema) traditionally relies on a face-to-face assessment by healthcare professionals, and may suffer from inter- and intra-rater variability. With the expanding role of telemedicine, several machine learning algorithms have been proposed to automatically assess AD severity from digital images. Th...

Background: Eczema is a common skin condition. Although topical corticosteroids have been a first-line treatment for eczema for decades, there are uncertainties over their optimal use. Objectives: To establish the effectiveness and safety of different ways of using topical corticosteroids for treating eczema. Search methods: We searched databa...

Core outcome sets (COS) are critically important outcomes that should be measured in clinical trials. Their absence in atopic dermatitis (AD) is a form of research waste and impedes combining evidence to inform patient care. Here, we articulate the rationale for COS in AD and review the work of the international Harmonising Outcome Measures for Ecz...

The UK Dermatology Clinical Trials Network (UK DCTN) formed in 2002 with the aim of developing and supporting high quality independent national clinical trials that address prioritised research questions for people with skin disease. Its philosophy is to democratise UK dermatological clinical research and to tackle important clinical questions that...

Linked Article: Guelimi et al. Br J Dermatol 2022; 10.1111/bjd.20908. Dear Editor, Guelimi et al. evaluated the redundancy, methodological quality and discrepancies in 47 network meta‐analyses (NMAs) on systemic treatments for psoriasis.¹ We had planned a similar study, but in light of this new study we have abandoned our project in order to reduce...

Introduction Meta-analysis traditionally uses aggregate data from published reports. Individual Participant Data (IPD) meta-analysis, which obtains and synthesises participant-level data, is potentially more informative, but resource-intensive. The impact on the findings of meta-analyses using IPD in comparison to aggregate data has rarely been for...

Background Palmar hyperlinearity is a feature of ichthyosis vulgaris, the monogenic skin disorder caused by FLG loss-of-function mutations. Objective To investigate how well the presence or absence of hyperlinear palms (HLP) detect FLG genotype in children. Methods STARD criteria are used to report this diagnostic accuracy study. Phenotype and ge...

Importance Atopic eczema is characterized by a heterogenous waxing and waning course, with variable age of onset and persistence of symptoms. Distinct patterns of disease activity such as early-onset/resolving and persistent disease have been identified throughout childhood; little is known about patterns into adulthood. Objective This study aimed...

Objective An umbrella review summarising all safety data from systematic reviews of topical corticosteroids (TCS) in adults and children with atopic eczema. Methods Embase, MEDLINE, PubMed, Cochrane Database of Systematic Reviews and the Centre of Evidence Based Dermatology map of eczema systematic reviews were searched until 7 November 2018 and E...

Background Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects 20% of children worldwide. Environmental factors including weather and air pollutants have been shown to be associated with AD symptoms. However, the time‐dependent nature of such a relationship has not been adequately investigated. This paper aims to assess wheth...

We present the first clinical integration of a prototype device based on integrated auto-fluorescence imaging and Raman spectroscopy (Fast Raman device) for intra-operative assessment of surgical margins during Mohs micrographic surgery of basal cell carcinoma (BCC). Fresh skin specimens from 112 patients were used to optimise the tissue pre-proces...

Background Food allergy is thought to develop through transcutaneous sensitization, especially in the presence of skin barrier impairment and inflammation. Regular moisturizer application to infant skin could potentially promote transcutaneous sensitization and the development of food allergy. Objectives We tested this hypothesis in the Enquiring...

Objective Eczema and food allergy start in infancy and have shared genetic risk factors that affect skin barrier. We aimed to evaluate whether skincare interventions can prevent eczema or food allergy. Design A prospectively‐planned individual participant data meta‐analysis was carried out within a Cochrane systematic review to determine whether s...

Background: Eczema and food allergy are common health conditions that usually begin in early childhood and often occur together in the same people. They can be associated with an impaired skin barrier in early infancy. It is unclear whether trying to prevent or reverse an impaired skin barrier soon after birth is effective in preventing eczema or...

Introduction Eczema care requires management of triggers and various treatments. We developed two online behavioural interventions to support eczema care called ECO (Eczema Care Online) for young people and ECO for families. This protocol describes two randomised controlled trials (RCTs) aimed to evaluate clinical and cost-effectiveness of the two...

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 Mea...

Background Basal cell carcinoma (BCC) is the commonest cancer affecting white‐skinned individuals, and worldwide incidence is increasing. Although rarely fatal, BCC is associated with significant morbidity and costs. First‐line treatment is usually surgical excision, but alternatives are available. New published studies and the development of non‐s...

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 Measu...

Background Systematic reviews suggest that narrowband ultraviolet B light combined with treatments such as topical corticosteroids may be more effective than monotherapy for vitiligo. Objective To explore the clinical effectiveness and cost-effectiveness of topical corticosteroid monotherapy compared with (1) hand-held narrowband ultraviolet B lig...

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....

Background Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects almost 20% of the paediatric population worldwide. Although environmental factors such as weather and air pollutants have been shown to be associated with AD symptoms, the time-dependent nature of the relationship between the environmental factors and subsequent A...

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 randomize...

Atopic dermatitis (AD), also known as eczema, is one of the most common chronic skin diseases. AD severity is primarily evaluated based on visual inspections by clinicians, but is subjective and has large inter- and intra-observer variability in many clinical study settings. To aid the standardisation and automating the evaluation of AD severity, t...

Background: Economic evidence for vitiligo treatments is absent. Objective: To determine the cost-effectiveness of (a) hand-held narrowband-UVB (NB-UVB) and (b) combination of topical corticosteroid (TCS) and NB-UVB compared to TCS for localised vitiligo. Methods: Cost-effectiveness analysis alongside a pragmatic, 3-arm, placebo-controlled RCT...

Background Atopic dermatitis (AD) is a chronic inflammatory skin disease with periods of flares and remission. Designing personalised treatment strategies for AD is challenging, given the apparent unpredictability and large variation in AD symptoms and treatment responses within and across individuals. Better prediction of AD severity over time for...

Background: Failure to collect outcome data in randomised trials can result in bias and loss of statistical power. Further evaluations of strategies to increase retention are required. We assessed the effectiveness of two strategies for retention in a randomised prevention trial using a two-by-two factorial randomised study within a trial (SWAT)....

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 suppl...

The “one-off” approach of systematic reviews is no longer sustainable; we need to move toward producing “living” evidence syntheses (i.e., comprehensive, based on rigorous methods, and up-to-date). This implies rethinking the evidence synthesis ecosystem, its infrastructure and management. The three distinct production systems — primary research, e...

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 adu...

Objective To examine the validity and findings of studies that examine the accuracy of algorithm based smartphone applications (“apps”) to assess risk of skin cancer in suspicious skin lesions. Design Systematic review of diagnostic accuracy studies. Data sources Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, CPCI, Zetoc...

Background: Skin barrier dysfunction precedes eczema development. We tested whether daily use of emollient in the first year could prevent eczema in high-risk children. Methods: We did a multicentre, pragmatic, parallel-group, randomised controlled trial in 12 hospitals and four primary care sites across the UK. Families were approached via ante...

Background: Food allergy diagnosis in clinical studies can be challenging. Oral food challenges (OFC) are time-consuming, carry some risk and may therefore not be acceptable to all study participants. Objective: To design and evaluate an algorithm for detecting IgE-mediated food allergy in clinical study participants who do not undergo OFC. Met...

Background Failure to collect outcome data in randomised trials can result in bias and loss of statistical power. Further evaluations of strategies to increase retention are required. We assessed the effectiveness of two strategies for retention in a randomised prevention trial using a two-by-two factorial randomised study within a trial (SWAT). M...

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease with periods of flares and remission. Designing personalised treatment strategies for AD is challenging, given the apparent unpredictability and large variation in AD symptoms and treatment responses within and across individuals. Better prediction of AD severity over time fo...

Background: Measuring patient-centered outcomes in clinical practice is valuable for monitoring patients and advancing real-world research. A new initiative from the Harmonising Outcome Measures for Eczema (HOME) group aims to recommend what might be recorded for atopic eczema (AE) patients in routine clinical care. Objectives: Prioritize outcom...