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Background Autofluorescence (AF)–Raman microspectroscopy 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 min. Objectives To determine the accuracy of the AF–Raman instrument in detecting incomplete BCC excisions during Mohs micrographic surgery (MMS), using histology as the reference standard. Methods Skin layers from 130 patients undergoing MMS at the Nottingham University Hospitals NHS Trust (September 2022–July 2023) were investigated with the AF–Raman instrument. The layers were measured when fresh, immediately after excision. The AF–Raman results and the intraoperative assessment by Mohs surgeons were compared with a postoperative consensus-derived reference produced by three dermatopathologists. The sensitivity, specificity, and positive and negative predictive values were calculated. The study was registered with ClinicalTrials.gov (NCT03482622). Results AF–Raman analysis was successfully completed for 125 of 130 layers and, on average, covered 91% of the specimen surface area, with the lowest surface area covered being 87% for the eyelid and the highest being 94% for forehead specimens. The AF–Raman instrument identified positive margins in 24 of 36 BCC-positive cases [67% sensitivity, 95% confidence interval (CI) 49–82] and negative margins in 65 of 89 BCC-negative cases (73% specificity, 95% CI 63–82). Only one of 12 false-negative cases was caused by misclassification by the AF–Raman algorithm. The other 11 false-negatives cases were a result of no valid Raman signal being recorded at the location of the residual BCC due to either occlusion by blood or poor contact between tissue and the cassette window. The intraoperative diagnosis by Mohs surgeons identified positive margins in 31 of 36 BCC-positive cases (86% sensitivity, 95% CI 70–95) and negative margins in 79 of 89 BCC-negative cases (89% specificity, 95% CI 81–95). Conclusions The AF–Raman instrument has the potential to provide intraoperative microscopic assessment of surgical margins in BCC surgery. Further improvements are required for tissue processing, to ensure complete coverage of the surgical specimens. [ABSTRACT FROM AUTHOR]

Background: Two online behavioural interventions (one website for parents/carers of children with eczema; and one for young people with eczema) have been shown in randomised controlled trials to facilitate a sustained improvement in eczema severity. Aim: To describe intervention use and examine potential mediators of intervention outcomes and contextual factors that may influence intervention delivery and outcomes. Design and setting: Quantitative process evaluation in UK primary care. Method: Parents/carers and young people were recruited through primary care. Intervention use was recorded and summarised descriptively. Logistic regression explored sociodemographic and other factors associated with intervention engagement. Mediation analysis investigated whether patient enablement (ability to understand and cope with health issues), treatment use, and barriers to adherence were mediators of intervention effect. Subgroup analysis compared intervention effects among pre-specified participant subsets. Results: A total of 340 parents/carers and 337 young people were recruited. Most parents/carers (87%, n = 148/171) and young people (91%, n = 153/168) in the intervention group viewed the core introduction by 24 weeks. At 24 weeks, users had spent approximately 20 minutes on average on the interventions. Among parents/carers, greater intervention engagement was associated with higher education levels, uncertainty about carrying out treatments, and doubts about treatment efficacy at baseline. Among young people, higher intervention use was associated with higher baseline eczema severity. Patient enablement (the ability to understand and cope with health issues) accounted for approximately 30% of the intervention effect among parents/carers and 50% among young people. Conclusion: This study demonstrated that positive intervention outcomes depended on a modest time commitment from users. This provides further support that the wider implementation of Eczema Care Online is justified. [ABSTRACT FROM AUTHOR]

Background The Harmonising Outcome Measures for Eczema (HOME) initiative has agreed upon the Core Outcome Set (COS) for use in atopic dermatitis (AD) clinical trials, but additional guidance is needed to maximize its uptake. Objectives To provide answers to some of the commonly asked questions about using the HOME COS; to provide data to help with the interpretation of trial results; and to support sample size calculations for future trials. Methods and results We provide practical guidance on the use of the HOME COS for investigators planning clinical trials in patients with AD. It answers some of the common questions about using the HOME COS, how to access the outcome measurement instruments, what training/resources are needed to use them appropriately and clarifies when the COS is applicable. We also provide exemplar data to inform sample size calculations for eczema trials and encourage standardized data collection and reporting of the COS. Conclusions By encouraging adoption of the COS and facilitating consistent reporting of outcome data, it is hoped that the results of eczema trials will be more comprehensive and readily combined in meta-analyses and that patient care will subsequently be improved. [ABSTRACT FROM AUTHOR]

Background There is no evidence base to support the use of 6-monthly monitoring blood tests for the early detection of liver, blood and renal toxicity during established anti-tumour necrosis factor alpha (TNFα) treatment. Objectives To evaluate the incidence and risk factors of anti-TNFα treatment cessation owing to liver, blood and renal side-effects, and to estimate the cost-effectiveness of alternate intervals between monitoring blood tests. Methods A secondary care-based retrospective cohort study was performed. Data from the British Association of Dermatologists Biologic and Immunomodulators Register (BADBIR) were used. Patients with at least moderate psoriasis prescribed their first anti-TNFα treatment were included. Treatment discontinuation due to a monitoring blood test abnormality was the primary outcome. Patients were followed-up from start of treatment to the outcome of interest, drug discontinuation, death, 31 July 2021 or up to 5 years, whichever came first. The incidence rate (IR) and 95% confidence intervals (CIs) of anti-TNFα discontinuation with monitoring blood test abnormality was calculated. Multivariate Cox regression was used to examine the association between risk factors and outcome. A mathematical model evaluated costs and quality-adjusted life years (QALYs) associated with increasing the length of time between monitoring blood tests during anti-TNFα treatment. Results The cohort included 8819 participants [3710 (42.1%) female, mean (SD) age 44.76 (13.20) years] that contributed 25 058 person-years (PY) of follow-up and experienced 125 treatment discontinuations owing to a monitoring blood test abnormality at an IR of 5.85 (95% CI 4.91–6.97)/1000 PY. Of these, 64 and 61 discontinuations occurred within the first year and after the first year of treatment start, at IRs of 8.62 (95% CI 6.74–11.01) and 3.44 (95% CI 2.67–4.42)/1000 PY, respectively. Increasing age (in years), diabetes and liver disease were associated with anti-TNFα discontinuation after a monitoring blood test abnormality [adjusted hazard ratios of 1.02 (95% CI 1.01–1.04), 1.68 (95% CI 1.00–2.81) and 2.27 (95% CI 1.26–4.07), respectively]. Assuming a threshold of £20 000 per QALY gained, no monitoring was most cost-effective, but all extended periods were cost-effective vs. 3- or 6-monthly monitoring. Conclusions Anti-TNFα drugs were uncommonly discontinued owing to abnormal monitoring blood tests after the first year of treatment. Extending the duration between monitoring blood tests was cost-effective. Our results produce evidence for specialist society guidance to reduce patient monitoring burden and healthcare costs. [ABSTRACT FROM AUTHOR]

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 frequency and associated factors within the first 9 weeks of life. Methods: Data were collected from 909 parent/newborn dyads recruited from 25 pediatric and family medicine clinics from the Meta‐network Learning and Research Center (Meta‐LARC) practice‐based research network (PBRN) consortium in Oregon, North Carolina, Colorado, and Wisconsin for the CASCADE trial. Ordinal logistic regression was used to conduct a cross‐sectional analysis of the association between bathing frequency (measured in baths per week) and demographic, medical, and lifestyle information about the infant, their family, and their household. Variables were selected using a backwards‐stepwise method and estimates from the reduced model are reported in the text. Results: Moisturizer use (OR = 2.03, 95% CI: 1.54–2.68), Hispanic or Latino ethnicity (OR = 1.97, 95% CI: 1.42–2.72), a parental education level lower than a 4‐year college degree (OR = 2.48, 95% CI: 1.70–3.62), living in North Carolina or Wisconsin (compared to Oregon; OR = 2.12 and 1.47, 95% CI: 1.53–2.93 and 1.04–2.08, respectively), and increasing child age (in days; OR = 1.02, 95% CI: 1.01–1.02) were significantly associated with more frequent bathing, while pet ownership (OR = 0.67, 95% CI: 0.52–0.87) was significantly associated with less frequent bathing. Conclusions: We found significant ethnic, geographic, and socioeconomic variation in bathing frequency before 9 weeks of age that may be of relevance to AD prevention studies. [ABSTRACT FROM AUTHOR]

This document is a commentary on a comparative randomized clinical trial that evaluated the efficacy and safety of tacrolimus versus hydrocortisone as a topical treatment for atopic dermatitis in children. The authors commend the study for comparing the effects of these treatments and providing useful data on adverse events. However, they raise concerns about the trial duration, choice of primary outcomes, randomization process, sample size rationale, lack of blinding, implausibility of skin atrophy data, and ethical concerns. The authors suggest that better reporting following the CONSORT statement could have rectified some of these concerns. [Extracted from the article]

The number of published systematic reviews has soared rapidly in recent years. Sadly, the quality of most systematic reviews in dermatology is substandard. With the continued increase in exposure to systematic reviews, and their potential to influence clinical practice, we sought to describe a sequence of useful tips for the busy clinician reader to determine study quality and clinical utility. Important factors to consider when assessing systematic reviews include: determining the motivation to performing the study, establishing if the study protocol was prepublished, assessing quality of reporting using the PRISMA checklist, assessing study quality using the AMSTAR 2 critical appraisal checklist, assessing for evidence of spin, and summarizing the main strengths and limitations of the study to determine if it could change clinical practice. Having a set of heuristics to consider when reading systematic reviews serves to save time, enabling assessment of quality in a structured way, and come to a prompt conclusion of the merits of a review article in order to inform the care of dermatology patients. [ABSTRACT FROM AUTHOR]

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 asynchronously through dedicated digital platforms such as the National Health Service e-referral service, with streamlined conversion to referral if clinically indicated. A&G with images is advocated as the main referral pathway to dermatology specialist services in England (excluding the 2-week wait suspected skin cancer pathway). Providing dermatological care through A&G requires specific clinical skill sets to ensure rapid, safe and collaborative delivery, and optimization of educational benefit. Little published guidance is available to signpost clinicians to what constitutes a high-quality A&G request and response. This educational article discusses good clinical practice based on extensive local and national experience from primary and secondary care doctors. We cover digital communication skills, shared decision making, clinical competency and building collaborative links between patients, referrers and specialists. High-quality A&G, with agreed turn-around times and optimization of technology, can significantly streamline patient care and strengthen links between clinicians, providing it is appropriately resourced within the wider planning of elective care and outpatient activity. [ABSTRACT FROM AUTHOR]

Predatory journals, first recognized in the early 2000s, are fraudulent publications characterized by aggressive marketing solicitations and deviation from best publishing practices. These journals claim to be legitimate scholarly publications, and accept articles with no or poor peer review processes or quality checks, with rapid publication on payment by authors. They are a global threat as they are dishonest, lack transparency and seek only financial gain. More recently, predatory conferences have emerged and are expanding rapidly. Although they appear to be legitimate scientific conferences, they are also characterized by an overriding profit motive, with no concern for academic values. Predatory journals and conferences are on the rise; dermatology trainees, readers and those new to publishing and conferences are vulnerable to predatory exploitation. The consequences of falling victim to such predation include damage to the external reputation of the authors and their institution, and heightened concerns about the legitimacy of the research. This educational review defines predatory journals and conferences, and summarizes their distinguishing features such as a poor or no peer review process, rapid acceptance, flattering language and lack of meeting. It highlights the consequences of publishing in a predatory journal or attending a predatory conference, and outlines several tools available that dermatology researchers can use to recognize and reduce the likelihood of falling prey to a predatory journal or conference. [ABSTRACT FROM AUTHOR]

Background There is a lack of well-conducted randomized 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 Eczema Care Online for young people with eczema. Objectives To explore the views and experiences of people who have used the Eczema Care Online interventions to provide insights into how the interventions worked and identify contextual factors that may impede users' engagement with the interventions. Methods Qualitative semistructured interviews were conducted with 17 parents/carers of children with eczema and 17 young people with eczema. Participants were purposively sampled from two randomized controlled trials of the interventions and recruited from GP surgeries in England. Transcripts were analysed using inductive thematic analysis, and intervention modifications were identified using the person-based approach table of changes method. Results Both young people and parents/carers found the interventions easy to use, relatable and trustworthy, and perceived that they helped them to manage their eczema, thus suggesting that Eczema Care Online may be acceptable to its target groups. Our analysis suggested that the interventions may reduce eczema severity by facilitating empowerment among its users, specifically through improved understanding of, and confidence in, eczema management, reduced treatment concerns, and improved treatment adherence and management of irritants/triggers. Reading about the experiences of others with eczema helped people to feel 'normal' and less alone. Some (mainly young people) expressed firmly held negative beliefs about topical corticosteroids, views that were not influenced by the intervention. Minor improvements to the design and navigation of the Eczema Care Online interventions and content changes were identified and made, ready for wider implementation. Conclusions People with eczema and their families can benefit from reliable information, specifically information on the best and safest ways to use their eczema treatments early in their eczema journey. Together, our findings from this study and the corresponding trials suggest wider implementation of Eczema Care Online (EczemaCareOnline.org.uk) is justified. [ABSTRACT FROM AUTHOR]

Objectives To investigate the association between vaccination against coronavirus disease 2019 (COVID-19) and autoimmune rheumatic disease (AIRD) flare. Material and methods Patients with AIRDs vaccinated against COVID-19 who consulted for disease flare between 1 December 2020 and 31 December 2021 were ascertained in Clinical Practice Research Datalink (Aurum). AIRD flare was defined as consultation for AIRD with CS prescription on the same day or the next day. Vaccination was defined using date of vaccination and product code. The observation period was partitioned into vaccine-exposed (21 days after vaccination), pre-vaccination (7 days before vaccination) and remaining vaccine-unexposed periods. Participants contributed data with multiple vaccinations and outcomes. Season adjusted incidence rate ratios (aIRR) and 95% CI were calculated using self-controlled case series analysis. Results Data for 3554 AIRD cases, 72% female, mean age 65 years and 68.3% with RA, were included. COVID-19 vaccination was associated with significantly fewer AIRD flares in the 21-day vaccine-exposed period when all vaccinations were considered [aIRR (95% CI) 0.89 (0.80, 0.98)]. Using dose-stratified analyses there was a statistically significant negative association in the 21 days after first COVID-19 vaccination but no association after the second or third COVID-19 vaccinations [aIRR (95% CI) 0.76 (0.66, 0.89), 0.94 (0.79, 1.11) and 1.01 (0.85, 1.20), respectively]. On AIRD-type stratified analyses, vaccination was not associated with disease flares. Vaccination without or after severe acute respiratory syndrome coronavirus 2 infection, and with vectored DNA or mRNA vaccines, associated with comparable reduced risk of AIRD flares in the vaccine-exposed period after first COVID-19 vaccination. Conclusions Vaccination against COVID-19 was not associated with increased AIRD flares regardless of prior COVID-19, AIRD type, and whether mRNA or DNA vaccination technology were used. [ABSTRACT FROM AUTHOR]

Machine learning (ML) models for skin cancer recognition may have variable perfor)mance across different skin phototypes and skin cancer types. Overall performance metrics alone are insufficient to detect poor subgroup performance. We aimed (1) to assess whether studies of ML models reported results separately for different skin phototypes and rarer skin cancers, and (2) to graphically represent the skin cancer training datasets used by current ML models. In this systematic review, we searched PubMed, Embase and CENTRAL. We included all studies in medical journals assessing an ML technique for skin cancer diagnosis that used clinical or dermoscopic images from 1 January 2012 to 22 September 2021. No language restrictions were applied. We considered rarer skin cancers to be skin cancers other than pigmented melanoma, basal cell carcinoma and squamous cell carcinoma. We identified 114 studies for inclusion. Rarer skin cancers were included by 8/114 studies (7.0%), and results for a rarer skin cancer were reported separately in 1/114 studies (0.9%). Performance was reported across all skin phototypes in 1/114 studies (0.9%), but performance was uncertain in skin phototypes I and VI from minimal representation of the skin phototypes in the test dataset (9/3756 and 1/3756, respectively). For training datasets, although public datasets were most frequently used, with the most widely used being the International Skin Imaging Collaboration (ISIC) archive (65/114 studies, 57.0%), the largest datasets were private. Our review identified that most ML models did not report performance separately for rarer skin cancers and different skin phototypes. A degree of variability in ML model performance across subgroups is expected, but the current lack of transparency is not justifiable and risks models being used inappropriately in populations in whom accuracy is low. [ABSTRACT FROM AUTHOR]

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 Allergies in Children (ISAAC). Using surveys, we assessed eczema prevalence, severity, and lifetime prevalence, in global centres participating in GAN Phase I (2015–2020) and one/ both of ISAAC Phase I (1993–1995) and Phase III (2001–2003). We fitted linear mixed models to estimate 10‐yearly prevalence trends, by age group, income, and region. Results: We analysed GAN Phase I data from 27 centres in 14 countries involving 74,361 adolescents aged 13–14 and 47,907 children aged 6–7 (response rate 90%, 79%). A median of 6% of children and adolescents had symptoms of current eczema, with 1.1% and 0.6% in adolescents and children, respectively, reporting symptoms of severe eczema. Over 27 years, after adjusting for world region and income, we estimated small overall 10‐year increases in current eczema prevalence (adolescents: 0.98%, 95% CI 0.04%–1.92%; children: 1.21%, 95% CI 0.18%–2.24%), and severe eczema (adolescents: 0.26%, 95% CI 0.06%–0.46%; children: 0.23%, 95% CI 0.02%–0.45%) with larger increases in lifetime prevalence (adolescents: 2.71%, 95% CI 1.10%–4.32%; children: 3.91%, 95% CI 2.07%–5.75%). There was substantial heterogeneity in 10‐year change between centres (standard deviations 2.40%, 0.58%, and 3.04%), and strong evidence that some of this heterogeneity was explained by region and income level, with increases in some outcomes in high‐income children and middle‐income adolescents. Conclusions: There is substantial variation in changes in eczema prevalence over time by income and region. Understanding reasons for increases in some regions and decreases in others will help inform prevention strategies. [ABSTRACT FROM AUTHOR]

Summary: Clinical question: Is monitoring of liver function, lipids and full blood count necessary in healthy people taking isotretinoin? Background: Routine blood testing was recommended in the original licence for Roaccutane™ (isotretinoin) in 1983. In recent years, less frequent monitoring has been suggested by various authors. Data sources We performed four individual systematic searches of the MEDLINE database, via PubMed, from origin to 2 May 2021, supplemented by a hand search of all references in the identified papers. Study selection: Inclusion criteria were any description of clinical symptoms, laboratory abnormalities and/or physical findings, and any paper that explicitly described the patients as asymptomatic, during treatment with oral isotretinoin. Data extraction: Two independent reviewers (J.A. and D.J.) assessed articles for eligibility of inclusion. Evaluation of the data was done also by two of the authors (A.A., D.J. and J.A.) for each section, with the aim to use the presented evidence including guidelines, databases, case series, case reports, cohort studies and randomized clinical trials to delineate the clinical presentation and frequency of adverse events that might be amenable to laboratory monitoring. Results: We identified 407 papers in our searches and reviewed 125 papers in four sections. Overall, reported adverse events were very rare (< 1 in 10 000) and were either idiosyncratic or not preventable by monitoring, accompanied by symptoms, or seen in identifiable predisposed individuals who might benefit from monitoring because of pre‐existing conditions. Recommendation for clinical care: We could not find evidence to support the benefit of monitoring to detect adverse events. We suggest that in healthy young people laboratory monitoring for oral isotretinoin is unnecessary and risks detecting nonserious biochemical abnormalities. However, we recognize that new information about adverse events may change that recommendation. [ABSTRACT FROM AUTHOR]

Summary: In Part 1 of this two‐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 summarized, using atopic dermatitis (AD) as an example. Different frameworks for defining skin disease for research purposes are articulated, including statistical, prognostic, operational, clinical and epidemiological approaches. All share the common aim of attempting to develop criteria that enable meaningful comparisons between groups of people. The desirable attributes of a good definition are described: diagnostic criteria should measure what they are meant to measure; the results should be the same for different assessors; the criteria should be coherent with what is known about that disease; they should reflect some degree of morbidity and not pick up subclinical disease; they should be easy to administer; and they should be applicable to a range of people of different ages, sexes/genders and ethnicities. Consensus‐based criteria are contrasted with epidemiological derivation methods that assess the performance of diagnostic criteria in relation to a reference standard. The sensitivity and specificity of a disease definition is explained, along with how the trade‐off between these two properties can vary, depending on the purpose of the study and the study setting. The review closes with some reflections on when it is appropriate to consider splitting a disease into more than one category and how diagnostic criteria can be interpreted in the clinical setting. [ABSTRACT FROM AUTHOR]

Background: There is significant overdiagnosis of milk allergy in young children in some countries, leading to unnecessary use of specialized 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: Delphi study involving two rounds of anonymous consensus building and an open meeting between January and July 2021. Seventeen experts in general practice, nutrition, midwifery, health visiting, lactation support and relevant areas of paediatrics participated, located in Europe, North America, Middle East, Africa, Australia and Asia. Five authors of previous milk allergy guidelines and seven parents provided feedback. Findings: Participants agreed on 38 essential recommendations through consensus. Recommendations highlighted the importance of reproducibility and specificity for diagnosing milk allergy in children with acute or delayed symptoms temporally related to milk protein ingestion; and distinguished between children directly consuming milk protein and exclusively breastfed infants. Consensus was reached that maternal dietary restriction is not usually necessary to manage milk allergy, and that for exclusively breastfed infants with chronic symptoms, milk allergy diagnosis should only be considered in specific, rare circumstances. Consensus was reached that milk allergy diagnosis does not need to be considered for stool changes, aversive feeding or occasional spots of blood in stool, if there is no temporal relationship with milk protein ingestion. When compared with previous guidelines, these consensus recommendations resulted in more restrictive criteria for detecting milk allergy and a more limited role for maternal dietary exclusions and specialized formula. Interpretation: These new milk allergy recommendations from non‐conflicted, multidisciplinary experts advise narrower criteria, more prominent support for breastfeeding and less use of specialized formula, compared with current guidelines. [ABSTRACT FROM AUTHOR]

Summary: The UK Dermatology Clinical Trials Network (UK DCTN) was formed in 2002 with the aim of developing and supporting high‐quality independent national clinical trials that address prioritized research questions for people with skin disease. Its philosophy is to democratize UK dermatological clinical research and to tackle important clinical questions that industry has no incentive to answer. The network also plays a key role in training and capacity development. Its membership of over 1000 individuals includes dermatology consultants, trainees, dermatology nurses, general practitioners, methodologists and patients. Its organizational structures are lean and include a co‐ordinating team based at the Centre of Evidence‐Based Dermatology in Nottingham, and an executive with independent members to ensure probity and business progression. A prioritization panel and steering group enable a pipeline of projects to be prioritized and refined for external funding from independent sources. The UK DCTN has supported and completed 12 national clinical trials, attracting investment of over £15 million into UK clinical dermatology research. Trials have covered a range of interventions from drugs such as doxycycline (BLISTER), silk clothing for eczema (CLOTHES) and surgical interventions for hidradenitis suppurativa (THESEUS). Trial results are published in prestigious journals and have global impact. Genuine partnership with patients and carers has been a strong feature of the network since its inception. The UK DCTN is proud of its first 20 years of collaborative work, and aims to remain at the forefront of independent dermatological health technology assessment, as well as expanding into areas including diagnostics, artificial intelligence, efficient studies and innovative designs. [ABSTRACT FROM AUTHOR]

Summary: In Part 1 of this 2‐part review of the 20th anniversary of the UK Dermatology Clinical Trials Network (UK DCTN), we described its role in developing and supporting clinical trial proposals, elaborating on structure, process and clinical trials activity. This review describes the diverse educational and training activities that the UK DCTN supports. Although not primarily set up as an educational organization, an education and training function emerged organically as the network grew. Education and training also embodies the democratization principle that drove the formation of the UK DCTN, allowing participation from a much wider group of individuals than just senior academics. Far from being a sideline, education and training has now become a major component of the UK DCTN that evolves constantly through changing training curricula and trial methodology developments. Formal UK DCTN training opportunities started in 2007 with competitively awarded annual fellowships for dermatology trainees, followed by similar schemes for general practitioners, Staff and Associate Specialist clinicians and dermatology nurses. These were followed in 2013 by larger groups of trainees who work up specific trial proposals with senior mentors. Finally, a virtual journal club emerged during the pandemic in 2020 in order to reach trainees with little access to academic training. Focused activities with dermatological nurses and patients/carers also take place. Such activities require considerable organization and volunteerism from the co‐ordinating centre and former fellows. Education and training has become an essential component for capacity building to develop clinical trials and succession planning for the UK DCTN. [ABSTRACT FROM AUTHOR]

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: To identify how parents and children experience and evaluate emollients.Design and Setting: Qualitative interview study, nested within a primary care trial of emollients (Best Emollients for Eczema [BEE] trial).Method: Semi-structured interviews with children with eczema and their parents were conducted. Participants were purposively sampled on emollient type (lotion, cream, gel, or ointment), age, and eczema severity.Results: Forty-four parents were interviewed, with children participating in 24 of those interviews. There was no clear preference for any one emollient type. The strongest theme was the variation of experience in each of the four types. Participants focused on thickness and absorbency, both positively and negatively, to frame their evaluations. Effectiveness and acceptability were both considered when evaluating an emollient but effectiveness was the primary driver for continued use. For some, participating in the trial had changed their knowledge and behaviour of emollients, resulting in use that was more regular and for a longer duration.Conclusion: There is no one emollient that is suitable for everyone, and parents/children prioritise different aspects of emollients. Future research could evaluate decision aids and/or tester pots of different types, which could enable clinicians and parents/children to work collaboratively to identify the best emollient for them. [ABSTRACT FROM AUTHOR]

Background: Childhood eczema is often poorly controlled owing to underuse of emollients and topical corticosteroids (TCS). Parents/carers report practical and psychosocial barriers to managing their child's eczema, including child resistance. Online interventions could potentially support parents/carers; however, rigorous research developing such interventions has been limited.Aim: To develop an online behavioural intervention to help parents/carers manage and co-manage their child's eczema.Design and Setting: Intervention development using a theory-, evidence-, and person-based approach (PBA) with qualitative research.Method: A systematic review and qualitative synthesis of studies (n = 32) and interviews with parents/carers (n = 30) were used to identify barriers and facilitators to effective eczema management, and a prototype intervention was developed. Think-aloud interviews with parents/carers (n = 25) were then used to optimise the intervention to increase its acceptability and feasibility.Results: Qualitative research identified that parents/carers had concerns about using emollients and TCS, incomplete knowledge and skills around managing eczema, and reluctance to transitioning to co-managing eczema with their child. Think-aloud interviews highlighted that, while experienced parents/carers felt they knew how to manage eczema, some information about how to use treatments was still new. Techniques for addressing barriers included providing a rationale explaining how emollients and TCS work, demonstrating how to use treatments, and highlighting that the intervention provided new, up-to-date information.Conclusion: Parents/carers need support in effectively managing and co-managing their child's eczema. The key output of this research is Eczema Care Online for Families, an online intervention for parents/carers of children with eczema, which is being evaluated in a randomised trial. [ABSTRACT FROM AUTHOR]

Introduction: Meta‐analysis traditionally uses aggregate data from published reports. Individual Participant Data (IPD) meta‐analysis, which obtains and synthesizes participant‐level data, is potentially more informative, but resource‐intensive. The impact on the findings of meta‐analyses using IPD in comparison with aggregate data has rarely been formally evaluated. Methods: We conducted a secondary analysis of a Cochrane systematic review of skincare interventions for preventing eczema and food allergy in infants to identify the impact of the analytical choice on the review's findings. We used aggregate data meta‐analysis only and contrasted the results against those of the originally published IPD meta‐analysis. All meta‐analysis used random effects inverse variance models. Certainty of evidence was evaluated using GRADE. Results: The pooled treatment effects for the Cochrane systematic review's co‐primary outcomes of eczema and food allergy were similar in IPD meta‐analysis (eczema RR 1.03, 95% CI 0.81, 1.31; I241%, 7 studies 3075 participants), and aggregate meta‐analysis (eczema RR 1.01 95% CI 0.77, 1.33; I253%, 7 studies, 3089 participants). In aggregate meta‐analysis, the statistical heterogeneity could not be explained but using IPD it was explained by one trial which used a different, bathing intervention. For IPD meta‐analysis, risk of bias was assessed as lower and more adverse event data were available compared with aggregate meta‐analysis. This resulted in higher certainty of evidence, especially for adverse events. IPD meta‐analysis enabled analysis of treatment interactions by age and hereditary eczema risk; and analysis of the effect of treatment adherence using pooled complier‐adjusted‐causal‐effect analysis, none of which was possible in aggregate meta‐analysis. Conclusions: For this systematic review, IPD did not significantly change primary outcome risk ratios compared with aggregate data meta‐analysis. However, certainty of evidence, safety outcomes, subgroup and adherence analyses were significantly different using IPD. This demonstrates benefits of adopting an IPD approach to meta‐analysis. [ABSTRACT FROM AUTHOR]

Objective The aim was to examine the incidence and pattern of MMF discontinuation associated with abnormal monitoring blood-test results. Methods Data from people prescribed MMF for common inflammatory conditions in the Clinical Practice Research Datalink were used. Participants were followed from the first MMF prescription. The primary outcome was drug discontinuation with an associated abnormal blood-test result within 60 days. Secondary outcomes were drug discontinuation for any reason and discontinuation associated with severely abnormal blood-test results within 60 days. Multivariable Cox regression was used to examine factors associated with the primary outcome. Results The cohort included 992 participants (68.9% female, mean age 51.95 years, 47.1% with SLE) contributing 1885 person-years of follow-up. The incidence of MMF discontinuation associated with any (severely) abnormal blood-test results was 153.46 (21.07) per 1000 person-years in the first year of prescription and 32.39 (7.91) per 1000 person-years in later years. Of those patients prescribed MMF, 11.5% (1.7%) discontinued treatment with any (severely) abnormal blood-test results in the first year of prescription. After this period, a mean of 2.6% (0.7%) of patients discontinued treatment with any (severely) abnormal blood-test results per year. Increased serum creatinine and cytopenia were more commonly associated with MMF discontinuation than elevated liver enzymes. Chronic kidney disease stage   3 or higher was significantly associated with MMF discontinuation with any blood-test abnormalities [adjusted hazard ratio (95% CI) 2.22 (1.47, 3.37)]. Conclusion MMF is uncommonly discontinued for blood-test abnormalities and even less often discontinued for severe blood-test abnormalities after the first year of prescription. Consideration can be given to less frequent monitoring after 1 year of treatment, especially in those without chronic kidney disease stage   3 or higher. [ABSTRACT FROM AUTHOR]

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 genotype data (four most prevalent FLG null mutations) were obtained from a total of 3656 children in three studies: the UK CLOTHES trial (children 1–5 years with moderate–severe atopic eczema); UK BEEP trial (2 year olds at high risk of developing atopic eczema); UK‐Irish eczema case collection (0–16 year olds with atopic eczema). All participants included in analyses of HLP as the index test and FLG genotype as the reference were of white European ancestry. Results: Thirty‐two percent of participants (1159/3656) had FLG null mutation(s) and 37% (1347/3656) had HLP. In 13% (464/3656), HLP was recorded as 'unsure' or not recorded. The sensitivity and specificity of HLP for detecting FLG mutations in each of the studies was: 67% (95% CI 55–78%) and 75% (67–82%) in CLOTHES; 46% (36–55%) and 89% (86–91%) in BEEP; 72% (68–75%) and 60% (57–62%) in the UK‐Irish case collection. Positive and negative likelihood ratios were: 2.73 (1.95–3.81) and 0.44 (0.31–0.62) in CLOTHES; 4.02 (2.99–5.40) and 0.61 (0.52–0.73) in BEEP; 1.79 (1.66–1.93) and 0.47 (0.42–0.53) in the UK‐Irish collection. Discussion: Trained observers were able to define palmar hyperlinearity in the majority (3191/3656, 87%) of cases. The presence of HLP is not a reliable sign to detect FLG mutations, but the absence of HLP excludes FLG null genotype with a reasonable degree of certainty. [ABSTRACT FROM AUTHOR]

Importance: Extenuating circumstances can trigger unplanned changes to randomized trials and introduce methodological, ethical, feasibility, and analytical challenges that can potentially compromise the validity of findings. Numerous randomized trials have required changes in response to the COVID-19 pandemic, but guidance for reporting such modifications is incomplete.Objective: As a joint extension for the CONSORT and SPIRIT reporting guidelines, CONSERVE (CONSORT and SPIRIT Extension for RCTs Revised in Extenuating Circumstances) aims to improve reporting of trial protocols and completed trials that undergo important modifications in response to extenuating circumstances.Evidence: A panel of 37 international trial investigators, patient representatives, methodologists and statisticians, ethicists, funders, regulators, and journal editors convened to develop the guideline. The panel developed CONSERVE following an accelerated, iterative process between June 2020 and February 2021 involving (1) a rapid literature review of multiple databases (OVID Medline, OVID EMBASE, and EBSCO CINAHL) and gray literature sources from 2003 to March 2021; (2) consensus-based panelist meetings using a modified Delphi process and surveys; and (3) a global survey of trial stakeholders.Findings: The rapid review yielded 41 673 citations, of which 38 titles were relevant, including emerging guidance from regulatory and funding agencies for managing the effects of the COVID-19 pandemic on trials. However, no generalizable guidance for all circumstances in which trials and trial protocols might face unanticipated modifications were identified. The CONSERVE panel used these findings to develop a consensus reporting guidelines following 4 rounds of meetings and surveys. Responses were received from 198 professionals from 34 countries, of whom 90% (n = 178) indicated that they understood the concept definitions and 85.4% (n = 169) indicated that they understood and could use the implementation tool. Feedback from survey respondents was used to finalize the guideline and confirm that the guideline's core concepts were applicable and had utility for the trial community. CONSERVE incorporates an implementation tool and checklists tailored to trial reports and trial protocols for which extenuating circumstances have resulted in important modifications to the intended study procedures. The checklists include 4 sections capturing extenuating circumstances, important modifications, responsible parties, and interim data analyses.Conclusions and Relevance: CONSERVE offers an extension to CONSORT and SPIRIT that could improve the transparency, quality, and completeness of reporting important modifications to trials in extenuating circumstances such as COVID-19. [ABSTRACT FROM AUTHOR]

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 whether real‐time data on weather and air pollutants can make short‐term prediction of AD severity scores. Methods: Using longitudinal data from a published panel study of 177 paediatric patients followed up daily for 17 months, we developed a statistical machine learning model to predict daily AD severity scores for individual study participants. Exposures consisted of daily meteorological variables and concentrations of air pollutants, and outcomes were daily recordings of scores for six AD signs. We developed a mixed‐effect autoregressive ordinal logistic regression model, validated it in a forward‐chaining setting and evaluated the effects of the environmental factors on the predictive performance. Results: Our model successfully made daily prediction of the AD severity scores, and the predictive performance was not improved by the addition of measured environmental factors. Potential short‐term influence of environmental exposures on daily AD severity scores was outweighed by the underlying persistence of preceding scores. Conclusions: Our data does not offer enough evidence to support a claim that weather or air pollutants can make short‐term prediction of AD signs. Inferences about the magnitude of the effect of environmental factors on AD severity scores require consideration of their time‐dependent dynamic nature. [ABSTRACT FROM AUTHOR]

While emollients have a well-established place in the management of eczema, we hope that Zhong et al's work does not lead to inappropriate enthusiasm for emollient application in infancy to prevent eczema. Correspondence to " Emollients in infancy to prevent atopic dermatitis: A systematic review and meta-analysis" Zhong et al1 report that emollients reduce atopic dermatitis in subgroups of infants at high risk and in those with continuous use of the intervention. [Extracted from the article]

The authors need to justify their replication in relation to author influence or conflicts of interest in previously published NMAs2-4. For example, if the NMA authors cite this being high-priority research, but do not cite this in comparison with a previously published NMA, they are not assessing priority in relation to the need for replication2. The assessment of this being a high-priority NMA should be made explicitly in relation to the need for replication of previously published NMAs. [Extracted from the article]

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease with periods of flares and remission. Designing personalized 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 individual patients could help to select optimum timing and type of treatment for improving disease control. Objective: We aimed to develop a proof of principle mechanistic machine learning model that predicts the patient‐specific evolution of AD severity scores on a daily basis. Methods: We designed a probabilistic predictive model and trained it using Bayesian inference with the longitudinal data from two published clinical studies. The data consisted of daily recordings of AD severity scores and treatments used by 59 and 334 AD children over 6 months and 16 weeks, respectively. Validation of the predictive model was conducted in a forward‐chaining setting. Results: Our model was able to predict future severity scores at the individual level and improved chance‐level forecast by 60%. Heterogeneous patterns in severity trajectories were captured with patient‐specific parameters such as the short‐term persistence of AD severity and responsiveness to topical steroids, calcineurin inhibitors and step‐up treatment. Conclusions: Our proof of principle model successfully predicted the daily evolution of AD severity scores at an individual level and could inform the design of personalized treatment strategies that can be tested in future studies. Our model‐based approach can be applied to other diseases with apparent unpredictability and large variation in symptoms and treatment responses such as asthma. [ABSTRACT FROM AUTHOR]

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 supplements such as Vitamin D have also not shown any benefit with the possible exception of omega-3 fatty acids. Systematic reviews suggest that probiotics could reduce AD incidence by around 20%, although the studies are quite variable and might benefit from individual patient data metaanalysis. Skin barrier enhancement from birth to prevent AD and food allergy has received recent interest, and results from national trials are awaited. It is possible that trying to influence major immunological changes that characterise AD at birth through infantdirected interventions may be too late, and more attention might be directed at fetal programming in utero. [ABSTRACT FROM AUTHOR]

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. Methods: An algorithm for trial participants in the Barrier Enhancement for Eczema Prevention (BEEP) study who were unwilling or unable to attend OFC was developed. BEEP is a pragmatic, multi‐centre, randomized‐controlled trial of daily emollient for the first year of life for primary prevention of eczema and food allergy in high‐risk infants (ISRCTN21528841). We built on the European iFAAM consensus guidance to develop a novel food allergy diagnosis algorithm using available information on previous allergenic food ingestion, food reaction(s) and sensitization status. This was implemented by a panel of food allergy experts blind to treatment allocation and OFC outcome. We then evaluated the algorithm's performance in both BEEP and Enquiring About Tolerance (EAT) study participants who did undergo OFC. Results: In 31/69 (45%) BEEP and 44/55 (80%) EAT study control group participants who had an OFC the panel felt confident enough to categorize children as "probable food allergy" or "probable no food allergy". Algorithm‐derived panel decisions showed high sensitivity 94% (95%CI 68, 100) BEEP; 90% (95%CI 72, 97) EAT and moderate specificity 67% (95%CI 39, 87) BEEP; 67% (95%CI 39, 87) EAT. Sensitivity and specificity were similar when all BEEP and EAT participants with OFC outcome were included. Conclusion: We describe a new algorithm with high sensitivity for IgE‐mediated food allergy in clinical study participants who do not undergo OFC. Clinical Relevance: This may be a useful tool for excluding food allergy in future clinical studies where OFC is not conducted. [ABSTRACT FROM AUTHOR]

Introduction Atopic dermatitis/eczema affects around 20% of children and is characterised by inflamed, dry, itchy skin. Guidelines recommend ‘leave-on’ emollients that are applied directly to the skin to add or trap moisture and used regularly, they can soothe, enhance the skin barrier and may prevent disease ‘flares’. However, the suitability of the many different emollients varies between people and there is little evidence to help prescribers and parents and carers decide which type to try first. Methods and analysis Design: pragmatic, multicentre, individually randomised, parallel group superiority trial of four types of emollient (lotions, creams, gel or ointments). Setting: general practitioner surgeries in England. Participants: children aged over 6 months and less than 12 years with mild-to- severe eczema and no known sensitivity to study emollients. Interventions: study-approved lotion, cream, gel or ointment as the only leave-on emollient for 16 weeks, with directions to apply twice daily and as required. Other treatments, such as topical corticosteroids, used as standard care. Follow-up: 52 weeks. Primary outcome: validated patient-orientated eczema measure measured weekly for 16 weeks. Secondary outcomes: eczema signs (Eczema Area Severity Index) by masked researcher, treatment use, parent satisfaction, adverse events, child and family quality of life (Atopic Dermatitis Quality of Life, Child Health Utility 9D and Dermatitis Family Impact). Sample size: 520 participants (130 per group). Analysis: intention-to- treat using linear mixed models for repeated measures. Nested qualitative study: audio-recording of sample of baseline appointments and up to 60 interviews with participants at 4 and 16 weeks, interviews to be transcribed and analysed thematically. Ethics and dissemination Ethics approval granted by the NHS REC (South West - Central Bristol Research Ethics Committee 17/SW/0089). Findings will be presented at conferences, published in open-access peer-reviewed journals and the study website; and summaries shared with key stakeholders. [ABSTRACT FROM AUTHOR]

This is the third article in a series relating to research and dermatology nursing, and describes why critical appraisal skills are necessary for dermatology nurses. It suggests a quick critical appraisal approach that can be used -- 'read, write and reflect'. The approach advises nurses to consider PICO, types of bias, and validity. The importance of utilising critical appraisal in practice is discussed, as well as the need for it to become a necessary skill for dermatology nurses. [ABSTRACT FROM AUTHOR]

Sadly, the same has happened to systematic reviews in dermatology, and the sin of spin can be appended to the seven top sins of dermatology systematic reviews that now haunt me (Table 1). Despite being one of the first to introduce systematic reviews into dermatology and forming the Cochrane Skin Group [[7]], publication of systematic reviews in dermatology has spun completely out of control. [Extracted from the article]