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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]

Immunosuppressive treatments inhibit vaccine-induced immunity against SARS-CoV-2. We evaluated whether a 2-week interruption of methotrexate treatment immediately after the COVID-19 vaccine booster improved antibody responses against the S1 receptor-binding domain (S1-RBD) of the SARS-CoV-2 spike protein compared with uninterrupted treatment in patients with immune-mediated inflammatory diseases. We did an open-label, prospective, two-arm, parallel-group, multicentre, randomised, controlled, superiority trial in 26 hospitals in the UK. We recruited adults from rheumatology and dermatology clinics who had been diagnosed with an immune-mediated inflammatory disease (eg, rheumatoid arthritis, psoriasis with or without arthritis, axial spondyloarthritis, atopic dermatitis, polymyalgia rheumatica, and systemic lupus erythematosus) and who were taking low-dose weekly methotrexate (≤25 mg per week) for at least 3 months. Participants also had to have received two primary vaccine doses from the UK COVID-19 vaccination programme. We randomly assigned the participants (1:1), using a centralised validated computer randomisation program, to suspend methotrexate treatment for 2 weeks immediately after their COVID-19 booster (suspend methotrexate group) or to continue treatment as usual (continue methotrexate group). Participants, investigators, clinical research staff, and data analysts were unmasked, while researchers doing the laboratory analyses were masked to group assignment. The primary outcome was S1-RBD antibody titres 4 weeks after receiving the COVID-19 booster vaccine dose, assessed in the intention-to-treat population. This trial is registered with ISRCT, ISRCTN11442263; following the pre-planned interim analysis, recruitment was stopped early. Between Sept 30, 2021 and March 3, 2022, we recruited 340 participants, of whom 254 were included in the interim analysis and had been randomly assigned to one of the two groups: 127 in the continue methotrexate group and 127 in the suspend methotrexate group. Their mean age was 59·1 years, 155 (61%) were female, 130 (51%) had rheumatoid arthritis, and 86 (34%) had psoriasis with or without arthritis. After 4 weeks, the geometric mean S1-RBD antibody titre was 22 750 U/mL (95% CI 19 314–26 796) in the suspend methotrexate group and 10 798 U/mL (8970–12 997) in the continue methotrexate group, with a geometric mean ratio (GMR) of 2·19 (95% CI 1·57–3·04; p<0·0001; mixed-effects model). The increased antibody response in the suspend methotrexate group was consistent across methotrexate dose, administration route, type of immune-mediated inflammatory disease, age, primary vaccination platform, and history of SARS-CoV-2 infection. There were no intervention-related serious adverse events. A 2-week interruption of methotrexate treatment for people with immune-mediated inflammatory diseases resulted in enhanced boosting of antibody responses after COVID-19 vaccination. This intervention is simple, low-cost, and easy to implement, and could potentially translate to increased vaccine efficacy and duration of protection for susceptible groups. National Institute for Health and Care Research. [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: 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]

OBJECTIVE Topical corticosteroids (CSs) are commonly used to treat inflammatory skin conditions including eczema and psoriasis. Although topical CS package inserts describe hyperglycemia and glycosuria as adverse drug reactions, it is unclear whether topical CS use in real life is also associated with an increased risk of type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS Two matched case-control studies and one cohort study were conducted using routinely collected health care data from Denmark and the U.K. A total of 115,218 and 54,944 adults were identified as case subjects with new-onset T2D in the Danish and U.K. case-control study, respectively. For the Danish cohort study, 2,689,473 adults were included. The main exposure was topical CSs, and the outcome was incident T2D. RESULTS Topical CS was significantly associated with T2D in the Danish (adjusted odds ratio [OR] 1.25 [95% CI 1.23–1.28]) and U.K. (adjusted OR 1.27 [95% CI 1.23–1.31]) case-control studies. Individuals who were exposed to topical CSs had significantly increased risk of incident T2D (adjusted hazard ratio 1.27 [95% CI 1.26–1.29]). We observed significant dose-response relationships between T2D and increasing potency of topical CSs in the two Danish studies. The results were consistent across all sensitivity analyses. CONCLUSIONS We found a positive association between topical CS prescribing and incident T2D in Danish and U.K. adult populations. Clinicians should be cognizant of possible diabetogenic effects of potent topical CSs. [ABSTRACT FROM AUTHOR]

We compared psychoeducation and problem solving (PEPS) therapy against usual treatment in a multisite randomized-controlled trial. The primary outcome was social functioning. We aimed to recruit 444 community-dwelling adults with personality disorder; however, safety concerns led to an early cessation of recruitment. A total of 154 people were randomized to PEPS and 152 to usual treatment. Follow-up at 72 weeks was completed for 68%. PEPS therapy was no more effective than usual treatment for improving social functioning (adjusted difference in mean Social Functioning Questionnaire scores = −0.73; 95% CI [−1.83, 0.38]; p = 0.19). PEPS therapy is not an effective treatment for improving social functioning of adults with personality disorder living in the community. [ABSTRACT FROM AUTHOR]

Background: Instruments for field diagnosis of eczema are increasingly used, and it is essential to understand specific limitations to make best use of their strengths. Our objective was to assess the validity of ISAAC and UK Working Party criteria for field diagnosis of eczema in children. Methods: We performed a cohort study in urban Brazil. Parents/guardians of 1,419 children answered ISAAC phase II questionnaire. Children were examined for skin lesions (UKWP protocol). Two dermatologists examined most cases of eczema (according to ISAAC or UKWP), and a sample without eczema. Results: Agreement between repeat questionnaires on the filter question was poor (kappa = 0.4). Agreement between the 2 dermatologists was fair (kappa = 0.6). False positive reports included scabies in 39% of ISAAC cases and 33% of UKWP cases. Sensitivity and PPV were low (ISAAC: 37.1% and 16.1%; UKWP: 28.6% and 23.8%). Specificity and NPV were high (ISAAC: 90.0% and 96.6%; UKWP: 95.3% and 96.2%). One-year prevalence of eczema was 11.3% (ISAAC), 5.9% (UKWP) and 4.9% (adjusted dermatologist diagnosis). Point prevalence of scabies (alone or not) was 43%, 33% and 18%, in eczemas according to ISAAC, to UKWP and to dermatologists. The reasons why children with eczema were not identified by ISAAC or UKWP were wrongly denying dry skin, itchy rash or personal history of atopic diseases. A limitation is that questionnaire was already validated in Brazil, but not field tested in this specific setting. Conclusions: Studies using UKWP or ISAAC criteria should include a validation arm, to contribute to the understanding of potential limitations of their use in different contexts and to explore solutions. We list specific recommendations. [ABSTRACT FROM AUTHOR]

Background: This paper describes the results of a feasibility study for a randomised controlled trial (RCT). Methods: Twenty-nine members of the UK Dermatology Clinical Trials Network (UK DCTN) expressed an interest in recruiting for this study. Of these, 17 obtained full ethics and Research & Development (R&D) approval, and 15 successfully recruited patients into the study. A total of 70 participants with a diagnosis of cellulitis of the leg were enrolled over a 5-month period. These participants were largely recruited from medical admissions wards, although some were identified from dermatology, orthopaedic, geriatric and general surgery wards. Data were collected on patient demographics, clinical features and willingness to take part in a future RCT. Results: Despite being a relatively common condition, cellulitis patients were difficult to locate through our network of UK DCTN clinicians. This was largely because patients were rarely seen by dermatologists, and admissions were not co-ordinated centrally. In addition, the impact of the proposed exclusion criteria was high; only 26 (37%) of those enrolled in the study fulfilled all of the inclusion criteria for the subsequent RCT, and were willing to be randomised to treatment. Of the 70 participants identified during the study as having cellulitis of the leg (as confirmed by a dermatologist), only 59 (84%) had all 3 of the defining features of: i) erythema, ii) oedema, and iii) warmth with acute pain/tenderness upon examination. Twenty-two (32%) patients experienced a previous episode of cellulitis within the last 3 years. The median time to recurrence (estimated as the time since the most recent previous attack) was 205 days (95% CI 102 to 308). Service users were generally supportive of the trial, although several expressed concerns about taking antibiotics for lengthy periods, and felt that multiple morbidity/old age would limit entry into a 3-year study. Conclusion: This pilot study has been crucial in highlighting some key issues for the conduct of a future RCT. As a result of these findings, changes have been made to i) the planned recruitment strategy, ii) the proposed inclusion criteria and ii) the definition of cellulitis for use in the future trial. [ABSTRACT FROM AUTHOR]

Editorial. Comments on A. Firooz and colleagues' (1999) study of the validity of Great Britain Working Party's Diagnostic Criteria for Atopic Dermatitis (AD). Attributes of a good validation study for diagnostic criteria; Implications of the study for making international epidemiological comparisons of AD; Other ways of defining the clinical concept of AD.

Determines the prevalence of childhood eczema in advantaged socioeconomic groups in Great Britain. Comparison between the prevalence of eczema among schoolchildren in social classes I and II and those in lower classes. Association of exposures with social classes; Genetic factors in the expression of childhood eczema.

The author discusses the significance of democratizing randomized clinical trials (RCTs) in the field of dermatology in Great Britain. He explains that RCTs are essential in assessing the efficacy of skin disease treatment but its usefulness is limited in the quality of design and reporting and the clinical question that the trials address. He cites that the challenges can be addressed by forming a network of like-minded people such as the UK Dermatology Clinical Trials Network (UK DCTN).

The article discusses research which compared effectiveness of ciclosporin and prednisolone in treating pyoderma gangrenosum. Topics explored include the speed of ulcer healing associated with these drugs, the daily drug dosage administered to research participants, and the adverse reactions recorded in both treatment groups such as acute kidney injury and infection.

INTRODUCTION: To investigate the association between vaccination against coronavirus disease 2019 (COVID-19) and inflammatory bowel disease (IBD) flare. METHODS: Patients with IBD vaccinated against COVID-19 who consulted for disease flare between December 1, 2020, and December 31, 2021, were ascertained from the Clinical Practice Research Datalink. IBD flares were identified using consultation and corticosteroid prescription records. Vaccinations were identified using product codes and vaccination dates. The study period was partitioned into vaccine-exposed (vaccination date and 21 days immediately after), prevaccination (7 days immediately before vaccination), and the remaining vaccine-unexposed periods. Participants contributed data with multiple vaccinations and IBD flares. Season-adjusted incidence rate ratios (aIRR) and 95% confidence intervals (CI) were calculated using self-controlled case series analysis. RESULTS: Data for 1911 cases with IBD were included; 52% of them were female, and their mean age was 49 years. Approximately 63% of participants had ulcerative colitis (UC). COVID-19 vaccination was not associated with increased IBD flares in the vaccine-exposed period when all vaccinations were considered (aIRR [95% CI] 0.89 [0.77-1.02], 0.79 [0.66-0.95], and 1.00 [0.79-1.27] in IBD overall, UC, and Crohn's disease, respectively). Analyses stratified to include only first, second, or third COVID-19 vaccinations found no significant association between vaccination and IBD flares in the vaccine-exposed period (aIRR [95% CI] 0.87 [0.71-1.06], 0.93 [0.75-1.15], and 0.86 [0.63-1.17], respectively). Similarly, stratification by COVID-19 before vaccination and by vaccination with vectored DNA or messenger RNA vaccine did not reveal an increased risk of flare in any of these subgroups. DISCUSSION: Vaccination against COVID-19 was not associated with IBD flares regardless of prior COVID-19 infection and whether messenger RNA or DNA vaccines were used. [ABSTRACT FROM AUTHOR]

Summary: Background: Basal-cell carcinoma is the most common form of skin cancer and its incidence is increasing worldwide. We aimed to assess the effectiveness of imiquimod cream versus surgical excision in patients with low-risk basal-cell carcinoma. Methods: We did a multicentre, parallel-group, pragmatic, non-inferiority, randomised controlled trial at 12 centres in the UK, in which patients were recruited between June 19, 2003, and Feb 22, 2007, with 3 year follow-up from June 26, 2006, to May 26, 2010. Participants of any age were eligible if they had histologically confirmed primary nodular or superficial basal-cell carcinoma at low-risk sites. We excluded patients with morphoeic or recurrent basal-cell carcinoma and those with Gorlin syndrome. Participants were randomly assigned (1:1) via computer-generated blocked randomisation, stratified by centre and tumour type, to receive either imiquimod 5% cream once daily for 6 weeks (superficial) or 12 weeks (nodular), or surgical excision with a 4 mm margin. The randomisation sequence was concealed from study investigators. Because of the nature of the interventions, masking of participants was not possible and masking of outcome assessors was only partly possible. The trial statistician was masked to allocation until all analyses had been done. The primary outcome was the proportion of participants with clinical success, defined as absence of initial treatment failure or signs of recurrence at 3 years from start of treatment. We used a prespecified non-inferiority margin of a relative risk (RR) of 0·87. Analysis was by a modified intention-to-treat population and per protocol. This study is registered as an International Standard Randomised Controlled Trial (ISRCTN48755084), and with ClinicalTrials.gov, number NCT00066872. Findings: 501 participants were randomly assigned to the imiquimod group (n=254) or the surgical excision group (n=247). At year 3, 401 (80%) patients were included in the modified intention-to-treat group. At 3 years, 178 (84%) of 213 participants in the imiquimod group were treated successfully compared with 185 (98%) of 188 participants in the surgery group (RR 0·84, 98% CI 0·78–0·91; p<0·0001). No clear difference was noted between groups in patient-assessed cosmetic outcomes. The most common adverse events were itching (211 patients in the imiquimod group vs 129 in the surgery group) and weeping (160 vs 81). We recorded serious adverse events in 99 (40%) of 249 participants in the imiquimod group and 97 (42%) of 229 in the surgery group had serious adverse events, but none were regarded as related to treatment. 12 (5%) participants in the imiquimod group withdrew because of adverse events compared with four (2%) in the surgery group. Interpretation: Imiquimod was inferior to surgery according to our predefined non-inferiority criterion. Although excisional surgery remains the best treatment for low-risk basal-cell carcinoma, imiquimod cream might still be a useful treatment option for small low-risk superficial or nodular basal-cell carcinoma dependent on factors such as patient preference, size and site of the lesion, and whether the patient has more than one lesion. Funding: Cancer Research UK. [ABSTRACT FROM AUTHOR]

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 variables, were undertaken alongside two independent, pragmatic, parallel group, unmasked randomized controlled trials, recruiting through primary care. Trial 1 recruited 340 parents/carers of children aged 0-12 years and Trial 2 337 young people aged 13-25 years with eczema scored ≥ 5 on Patient-Oriented Eczema Measure (POEM). Participants were randomized (1:1) to online intervention plus usual care or usual care alone. Resource use, collected via medical notes review, was valued using published unit costs in UK £Sterling 2021. Quality-of-life was elicited using proxy CHU-9D in Trial 1 and self-report EQ-5D-5L in Trial 2., Results: The intervention was dominant (cost saving and more effective) with a high probability of cost-effectiveness (> 68%) in most analyses. The exception was the complete case cost-utility analysis for Trial 1 (omitting participants with children aged < 2), with adjusted incremental cost savings of -£34.15 (95% CI  - 104.54 to 36.24) and incremental QALYs of - 0.003 (95% CI  - 0.021 to 0.015) producing an incremental cost per QALY of £12,466. In the secondary combined (Trials 1 and 2) cost-effectiveness analysis, the adjusted incremental cost was -£20.35 (95% CI  - 55.41 to 14.70) with incremental success (≥ 2-point change on POEM) of 10.3% (95% CI 2.3-18.1%)., Conclusion: The free at point of use online eczema self-management intervention was low cost to run and cost-effective., Trial Registration: This trial was registered prospectively with the ISRCTN registry (ISRCTN79282252). URL www.EczemaCareOnline.org.uk ., (© 2024. The Author(s).)

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, pragmatic, two-arm, parallel-group randomised controlled prevention trial with follow-up to 5 years., Setting: Twelve secondary and four primary care centres., Participants: Healthy infants (at least 37 weeks' gestation) at high risk of developing eczema, screened and consented during the third trimester or post delivery., Interventions: Infants were randomised (1 : 1) within 21 days of birth to apply emollient (Doublebase Gel®; Dermal Laboratories Ltd, Hitchin, UK or Diprobase Cream®) daily to the whole body (excluding scalp) for the first year, plus standard skin-care advice (emollient group) or standard skin-care advice only (control group). Families were not blinded to allocation., Main Outcome Measures: Primary outcome was eczema diagnosis in the last year at age 2 years, as defined by the UK Working Party refinement of the Hanifin and Rajka diagnostic criteria, assessed by research nurses blinded to allocation. Secondary outcomes up to age 2 years included other eczema definitions, time to onset and severity of eczema, allergic rhinitis, wheezing, allergic sensitisation, food allergy, safety (skin infections and slippages) and cost-effectiveness., Results: One thousand three hundred and ninety-four newborns were randomised between November 2014 and November 2016; 693 emollient and 701 control. Adherence in the emollient group was 88% (466/532), 82% (427/519) and 74% (375/506) at 3, 6 and 12 months. At 2 years, eczema was present in 139/598 (23%) in the emollient group and 150/612 (25%) in controls (adjusted relative risk 0.95, 95% confidence interval 0.78 to 1.16; p = 0.61 and adjusted risk difference -1.2%, 95% confidence interval -5.9% to 3.6%). Other eczema definitions supported the primary analysis. Food allergy (milk, egg, peanut) was present in 41/547 (7.5%) in the emollient group versus 29/568 (5.1%) in controls (adjusted relative risk 1.47, 95% confidence interval 0.93 to 2.33). Mean number of skin infections per child in the first year was 0.23 (standard deviation 0.68) in the emollient group versus 0.15 (standard deviation 0.46) in controls; adjusted incidence rate ratio 1.55, 95% confidence interval 1.15 to 2.09. The adjusted incremental cost per percentage decrease in risk of eczema at 2 years was £5337 (£7281 unadjusted). No difference between the groups in eczema or other atopic diseases was observed during follow-up to age 5 years via parental questionnaires., Limitations: Two emollient types were used which could have had different effects. The median time for starting emollients was 11 days after birth. Some contamination occurred in the control group (< 20%). Participating families were unblinded and reported on some outcomes., Conclusions: We found no evidence that daily emollient during the first year of life prevents eczema in high-risk children. Emollient use was associated with a higher risk of skin infections and a possible increase in food allergy. Emollient use is unlikely to be considered cost-effective in this context., Future Research: To pool similar studies in an individual patient data meta-analysis., Trial Registration: This trial is registered as ISRCTN21528841., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/67/12) and is published in full in Health Technology Assessment ; Vol. 28, No. 29. See the NIHR Funding and Awards website for further award information.

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 (≥18 years) with a diagnosis of an immune mediated inflammatory disease who were prescribed methotrexate by their general practitioner for six months or more during 2007-19., Main Outcome Measure: Discontinuation of methotrexate owing to abnormal monitoring blood test result. Patients were followed-up from six months after their first prescription for methotrexate in primary care to the earliest of outcome, drug discontinuation for any other reason, leaving the practice, last data collection from the practice, death, five years, or 31 December 2019. Cox regression was performed to develop the risk equation, with bootstrapping used to shrink predictor effects for optimism. Multiple imputation handled missing predictor data. Model performance was assessed in terms of calibration and discrimination., Results: Data from 13 110 (854 events) and 23 999 (1486 events) participants were included in the development and validation cohorts, respectively. 11 candidate predictors (17 parameters) were included. In the development dataset, the optimism adjusted R 2 was 0.13 and the optimism adjusted Royston D statistic was 0.79. The calibration slope and Royston D statistic in the validation dataset for the entire follow-up period was 0.94 (95% confidence interval 0.85 to 1.02) and 0.75 (95% confidence interval 0.67 to 0.83), respectively. The prognostic model performed well in predicting outcomes in clinically relevant subgroups defined by age group, type of immune mediated inflammatory disease, and methotrexate dose., Conclusion: A prognostic model was developed and validated that uses information collected during routine clinical care and may be used to risk stratify the frequency of monitoring blood test during long term methotrexate treatment., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the National Institute for Health and Care Research. AA has received institutional research grants from AstraZeneca and Oxford Immunotech and personal fees from UpToDate (royalty), Springer (royalty), Cadilla Pharmaceuticals (lecture fees), NGM Bio (consulting), and Limbic (consulting), and personal fees from Inflazome (consulting) unrelated to the work. GP Aithal has received consulting fees from Clinipace, Amryth, GSK, DNDi, Pfizer, BenevolentAI Bio, Albireo Pharma, Abbott Products Operations, AstraZeneca, Merck, and PureTech paid to the University of Nottingham unrelated to the work. CPF has received consultancy or advisory board fees from Abbvie, GenMab, Incyte, Lily, Morphosys, Roche, Takeda, Ono, Kite/Gilead, BMS/Celgene, and BTG/Veriton and departmental research funding from BeiGene unrelated to the work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2022 The Authors. Clinical and Experimental Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

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., (© 2022 The Authors. Clinical and Experimental Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Rationale: Clinical trials are the gold standard for testing interventions. COVID-19 has further raised their public profile and emphasised the need to deliver better, faster, more efficient trials for patient benefit. Considerable overlap exists between data required for trials and data already collected routinely in electronic healthcare records (EHRs). Opportunities exist to use these in innovative ways to decrease duplication of effort and speed trial recruitment, conduct and follow-up., Approach: The National Institute of Health Research (NIHR), Health Data Research UK and Clinical Practice Research Datalink co-organised a national workshop to accelerate the agenda for 'data-enabled clinical trials'. Showcasing successful examples and imagining future possibilities, the plenary talks, panel discussions, group discussions and case studies covered: design/feasibility; recruitment; conduct/follow-up; collecting benefits/harms; and analysis/interpretation., Reflection: Some notable studies have successfully accessed and used EHR to identify potential recruits, support randomised trials, deliver interventions and supplement/replace trial-specific follow-up. Some outcome measures are already reliably collected; others, like safety, need detailed work to meet regulatory reporting requirements. There is a clear need for system interoperability and a 'route map' to identify and access the necessary datasets. Researchers running regulatory-facing trials must carefully consider how data quality and integrity would be assessed. An experience-sharing forum could stimulate wider adoption of EHR-based methods in trial design and execution., Discussion: EHR offer opportunities to better plan clinical trials, assess patients and capture data more efficiently, reducing research waste and increasing focus on each trial's specific challenges. The short-term emphasis should be on facilitating patient recruitment and for postmarketing authorisation trials where research-relevant outcome measures are readily collectable. Sharing of case studies is encouraged. The workshop directly informed NIHR's funding call for ambitious data-enabled trials at scale. There is the opportunity for the UK to build upon existing data science capabilities to identify, recruit and monitor patients in trials at scale., Competing Interests: Competing interests: JW reports grants, personal fees and other from AstraZeneca, other from Astellas, other from Boehringer Ingelheim, other from Lilly, other from Napp, grants, personal fees and other from Novo Nordisk, other from Sanofi, grants, personal fees and other from Takeda, other from Rhythm Pharma, outside the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

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 About Tolerance (EAT) study population., Methods: The EAT study was a population-based randomized clinical trial conducted from January 15, 2008, to August 31, 2015, and recruited 1303 exclusively breastfed 3-month-old infants and their families from England and Wales. At enrollment at 3 months, families completed a questionnaire that included questions about frequency and type of moisturizer applied, use of corticosteroid creams, and parental report of dry skin or eczema. Infants were examined for visible eczema at the enrollment visit., Results: A statistically significant dose-response relationship was observed between parent-reported moisturization frequency at 3 months of age and the subsequent development of food allergy. Each additional moisturization per week was associated with an adjusted odds ratio of 1.20 (95% CI, 1.13-1.27; P < .0005) for developing food allergy. For infants with no visible eczema at the enrollment visit, the corresponding adjusted odds ratio was 1.18 (95% CI, 1.07-1.30; P = .001) and for those with eczema at the enrollment visit, 1.20 (95% CI, 1.11-1.31; P < .0005). Moisturizer frequency showed similar dose-response relationships with the development of both food and aeroallergen sensitization at 36 months., Conclusions: These findings support the notion that regular application of moisturizers to the skin of young infants may promote the development of food allergy through transcutaneous sensitization., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

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 light monotherapy and (2) hand-held narrowband ultraviolet B light/topical corticosteroid combination treatment for localised vitiligo., Design: Pragmatic, three-arm, randomised controlled trial with 9 months of treatment and a 12-month follow-up., Setting: Sixteen UK hospitals - participants were recruited from primary and secondary care and the community., Participants: Adults and children (aged ≥ 5 years) with active non-segmental vitiligo affecting ≤ 10% of their body area., Interventions: Topical corticosteroids [mometasone furoate 0.1% (Elocon ® , Merck Sharp & Dohme Corp., Merck & Co., Inc., Whitehouse Station, NJ, USA) plus dummy narrowband ultraviolet B light]; narrowband ultraviolet B light (narrowband ultraviolet B light plus placebo topical corticosteroids); or combination (topical corticosteroids plus narrowband ultraviolet B light). Topical corticosteroids were applied once daily on alternate weeks and narrowband ultraviolet B light was administered every other day in escalating doses, with a dose adjustment for erythema. All treatments were home based., Main Outcome Measures: The primary outcome was self-assessed treatment success for a chosen target patch after 9 months of treatment ('a lot less noticeable' or 'no longer noticeable' on the Vitiligo Noticeability Scale). Secondary outcomes included blinded assessment of primary outcome and percentage repigmentation, onset and maintenance of treatment response, quality of life, side effects, treatment burden and cost-effectiveness (cost per additional successful treatment)., Results: In total, 517 participants were randomised (adults, n  = 398; and children, n  =  119; 52% male; 57% paler skin types I-III, 43% darker skin types IV-VI). At the end of 9 months of treatment, 370 (72%) participants provided primary outcome data. The median percentage of narrowband ultraviolet B light treatment-days (actual/allocated) was 81% for topical corticosteroids, 77% for narrowband ultraviolet B light and 74% for combination groups; and for ointment was 79% for topical corticosteroids, 83% for narrowband ultraviolet B light and 77% for combination. Target patch location was head and neck (31%), hands and feet (32%), and rest of the body (37%). Target patch treatment 'success' was 20 out of 119 (17%) for topical corticosteroids, 27 out of 123 (22%) for narrowband ultraviolet B light and 34 out of 128 (27%) for combination. Combination treatment was superior to topical corticosteroids (adjusted risk difference 10.9%, 95% confidence interval 1.0% to 20.9%; p  = 0.032; number needed to treat = 10). Narrowband ultraviolet B light was not superior to topical corticosteroids (adjusted risk difference 5.2%, 95% confidence interval -4.4% to 14.9%; p  = 0.290; number needed to treat = 19). The secondary outcomes supported the primary analysis. Quality of life did not differ between the groups. Participants who adhered to the interventions for > 75% of the expected treatment protocol were more likely to achieve treatment success. Over 40% of participants had lost treatment response after 1 year with no treatment. Grade 3 or 4 erythema was experienced by 62 participants (12%) (three of whom were using the dummy) and transient skin thinning by 13 participants (2.5%) (two of whom were using the placebo). We observed no serious adverse treatment effects. For combination treatment compared with topical corticosteroids, the unadjusted incremental cost-effectiveness ratio was £2328.56 (adjusted £1932) per additional successful treatment (from an NHS perspective)., Limitations: Relatively high loss to follow-up limits the interpretation of the trial findings, especially during the post-intervention follow-up phase., Conclusion: Hand-held narrowband ultraviolet B light plus topical corticosteroid combination treatment is superior to topical corticosteroids alone for treatment of localised vitiligo. Combination treatment was relatively safe and well tolerated, but was effective in around one-quarter of participants only. Whether or not combination treatment is cost-effective depends on how much decision-makers are willing to pay for the benefits observed., Future Work: Development and testing of new vitiligo treatments with a greater treatment response and longer-lasting effects are needed., Trial Registration: Current Controlled Trials ISRCTN17160087., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 24, No. 64. See the NIHR Journals Library website for further project information.

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 antenatal or postnatal services for recruitment of term infants (at least 37 weeks' gestation) at high risk of developing eczema (ie, at least one first-degree relative with parent-reported eczema, allergic rhinitis, or asthma, diagnosed by a doctor). Term newborns with a family history of atopic disease were randomly assigned (1:1) to application of emollient daily (either Diprobase cream or DoubleBase gel) for the first year plus standard skin-care advice (emollient group) or standard skin-care advice only (control group). The randomisation schedule was created using computer-generated code (stratified by recruiting centre and number of first-degree relatives with atopic disease) and participants were assigned to groups using an internet-based randomisation system. The primary outcome was eczema at age 2 years (defined by UK working party criteria) with analysis as randomised regardless of adherence to allocation for participants with outcome data collected, and adjusting for stratification variables. This trial is registered with ISRCTN, ISRCTN21528841. Data collection for long-term follow-up is ongoing, but the trial is closed to recruitment., Findings: 1394 newborns were randomly assigned to study groups between Nov 19, 2014, and Nov 18, 2016; 693 were assigned to the emollient group and 701 to the control group. Adherence in the emollient group was 88% (466 of 532) at 3 months, 82% (427 of 519) at 6 months, and 74% (375 of 506) at 12 months in those with complete questionnaire data. At age 2 years, eczema was present in 139 (23%) of 598 infants with outcome data collected in the emollient group and 150 (25%) of 612 infants in the control group (adjusted relative risk 0·95 [95% CI 0·78 to 1·16], p=0·61; adjusted risk difference -1·2% [-5·9 to 3·6]). Other eczema definitions supported the results of the primary analysis. Mean number of skin infections per child in year 1 was 0·23 (SD 0·68) in the emollient group versus 0·15 (0·46) in the control group; adjusted incidence rate ratio 1·55 (95% CI 1·15 to 2·09)., Interpretation: We found no evidence that daily emollient during the first year of life prevents eczema in high-risk children and some evidence to suggest an increased risk of skin infections. Our study shows that families with eczema, asthma, or allergic rhinitis should not use daily emollients to try and prevent eczema in their newborn., Funding: National Institute for Health Research Health Technology Assessment., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Previous studies have reported national and regional Global Burden of Disease (GBD) estimates for the UK. Because of substantial variation in health within the UK, action to improve it requires comparable estimates of disease burden and risks at country and local levels. The slowdown in the rate of improvement in life expectancy requires further investigation. We use GBD 2016 data on mortality, causes of death, and disability to analyse the burden of disease in the countries of the UK and within local authorities in England by deprivation quintile., Methods: We extracted data from the GBD 2016 to estimate years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), and attributable risks from 1990 to 2016 for England, Scotland, Wales, Northern Ireland, the UK, and 150 English Upper-Tier Local Authorities. We estimated the burden of disease by cause of death, condition, year, and sex. We analysed the association between burden of disease and socioeconomic deprivation using the Index of Multiple Deprivation. We present results for all 264 GBD causes of death combined and the leading 20 specific causes, and all 84 GBD risks or risk clusters combined and 17 specific risks or risk clusters., Findings: The leading causes of age-adjusted YLLs in all UK countries in 2016 were ischaemic heart disease, lung cancers, cerebrovascular disease, and chronic obstructive pulmonary disease. Age-standardised rates of YLLs for all causes varied by two times between local areas in England according to levels of socioeconomic deprivation (from 14 274 per 100 000 population [95% uncertainty interval 12 791-15 875] in Blackpool to 6888 [6145-7739] in Wokingham). Some Upper-Tier Local Authorities, particularly those in London, did better than expected for their level of deprivation. Allowing for differences in age structure, more deprived Upper-Tier Local Authorities had higher attributable YLLs for most major risk factors in the GBD. The population attributable fractions for all-cause YLLs for individual major risk factors varied across Upper-Tier Local Authorities. Life expectancy and YLLs have improved more slowly since 2010 in all UK countries compared with 1990-2010. In nine of 150 Upper-Tier Local Authorities, YLLs increased after 2010. For attributable YLLs, the rate of improvement slowed most substantially for cardiovascular disease and breast, colorectal, and lung cancers, and showed little change for Alzheimer's disease and other dementias. Morbidity makes an increasing contribution to overall burden in the UK compared with mortality. The age-standardised UK DALY rate for low back and neck pain (1795 [1258-2356]) was higher than for ischaemic heart disease (1200 [1155-1246]) or lung cancer (660 [642-679]). The leading causes of ill health (measured through YLDs) in the UK in 2016 were low back and neck pain, skin and subcutaneous diseases, migraine, depressive disorders, and sense organ disease. Age-standardised YLD rates varied much less than equivalent YLL rates across the UK, which reflects the relative scarcity of local data on causes of ill health., Interpretation: These estimates at local, regional, and national level will allow policy makers to match resources and priorities to levels of burden and risk factors. Improvement in YLLs and life expectancy slowed notably after 2010, particularly in cardiovascular disease and cancer, and targeted actions are needed if the rate of improvement is to recover. A targeted policy response is also required to address the increasing proportion of burden due to morbidity, such as musculoskeletal problems and depression. Improving the quality and completeness of available data on these causes is an essential component of this response., Funding: Bill & Melinda Gates Foundation and Public Health England., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Patient-reported outcomes measures in clinical trials ensure that evaluations of effectiveness focus on outcomes that are important to patients. In relapsing-remitting conditions, such as eczema, repeated measurements may allow a more accurate reflection of disease burden and treatment effect than less frequent measurements. We asked parents/carers of children with eczema taking part in a trial of bath emollients to complete weekly questionnaires for 16 weeks., Methods: The objective of this study was to determine the acceptability and practicality of collecting weekly measures of eczema severity online for 16 weeks in children aged 1 to 11 years as part of the BATHE study. BATHE randomised patients to bath emollients plus standard eczema care or standard eczema care only. The primary outcome was eczema severity, measured by the seven-item Patient-Oriented Eczema Measure (POEM) repeated weekly for 16 weeks. Acceptability was explored through qualitative interviews with 10 participants. Interviews were audio-recorded, transcribed and analysed thematically. Practicality was assessed by exploring the completeness of the data and keeping a log of any problems., Results: Four hundred and eighty-two participants were recruited to the trial and 429 opted to complete measures online (89.0%). Data were collected online for 83% of time points over the 16-week period and there was no association between socio-demographic characteristics and data completeness. Two hundred and six (48%) completed their weekly data every week for 16 weeks and 341 (79%) completed it at least 80% of the time. The mean number of weeks completed was 13.3 out of 16 (SD 4.2). Interviewees said that they understood the rationale behind weekly collection and some welcomed this as it helped them realise how their child's eczema changed weekly. Whilst some interviewees spoke of weekly questionnaires as onerous, others said that they found them quick and easy. Reminders were welcomed. Parents/carers seemed happy to receive telephone reminders and it was sometimes useful for eliciting problems relating to obtaining trial medication or password problems for online data collection., Conclusions: Amongst this population, high levels of data completeness suggests that weekly completion of the online questionnaire appears to be acceptable and feasible over a 16-week period., Trial Registration: ISRCTN84102309 . Registered on 9 December 2013.

Background: Childhood eczema is very common. Treatment often includes emollient bath additives, despite there being little evidence of their effectiveness., Objectives: To determine the clinical effectiveness and cost-effectiveness of emollient bath additives in the management of childhood eczema., Design: Pragmatic, randomised, open-label, multicentre superiority trial with two parallel groups., Setting: Ninety-six general practices in Wales, the west of England and southern England. Invitation by personal letter or opportunistically., Participants: Children aged between 12 months and 12 years fulfilling the UK Diagnostic Criteria for Atopic Eczema. Children with inactive or very mild eczema (a score of ≤ 5 on the Nottingham Eczema Severity Scale) were excluded, as were children who bathed less than once per week or whose parents/carers were not prepared to accept randomisation., Interventions: The intervention group were prescribed bath additives by their usual clinical team and were asked to use them regularly for 12 months. The control group were asked to use no bath additives for 12 months. Both groups continued standard eczema management, including regular leave-on emollients and topical corticosteroids (TCSs) when required., Main Outcome Measures: The primary outcome was eczema control measured by Patient Oriented Eczema Measure [POEM, 0 (clear) to 28 (severe)] weekly for 16 weeks. The secondary outcomes were eczema severity over 1 year (4-weekly POEM), number of eczema exacerbations, disease-specific quality of life (QoL) (Dermatitis Family Impact Questionnaire), generic QoL (Child Health Utility-9 Dimensions) and type and quantity of topical steroid/calcineurin inhibitors prescribed. Children were randomised (1 : 1) using online software to either bath additives plus standard eczema care or standard eczema care alone, stratified by recruiting centre, and there was open-label blinding., Results: From December 2014 to May 2016, 482 children were randomised: 51% were female, 84% were white and the mean age was 5 years ( n  = 264 in the intervention group, n  = 218 in the control group). Reported adherence to randomised treatment allocation was > 92% in both groups, with 76.7% of participants completing at least 12 (80%) of the first 16 weekly questionnaires for the primary outcome. Baseline POEM score was 9.5 [standard deviation (SD) 5.7] in the bath additives group and 10.1 (SD 5.8) in the no bath additives group. Average POEM score over the first 16 weeks was 7.5 (SD 6.0) in the bath additives group and 8.4 (SD 6.0) in the no bath additives group, with no statistically significant difference between the groups. After controlling for baseline severity and confounders (ethnicity, TCS use, soap substitute use) and allowing for clustering of participants within centres and responses within participants over time, POEM scores in the no bath additive group were 0.41 points higher than in the bath additive group (95% confidence interval -0.27 to 1.10), which is well below the published minimal clinically important difference of 3 points. There was no difference between groups in secondary outcomes or in adverse effects such as redness, stinging or slipping., Limitations: Simple randomisation resulted in an imbalance in baseline group size, although baseline characteristics were well balanced between groups., Conclusion: This trial found no evidence of clinical benefit of including emollient bath additives in the standard management of childhood eczema., Future Work: Further research is required on optimal regimens of leave-on emollients and the use of emollients as soap substitutes., Trial Registration: Current Controlled Trials ISRCTN84102309., Funding: This project was funded by the NIHR Health Technology Assessment Programme and will be published in full in Health Technology Assessment ; Vol. 22, No. 57. See the NIHR Journals Library website for further project information., Competing Interests: Matthew J Ridd is a member of the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) General Board. Nick A Francis was a member of the HTA Antimicrobial Resistance Themed Call Board during the study. Amanda Roberts is a member of the HTA General Board. As patient and public involvement co-applicant, Amanda Roberts also received an attendance allowance and travel expenses from the University of Southampton in order to attend meetings. Emma Thomas-Jones reports grants from the NIHR HTA programme during the conduct of the study. Hywel C Williams is Director of the NIHR HTA programme. Paul Little is a member of the NIHR Journals Library Board.

Electronic health records hold great promise for clinical and epidemiologic research. Undertaking atopic eczema (AE) research using such data is challenging because of its episodic and heterogeneous nature. We sought to develop and validate a diagnostic algorithm that identifies AE cases based on codes used for electronic records used in the UK Health Improvement Network. We found that at least one of five diagnosis codes plus two treatment codes for any skin-directed therapy were likely to accurately identify patients with AE. To validate this algorithm, a questionnaire was sent to the physicians of 200 randomly selected children and adults. The primary outcome, positive predictive value for a physician-confirmed diagnosis of AE, was 86% (95% confidence interval = 80-91). Additional criteria increased the PPV up to 95% but would miss up to 89% of individuals with physician-confirmed AE. The first and last entered diagnosis codes for individuals showed good agreement with the physician-confirmed age at onset and last disease activity; the mean difference was 0.8 years (95% confidence interval = -0.3 to 1.9) and -1.3 years (95% confidence interval = -2.5 to -0.1), respectively. A combination of diagnostic and prescription codes can be used to reliably estimate the diagnosis and duration of AE from The Health Improvement Network primary care electronic health records in the UK., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: One-third of stroke patients are dependent on others to get outside their homes. This can cause people to become housebound, leading to increased immobility, poor health, isolation and misery. There is some evidence that outdoor mobility rehabilitation can reduce these limitations., Objective: To test the clinical effectiveness and cost-effectiveness of an outdoor mobility rehabilitation intervention for stroke patients., Design: Multicentre, parallel-group randomised controlled trial, with two groups allocated at a 1 : 1 ratio plus qualitative participant interviews., Setting: Fifteen UK NHS stroke services throughout England, Scotland and Wales., Participants: A total of 568 stroke patients who wished to get out of the house more often, mean age of 71 years: 508 reached the 6-month follow-up and 10 were interviewed., Intervention: Control was delivered prior to randomisation to all participants, and consisted of verbal advice and transport and outdoor mobility leaflets. Intervention was a targeted outdoor mobility rehabilitation programme delivered by 29 NHS therapists to 287 randomly chosen participants for up to 12 sessions over 4 months., Main Outcome Measures: Primary outcome was participant health-related quality of life, measured by the Short Form questionnaire-36 items, version 2 (Social Function domain), 6 months after baseline. Secondary outcomes were functional ability, mobility, number of journeys (from monthly travel diaries), satisfaction with outdoor mobility (SWOM), psychological well-being and resource use [health care and Personal Social Services (PSS)] 6 months after baseline. Carer well-being was recorded. All outcome measures were collected by post and repeated 12 months after baseline. Outcomes for the groups were compared using statistical significance testing and adjusted for multiple membership to account for the effect of multiple therapists at different sites. Interviews were analysed using interpretive phenomenology to explore confidence., Results: A median of seven intervention sessions [interquartile range (IQR) 3-7 sessions], median duration of 369 minutes (IQR 170-691.5 minutes) per participant was delivered. There was no significant difference between the groups on health-related quality of life (social function). There were no significant differences between groups in functional ability, psychological well-being or SWOM at 6- or 12-month follow-ups. There was a significant difference observed for travel journeys with the intervention group being 42% more likely to make a journey compared with the control group [rate ratio 1.42, 95% confidence interval (95% CI) 1.14 to 1.67] at 6 months and 76% more likely (rate ratio 1.76, 95% CI 1.36 to 1.95) at 12 months. The number of journeys was affected by the therapist effect. The mean incremental cost (total NHS and PSS cost) of the intervention was £3413.75 (95% CI -£448.43 to £7121.00), with an incremental quality-adjusted life-year gain of -0.027 (95% CI -0.060 to 0.007) according to the European Quality of Life-5 Dimensions and -0.003 (95% CI -0.016 to 0.006) according to the Short Form questionnaire-6 Dimensions. At baseline, 259 out of 281 (92.2%) participants in the control group were dissatisfied with outdoor mobility but at the 6-month assessment this had reduced to 77.7% (181/233), a 15% reduction. The corresponding reduction in the intervention group was slightly greater (21%) than 268 out of 287 (93.4%) participants dissatisfied with outdoor mobility at baseline to 189 out of 261 (72.4%) at 6 months. Participants described losing confidence after stroke as being detrimental to outdoor mobility. Recruitment and retention rates were high. The intervention was deliverable by the NHS but had a neutral effect in all areas apart from potentially increasing the number of journeys. This was dependent on the therapist effect, meaning that some therapists were more successful than others. The control appeared to affect change., Conclusions: The outdoor mobility intervention provided in this study to these stroke patients was not clinically effective or cost-effective. However, the provision of personalised information and monthly diaries should be considered for all people who wish to get out more., Trial Registration: Current Controlled Trials ISRCTN58683841., Funding: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 29. See the NIHR Journals Library website for further project information.