International, prospective cohort study comparing non-absorbable versus absorbable sutures for skin surgery: CANVAS service evaluation.

BACKGROUND: Absorbable or non-absorbable sutures can be used for superficial skin closure following excisional skin surgery. There is no consensus among clinicians nor high-quality evidence supporting the choice of suture. The aim of the present study was to determine current suture use and complications at 30 days after excisional skin surgery. METHODS: An international, prospective service evaluation of adults undergoing excision of skin lesions (benign and malignant) in primary and secondary care was conducted from 1 September 2020 to 15 April 2021. Routine patient data collected by UK and Australasian collaborator networks were uploaded to REDCap©. Choice of suture and risk of complications were modelled using multivariable logistic regression. RESULTS: Some 3494 patients (4066 excisions) were included; 3246 (92.9 per cent) were from the UK and Ireland. Most patients were men (1945, 55.7 per cent), Caucasian (2849, 81.5 per cent) and aged 75-84 years (965, 27.6 per cent). The most common clinical diagnosis was basal cell carcinoma (1712, 42.1 per cent). Dermatologists performed most procedures, with 1803 excisions (44.3 per cent) on 1657 patients (47.4 per cent). Most defects were closed primarily (2856, 81.9 per cent), and there was equipoise in regard to use of absorbable (2127, 57.7 per cent) or non-absorbable (1558, 42.2 per cent) sutures for superficial closure. The most common complications were surgical-site infection (103, 2.9 per cent) and delayed wound healing (77, 2.2 per cent). In multivariable analysis, use of absorbable suture type was associated with increased patient age, geographical location (UK and Ireland), and surgeon specialty (oral and maxillofacial surgery and plastic surgery), but not with complications. CONCLUSION: There was equipoise in suture use, and no association between suture type and complications. Definitive evidence from randomized trials is needed.

Using the Vitiligo Noticeability Scale in clinical trials: construct validity, interpretability, reliability and acceptability.

BACKGROUND: Validated outcome measures are needed for vitiligo trials. OBJECTIVES: To assess construct validity, interpretability, reliability and acceptability of the Vitiligo Noticeability Scale (VNS). METHODS: We used images of vitiligo before and after treatment, plus outcome data, from the HI-Light Vitiligo trial. We compared outcome assessments made by trial participants with assessments of images by clinicians and people with vitiligo who were not trial participants [Patient and Public Involvement (PPI) panel]. Hypothesis testing assessed psychometric properties of the VNS, with κ statistics to assess agreement between outcomes. Three focus groups and two online discussion groups provided insight into the use of VNS by people with vitiligo. RESULTS: Our hypothesis of a positive association between VNS and participant-reported global treatment success was supported for trial participants (κ = 0·41 if VNS success was defined as ≥ 4; κ = 0·71 if VNS success was defined as ≥ 3), but not for the blinded PPI panel (κ = 0·28). As hypothesized, the association with participant-reported global success was higher for VNS (κ = 0·41) than for clinician-reported percentage repigmentation (κ = 0·17). Seventy-five per cent of trial participants valued a VNS of 3 (partial response) as a treatment success. Test-retest reliability was good: κ = 0·69 (95% confidence interval 0·63-0·74). Age and skin phototype did not influence interpretation of the VNS scores. To people with vitiligo, the VNS is an acceptable and meaningful patient-reported outcome measure. CONCLUSIONS: Trial participants may assess their vitiligo differently compared with blinded assessors. A VNS score of 3 may be more highly valued by people undergoing vitiligo treatment than was previously thought. What is already known about this topic? Vitiligo is a common condition, and can have a considerable psychological impact. A Vitiligo Core Outcome Set is being developed, to enable the results of vitiligo trials to be compared and combined more easily. The Vitiligo Noticeability Scale (VNS) is a patient-reported outcome measure (PROM) developed in partnership with people with vitiligo; initial validation studies have been promising. What does this study add? The VNS shows good construct validity, reliability and acceptability; it can be used in all ages and skin phototypes. All five levels of the VNS scale should be reported for transparency, to aid interpretation of trial findings, and to facilitate meta-analysis in systematic reviews. VNS assessments made by trial participants and independent observers are likely to be qualitatively different, making blinded assessment of VNS by independent observers difficult to interpret. Blinding of participants to trial interventions is recommended whenever possible. What are the clinical implications of the work? The VNS can be used as a PROM to assess the cosmetic acceptability of repigmentation at individual patches of vitiligo. A VNS score of 3 or more is likely to be valued by patients as a treatment success.

Prescribing and using vitiligo treatments: lessons from a nested process evaluation within the HI-Light vitiligo randomized controlled trial.

BACKGROUND: The HI-Light Trial demonstrated that for active, limited vitiligo, combination treatment with potent topical corticosteroid (TCS) and handheld narrowband ultraviolet B offers a better treatment response than potent TCS alone. However, it is unclear how to implement these findings. AIM: We sought to answer three questions: (i) Can combination treatment be used safely and effectively by people with vitiligo?; (ii) Should combination treatment be made available as routine clinical care?; and (iii) Can combination treatment be integrated within current healthcare provision? METHODS: This was a mixed-methods process evaluation, including semi-structured interviews with a purposive sample of trial participants, structured interviews with commissioners, and an online survey and focus groups with trial staff. Transcripts were coded by framework analysis, with thematic development by multiple researchers. RESULTS: Participants found individual treatments easy to use, but the combination treatment was complicated and required nurse support. Both participants and site investigators felt that combination treatment should be made available, although commissioners were less certain. There was support for the development of services offering combination treatment, although this might not be prioritized above treatment for other conditions. A 'mixed economy' model was suggested, involving patients purchasing their own devices, although concerns regarding the safe use of treatments mean that training, monitoring and ongoing support are essential. The need for medical physics support may mean that a regional service is more practical. CONCLUSION: Combination treatment should be made available for people seeking treatment for vitiligo, but services require partnership with medical physics and ongoing training and support for patients.

Home-based narrowband UVB, topical corticosteroid or combination for children and adults with vitiligo: HI-Light Vitiligo three-arm RCT.

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.

The Home Interventions and Light therapy for the treatment of vitiligo (HI-Light Vitiligo) trial aimed to find out whether or not treating vitiligo at home with a narrowband ultraviolet B light, either by itself or with a steroid ointment, is better than treatment using a steroid ointment only. We enrolled 517 children (aged ≥ 5 years) and adults who had small, active (i.e. recently changing) patches of vitiligo into the study. Participants received one of three possible treatment options: steroid ointment (plus dummy light), hand-held narrowband ultraviolet B light therapy (plus placebo ointment) or both treatments used together. We asked participants to judge how noticeable their target vitiligo patch was after 9 months of treatment. We considered the treatment to be successful if the participants' responses were either 'a lot less noticeable' or 'no longer noticeable'. The results showed that using both treatments together was better than using a steroid ointment on its own. Around one-quarter of participants (27%) who used both treatments together said that their vitiligo was either 'no longer noticeable' or 'a lot less noticeable' after 9 months of treatment. This was compared with 17% of those using steroid ointment on its own and 22% of those using narrowband ultraviolet B light on its own. All treatments were able to stop the vitiligo from spreading. Patches on the hands and feet were less likely to respond to treatment than patches on other parts of the body. The trial found that the vitiligo tended to return once treatments were stopped, so ongoing intermittent treatment may be needed to maintain the treatment response. The treatments were found to be relatively safe and easy to use, but light treatment required a considerable time commitment (approximately 20 minutes per session, two or three times per week). This trial showed that using steroid ointment and narrowband ultraviolet B light together is likely to be better than steroid ointment alone for people with small patches of vitiligo. Steroid ointment alone can still be effective for some people and remains a useful treatment that is able to stop vitiligo from spreading. The challenge is to make hand-held narrowband ultraviolet B light treatment available as normal care in the NHS for people with vitiligo.

Silk garments plus standard care compared with standard care for treating eczema in children: A randomised, controlled, observer-blind, pragmatic trial (CLOTHES Trial).

BACKGROUND: The role of clothing in the management of eczema (also called atopic dermatitis or atopic eczema) is poorly understood. This trial evaluated the effectiveness and cost-effectiveness of silk garments (in addition to standard care) for the management of eczema in children with moderate to severe disease. METHODS AND FINDINGS: This was a parallel-group, randomised, controlled, observer-blind trial. Children aged 1 to 15 y with moderate to severe eczema were recruited from secondary care and the community at five UK medical centres. Participants were allocated using online randomisation (1:1) to standard care or to standard care plus silk garments, stratified by age and recruiting centre. Silk garments were worn for 6 mo. Primary outcome (eczema severity) was assessed at baseline, 2, 4, and 6 mo, by nurses blinded to treatment allocation, using the Eczema Area and Severity Index (EASI), which was log-transformed for analysis (intention-to-treat analysis). A safety outcome was number of skin infections. Three hundred children were randomised (26 November 2013 to 5 May 2015): 42% girls, 79% white, mean age 5 y. Primary analysis included 282/300 (94%) children (n = 141 in each group). The garments were worn more often at night than in the day (median of 81% of nights [25th to 75th centile 57% to 96%] and 34% of days [25th to 75th centile 10% to 76%]). Geometric mean EASI scores at baseline, 2, 4, and 6 mo were, respectively, 9.2, 6.4, 5.8, and 5.4 for silk clothing and 8.4, 6.6, 6.0, and 5.4 for standard care. There was no evidence of any difference between the groups in EASI score averaged over all follow-up visits adjusted for baseline EASI score, age, and centre: adjusted ratio of geometric means 0.95, 95% CI 0.85 to 1.07, (p = 0.43). This confidence interval is equivalent to a difference of -1.5 to 0.5 in the original EASI units, which is not clinically important. Skin infections occurred in 36/142 (25%) and 39/141 (28%) of children in the silk clothing and standard care groups, respectively. Even if the small observed treatment effect was genuine, the incremental cost per quality-adjusted life year was £56,811 in the base case analysis from a National Health Service perspective, suggesting that silk garments are unlikely to be cost-effective using currently accepted thresholds. The main limitation of the study is that use of an objective primary outcome, whilst minimising detection bias, may have underestimated treatment effects. CONCLUSIONS: Silk clothing is unlikely to provide additional benefit over standard care in children with moderate to severe eczema. TRIAL REGISTRATION: Current Controlled Trials ISRCTN77261365.

Randomised controlled trial of silk therapeutic garments for the management of atopic eczema in children: the CLOTHES trial.

BACKGROUND: Atopic eczema (AE) is a chronic, itchy, inflammatory skin condition that affects the quality of life of children and their families. The role of specialist clothing in the management of AE is poorly understood. OBJECTIVES: To assess the effectiveness and cost-effectiveness of silk garments for the management of AE in children with moderate to severe disease. DESIGN: Parallel-group, observer-blind, randomised controlled trial of 6 months' duration, followed by a 2-month observational period. A nested qualitative study evaluated the beliefs of trial participants, health-care professionals and health-care commissioners about the use of silk garments for AE. SETTING: Secondary care and the community in five UK centres. PARTICIPANTS: Children aged 1-15 years with moderate or severe AE. INTERVENTIONS: Participants were randomised (1 : 1 using online randomisation) to standard care or standard care plus 100% silk garments made from antimicrobially protected knitted sericin-free silk [DermaSilkTM (AlPreTec Srl, San Donà di Piave, Italy) or DreamSkinTM (DreamSkin Health Ltd, Hatfield, UK)]. Three sets of garments were supplied per participant, to be worn for up to 6 months (day and night). At 6 months the standard care group received the garments to use for the remaining 2-month observational period. MAIN OUTCOME MEASURES: Primary outcome - AE severity using the Eczema Area and Severity Index (EASI) assessed at 2, 4 and 6 months, by nurses blinded to treatment allocation. EASI scores were log-transformed for analysis. Secondary outcomes - patient-reported eczema symptoms (Patient Oriented Eczema Measure); global assessment of severity (Investigator Global Assessment); quality of life of the child (Atopic Dermatitis Quality of Life, Child Health Utility - 9 Dimensions), family (Dermatitis Family Impact Questionnaire) and main carer (EuroQoL-5 Dimensions-3 Levels); use of standard eczema treatments (e.g. emollients, topical corticosteroids); and cost-effectiveness. The acceptability and durability of the clothing, and adherence to wearing the garments, were assessed by parental/carer self-report. Safety outcomes - number of skin infections and hospitalisations for AE. RESULTS: A total of 300 children were randomised (26 November 2013 to 5 May 2015): 42% female, 79% white, mean age 5 years. The primary analysis included 282 out of 300 (94%) children (n = 141 in each group). Garments were worn for at least 50% of the time by 82% of participants. Geometric mean EASI scores at baseline, 2, 4 and 6 months were 8.4, 6.6, 6.0, 5.4 for standard care and 9.2, 6.4, 5.8, 5.4 for silk clothing, respectively. There was no evidence of difference between the groups in EASI score averaged over all follow-up visits adjusted for baseline EASI score, age and centre (ratio of geometric means 0.95, 95% confidence interval 0.85 to 1.07; p = 0.43). This confidence interval is equivalent to a difference of -1.5 to 0.5 in the original EASI scale units. Skin infections occurred in 39 out of 141 (28%) and 36 out of 142 (25%) participants for standard care and silk clothing groups, respectively. The incremental cost per QALY of silk garments for children with moderate to severe eczema was £56,811 from a NHS perspective in the base case. Sensitivity analyses supported the finding that silk garments do not appear to be cost-effective within currently accepted thresholds. LIMITATIONS: Knowledge of treatment allocation may have affected behaviour and outcome reporting for some of the patient-reported outcomes. CONCLUSIONS: The addition of silk garments to standard AE care is unlikely to improve AE severity, or to be cost-effective compared with standard care alone, for children with moderate or severe AE. This trial adds to the evidence base to guide clinical decision-making. FUTURE WORK: Non-pharmacological interventions for the management of AE remain a research priority among patients. TRIAL REGISTRATION: Current Controlled Trials ISRCTN77261365. 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. 21, No. 16. See the NIHR Journals Library website for further project information.

Survey and online discussion groups to develop a patient-rated outcome measure on acceptability of treatment response in vitiligo.

BACKGROUND: Vitiligo is a chronic depigmenting skin disorder which affects around 0.5-1% of the world's population. The outcome measures used most commonly in trials to judge treatment success focus on repigmentation. Patient-reported outcome measures of treatment success are rarely used, although recommendations have been made for their inclusion in vitiligo trials. This study aimed to evaluate the face validity of a new patient-reported outcome measure of treatment response, for use in future trials and clinical practice. METHOD: An online survey to gather initial views on what constitutes treatment success for people with vitiligo or their parents/carers, followed by online discussion groups with patients to reach consensus on what constitutes treatment success for individuals with vitiligo, and how this can be assessed in the context of trials. Participants were recruited from an existing database of vitiligo patients and through posts on the social network sites Facebook and Twitter. RESULTS: A total of 202 survey responses were received, of which 37 were excluded and 165 analysed. Three main themes emerged as important in assessing treatment response: a) the match between vitiligo and normal skin (how well it blends in); b) how noticeable the vitiligo is and c) a reduction in the size of the white patches. The majority of respondents said they would consider 80% or more repigmentation to be a worthwhile treatment response after 9 months of treatment. Three online discussion groups involving 12 participants led to consensus that treatment success is best measured by asking patients how noticeable their vitiligo is after treatment. This was judged to be best answered using a 5-point Likert scale, on which a score of 4 or 5 represents treatment success. CONCLUSIONS: This study represents the first step in developing a patient reported measure of treatment success in vitiligo trials. Further work is now needed to assess its construct validity and responsiveness to change.

Treatment of ulcerated necrobiosis lipoidica with intravenous immunoglobulin and methylprednisolone.

The authors report a female patient with recalcitrant ulcerated necrobiosis lipoidica (NL) that was resistant to numerous systemic agents and who responded to treatment with intravenous immunoglobulin (IVIG), leading to resolution of the ulcerated areas for several months. Subsequent treatment with two further courses of IVIG was less effective, but a course of intravenous methylprednisolone led to regression of the lesions. As well as briefly reviewing the literature on treatments used to treat ulcerated NL, we outline the pathological mechanisms thought to be involved in the condition and how the modes of action of IVIG might explain its apparent efficacy in this case. As far as we are aware, the response of ulcerated NL to IVIG or methylprednisolone has not been reported previously, although other systemic preparations of corticosteroids have been used.

Use of the DISCERN instrument by patients and health professionals to assess information resources on treatments for asthma and atopic dermatitis.

BACKGROUND: As patients share in the decision-making process regarding treatments they receive, it is important that they can discriminate between reliable and unreliable sources of information about potential treatments. METHODS: In this study, health professionals and patients were asked to assess the reliability of information contained in pamphlets on treatments for asthma and atopic dermatitis using a new Japanese translation of an instrument called DISCERN. The scores given by both groups were analyzed to assess inter-rater agreement. The same DISCERN instrument was used by health professionals to evaluate websites on treatments for atopic dermatitis and the degree of inter-rater agreement was assessed again. RESULTS: There was a greater inter-rater agreement between health professionals than between patients. When health professionals used the instrument to evaluate websites, the final rankings given were consistent between different raters, showing good inter-rater agreement. CONCLUSIONS: We conclude that DISCERN is useful for evaluating the reliability of medical information both in pamphlets and on the internet, although it is used more effectively by health professionals than by patients. Further studies are needed on the use of DISCERN by patients in evaluating websites containing medical information.