Expert opinion on characteristics of vulval LS: initial identification of important clinical features through an international electronic-Delphi consensus study.

BACKGROUND: Lichen sclerosus (LS) is a chronic inflammatory condition mainly affecting genital skin. It causes distressing symptoms that impact daily quality of life as well as progressive anatomical changes and potential risk of cancer. Vulval LS is often misdiagnosed and treatment delayed. If non-experts are supported to identify clinical features of LS, they may diagnose the condition sooner and commence timely treatment or refer to specialist services for assessment and confirmatory biopsy. OBJECTIVES: To reach international expert consensus on clinical diagnostic features for vulval LS. METHODS: Between March and May 2023, a four-stage electronic-Delphi consensus exercise was conducted. In the first three rounds, participants were asked to rate the importance of a list of clinical features. Responses from round one were summarised and presented in rounds two and three, along with additional features suggested by participants. Any items which met the definition of consensus as 'very important/critical', or 'not important' were not voted upon again in subsequent rounds. In round four, items which met agreement for 'important but not critical' were ranked in order of their importance. Consensus was defined a priori, and all rounds were conducted anonymously. RESULTS: A total of 47 participants from 14 countries completed round one with 42 (89%) retained by round 3 when consensus was determined. Round four was completed by 36 (77%) participants. Participants completing all four rounds predominantly included healthcare professionals (78%, n=28) and patient support group representatives (19%, n=7). In round one, 21 diagnostic features were voted upon. Participants suggested an additional 10 features which were subsequently added to the round two survey. After three rounds, consensus was achieved for five diagnostic features: whiteness, itch, changes in anatomy, burying of the clitoral area, and improvement in response to topical steroids. There were also 12 features voted as 'important but not critical' and participants subsequently ranked them in the 4th round. CONCLUSIONS: Experts have agreed on five critical diagnostic features for vulval LS in adults and an additional 12 features that may also be important. Future research should assess these clinical features for diagnostic validity through a multicentre diagnostic test accuracy study.

Core outcome domains for lichen sclerosus: a CORALS initiative consensus statement.

BACKGROUND: Lichen sclerosus (LS) is a chronic inflammatory condition mainly affecting genital skin. It causes distressing symptoms that impact daily quality of life (QoL). It causes progressive anatomical changes and a potential risk of cancer. Published randomized controlled trials are of varying methodological quality and difficult to combine in meta-analyses. This is partly due to lack of agreed outcome measures to assess treatment response. Identification of core outcome sets (COSs), which standardize key outcomes to be measured in all future trials, is a solution to this problem. OBJECTIVES: To obtain international agreement on which outcome domains should be measured in interventional trials of genital LS. METHODS: Recommended best practice for COS domain development was followed: (i) identification of potential outcome domains: a long list was generated through an up-to-date LS literature search, including information collected during the LS priority-setting partnership; (ii) provisional agreement of outcome domains: a three-stage multi-stakeholder international electronic-Delphi (e-Delphi) consensus study; (iii) final agreement of outcome domains: online consensus meeting with international stakeholders including anonymized voting. RESULTS: In total, 123 participants (77 patients, 44 health professionals, 2 researchers) from 20 countries completed three rounds of the e-Delphi study. Eleven outcome domains were rated as 'critical' and were discussed at the online consensus meetings. The first set of consensus meetings involved 42 participants from 12 countries. Consensus was met for 'symptoms' (100% agreed) and 'QoL - LS-specific' (92% agreed). After the second set of meetings, involving 29 participants from 12 countries, 'clinical (visible) signs' also met consensus (97% agreed). CONCLUSIONS: The international community has agreed on three key outcome domains to measure in all future LS clinical trials. We recommend that trialists and systematic reviewers incorporate these domains into study protocols with immediate effect. CORALS will now work with stakeholders to select an outcome measurement instrument per prioritized core domain.

Barriers to identifying, diagnosing, and treating vulval lichen sclerosus in primary care: a mixed methods survey study.

BACKGROUND: Vulval lichen sclerosus (VLS) is a skin condition which causes pain, itching, anatomical changes, and increases vulval cancer risk by up to 22 times. VLS is treatable, with use of topical steroids allowing symptom resolution and complication prevention. Diagnostic delay and misdiagnosis of VLS is common. Previous studies found that women attribute this to poor interactions with and knowledge of clinicians. Most VLS is diagnosed in primary care. AIM: To investigate primary care clinicians' views on confidence in identifying and managing vulval skin disease and VLS, barriers to diagnosis, education on vulval skin disease, and diagnostic criteria for VLS. METHOD: A mixed methods survey was distributed via professional events and networks. Qualitative data was analysed in NVivo using inductive thematic analysis. Spearman's rank correlation was used to correlate participant characteristics and confidence. RESULTS: There were 122 responses, the majority from GP trainees (48%) and GPs (43%). Confidence in diagnosing, identifying, and treating VLS positively correlated with female gender, time in role, and examination frequency. Themes identified include patients not knowing normal, male clinicians: deskilling and reluctance, lack of clinician knowledge, and uncertainty around diagnosis and treatment. 38% of participants never participated in teaching or learning on vulval skin disease. Almost all (98%) participants feel diagnostic criteria would be helpful. CONCLUSION: This study illuminates the multiple barriers to diagnosis and treatment of VLS. The results confirm that clinicians share patient concerns that knowledge is poor, highlight the importance of developing clear diagnostic criteria, and will allow us to target training to those lacking in confidence.

The critical role of technologies in neonatal care.

Neonatal care has made significant advances in the last few decades. As a result, mortality and morbidity in high-risk infants, such as extremely preterm infants or those infants with birth-related brain injury, has reduced significantly. Many of these advances have been facilitated or delivered through development of medical technologies allowing clinical teams to be better supported with the care they deliver or provide new therapies and diagnostics to improve management. The delivery of neonatal intensive care requires the provision of medical technologies that are easy to use, reliable, accurate and ideally developed for the unique needs of the newborn population. Many technologies have been developed and commercialised following adult trials without ever being studied in neonatal patients despite the unique characteristics of this population. Increasingly, funders and industry are recognising this major challenge which has resulted in initiatives to develop new ideas from concept through to clinical care. This review explores some of the key medical technologies used in neonatal care and the evidence to support their adoption to improve outcomes. A number of devices have yet to realise their full potential and will require further development to optimise and find their ideal target population and clinical benefit. Examples of emerging technologies, which may soon become more widely used, are also discussed. As neonatal care relies more on medical technologies, we need to be aware of the impact on care pathways, especially from a human factors approach, the associated costs and subsequent benefits to patients alongside the supporting evidence.

Metronidazole for the treatment of cutaneous vulval Crohn disease: A systematic review.

Background: Cutaneous vulval Crohn disease (VCD) is an under-recognised extra-intestinal manifestation of Crohn disease (CD) which is challenging to identify and treat. It causes significant oedema, painful deep fissures, and has potential to cause permanent disfiguring changes to vulval anatomy. There is no agreement on the best management for VCD. Objectives: This systematic review evaluates the use of metronidazole for the treatment of VCD in women and children. Methods: We conducted a systematic review (PROSPERO CRD42021285033) of the use of metronidazole in clinically or histologically diagnosed non-contiguous VCD in patients of all ages and ethnicities. We recorded clinical improvement, reduction in flares, relapse and adverse events using a standardised form. Results: 49 records (40 case reports and 9 case series) met inclusion criteria, comprising a total of 57 patients with an age range of 5-61 years. The most reported presenting features in VCD were: oedema, erythema, ulcers/fissures and induration/thickening. Gastrointestinal CD was present in 33/57 (58%). Vulval biopsies were undertaken in 47/57 (83%). Daily doses ranged from 250 to 1500 mg with treatment duration 8 days to 18 months. Improvement of any magnitude was observed in 40/57 (70%) cases. Relapse was described in 11/57 (19%) cases. No response/worsening was reported in 17/57 (30%) cases. Adverse events occurred in two patients. Conclusion: Metronidazole appears to be useful in managing VCD, either as a primary treatment or adjunctive therapy. However, the evidence is insufficient for firm conclusions to be drawn. Further studies including randomised controlled trials are recommended.

Considerations for disease impact and outcome measures in vulvar disease.

OBJECTIVE: Reliable and valid outcome measures are essential both in clinical practice and in clinical trials to be able to monitor response to treatments. In this review, we consider existing outcome measures currently used in clinical practice and discuss the need for vulvar specific measures. MATERIALS AND METHODS: We have reviewed the existing literature describing outcome measure and disease impact scales for dermatologic and vulvar conditions. RESULTS: A combination of measures including clinician-determined severity and patient-related quality-of-life indices are often used to assess different aspects of a disease. Health-related quality-of-life measures as scored by the patient are being increasingly recognized as the main driver in therapeutic decision making and are also important in developing service provision. Numerous disease-specific severity scores exist within dermatology, as do quality-of-life indices. However, none has been specifically designed to cover all aspects of vulvar disease. CONCLUSIONS: It is timely to consider the assessment of vulvar disease both in terms of impact on the patient and disease severity as assessed by the clinician to design well-constructed clinical trials for the management of vulvar disease. Owing to the sensitive nature of the problem, patients' needs and expectations are often different from general dermatology patients. We suggest that scales to monitor outcomes in the vulvar population should be devised by adapting and combining existing scales so they are relevant to our patients' needs.

Testing the clinical validity of the Bemelman Rib Fracture Management Guideline.

Whilst surgical stabilization of rib fractures (SSRF) results in better outcomes, selection algorithms are lacking. We aimed to validate the Rib Fracture Management Guideline proposed by Bemelman. From a cohort of 792 patients with multiple rib fractures, 2 sequential cohorts were selected: 48 patients who underwent SSRF and 48 patients who managed conservatively. Admission computed tomography scans and records were reviewed by an investigator blinded to the SSRF outcome. Adherence to the Bemelman guideline, revised to take account of consensus rib fracture definitions, was tested. Fifty-seven patients had multiple rib fractures only, and 39 patients also had a flail segment. Thirty-nine patients with flail segment underwent SSRF, and 18 patients were managed conservatively. Of the patients that the guideline predicted should have received surgery, 87% did. Of those that it predicted should not receive SSRF, 98% did not. The guideline displayed a sensitivity (95% confidence interval) and specificity for predicting the fixation of 0.98 (0.89-0.9995) and 0.83 (0.70-0.93), respectively. The positive and negative predictive values for surgical fixation were 0.87 (0.76-0.92) and 0.98 (0.85-0.99), respectively. The Bemelman guideline was thus a good predictor of SSRF in retrospective cohort but should be used in conjunction with clinical judgement. Further validation is indicated in a prospective study.

Determining the clinical significance of the Chest Wall Injury Society taxonomy for multiple rib fractures.

BACKGROUND: The Chest Wall Injury Society (CWIS) proposals for standardized nomenclature for multiple rib fracture (MRF) classifications were derived by international expert Delphi consensus. This study aimed to validate the CWIS taxonomy using a single-instituion clinical database. METHODS: Computed tomography (CT) scans, of 539 consecutive patients with MRFs admitted to a regional major trauma center over a 33-month period, were reviewed (blinded for clinical outcomes). Every rib fracture in every patient was assessed according to each of the CWIS criteria (the degree of displacement, characterization of the fracture line, location of each fracture, and the relationship to neighboring fractures). The clinical significance of the proposed CWIS definitions were determined from independently coded, routinely collected Hospital Episodes Statistics data. RESULTS: The radiologic aspects of 3,944 individual rib fractures were assessed. Indicators of injury severity (severe displacement greater series length, and flail segment) were positively associated with other fractures (p < 0.001), hemopneumothorax (p < 0.001), pulmonary complications (p = 0.002), adverse outcomes (p = 0.006), mechanical ventilation (p < 0.001) and prolonged hospital and intensive therapy unit length of stay (p = 0.006, p = 0.007 respectively). Four of the CWIS-proposed definitions were correlated with pulmonary complications and adverse outcomes: the categories of displacement, the definition of individual fracture characterization, the presence of a flail segment. Two definitions for which there was CWIS consensus were not correlated with clinical outcomes: the definition of a series to describe associated fractures on neighboring ribs, the inclusion of a paravertebral sector for fracture localization. CONCLUSION: The CWIS rib fracture taxonomy demonstrates clinical relevance. There were associations between the severity of category groups within three of the proposed definitions, based on the clinical outcomes observed. Clinical outcome assessment proved inconclusive for four agreed definitions. Comprehensive, multiinstitutional data collection would be required to provide validation for all the CWIS-proposed definitions. LEVELS OF EVIDENCE: Level IV.

Systemic therapy for vulval Erosive Lichen Planus (the 'hELP' trial): study protocol for a randomised controlled trial.

BACKGROUND: Erosive lichen planus affecting the vulva (ELPV) is a relatively rare, chronic condition causing painful raw areas in the vulvovaginal region. Symptoms are pain and burning, which impact upon daily living. There is paucity of evidence regarding therapy. A 2012 Cochrane systematic review found no randomised controlled trials (RCTs) in this field. Topically administered corticosteroids are the accepted first-line therapy: however, there is uncertainty as to which second-line treatments to use. Several systemic agents have been clinically noted to show promise for ELPV refractory to topically administered corticosteroids but there is no RCT evidence to support these. The 'hELP' study is a RCT with an internal pilot phase designed to provide high-quality evidence. METHODS/DESIGN: The objective is to test whether systemic therapy in addition to standard topical therapy is a beneficial second-line treatment for ELPV. Adjunctive systemic therapies used are hydroxychloroquine, methotrexate, mycophenolate mofetil and prednisolone. Topical therapy plus a short course of prednisolone given orally is considered the comparator intervention. The trial is a four-armed, open-label, pragmatic RCT which uses a blinded independent clinical assessor. To provide 80 % power for each comparison, 96 participants are required in total. The pilot phase aims to recruit 40 participants. The primary clinical outcome is the proportion of patients achieving treatment success at 6 months. 'Success' is defined by a composite measure of Patient Global Assessment score of 0 or 1 on a 4-point scale plus improvement from baseline on clinical photographs scored by a clinician blinded to treatment allocation. Secondary clinical outcomes include 6-month assessment of: (1) Reduction in pain/soreness; (2) Global assessment of disease; (3) Response at other affected mucosal sites; (4) Hospital Anxiety and Depression Scale scores; (5) Sexual function; (6) Health-related quality of life using 'Short Form 36' and 'Skindex-29' questionnaires; (7) Days of topical steroid use; (8) Treatment satisfaction; (9) Discontinuation of medications due to treatment failure; (10) Per participant cost of intervention in each treatment group. Adverse events will also be reported. DISCUSSION: 'hELP' is the first RCT to address second-line treatment of ELPV. The trial has encountered unique methodological challenges and has required collaborative efforts of the UK Dermatology Clinical Trials Network alongside expert clinicians. CURRENT CONTROLLED TRIALS: ISRCTN 81883379 . Date of registration 12 June 2014.

Paediatric vulvar disease.

Paediatric vulvar skin conditions are relatively common but often cause diagnostic difficulties for clinicians, which can lead to anxiety within the children's families. Vulvar skin conditions can be caused by various underlying aetiologies. Most are general dermatologic conditions that occur in the vulvar area, such as eczema, psoriasis, skin lesions or infections. However, other conditions such as lichen sclerosus and napkin dermatitis ('nappy rash') only affect the genital region. Every affected child needs a sensitive evaluation of the complaint including an assessment of the impact of the condition on the patient and her family. Paediatric vulvar disease often influences bowel and bladder habits and may lead to behavioural problems. General measures such as avoidance of irritants or soap substitution and regular use of emollients are helpful for all patients. Specific therapy depends upon the underlying diagnosis. Time spent reassuring the families, reinforcing regimens and providing written documentation can all be very helpful in successful management of paediatric vulvar skin conditions.