Development of a core outcome set for venous leg ulceration (CoreVen) research evaluations (protocol)

BackgroundA venous leg ulcer is a chronic leg wound caused by poor venous blood circulation in the lower limbs. It is a recurring condition causing pain, malodour, reduced mobility, and depression. Randomised controlled trials evaluating treatments for venous leg ulcers provide important evidence to inform clinical decision-making. However, for findings to be useful, outcomes need to be clinically meaningful, consistently reported across trials, and fully reported. Research has identified the large number of outcomes reported in venous leg ulcer trials, impacting both synthesis of results, and clinical decision-making. To address this, a core outcome set will be developed. A core outcome set is an agreed standardised set of outcomes which should be, as a minimum, measured and reported in all trials which evaluate treatment effectiveness for a given indication. A core outcome set has the potential to reduce research waste, improve the utility of RCTs, reduce reporting bias, facilitate treatment comparisons across different sources of evidence and expedite the production of systematic reviews, meta-analyses and evidence-based clinical guidelines.AimThe aim of this project is to develop a core outcome set for research evaluating the effectiveness of interventions for treating venous leg ulceration.MethodsThrough a scoping review of the literature on venous leg ulceration, we will firstly identify a list of candidate outcome domains (broad categories in relation to what is being measured) from randomised controlled trials and qualitative research, and outcomes (specific methods in relation to what is being measured). In two further stages, we will use the resulting lists of outcome domains and outcomes to design two online surveys. A range of stakeholders will be invited to participate in the surveys and they will be asked to indicate which outcome domains and outcomes are most important and should be considered as core in future research reports.     

Effect of PD-L1 testing on the cost-effectiveness and budget impact of pembrolizumab for advanced urothelial carcinoma of the bladder in the United States

Purpose

Our purpose was to evaluate the effect of PD-L1 testing on the cost-effectiveness of pembrolizumab for second-line treatment of advanced urothelial carcinoma in the bladder from the U.S. societal perspective.

‘The body is a battleground for unwanted and unexpressed emotions’: exploring eating disorders and the role of emotional intelligence

Emotional difficulties have been observed in individuals with eating disorders across awide range of studies, including poor interoceptive awareness, confusion of emotional states and difficulties with emotional language. Literature has linked these difficulties with emotional functioning as being an important factor related to the core aetiology ofeating disorders, however limited knowledge exists to how this impacts on professionalability to engage patients within treatment as a result of such dysfunction. Using aqualitative design this paper explores how facets of Emotional intelligence (EI) are related to the experience of an eating disorder. The study sampled a total of 32 participants with either a professional background working with eating disorders (n=27)or participants with personal lived experience (n=5), with a number of the participants (n=13) identified as having dual roles. The findings of the study show that aspects of EIsuch as emotional regulation and lack of an emotional language are considered to beat the core of the onset and maintenance of these disorders. Additional aspects of emotional awareness and expression were found to be related to treatment disengagement and difficulties. Building on previous literature, this paper found suchemotional deficits as a transdiagnostic issue rather than specifically anorexia nervosa. Furthermore, such dysfunction was seen by professionals to have a considerable impact on therapeutic relationships and successful treatment. These findings provide insight into the potential applications that EI may have in addressing aspects of theeating disorder to create better outcomes for treatment and intervention models.     

The mutational landscape of melanoma brain metastases presenting as the first visceral site of recurrence

Brain metastases are a major cause of melanoma-related mortality and morbidity. We undertook whole-exome sequencing of 50 tumours from patients undergoing surgical resection of brain metastases presenting as the first site of visceral disease spread and validated our findings in an independent dataset of 18 patients. Brain metastases had a similar driver mutational landscape to cutaneous melanomas in TCGA. However, KRAS was the most significantly enriched driver gene, with 4/50 (8%) of brain metastases harbouring non-synonymous mutations. Hotspot KRAS mutations were mutually exclusive from BRAF^V600, NRAS and HRAS mutations and were associated with a reduced overall survival from the resection of brain metastases (HR 10.01, p = 0.001). Mutations in KRAS were clonal and concordant with extracranial disease, suggesting that these mutations are likely present within the primary. Our analyses suggest that KRAS mutations could help identify patients with primary melanoma at higher risk of brain metastases who may benefit from more intensive, protracted surveillance.Subject terms: CNS cancer, Metastasis, Melanoma, Tumour biomarkers, Cancer