The independent and joint risks of alcohol consumption, smoking, and excess weight on morbidity and mortality: a systematic review and meta-analysis exploring synergistic associations.

OBJECTIVE: Alcohol consumption, smoking, and excess weight independently increase the risk of morbidity/mortality. Less is known about how they interact. This research aims to quantify the independent and joint associations of these exposures across health outcomes and identify whether these associations are synergistic. STUDY DESIGN: The protocol for this systematic review and meta-analysis was pre-registered (PROSPERO CRD42021231443). METHODS: Medline and Embase were searched between 1 January 2010 and 9 February 2022. Eligible peer-reviewed observational studies had to include adult participants from Organisation for Co-Operation and Development countries and report independent and joint associations between at least two eligible exposures (alcohol, smoking, and excess weight) and an ICD-10 outcome (or equivalent). For all estimates, we calculated the synergy index (SI) to identify whether joint associations were synergistic. Meta-analyses were conducted for outcomes with sufficiently homogenous data. RESULTS: The search returned 26,290 studies, of which 98 were included. Based on 138,130 participants, the combined effect (SI) of alcohol and smoking on head and neck cancer death/disease was 3.78 times greater than the additive effect of each exposure (95% confidence interval [CI] = 2.61, 5.48). Based on 2,603,939 participants, the combined effect of alcohol and excess weight on liver disease/death was 1.55 times greater than the additive effect of each exposure (95% CI = 1.33, 1.82). CONCLUSION: Synergistic associations suggest the true population-level risk may be underestimated. In the absence of bias, individuals with multiple risks would experience a greater absolute risk reduction from an intervention that targets a single exposure than individuals with a single risk.

A 10-year review of surgical management of dermatofibrosarcoma protuberans.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare skin cancer. Standard treatment in the UK is either wide local excision (WLE) or Mohs micrographic surgery (MMS). It is unclear which approach has the lower recurrence rate. OBJECTIVES: We undertook a retrospective comparative review of surgical management of DFSP in the UK National Health Service in order to define (i) current surgical practice for primary and recurrent DFSP, (ii) local recurrence rates for primary DFSP and (iii) survival outcomes for DFSP. METHODS: A retrospective clinical case-note review of patients with histologically confirmed DFSP (January 2004 to December 2013) who have undergone surgical treatment. RESULTS: The surgical management of 483 primary and 64 recurrent DFSP in 11 plastic surgery and 15 dermatology departments was analysed. Almost 75% of primary DFSP (n = 362) were treated with WLE and 20% (n = 97) with MMS. For recurrent DFSP, 69% (n = 44) and 23% (n = 15) of patients underwent WLE and MMS, respectively. Recurrent primary DFSP occurred in six patients after WLE and none after MMS. The median follow-up time was 25·5 months (interquartile range 6·8-45·1) for new and 19·8 (IQR 4·5-44·5) for recurrent DFSP [Correction added on 1 Feb 2021, after first online publication: 4.8 years (interquartile range 3.5-5.8) was incorrect], with eight reported deaths during the follow-up analysis period (one confirmed to be DFSP related). CONCLUSIONS: WLE was the most common surgical modality used to treat DFSP across the UK. The local recurrence rate was very low, occurring only after WLE. Although a prospective randomized controlled trial may provide more definitive outcomes, in the absence of a clearly superior surgical modality, treatment decisions should be based on patient preference, clinical expertise and cost.

Vestibular rehabilitation in multiple sclerosis: study protocol for a randomised controlled trial and cost-effectiveness analysis comparing customised with booklet based vestibular rehabilitation for vestibulopathy and a 12 month observational cohort study of the symptom reduction and recurrence rate following treatment for benign paroxysmal positional vertigo.

BACKGROUND: Symptoms arising from vestibular system dysfunction are observed in 49-59% of people with Multiple Sclerosis (MS). Symptoms may include vertigo, dizziness and/or imbalance. These impact on functional ability, contribute to falls and significant health and social care costs. In people with MS, vestibular dysfunction can be due to peripheral pathology that may include Benign Paroxysmal Positional Vertigo (BPPV), as well as central or combined pathology. Vestibular symptoms may be treated with vestibular rehabilitation (VR), and with repositioning manoeuvres in the case of BPPV. However, there is a paucity of evidence about the rate and degree of symptom recovery with VR for people with MS and vestibulopathy. In addition, given the multiplicity of symptoms and underpinning vestibular pathologies often seen in people with MS, a customised VR approach may be more clinically appropriate and cost effective than generic booklet-based approaches. Likewise, BPPV should be identified and treated appropriately. METHODS/ DESIGN: People with MS and symptoms of vertigo, dizziness and/or imbalance will be screened for central and/or peripheral vestibulopathy and/or BPPV. Following consent, people with BPPV will be treated with re-positioning manoeuvres over 1-3 sessions and followed up at 6 and 12 months to assess for any re-occurrence of BPPV. People with central and/or peripheral vestibulopathy will be entered into a randomised controlled trial (RCT). Trial participants will be randomly allocated (1:1) to either a 12-week generic booklet-based home programme with telephone support or a 12-week VR programme consisting of customised treatment including 12 face-to-face sessions and a home exercise programme. Customised or booklet-based interventions will start 2 weeks after randomisation and all trial participants will be followed up 14 and 26 weeks from randomisation. The primary clinical outcome is the Dizziness Handicap Inventory at 26 weeks and the primary economic endpoint is quality-adjusted life-years. A range of secondary outcomes associated with vestibular function will be used. DISCUSSION: If customised VR is demonstrated to be clinically and cost-effective compared to generic booklet-based VR this will inform practice guidelines and the development of training packages for therapists in the diagnosis and treatment of vestibulopathy in people with MS. TRIAL REGISTRATION: ISRCTN Number: 27374299 Date of Registration 24/09/2018 Protocol Version 15 25/09/2019.

Do airline pilots and cabin crew have raised risks of melanoma and other skin cancers? Systematic review and meta-analysis.

BACKGROUND: Airline pilots and cabin crew are potentially exposed to hazardous ultraviolet and cosmic radiation, which may increase their risk of melanoma and other skin cancers. OBJECTIVES: To establish precise risks of melanoma and keratinocyte cancer (KC) for airline pilots and for cabin crew based on all studies published to date. METHODS: We searched MEDLINE, ISI Science Citation Index, Embase, SCOPUS and CINAHL to June 2018. All studies of melanoma and KC risk and mortality in airline pilots and cabin crew compared with the general population were eligible. Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) were pooled using random effects models. RESULTS: From 5866 papers retrieved, we reviewed 44 full-text articles, of which 12 studies with data collected mostly between the 1970s and 1990s were eligible for inclusion. The pooled SIR (pSIR) for melanoma in pilots was 2.03 [95% confidence interval (CI) 1.71-2.40] and in cabin crew it was 2.12 (95% CI 1.71-2.62). For pilots, the pooled SMR for melanoma was 1.99 (95% CI 1.17-3.40) and for cabin crew it was 1.18 (95% CI 0.73-1.89). For KC, the pSIR was 1.86 (95% CI 1.54-2.25) in pilots and 1.97 (95% CI 1.25-2.96) in cabin crew. There was no evidence of study heterogeneity. CONCLUSIONS: The available evidence shows that airline pilots and cabin crew have about twice the risk of melanoma and other skin cancers than the general population, with pilots more likely to die from melanoma. However, most of the evidence was collected several decades ago and their relevance to contemporary levels of risk is uncertain.

Big Data, Predictive Analytics, and Quality Improvement in Kidney Transplantation: A Proof of Concept.

We sought proof of concept of a Big Data Solution incorporating longitudinal structured and unstructured patient-level data from electronic health records (EHR) to predict graft loss (GL) and mortality. For a quality improvement initiative, GL and mortality prediction models were constructed using baseline and follow-up data (0-90 days posttransplant; structured and unstructured for 1-year models; data up to 1 year for 3-year models) on adult solitary kidney transplant recipients transplanted during 2007-2015 as follows: Model 1: United Network for Organ Sharing (UNOS) data; Model 2: UNOS & Transplant Database (Tx Database) data; Model 3: UNOS, Tx Database & EHR comorbidity data; and Model 4: UNOS, Tx Database, EHR data, Posttransplant trajectory data, and unstructured data. A 10% 3-year GL rate was observed among 891 patients (2007-2015). Layering of data sources improved model performance; Model 1: area under the curve (AUC), 0.66; (95% confidence interval [CI]: 0.60, 0.72); Model 2: AUC, 0.68; (95% CI: 0.61-0.74); Model 3: AUC, 0.72; (95% CI: 0.66-077); Model 4: AUC, 0.84, (95 % CI: 0.79-0.89). One-year GL (AUC, 0.87; Model 4) and 3-year mortality (AUC, 0.84; Model 4) models performed similarly. A Big Data approach significantly adds efficacy to GL and mortality prediction models and is EHR deployable to optimize outcomes.

Randomised feasibility study of physiotherapy for patients with functional motor symptoms.

OBJECTIVE: To determine the feasibility of conducting a randomised controlled trial of a specialist physiotherapy intervention for functional motor symptoms (FMS). METHODS: A randomised feasibility study was conducted recruiting patients with a clinically established diagnosis of FMS from a tertiary neurology clinic in London, UK. Participants were randomised to the intervention or a treatment as usual control. Measures of feasibility and clinical outcome were collected and assessed at 6 months. RESULTS: 60 individuals were recruited over a 9-month period. Three withdrew, leaving 29 intervention and 28 controls participants in the final analysis. 32% of patients with FMS met the inclusion criteria, of which 90% enrolled. Acceptability of the intervention was high and there were no adverse events. At 6 months, 72% of the intervention group rated their symptoms as improved, compared to 18% in the control group. There was a moderate to large treatment effect across a range of outcomes, including three of eight Short Form 36 (SF36) domains (d=0.46-0.79). The SF36 Physical function was found to be a suitable primary outcome measure for a future trial; adjusted mean difference 19.8 (95% CI 10.2 to 29.5). The additional quality adjusted life years (QALY) with intervention was 0.08 (95% CI 0.03 to 0.13), the mean incremental cost per QALY gained was £12 087. CONCLUSIONS: This feasibility study demonstrated high rates of recruitment, retention and acceptability. Clinical effect size was moderate to large with high probability of being cost-effective. A randomised controlled trial is needed. TRIAL REGISTRATION NUMBER: NCT02275000; Results.

Effect of topical imiquimod as primary treatment for lentigo maligna: the LIMIT-1 study.

BACKGROUND: Topical imiquimod is sometimes used for lentigo maligna (LM) in situ melanoma instead of surgery, but frequency of cure is uncertain. Pathological complete regression (pCR) is a logical surrogate marker for cure after imiquimod, although residual LM and atypical melanocytic hyperplasia may not be reliably distinguished. A trial comparing imiquimod vs. surgery might be justified by a high imiquimod pCR rate. OBJECTIVES: Primary: to estimate the pCR rate for LM following imiquimod. Secondary: to assess the accuracy of prediction of pCR, using clinical complete regression (cCR) plus negative post-treatment biopsies, tolerability, resource use, patients' preferences and induced melanoma immunity. METHODS: This was a single-arm phase II trial of 60 imiquimod applications over 12 weeks for LM then radical resection. A pCR rate ≥ 25 out of 33 would reliably discriminate between pCR rates < 60% and ≥ 85%. Clinical response was assessed and biopsies taken after imiquimod. Patients recorded adverse events in diaries. Patient preference was measured after surgery using a standard gamble tool. RESULTS: The pCR rate was 10 of 27 (37%, 95% confidence interval 19-58%). The rate of cCR plus negative biopsies was 12 of 28, of whom seven of 11 had pCR on subsequent surgery. The median dose intensity was 86·7%. Of the 16 surveyed patients, eight preferred primary imiquimod over surgery if the cure rate for imiquimod was 80%, and four of 16 if it was ≤ 40%. CONCLUSIONS: The pCR rate was insufficient to justify phase III investigation of imiquimod vs. SURGERY: Clinical complete response and negative targeted biopsies left uncertainty regarding pathological clearance. Some patients would trade less aggressive treatment of LM against efficacy.

Standing up in multiple sclerosis (SUMS): protocol for a multi-centre randomised controlled trial evaluating the clinical and cost effectiveness of a home-based self-management standing frame programme in people with progressive multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an incurable, unpredictable but typically progressive neurological condition. It is the most common cause of neurological disability in young adults. Within 15 years of diagnosis, approximately 50 % of affected people are unable to walk unaided, and over time an estimated 25 % depend on a wheelchair. Typically, people with such limited mobility are excluded from clinical trials. Severely impaired people with MS spend much of their day sitting, often with limited ability to change position. In response, secondary complications can occur including: muscle wasting, pain, reduced skin integrity, spasms, limb stiffness, constipation, and associated psychosocial problems such as depression and lowered self-esteem. Effective self-management strategies, which can be implemented relatively easily and cheaply within people's homes, are needed to improve or maintain mobility and reduce sedentary behaviour. However this is challenging, particularly in the latter stages of disease. Regular supported standing using standing frames is one potential option. METHODS/DESIGN: SUMS is a pragmatic multi-centre randomised controlled trial evaluating use of Oswestry standing frames with blinded outcome assessment and full economic evaluation. Participants will be randomly allocated (1:1) to either a home-based, self-management standing programme (with advice and support) along with their usual care or to usual care alone. Those in the intervention group will be asked to stand for a minimum of 30 min three times weekly over 20 weeks. Each participant will be followed-up at 20 and 36 weeks post baseline. The primary clinical outcome is motor function, assessed using the Amended Motor Club Assessment. The primary economic endpoint is quality-adjusted life years. The secondary outcomes include measures of explanatory physical impairments, key clinical outcomes, and health-related quality of life. An embedded qualitative component will explore participant's and carer's experiences of the standing programme. DISCUSSION: This is the first large scale multi-centre trial to assess the clinical and cost effectiveness of a home based standing frame programme for people who are severely impaired by MS. If demonstrated to be effective and cost-effective, we will use this evidence to develop recommendations for a health service delivery model which could be implemented across the United Kingdom. TRIAL REGISTRATION: ISRCTN69614598 DATE OF REGISTRATION: 3.2.16 (retrospectively registered).

BRAF mutation testing algorithm for vemurafenib treatment in melanoma: recommendations from an expert panel.

The incidence of melanoma has increased rapidly over the past 30 years, and the disease is now the sixth most common cancer among men and women in the U.K. Many patients are diagnosed with or develop metastatic disease, and survival is substantially reduced in these patients. Mutations in the BRAF gene have been identified as key drivers of melanoma cells and are found in around 50% of cutaneous melanomas. Vemurafenib (Zelboraf(®) ; Roche Molecular Systems Inc., Pleasanton, CA, U.S.A.) is the first licensed inhibitor of mutated BRAF, and offers a new first-line option for patients with unresectable or metastatic melanoma who harbour BRAF mutations. Vemurafenib was developed in conjunction with a companion diagnostic, the cobas(®) 4800 BRAF V600 Mutation Test. The purpose of this paper is to make evidence-based recommendations to facilitate the implementation of BRAF mutation testing and targeted therapy in patients with metastatic melanoma in the U.K. The recommendations are the result of a meeting of an expert panel and have been reviewed by melanoma specialists and representatives of the National Cancer Research Network Clinical Study Group on behalf of the wider melanoma community. This article is intended to be a starting point for practical advice and recommendations, which will no doubt be updated as we gain further experience in personalizing therapy for patients with melanoma.

An exploratory study into the unmet supportive needs of breast cancer patients.

This study explores the unmet supportive needs of people with breast cancer attending a London NHS Foundation Trust Hospital. A mixed methods approach was used. One hundred and one patients completed a specially designed questionnaire focusing on their concerns in the previous week, and whether they felt they had been offered sufficient support from health professionals. Seven semi-structured interviews were then completed in order to gain insight into the need for future developments of services for patients with breast cancer. Pearson's chi-squared analysis was used to examine whether symptoms reported within 1 year of diagnosis differed from symptoms reported more than 1 year post diagnosis. Fatigue was the most common concern expressed (53%) with no significant difference between the two groups. Emotional concerns and pain were also highly reported (35% and 36%). Only 32% of the questionnaire participants reported that they had been offered support in dealing with their concerns. Most participants (65%) would have liked more support from the healthcare team. From the interviews it was clear that whilst there are gaps in services available, participants were not aware of the range of services already available for people with breast cancer. The results of this study have helped to inform service development, particularly around the management of fatigue.

Optimization of an amplicon sequencing-based microsatellite panel and protocol for stock identification and kinship inference of lake trout (Salvelinus namaycush).

Kinship-based methods of population assessment such as close-kin mark-recapture require accurate and efficient genotyping methods capable of resolving complex relationships among kin. Inference of such relationships can be difficult using biallelic loci due to the large number of markers required to obtain the necessary power. Sequencing-based microsatellite panels offer an efficient alternative, combining high polymorphism with efficient next-generation methods. Here we construct, optimize, and test one such panel for lake trout (Salvelinus namaycush) using a combination of previously-published loci adapted for sequencing and de novo loci mined from a genome assembly. We performed three rounds of primer optimization, yielding a final panel of 131 loci, followed by testing with two different levels of PCR multiplexing (all primers in one or two groups) and two different reaction volumes (5 and 10 µL). Our results showed that the use of the largest multiplex and smallest reaction volume did not substantially change results, allowing significant cost and time savings. To test panel accuracy, we used both a set of 153 known-origin samples from origins of management interest and a series of hatchery crosses representing nine families with parent-offspring, half-sibling, and largely-unrelated pairs. Our results indicate that sequencing-based microsatellite panels can efficiently and accurately provide the information required for a population genetics analyses including population assignment, calculation of between-population F ST, and kinship-based population estimation techniques. Such techniques are seeing increasing applications for a wide range of taxa; our findings should provide insight and guidance for the development of the necessary molecular resources.

Effect of different durations of using a standing frame on the rate of hip migration in children with moderate to severe cerebral palsy: a feasibility study for a randomised controlled trial.

AIM: To assess the feasibility of a randomised controlled trial (RCT) to evaluate the effect of different doses of standing time on hip migration rate in children with cerebral palsy (CP). METHOD: Children aged 1-12 years with CP GMFCS levels III-V were recruited and randomised to either doubling or continuing with their usual time in their standing frame. Caregivers kept a standing time diary. The primary outcome measure was Reimers hip migration percentage, measured at baseline, 12 and 24 months. A blinded assessor measured secondary clinical outcomes at baseline, 6 and 12 months. Feasibility results are reported following CONSORT guidelines. RESULTS: Twenty-five children were recruited. Nineteen were randomised and 10 completed the 12-month intervention. The mean daily standing time in the intervention group was 49minutes (SD 39.1) (Monday-Sunday) and 58.1 (SD 44.1) minutes during weekdays. In children remaining in the trial, primary and secondary clinical outcome measures were available in 54% and 90% of children respectively. There were three serious adverse events, unrelated to standing. CONCLUSIONS: It may be feasible to conduct an RCT to assess the effect of duration of standing on hip migration in children with CP with an altered protocol. The suggested target dose is 60minutes five times per week compared to a control group standing for 30minutes three times per week, over twelve months. Use of botulinum toxin need not be a criterion for exclusion and radiography should be included as a research cost. NHS Health Research Committee, South West ethics approval (ref 13/SW/0228).

Phase I/II trial of a dendritic cell vaccine transfected with DNA encoding melan A and gp100 for patients with metastatic melanoma.

This trial tested a dendritic cell (DC) therapeutic cancer vaccine in which antigen is loaded using a novel non-viral transfection method enabling the uptake of plasmid DNA condensed with a cationic peptide. Proof of principle required the demonstration of diverse T lymphocyte responses following vaccination, including multiple reactivities restricted through both major histocompatibility complex (MHC) class I and II. Patients with advanced melanoma were offered four cycles of vaccination with autologous DC expressing melan A and gp100. Disease response was measured using Response Evaluation Criteria in Solid Tumours. Circulating MHC class I- and II-restricted responses were measured against peptide and whole antigen targets using interferon-γ ELIspot and enzyme-linked immunosorbent assay assays, respectively. Responses were analyzed across the trial population and presented descriptively for some individuals. Twenty-five patients received at least one cycle. Vaccination was well tolerated. Three patients had reduction in disease volume. Across the trial population, vaccination resulted in an expansion of effector responses to both antigens, to the human leukocyte antigen A2-restricted modified epitope, melan A ELAGIGILTV, and to a panel of MHC class I- and II-restricted epitopes. Vaccination with mature DC non-virally transfected with DNA encoding antigen had biological effect causing tumour regression and inducing diverse T lymphocyte responses.

Toxic epidermal necrolysis: retrospective analysis of 21 consecutive cases managed at a tertiary centre.

BACKGROUND: Toxic epidermal necrolysis (TEN) is a rare, severe blistering disease. Outcome data in British patients is limited to case reports or small series. AIMS: To characterize the aetiology, clinical features, complications and outcome in TEN, and to evaluate the effect of treatments including intravenous immunoglobulin (IVIg). METHODS: This was a retrospective study of 21 consecutive patients with histologically confirmed TEN presenting between 1995 and 2007 to a tertiary referral unit for TEN in a university hospital in the UK. RESULTS: The mean age of the patients was 53.5 years. The mean surface area of denuded skin was 44% (range 30-90%). An adverse drug reaction was implicated in all patients, with mean time of TEN onset being 17 days (range 2-41 days) after initial drug exposure. The SCORTEN index was calculated in 19 patients (median SCORTEN 3, range 2-5). The SCORTEN predicted 7.3 deaths in this cohort, and 7 deaths were seen in the group of patients for whom SCORTEN was calculated. The overall mortality was 8/21 (38%). Ten patients received corticosteroids before transfer to our centre. In the steroid-treated group 4/10 patients (40%) died, and 4/11 patients (36%) who were not treated with steroids also died. Between 1995 and 2000, patients were treated with cyclophosphamide 1.5 mg/kg/day (n=2; both died) and subsequently with ciclosporin 2.5-4 mg/kg/day (n=3; 2 deaths). From 2000, patients were treated with IVIg 0.4-1 g/kg/day (n=14; 3 deaths); the SCORTEN-predicted mortality in this group was 5 deaths. Complications included sepsis (n=18), and organisms included Enterococcus, Acinetobacter, Staphylococcus aureus and methicillin-resistant S. aureus strains). Other complications included anaemia (n=17), lymphopenia (n=11) and neutrophilia (n=9). The presence of neutropenia (n=6; 4 deaths), renal impairment (n=5; 4 deaths) and disseminated intravascular coagulation (n=4; all died) were strong risk factors for mortality. Of 12 patients with ocular involvement, 6 (50%) developed symblepharon and/or visual impairment. CONCLUSIONS: This study confirmed the validity of SCORTEN in our series. In the subgroup treated with IVIg, there were three deaths, compared with the SCORTEN predicted mortality of five deaths. Corticosteroids did not seem to be beneficial.

Standardizing the intensity of upper limb treatment in rehabilitation medicine.

OBJECTIVE: To describe a treatment protocol for the upper limb that standardizes intensity of therapy input regardless of the severity of presentation. DESIGN: The protocol is described (Part 1) and feasibility and effect explored (Part 2). SUBJECTS: Participants (n = 11) had a single ischaemic stroke in the middle cerebral artery territory more than one year previously, and had residual weakness of the hand with some extension present at the wrist and the ability to grasp. INTERVENTIONS: Following two baseline assessments, participants attended therapy for 1 hour a day for 10 consecutive working days. Treatment consisted of a combination of strength and functional task training. Outcomes were measured immediately after training, at one month and three months. OUTCOME MEASURES: Intensity was measured with Borg Rating of Perceived Exertion. Secondary outcome measures included Action Research Arm Test (ARAT), nine-hole peg test, and Goal Attainment Scale. RESULTS: Borg scores indicated that the level of intensity was appropriate and similar across all participants despite individual differences in the severity of their initial presentation (median (interquartile range) = 14 (13-15)). The mean ARAT score significantly increased by 6.8 points (chi(2)(3) = 15.618, P<0.001), and was maintained at three-month follow-up (z = - 2.384, P = 0.016). The nine-hole peg test also showed a main effect of time and 88% of goals set were achieved. CONCLUSIONS: The physiotherapy protocol standardized intensity of treatment by grading exercise and task-related practice according to the person's residual ability, rather than simply standardizing treatment times. It was feasible and well tolerated in this group.

Repeatability of plantar pressure assessment during barefoot walking in people with stroke.

PURPOSE: Stroke-related changes in foot structure and function affect balance and mobility and quantifying foot function following stroke could offer clinically useful information to inform rehabilitation. The aim of this work was to explore the feasibility of undertaking plantar pressure assessment during barefoot walking in people with stroke, and evaluate the repeatability of the assessment protocol and regional footprint analysis as a measure of dynamic foot characteristics. MATERIALS & METHODS: Plantar pressure analysis was undertaken using a pressure platform (Tekscan HR Mat) on two test sessions, approximately two weeks apart (mean = 15.64 ± 11.64 days). Peak plantar pressure (kPa) and contact area (cm2) for foot regions were extracted and repeatability analysis undertaken. Descriptive evaluation of field notes and experiences of the participants was undertaken to inform the feasibility of the data collection protocol. RESULTS: Twenty-one participants (61.8 ± 9.2 years; 11 male, 10 female; 8 right-sided, 13 left-sided stroke) were recruited and 18 returned for retesting. Full data capture was achieved from 14 participants. Peak pressure and contact area demonstrated moderate to good repeatability for at the toes (ICC 0.76 and 0.58 respectively) and good to excellent repeatability for the other foot regions (ICC ≥ 0.82). CONCLUSION: The protocol adopted in this study was feasible and yielded good to excellent repeatability for the foot regions, except the toes. The challenges with data collection in our study cohort could help inform future studies adopting similar protocols. This work also has relevance for use of pressure technology in clinical practice for assessing and monitoring foot function following stroke.

Current role of sentinel lymph node biopsy in the management of cutaneous melanoma: A UK consensus statement.

Sentinel node biopsy (SNB) has been at the forefront of the surgical staging of melanoma patients for the past 15 years. The high accuracy of this prognostic staging procedure is now recognised in all international guidelines for melanoma. However during this period there have been a number of important changes in the management of melanoma, many occurring within the past five years. The outcomes of five recent randomised Phase 3 trials have established the role of adjuvant targeted therapy and immunotherapy in resected Stage 3 and Stage 4 disease and have potentially changed the role of SNB. Two landmark international prospective studies have examined the benefit of performing a completion lymph node dissection (CLND) following the detection of microscopicallyinvolved sentinel nodes. Finally, the marked increase in the incidence of melanoma and the role of SNB in potentially guiding therapy has resulted in a significant increase in the pathological workload of the dermatopathology services. To address these issues a multi-disciplinary consensus meeting involving many melanoma experts from the UK was convened in May 2018. Three main areas were considered: oncology, surgery and pathology. This report is a summary of the conclusions reached, which were agreed by the clinicians attending the meeting and then externally peer reviewed. The recommendations summarised in this Consensus Statement.

Surgery and radiotherapy in the treatment of cutaneous melanoma.

Adequate surgical management of primary melanoma and regional lymph node metastasis, and rarely distant metastasis, is the only established curative treatment. Surgical management of primary melanomas consists of excisions with 1-2 cm margins and primary closure. The recommended method of biopsy is excisional biopsy with a 2 mm margin and a small amount of subcutaneous fat. In specific situations (very large lesions or certain anatomical areas), full-thickness incisional or punch biopsy may be acceptable. Sentinel lymph node biopsy provides accurate staging information for patients with clinically unaffected regional nodes and without distant metastases, although survival benefit has not been proved. In cases of positive sentinel node biopsy or clinically detected regional nodal metastases (palpable, positive cytology or histopathology), radical removal of lymph nodes of the involved basin is indicated. For resectable local/in-transit recurrences, excision with a clear margin is recommended. For numerous or unresectable in-transit metastases of the extremities, isolated limb perfusion or infusion with melphalan should be considered. Decisions about surgery of distant metastases should be based on individual circumstances. Radiotherapy is indicated as a treatment option in select patients with lentigo maligna melanoma and as an adjuvant in select patients with regional metastatic disease. Radiotherapy is also indicated for palliation, especially in bone and brain metastases.