1H Nuclear Magnetic Resonance Spectroscopy Reveals Changes in Metabolic Phenotype Associated with Disease Stage in Patients with Chronic Venous Disease.

OBJECTIVE: Chronic venous disease (CVD) is a condition presenting a great burden to patients and society, with poorly characterised pathophysiology. Metabolic phenotyping can elucidate mechanisms of disease and identify candidate biomarkers. The aim of this study was to determine differences in the metabolic signature between symptomatic patients with CVD and asymptomatic volunteers using proton nuclear magnetic resonance spectroscopy (1H-NMR). METHODS: This was a prospective case-control study of consecutive patients with symptomatic CVD and asymptomatic volunteers recruited from a single centre. Participants underwent clinical assessment, venous duplex ultrasound, and blood and urine sampling. Disease stage was defined according to the Clinical-Etiology-Anatomy-Pathophysiology (CEAP) classification. 1H-NMR experiments were performed, with data analysed via multivariate statistical techniques. RESULTS: A total of 622 participants were recruited, including 517 symptomatic patients with CVD (telangiectasia [C1] 0.6%, varicose veins [C2] 48.5%, swelling [C3] 12.0%, skin changes [C4] 27.7%, healed or active ulceration [C5/6] 11.2%) and 105 asymptomatic participants (no disease [C0] 69.5%, telangiectasia [C1] 29.6%). Multivariate analysis revealed differences between the metabolic profile of the symptomatic CVD and asymptomatic groups, and between CEAP clinical classes in the CVD group. Serum aromatic amino acids positively correlated with increasing CEAP clinical class (p < .001). Urinary formate, creatinine, glycine, citrate, succinate, pyruvate, and 2-hydroxyisobutyrate negatively correlated with increasing CEAP clinical class (p < .001). These metabolites are involved in the tricarboxylic acid cycle, hypoxia inducible factor pathway, and one carbon metabolism. CONCLUSION: Untargeted biofluid analysis via 1H-NMR has detected metabolites associated with the presence and severity of CVD, highlighting biological pathways of relevance and providing candidate biomarkers to explore in future research.

Development of a core outcome set for use in research evaluations of interventions for venous leg ulceration: International eDelphi consensus.

INTRODUCTION: Venous leg ulceration (VLU) is a chronic, recurring condition with associated pain, malodour, impaired mobility and susceptibility to infection which in turn significantly impacts an individual's health-related quality of life. Randomised controlled trials (RCTs) aim to determine the efficacy of interventions to improve outcomes. To be useful, these outcomes should be consistently and fully reported across RCTs. A core outcome set (COS) is an agreed-upon standardised set of outcomes which should be, at a minimum, reported in all RCTs for a given indication including that of VLU. AIM: To gain consensus on which outcome domains and outcomes should be considered as core and therefore included in all RCTs of interventions in VLU treatment. METHOD: Two sequential, two round e-Delphi surveys were completed. The first gained consensus on core outcome domains and the second on core outcomes within those domains. Participants included: people with direct experience of having VLUs and their carers, healthcare professionals whose practice included VLU care and researchers within wound care (clinical, academic, industry). RESULTS: Five outcome domains; healing, pain, quality of life, resource use and adverse events, and 11 outcomes were rated as core by participants. The patient and not the limb or ulcer was the preferred unit of analysis for reporting. RECOMMENDATIONS: We recommend investigators report on all five outcome domains, regardless of the type of intervention being evaluated. Future research is needed to identify measurement methods for the 11 identified outcomes. We also recommend investigators follow the CONSORT guidelines (http://www.consort-statement.org/).

Wound care in hard-to-reach populations: rough sleepers.

People sleeping rough commonly develop wounds and other skin disorders. Wounds vary and develop for multiple reasons. They include acute wounds such as burns, infected injection sites, abscesses and cellulitis, as well as chronic wounds such as pressure ulcers; rough sleepers have a high prevalence of lower limb wounds. Skin and soft tissue infections are common, especially in people who inject drugs via subcutaneous or intramuscular routes. Emergency departments are often the pathways into healthcare for homeless people as traditional health and care systems often fail to meet their needs. Across England, initiatives have been developed to improve access to wound care for those who sleep rough. A case study illustrates the care of a homeless man presenting with a lower limb wound.

Comparison of compression therapy use, lower limb wound prevalence and nursing activity in England: a multisite audit.

OBJECTIVE: This audit was designed to identify the need of the population and the clinical activity associated with wounds and the management of lower limb swelling. The exploration focused on lower leg wound management, access to diagnostics and compression therapy across each audit site. The variation across the sites was explored to gather insight into the real-world barriers to providing evidence-based management for leg ulceration. METHOD: We undertook wound prevalence audits across six diverse community provider sites in England. The audit was undertaken by the local providers, with the inclusion of tissue viability and podiatry leads and key local stakeholders, often local quality leads, primary care leads and nursing directors. Each audit was undertaken with full engagement of local clinicians. Data were collected centrally, and each audit site received their own local analysis and report, with additional analytical support from the local tissue viability lead to ensure the feedback was contextualised for their stakeholders. Analysis was provided by Accelerate CIC Lymphoedema & Leg Ulcer Clinic. RESULTS: A total of 2885 patients were reviewed via an online or a paper audit tool. In total, 2721 patients had one or more active wounds. However, 1350 patients had one or more lower leg wounds, with 164 patients being managed for lower limb swelling or prevention of leg ulceration; bilateral conditions ranged from 11-43% across audit sites. Of the six sites, two included both community and primary care providers, thus generating wound point prevalence data. The remaining four sites audited community nursing and podiatry services only, with two sites collecting data on lower limb wounds only rather than all wounds, generating point prevalence for their services only. Compression usage varied across care locations, with the greatest use being seen in community leg ulcer clinics, where it was >96% for 234 residents. Compression usage was lower in the home with a range of 14-62% among 692 residents. For 263 residents, where the cause of their lower leg wound was unknown, compression usage was very low at 12%. Compression usage decreased with age; for three audit sites this was noteworthy, with 65% of those aged >80 years not in receipt of compression. Compression usage had a direct impact on nursing activity; non-use of compression increased activity by 37%. CONCLUSION: Through the identification of wound location, this series of wound prevalence audits identified a greater number of patients with lower limb wounds than those recognised and classified as a leg ulcer. Substantial variation in access to diagnostics and compression therapy was observed between audit sites, and also between locations within their boroughs. The factors that reduced access to compression therapy included not classifying the lower leg wound as a leg ulcer, being cared for in the home and increasing age of the patient. Lack of compression usage increased nursing activity. Where there is lack of access to therapeutic intervention, the resultant patient harm is not systematically recognised or documented.

Identifying outcomes reported in trials of interventions in venous leg ulceration for a core outcome set development: A scoping review.

BACKGROUND: Venous leg ulceration is a chronic, recurring, condition causing significant patient morbidity. Randomised controlled trials evaluating treatments for venous leg ulceration provide evidence for clinical decision-making. For trial findings to be useful, outcomes measured need to be clinically meaningful, and consistently and fully reported across trials. A core outcome set is an agreed and standardised set of outcomes which should be, as a minimum, reported in all trials for a given indication. AIM: To identify the outcome domains and outcomes reported in trials of interventions for venous leg ulceration. METHODS: A scoping review of the literature was carried out. Randomised controlled trials within Cochrane systematic reviews looking at venous leg ulceration interventions and qualitative studies exploring venous leg ulceration were included. RESULTS: The review identified 807 outcomes from randomised controlled trials and 15 outcomes from qualitative studies, and these were grouped into 11 outcome domains: healing, patient reported symptoms, clinician reported symptoms, carer reported symptoms, life impacts, clinical signs, clinical measurement, performance of the intervention, resource use (supplies and clinician time) and adverse events. The outcome domain 'healing' included 111 outcomes, 'symptoms' 109, 'life impacts' 30, 'clinical signs' 88, 'clinical measurement' 184, 'performance of the intervention' 58, 'resource use' 52 and 'adverse events' 190. CONCLUSION: The scoping review identified a large number of outcomes (n = 822) across 11 related outcome domains, supporting the need for a core outcome set.

Graducheck®-a novel device to measure sub-bandage pressures during application of compression.

Graduated compression, using bandaging or compression stockings, is the gold-standard treatment for the management of venous leg ulcers (VLUs) and preventing recurrence. However, achieving the required pressures on different parts of the leg is extremely difficult, even for experienced practitioners. Inappropriately applied compression can result in delayed healing and poor compliance. Graducheck® is a pressure sensor system that ensures that the prescribed level of compression is being applied accurately. This study aimed to determine if two experienced tissue viability nurses (TVNs) could achieve accurate pressures using four commonly used bandage systems, as measured using Graducheck sensor strips. Ideal pressures were not achieved, but in two systems, once the application pressure was adjusted according to the sensor level, ideal compression was achieved. In the remaining two systems, ideal pressures could not be produced, even after adjustments to application. Clinically, the Graducheck system could improve the standard of compression therapy, as real-time feedback ensures that corrections can be made. However, further work is required to determine why ideal pressures were not achieved in two of the tested systems.

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

BACKGROUND: A 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. AIM: The aim of this project is to develop a core outcome set for research evaluating the effectiveness of interventions for treating venous leg ulceration. METHODS: Through 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.

Marginalised voices in wound care: Experiences of people who inject drugs living with leg ulceration "The Gutter, the Nick or a Box!!"

Portraying the authentic voice of people who inject drugs (PWID) through narrative means is novel in contemporary literature. The study explored the experiences of PWID living with chronic leg ulceration using qualitative methodology set in a naturalistic paradigm. Led from the perspective of a nurse-researcher in the field of wound management, the study is original from a purist narrative perspective and offers a unique opportunity to gain a rare glimpse into the daily life of PWID as reported in their own words. The methodology chosen was diaries conducted over four weeks, followed by semi-structured interviews. The study was set in North London (UK); participants were recruited from three sites: a general acute NHS hospital, the community and a non-NHS clinical facility. Complete data collection took over 12 months. Open coding was used for word-by-word scrutiny of each diary entry and thematic analysis. The qualitative data software tool NVivo Version-10 was used to support this analysis. Ten participants completed the data collection process: seven males and three females (age range 35-62 years), with heterogeneous socio-economic and cultural backgrounds. The findings revealed the detailed suffering participants endured living with their ulcer: pain, shame and healing were among the emerging themes. The self-blame and punishment triggered by stigma was a detriment to the mental and physical health of participants. Those in contact with specialist wound care services saw a significant improvement in wound healing and this had a positive impact on their wellbeing and their overall outlook on life. This research contributes to science and practice by understanding the lives of PWID living with leg ulceration. It provides a platform from which to engage both generalist and specialist healthcare practitioners and has the potential to inform and improve current service provision of leg ulcer care for this population and to influence medical and social policy-making in this field.

An audience survey of practice relating to pain in the management of chronic venous leg ulcers.

Venous leg ulcers (VLU) respond well to compression, yet many ulcers remain unhealed after 1 year. Practitioners could be reluctant to apply compression to patients with significant ulcer pain. This study aimed to capture the views of practitioners on compression therapy for patients with painful VLU. A survey was conducted at a UK meeting in 2019 using handheld voting pads to capture the anonymous responses to four questions to which a mean of 90 practitioners responded. Nearly 40% of practitioners treat six or more patients a day with painful lower-limb ulcers. Some 80% felt confident in managing patients with painful ulcers; yet, most practitioners suggested they would refer onward for pain management. Some 40% would omit or reduce compression therapy as a pain management strategy. This survey supports the need for technological solutions that reduce VLU pain so that patients receive effective compression therapy.

Why nurses in primary care need to be research active: the case of venous leg ulceration.

Venous leg ulceration (VLU) is predominantly managed in primary care by district nurses, however much of the research takes place in secondary care. This study aimed to identify to what extent nurses are involved in publishing VLU research and to ascertain how much VLU research is conducted in primary care. Three searches of literature published between 2015 and 2020 were undertaken, reviewing VLU publications on interventions, quality of life and qualitative research. Some 37% of intervention studies had one or more nurse authors, compared with 65% of quality of life studies and 86% of qualitative research publications. Of papers that providing details of recruitment, 39% of intervention and quality of life studies included primary care as a recruitment setting. Qualitative studies were more likely to recruit from primary as well as secondary care (50%). Nurses are involved in leading VLU research but are more likely to publish quality of life and qualitative research than intervention studies. The majority of nurse authors in this field are based in academic institutions. A minority of studies utilise primary care as a recruitment setting for VLU research. More must be done to enable VLU research in community settings and to promote the involvement of clinical nurses in research.

Two-layer reduced compression system for lower limb wounds: a non-comparative evaluation.

Leg ulceration is a debilitating condition in which various factors play a role in determining patients' quality of life (QoL), and compression therapy has been shown to improve QoL. The 3M Coban 2 Lite Compression System provides reduced compression (25-30 mmHg) ideal for patients with painful venous leg ulcers (VLU) who are unable to tolerate high-strength compression or those with mixed-aetiology leg ulcers (MLU) who have an ankle-brachial pressure index (ABPI)≥0.5. This non-comparative evaluation aims to report the initial clinical experiences with 3M Coban 2 Lite and evaluate the performance of this two-layer reduced compression bandage system in treating chronic VLUs and MLUs. In total, 30 patients (12 men (40%); mean age=68.5 years) were enroled for evaluation. The duration of the chronic wounds was 28 months (range=1.5-144 months); 16 patients had VLUs, while 14 had MLUs. Complete healing was achieved in 6 (20%) patients, and an overall mean reduction in wound surface area (4.11 cm2) was observed between the baseline and study endpoint (16 weeks). Thus, 3M Coban 2 Lite seems safe and effective for treating painful VLUs and MLUs in patients unable to tolerate high-strength compression.

Primary care survey of venous leg ulceration management and referral pre-EVRA trial.

Venous leg ulceration (VLU) is a public health concern that is largely managed in community settings. The present study aimed to survey current VLU management in the community. A 14-question survey was distributed to primary care professionals, and 90 responses were received. Some 54% of respondents stated that they would assess ankle brachial pressure indices (ABPI) for those with VLU, while 25% reported that they would not. Additionally, 62% reported not organising duplex ultrasound scanning. Compression therapy was offered by 82% of respondents. When asked whether VLU patients were referred to specialist services in secondary or tertiary care, some 32% reported that they would. However, 57% reported that, if a study suggested that referral to specialist services was beneficial, they would change their practice. On the basis of the findings, the authors concluded that there is diversity in VLU diagnostic and treatment pathways. New, high-quality evidence may improve practice, but care delivery is influenced by local factors including time and resource distribution.

Metabolic Phenotyping in Venous Disease: The Need for Standardization.

Venous thromboembolism (VTE), chronic venous disease (CVD), and venous leg ulceration (VLU) are clinical manifestations of a poorly functioning venous system. Though common, much is unknown of the pathophysiology and progression of these conditions. Metabolic phenotyping has been employed to explore mechanistic pathways involved in venous disease. A systematic literature review was performed: full text, primary research articles on the applications of nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS) in human participants and animals were included for qualitative synthesis. Seventeen studies applying metabolic phenotyping to venous disease were identified: six on CVD, two on VLU, and nine on VTE; both animal (n = 6) and human (n = 10) experimental designs were reported, with one study including both. NMR, MS, and MS imaging were employed to characterize serum, plasma, urine, wound fluid, and tissue. Metabolites found to be upregulated in CVD included lipids, branched chain amino acids (BCAA), glutamate, taurine, lactate, and myo-inositol identified in vein tissue. Upregulated metabolites in VLU included lactate, BCAA, lysine, 3-hydroxybutyrate, and glutamate identified in wound fluid and ulcer biopsies. VTE cases were associated with reduced carnitine levels, upregulated aromatic amino acids, 3-hydroxybutyrate, BCAA, and lipids in plasma, serum, thrombus, and vein wall; kynurenine and tricarboxylic acid pathway dysfunction were reported. Future research should focus on targeted studies with internal and external validation.

Updated leg ulcer pathway: improving healing times and reducing costs.

Regardless of the amount of literature and evidence on leg ulcer management, there are still significant variations in treatment. Implementing a standardised leg ulcer pathway to ensure patients are appropriately and timely assessed could help reduce nursing time and overall costs, while improving healing outcomes and patients' quality of life. Such a pathway was introduced in Lincolnshire and Leicestershire, UK, to treat venous leg ulcers (VLUs). The results showed improved healing times, reduced costs and fewer nurse visits, among other findings.

Chronic venous leg ulcer care: Putting the patient at the heart of leg ulcer care Part 2: Development and evaluation of the consultation template.

Part 2 in this article series summarises the final two phases of a study which explored the experiences of patients with leg ulcers and the impact of this condition on their quality of life. Early phases of the study revealed a mismatch between issues that affected a patient's quality of life and what they discussed during subsequent health care consultations. In light of this, a nominal group technique was employed to facilitate the development of a new leg ulcer consultation template with patient partners. The aim of this was to include many of the issues raised in phases 1. The new template was evaluated in terms of its utility, significance and clinical potential. The application of this template during routine consultations appears to encourage the patient to disclose issues that are important to them and may have otherwise been overlooked.

Can early detection prevent venous leg ulceration?

Venous leg ulceration is the most common form of leg ulceration, affecting 1.5% of the UK adult population. This was reviewed within the latest best practice statement (2016) which set out to create clear guidance on the assessment, management and preventing the reoccurrence of venous leg ulceration. With a growing elderly population at risk of venous insufficiency, early identification of those at risk is vital in the fight to reduce the number of people suffering with chronic venous ulceration. This article looks at the need for early assessment and commencement of appropriate treatment in order to reduce the occurrence of venous ulceration and improve clinical processes across the UK.

Treating patients with venous leg ulcers in the acute setting: part 1.

Leg ulcers present with a variety of aetiologies, sometimes in combination. The most common aetiology is venous, with treament involving compression, elevation and exercise; the most common treatment setting is the community. However, people with leg ulcers do sometimes require admission to hospital for conditions and situations which may, or may not, be ulcer-related. There is a lack of contemporary evidence on the experience of inpatients and insufficient analysis of the impact on healing and complications to the lower limb when patients with leg ulcers and compression therapy are admitted to hospital. Admission to hospital presents an ideal opportunity for a focus on leg care and potentially enhancing healing rates of patients. The reality for patients with venous leg ulceration being treated with compression therapy is that this does not continue if they are admitted to hospital as inpatients-having been interrupted for MRSA screening and skin assessment, often no-one is available to reinstate the therapy. This article highlights key issues in the ongoing care of these patients and offers suggestions for basic management until a more acceptable and evidence-based solution can be found. Part 2 will deal with the preparation for discharge and options for the treatment of patients who are not already in the care of community services.

Progressive compression versus graduated compression for the management of venous insufficiency.

Venous leg ulceration (VLU) is a chronic condition associated with chronic venous insufficiency (CVI), where the most frequent complication is recurrence of ulceration after healing. Traditionally, graduated compression therapy has been shown to increase healing rates and also to reduce recurrence of VLU. Graduated compression occurs because the circumference of the limb is narrower at the ankle, thereby producing a higher pressure than at the calf, which is wider, creating a lower pressure. This phenomenon is explained by the principle known as Laplace's Law. Recently, the view that compression therapy must provide a graduated pressure gradient has been challenged. However, few studies so far have focused on the potential benefits of progressive compression where the pressure profile is inverted. This article will examine the contemporary concept that progressive compression may be as effective as traditional graduated compression therapy for the management of CVI.

Venous leg ulceration pathophysiology and evidence based treatment.

Venous leg ulceration (VLU) is one of the most predominate medical disorders worldwide and in the western hemisphere it affects around 1.5% of the general population and up to 5% of the elderly population. Unfortunately, this trend will only increase given the growth of an aging population worldwide. Understanding its pathophysiology that begins with venous hemodynamic abnormalities and leads to inflammatory alterations with microcirculatory changes is critical to delivering effective curative therapy. As such, the main component to treatment is reversing the underlying venous hypertension and pro-inflammatory milieu using compression treatment along with various adjuvant therapies. Given its impact, a comprehensive multi-pronged approach to care, treatment and prevention is required to reverse the increasing trend that is observed worldwide.

A new quality of life consultation template for patients with venous leg ulceration.

OBJECTIVE: Chronic venous leg ulcers (CVLUs) are common and recurrent, however, care for patients predominantly has a focus which overlooks the impact of the condition on quality of life. The aim of this study was to develop a simple, evidence-based consultation template, with patients and practitioners, which focuses consultations on quality of life themes. METHOD: A nominal group was undertaken to develop a new consultation template for patients with CVLUs based on the findings of earlier qualitative study phases. RESULTS: A user-friendly two-sided A4 template was designed to focus nurse-patient consultations on the quality of life challenges posed by CVLUs. CONCLUSION: CVLUs impact negatively on the quality of life of the patient but this receives inadequate attention during current consultations. This new template will help to ensure that key concerns are effectively raised, explored and addressed during each consultation. DECLARATION OF INTEREST: The NHS West Midlands Strategic Health Authority funded this study. The authors have no conflicts of interest to declare.