Computational therapeutic repurposing of tavaborole targeting arginase-1 for venous leg ulcer.

Venous leg ulcers (VLUs) pose a growing healthcare challenge due to aging, obesity, and sedentary lifestyles. Despite various treatments available, addressing the complex nature of VLUs remains difficult. In this context, this study investigates repurposing boronated drugs to inhibit arginase 1 activity for VLU treatment. The molecular docking study conducted by Schrodinger GLIDE targeted the binuclear manganese cluster of arginase 1 enzyme (2PHO). Further, the ligand-protein complex was subjected to molecular dynamic studies at 500 ns in Gromacs-2019.4. Trajectory analysis was performed using the GROMACS simulation package of protein RMSD, RMSF, RG, SASA, and H-Bond. The docking study revealed intriguing results where the tavaborole showed a better docking score (-3.957 Kcal/mol) compared to the substrate L-arginine (-3.379 Kcal/mol) and standard L-norvaline (-3.141 Kcal/mol). Tavaborole interaction with aspartic acid ultimately suggests that the drug molecule binds to the catalytic site of arginase 1, potentially influencing the enzyme's function. The dynamics study revealed the compounds' stability and compactness of the protein throughout the simulation. The RMSD, RMSF, SASA, RG, inter and intra H-bond, PCA, FEL, and MMBSA studies affirmed the ligand-protein and protein complex flexibility, compactness, binding energy, van der waals energy, and solvation dynamics. These results revealed the stability and the interaction of the ligand with the catalytic site of arginase 1 enzyme, triggering the study towards the VLU treatment.

Effectiveness of the Use of the Human Recombinant Epidermal Growth Factor in the Subsidized Regime vs The Contributive Regime in Patients with Venous Ulcers in Bogotá.

Introduction: Vascular ulcers constitute a serious global public health problem, responsible for causing a significant social and economic impact due to their recurrent, disabling nature and the need for prolonged therapies to cure them. Objective: To evaluate the use and efficacy of the rhEGF in the epithelialization of patients with a diagnosis of CEAP stage 6 venous insufficiency, in the two regimes of the health system in Colombia, the contributive (equivalent to a health system where citizens with payment capacity contribute a percentage of their salary) and the subsidized (equivalent to a health system where the state covers the vulnerable population and low socioeconomic level) versus the other treatments used. Methodology: Observational, descriptive, retrospective, multicenter study, in which 105 medical records with 139 ulcers were reviewed, in 2 centers, one belonging to the subsidized system and the other to the contributive system in Colombia. Results: The association with the epithelialization variable of the different treatment groups for ulcers according to the application of the mixed effect model test, for both regimes was for the Biologicals (EC 34.401/p = 0.000), Bioactive Agents (Hydrogels) (EC 24.735/p = 0.005) groups; for the rest of the treatment groups, the results were neither associated nor statistically significant. Conclusion: Intra- and perilesional therapy with rhEGF expands the therapeutic spectrum in patients with venous ulcers, regardless of the type of health system in which it will be applied, shortening the healing time and reaching a possible therapeutic goal, which according to this study there is an association with epithelialization regardless of the regime applied.

The combination of hyaluronic acid and collagenase in the treatment of skin ulcers: an open, multicenter clinical study assessing safety and tolerability of Bionect Start®.

OBJECTIVE: Several clinical studies have shown that hyaluronic acid collagenase is well-tolerated and very effective in managing chronic venous ulcers. The aim of the present study is to confirm the safety and tolerability of daily application in patients suffering from cutaneous ulcers of different etiologies. The efficacy of the treatment and its impact on patients' quality of life are also assessed. PATIENTS AND METHODS: Patients with a clinical diagnosis of skin ulcer with devitalized/fibrinous/slough tissue that could delay the healing process were enrolled in the study. The hyaluronic acid/collagenase ointment was applied topically until wound closure or total debridement of non-viable tissue was achieved, however, with a limit of 30 days. Monitoring was performed weekly, either through outpatient visits or telephone surveys. Assessments included adverse events, local irritation reactions, pain at dressing changes, and wound bed status. Patients were also requested to complete a quality-of-life questionnaire. RESULTS: The study involved 96 patients with a mean age of 71 years. The patients suffered mainly from traumatic (21.9%), venous (15.6%), or pressure ulcers (12.5%); in 26% of cases, ulcers had mixed etiology. In approximately 32% of patients, the ulcer had been present for more than 6 months, and 18.1% of subjects had previously undergone surgical wound debridement. CONCLUSIONS: Daily application of hyaluronic acid-collagenase achieved the following results: i) absence of adverse events related to the use of the product; ii) significant reduction in the degree of localized irritation and pain at dressing changes; iii) significant support to wound bed preparation; iv) trend towards improvement in the quality of life and health status of the patients.

Neuroimmunomodulatory effect of Nitric Oxide on chronic wound healing after photodynamic therapy.

Neuroimmunomodulation is the capacity of the nervous system to regulate immune processes. The existence of neurotransmitter receptors in immune cells enables this phenomenon to take place. Neuronal mediators possess the capacity to direct and control several occurrences during the wound healing process. Nitric oxide (NO) functions as a neuromodulator, playing a crucial role in the regulation of vascular tone and blood pressure with antimicrobial properties. Photodynamic therapy has been shown to augment the function of immune cells involved in the healing process of venous leg ulcers. Nitric oxide can be secreted into the extracellular environment by these cells. In lesions treated with PDT, the synthesis of iNOs (the enzyme that releases NO) increased, as demonstrated by the experimental results. Therefore the significance of PDT in enhancing the clinical condition of the lesion is thus highlighted.

Cost-effectiveness of ChloraSolv in treating hard-to-heal venous leg ulcers.

OBJECTIVE: To estimate whether the topical, amino acid-buffered hypochlorite debriding gel ChloraSolv (RLS Global AB, Sweden) could potentially afford the UK's health services a cost-effective intervention for hard-to-heal venous leg ulcers (VLUs). METHOD: A Markov model representing the management of hard-to-heal VLUs with ChloraSolv plus standard care (SC) or SC alone was populated with inputs from an indirect comparison of two propensity score-matched cohorts. The model estimated the relative cost-effectiveness of ChloraSolv in terms of the incremental cost per quality-adjusted life year (QALY) gained at 2021/2022 prices. RESULTS: Addition of ChloraSolv to an SC protocol was found to increase the probability of healing by 36% (from 0.14 to 0.19) after 12 weeks, and by 79% (from 0.24 to 0.43) after 24 weeks. This led to a marginal increase in health-related quality of life. Treatment with ChloraSolv plus SC instead of SC alone reduced the total cost of wound management by 8% (£189 per VLU) at 12 weeks and by 18% (£796 per VLU) at 24 weeks. Use of ChloraSolv was estimated to improve health outcomes at reduced cost. Sensitivity analysis showed that use of ChloraSolv plus SC remained a cost-effective treatment with plausible variations in costs and effectiveness. CONCLUSION: Within the limitations of the study, the addition of ChloraSolv to an SC protocol potentially affords a cost-effective treatment to the UK's health services for managing hard-to-heal VLUs.

Healing of Venous Leg Ulcers Influenced by Individual Aspects: Cluster Analysis in a Specialist Wound Management Clinic.

INTRODUCTION/OBJECTIVE: Venous Leg Ulcers (VLU) present a challenging healing process. Attaining healing is a primary treatment objective, commonly pursued in Primary Health Care (PHC) or Specialist Wound Management Clinics. Our objective was to examine the association and interplay between sociodemographic, health, clinical, and care factors with the outcomes of VLU treatment in patients undergoing care at a Specialist Wound Management Clinic. METHODS: Longitudinal, observational study took place in a center for the treatment of chronic injuries linked to PHC. The sociodemographic aspects, health status and habits, clinical and care aspects of patients with VLU were scrutinized over a 1-year period. RESULTS: The sample comprised 103 participants, with some still under treatment (Treatment Group-TG/ n = 60) and others having achieved VLU healing (Healing Group-HG/ n = 43). An association between sociodemographic, health, clinical, and care factors and the healing outcome (HG) was identified. A moderate correlation was observed between factors predisposing to healing in the sociodemographic group and health habits. Notably, among sociodemographic factors, the older age group and improvements in health, particularly the reduced use of alcohol/smoking, appeared to exert the most significant influence on healing. Additionally, specialized service monitoring and the application of compression therapy were contributory factors. CONCLUSIONS: These findings substantiate the hypothesis that sociodemographic, health, clinical, and care-related aspects are intertwined with VLU healing. Protective factors associated with healing interacted synergistically, fostering a positive outcome over one year of treatment.

The Potential of Bacteriophage Therapy as an Alternative Treatment Approach for Antibiotic-Resistant Infections.

OBJECTIVE: This study aimed to provide a comprehensive overview of the current state of the literature on the therapeutical application of bacteriophages. METHODS: First, a bibliometric analysis was performed using the database Web of Science to determine annual number of publications and citations. Second, a systematic literature review was conducted on randomized-controlled trials (RCTs) of phage therapy in PubMed. RESULTS: Over the past decade, the number of publications on bacteriophage therapy increased more than fourfold with 212 articles in 2011 and 739 in 2022. The systematic search in PubMed yielded 7 RCTs eligible for inclusion, reporting on a total of 418 participants. Identified indications in this study included bacterial diarrhea, urinary tract infections, infected burn wounds, chronic otitis, chronic venous leg ulcers, and chronic rhinosinusitis. In three studies, mild to moderate adverse events were reported in 10/195 participants (5.1%). Three of the studies reported a statistically significant difference in outcomes comparing phage therapy with standard of care or placebo. CONCLUSION: Phage therapy has gained increasing interest over the years. RCTs on different indications suggest the safety of phage therapy; however, reasons why phage therapy is not yet well accepted are limitations in the study designs. For a successful translation into clinical practice researchers and clinicians should learn from the earlier experiences and consider issues such as the quality of phage preparation, sensitivity testing, titer and dosages, as well as access to the infection site and stability for standardized protocols and future trials.

Testing the feasibility of a co-designed intervention, comprising self-managed, home-based, exercise training with embedded behavioural support and compression therapy for people with venous leg ulcers receiving treatment at home (FISCU-II).

BACKGROUND: Venous leg ulcers (VLUs) heal slowly, are painful for patients and are costly for healthcare systems; they also affect patients' quality of life. Previous work suggests that supervised exercise training used in combination with compression therapy may offer clinical benefits. However, a large population of people with VLUs are unable to access such an intervention due to frailty and age. OBJECTIVES: To assess the feasibility of 'FISCU Home' (a co-designed, 12-week home-based self-managed lifestyle programme based on exercise and behaviour support) as an adjunct therapy to compression in people with VLUs. METHODS: Forty people with VLUs, receiving treatment at home, were recruited from community nursing and tissue viability teams, and via a newspaper advertisement. Participants were randomized 1 : 1 either to exercise with behaviour support (three times per week) plus compression therapy or compression only. The feasibility of the programme was assessed using progression criteria that included exercise attendance rate, loss to follow-up, patient preference(s) and adverse events (AEs). Baseline assessments were repeated at 12 weeks and 6 months. Secondary outcomes (i.e. ulcer recurrence, healing rate and healing time) were also documented at these intervals. Intervention and healthcare utilization costs were calculated. RESULTS: The study recruitment rate was 65%, while 75% of the exercise group participants attended all scheduled exercise sessions. All participants completed compression therapy. No serious AEs or exercise-related AEs were reported. Median (interquartile range) ulcer healing time was shorter in the exercise group [29 (7-108) vs. 42 (6-116) weeks]. CONCLUSIONS: The feasibility and acceptability of both a home- and exercise-based lifestyle intervention in conjunction with compression therapy and the study procedures are supported.

Cost-effectiveness analysis of intralesional and perilesional recombinant human epidermal growth factor vs hydrocolloid therapy in venous ulcer treatment in the Colombian context.

OBJECTIVE: To perform a comparative analysis of health care expenses and outcomes in response to the question: What is the cost-effectiveness of intralesional and perilesional recombinant human epidermal growth factor (rhEGF) compared with hydrocolloid therapy in patients diagnosed with chronic venous insufficiency without infection in Colombia? METHODS: A Markov model was used to determine cost effectiveness over a 5-year period, considering the perspective of the health system in Colombia. The study included patients aged >18 years diagnosed with chronic venous insufficiency and used clinical studies to calculate the probabilities of epithelialization, infection, recurrence, and mortality. RESULTS: RhEGF is more expensive per unit than hydrocolloids, but it is proven to be effective at healing ulcers in 8 to 12 weeks, even in complex cases. Hydrocolloids, in contrast, typically require 29.5 weeks on average, and ≤46 weeks for complex cases. Despite the cost, rhEGF is more cost effective because it achieves results comparable with hydrocolloid therapy at a lower cost per additional quality-adjusted life-year. CONCLUSIONS: Based on cost-effectiveness analysis, rhEGF is a superior alternative to hydrocolloids for treating venous ulcers in Colombia. Not only is it more affordable, but it also enhances patients' quality of life and streamlines the health care system's resource use.

Application of StyleGAN Architecture for Generating Venous Leg Ulcer Images.

Leg ulcers caused by impaired venous blood return are the most typical chronic wound form and have a significant negative impact on the lives of people living with these wounds. Thus, it is important to provide early assessment and appropriate treatment of the wounds to promote their healing in the normal trajectory. Gathering quality wound data is an important component of good clinical care, enabling monitoring of healing progress. This data can also be useful to train machine learning algorithms with a view to predicting healing. Unfortunately, a high volume of good-quality data is needed to create datasets of suitable volume from people with wounds. In order to improve the process of gathering venous leg ulcer (VLU) data we propose the generative adversarial network based on StyleGAN architecture to synthesize new images from original samples. We utilized a dataset that was manually collected as part of a longitudinal observational study of VLUs and successfully synthesized new samples. These synthesized samples were validated by two clinicians. In future work, we plan to further process these new samples to train a fully automated neural network for ulcer segmentation.

Evaluation of factors affecting the healing process of venous ulcers: A 12-week longitudinal study.

The process of healing venous ulcers is complex and influenced by many factors. By identifying the risk factors that influence a slower healing process, it is possible to predict impending delays and plan an individualised care plan. We analysed our database of patients with venous ulcers and identified clinical and demographic factors that delay the healing process. The research analysed the medical records of 754 patients with VLUs at Chronic Wound Treatment Unit of the University Hospital treated between 2001 and 2019. In study, the majority (64.3%) were women, the mean age was 65.7 years. The median duration of Chronic Venous Insufficiency was 24 years, 52% patients had had the disease >20 years, and 296 (39.3%) had experienced ulceration >12 months. Most of the patients (85.8%) had comorbidities, 84% were obese. At 12-week follow-up, 432 of the 754 ulcers had healed. Identified independent predictors of slower ulcer healing rates: wound area greater than 8.25 cm2 , location of the ulceration other than the medial ankle area, underlying disease >20 years, the presence of multiple comorbidities, depth of the ulcer, the presence of an unpleasant smell and alert pathogens. The presence of redness resulted in faster healing of VLUc. Many factors influence the healing process of venous ulceration. The results of the study can help in planning patient care and implementing appropriate early strategies to promote healing.

Aetiological treatment of venous leg ulcers with compression therapy: real-life outcomes with two different procedures.

OBJECTIVE: To evaluate the healing outcomes and costs associated with the aetiological management of venous leg ulcers (VLUs) treated with recommended multicomponent bandages (MCBs) and short-stretch bandages (SSBs). METHOD: This observational study is a retrospective comparative study (Level 2b), based on the French administrative healthcare database (Système National des Données de Santé, SNDS). It includes patients treated from onset with reimbursed MCBs and SSBs for a VLU episode, between July 2018 and September 2020. Although other compression systems, such as long-stretch bandages, are commonly used for the treatment of VLUs, they are not recommended by health authorities in France and thus, were not considered for this study. A binomial regression model was performed to estimate the adjusted relative risk of wound closure rates at three months for each group, based on potential confounding factors including, notably, age, sex, key comorbidities, and wound dressing size. The mean healthcare cost was calculated for patients whose VLUs healed within the study period. RESULTS: The reimbursement data (including prescribed compression systems and nursing care) of the 25,255 selected patients were analysed in the study. There were no significant differences between the MCBs and SSBs groups when considering patient characteristics. The healing rates after three months' treatment, were 42% and 35% (p<0.001) in the MCBs and SSBs groups, respectively. When adjusting the statistical model, the chance of healing at three months was still 12% higher with MCBs compared with SSBs (p<0.0001). The median healing time was estimated at 115 (interquartile range (IQR): 60-253) days in the MCB group versus 137 (IQR: 68-300) days in the SSBs group. The average treatment cost per patient with a healed ulcer was €2875±3647 in the MCB group and €3580±5575) in the SSBs group (p=0.0179), due to lower hospital stay and nursing costs in the MCB group. Differences in wound characteristics between the two groups cannot be totally excluded, due to the limited content of the database in terms of clinical data, but should have been addressed, to some extent, through the study selection criteria and the chosen regression model. CONCLUSION: In this study, this SNDS analysis seemed to confirm that the healing outcomes achieved in real-life with MCBs were in line with those reported in clinical trials, and superior to SSBs, which reinforces the current position from the guidelines.

A simple index to predict healing in venous leg ulcers: a secondary analysis from four randomised controlled trials.

OBJECTIVE: To investigate whether the use of a simple baseline measurement predicts venous leg ulcer healing at 12 and 24 weeks. METHOD: This was a secondary analysis of a cohort of four randomised controlled trials (RCTs) of treatments adjuvant to compression. Self-reported ulcer duration, and measured ulcer length and width, to calculate estimated ulcer area, were used to obtain a Margolis index score. The score created three prognostic strata for likelihood to heal within 24 weeks, and the number of participants healed and time-to-healing were compared. RESULTS: There were a total of 802 participants across the four RCTs-408 (50.9%) in two 12-week trials and 394 (49.1%) in two 24-week trials. The mean age of participants was 63.7±17.6 years, and 372 were female (46.4%). The Margolis index score at baseline was 0 for 320 participants (predicted normal healing); 1 for 334 participants; and 2 for 148 participants (both 1 and 2 predicted slow-to-heal). Overall, 248 (77.5%) of those participants who scored 0 at baseline healed within 24 weeks, compared with 182 (54.5%) of participants who scored 1, and 30 (20.3%) participants who scored 2. The median time-to-healing was 40 (24-62) days, 57 (35-100) days and 86.5 (56-151) days, respectively. The area under the receiver operating characteristic curve was 0.69 and 0.77, respectively, for the 12 and 24 week trials. CONCLUSION: A simple baseline index identifies participants with normal or slow-to-heal wounds and could be used to demonstrate prognostic balance between treatment groups in trials. This approach could also be used in clinical practice to assist with managing expectations and for early identification of patients who may best benefit from adjuvant treatments.

Use of Intralesional and Perilesional Human Recombinant Epidermal Growth Factor (hrEGF) in the Local Treatment of Venous Ulcer - Review Article - Expert Recommendation.

Venous Ulcers (VU) represent 60-80% of all leg ulcers and are the final stage of the disease secondary to venous hypertension or valve insufficiency. Conventional treatment that focuses on its etiological factors continues to be the gold standard; however, 30% of ulcers do not heal with this treatment; thus, it has been seen that the use of growth factor can be used as an adjuvant for this pathology. A literature review was carried out to evaluate the evidence from systematic reviews, meta-analyses, case studies, and quantitative studies that respond to the objective of this analysis review in the different databases with specific inclusion criteria with publications between 2002 and 2022, initially finding the topical application of the factor and later, more recently, the intralesional and perilesional application, the latter being an alternative treatment for this type of pathology and generating some recommendations for using the Factor.

Efficacy and safety of pentoxifylline for chronic venous leg ulcers: study protocol for a multicenter randomized controlled trial in China (ESPECT study).

BACKGROUND: Venous leg ulcers (VLUs) are the most severe manifestation of chronic venous disease, with long healing time and a high recurrence rate. It imposes a heavy burden on patients, their families, and the health care system. Chronic inflammation triggered by sustained venous hypertension is now recognized as the hallmark of chronic venous disease. The anti-inflammatory effect of pentoxifylline may offer a promising avenue to treat VLUs. However, current evidence of pentoxifylline for VLUs is relatively small and of low quality. The aim of this study is to evaluate the efficacy and safety of pentoxifylline for VLUs in the Chinese population. METHODS: This is a randomized, double-blinded, double-dummy, multi-center, placebo-controlled clinical trial. A total of 240 patients will be randomized to receive pentoxifylline (400 mg, twice daily) or placebo for 24 weeks. All participants will receive diosmin treatment and standard care of VLUs and other comorbidities. The primary outcome is the difference in the wound healing rate within 12 weeks between pentoxifylline and placebo. Secondary outcomes include (1) percent wound size changes at 12 weeks, (2) the levels of TNF-α and IL-6, (3) venous clinical severity score and chronic venous insufficiency quality of life score, and (4) ulcer recurrence within 24 weeks. DISCUSSION: This study would evaluate the efficacy and safety of pentoxifylline for VLUs in the Chinese population. If confirmed, it wound offer another effective and safe therapeutic option for treatment of VLUs. TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trial Registry (No. ChiCTR-2100053053). Registered on 10 November, 2021, https://www.chictr.org.cn/showproj.aspx?proj=137010.

Cost-effectiveness of two reduced pressure compression systems in treating newly diagnosed venous leg ulcers.

OBJECTIVE: To assess the clinical outcomes and cost-effectiveness of using two different reduced pressure compression systems in treating newly diagnosed venous leg ulcers (VLUs) in clinical practice, from the perspective of the UK's National Health Service (NHS). METHODS: This was a modelling study based on a retrospective cohort analysis of the case records of patients with a newly diagnosed VLU, randomly extracted from The Health Improvement Network (THIN) database, who were initially treated with a two-layer cohesive compression bandage (TLCCB Lite; Coban 2 Lite, 3M, US) or a two-layer compression system (TLCS Reduced; Ktwo Reduced, Urgo, France). No significant differences were detected between the groups. Nevertheless, analysis of covariance (ANCOVA) was performed to enable differences in patients' outcomes between the groups to be adjusted for any heterogeneity in baseline covariates. Clinical outcomes and cost-effectiveness of the alternative compression systems were estimated over 12 months after starting treatment. RESULTS: Time from wound onset to starting compression was a mean of two months. The probability of healing at 12 months was 0.59 in the TLCCB Lite group and 0.53 in the TLCS Reduced group. Patients in the TLCCB Lite group experienced a marginally better health-related quality of life (HRQoL) of 0.02 quality-adjusted life years (QALYs) per patient compared to those in the TLCS Reduced group. The 12-month NHS wound management cost was £3883 per patient treated with TLCCB Lite and £4235 per patient treated with TLCS Reduced. When the analysis was repeated without ANCOVA, the findings from the base case analysis remained unchanged (i.e., use of TLCCB Lite improved outcomes at lower cost). CONCLUSION: Within the study's limitations, treating newly diagnosed VLUs with TLCCB Lite instead of TLCS Reduced potentially affords a cost-effective use of NHS-funded resources in clinical practice, since it is expected to result in an increased healing rate, better HRQoL and a lower NHS wound management cost.

Prospective study on the clinical and economic burden of venous leg ulcers in the tropics.

OBJECTIVE: Venous leg ulcers (VLUs) are both chronic and recurrent. The treatment of such ulcers often require multiple outpatient visits and dressing changes. Several reports on the costs of treating such VLUs have been reported in the west. We prospectively evaluated the clinical and economic burden of VLUs in a population of Asian patients in the tropics. METHODS: Patients from a prospective two-center study conducted at two tertiary hospitals in Singapore, as a part of the Wound Care Innovation in the Tropics program, between August 2018 and September 2021 were recruited. The patients were followed up for 12 weeks (visit 1 to visit 12), until index ulcer healing, death, or lost to follow-up (whichever came first). These patients were then followed up 12 weeks later to determine the longer term outcome of the wound (healed, recurrence, remained unhealed). The itemized costs derived from the medical service were retrieved from the relevant departments of the study sites. The patients' health-related quality of life was assessed at baseline and the last visit of the 12-week follow-up period (or until index ulcer healing), using the official Singapore version of the EuroQol five-dimension-5L questionnaire, which also includes a visual analog scale (EQ-VAS). RESULTS: A total of 116 patients were enrolled; 63% were men, and the mean patient age was 64.7 years. Of the 116 patients, 85 (73%) had a healed ulcer at 24 weeks (mean duration to ulcer healing, 49 days), and 11 (12.9%) had experienced ulcer recurrence within the study period. Within the 6-month follow-up period, the mean direct healthcare cost per patient was USD$1998. The patients with healed ulcers had significantly lower costs per patient compared with those with unhealed ulcers (USD$1713 vs USD$2780). Regarding health-related quality of life, 71% of the patients had a lower quality of life at baseline, which had improved at 12 weeks of follow-up, with only 58% of the patients reported to have a lower quality of life. Also, the patients with healed ulcers scored higher for both utilities (societal preference weights) and EQ-VAS at follow-up (P < .001). In contrast, patients with unhealed ulcers only scored higher EQ-VAS at follow-up (P = .003). CONCLUSIONS: The findings from this exploratory study provide information on the clinical, quality of life, and economic burden of VLUs in an Asian population and suggest the importance of healing VLUs to reduce the effects on patients. The present study provides data as a basis for economic evaluation as a consideration for the treatment of VLUs.

Hyperbaric Oxygen as an Adjunct in the Treatment of Venous Ulcers: A Systematic Review.

BACKGROUND: The use of Hyperbaric Oxygen Therapy (HBOT) in diabetic wounds has been studied extensively. Even though venous insufficiency is the most common cause of lower limb ulceration, there is comparatively little evidence regarding the use of HBOT for Venous Leg Ulcers (VLU). We performed a systematic-review to evaluate and synthesise available evidence, to evaluate whether patients with VLU, when treated with HBOT, had greater rates of (i) complete VLU healing or (ii) reduction in VLU area, than controls. METHODS: In keeping with PRISMA guidelines, database searches of PubMed, Scopus and Embase was performed. After removal of duplicates, titles were screened for relevance by two authors, then abstracts, and in turn full text manuscripts. Data were extracted from relevant sources including one published abstract. Included studies were assessed for risk of bias using the Risk of Bias 2 (RoB-2) and Risk Of Bias In Nonrandomized Studies (ROBINS-I) tools. RESULTS: Six studies were included. There was significant heterogeneity across the studies, with no standard control intervention, method of outcome reporting, or duration of follow up. Two studies reported 12 week follow up results and pooled analysis of complete ulcer healing showed no statistically significant difference between HBOT and controls for the outcome of complete ulcer healing OR 1.54 (95%CI = .50-4.75) P = .4478. A similar non-signifiacnt result was seen in four studies reporting 5-6 week follow up; OR 5.39 (95%CI = .57-259.57) P = .1136. Change in VLU area was reported in all studies, and pooled standardised mean difference was 1.70 (95%CI = .60 to 2.79) P = .0024, indicating a statistically significant benefit of HBOT in reducing ulcer area. CONCLUSION: Existing evidence suggests that HBOT does not significantly affect complete healing of VLU. There is a statistically significant benefit in terms of reducing ulcer size, though in the absence of ulcer healing the clinical significance of this is not established. Current evidence does not justify widespread use of HBOT for VLU.

Relative cost-effectiveness of three compression bandages in treating newly diagnosed venous leg ulcers in the UK.

OBJECTIVE: To assess the clinical outcomes and cost-effectiveness of using a two-layer cohesive compression bandage (TLCCB; Coban 2, 3M, US) compared with a two-layer compression system (TLCS; KTwo, Urgo, France) and a cohesive inelastic bandage system (CIBR; Actico, L&R, Germany) in treating newly diagnosed venous leg ulcers (VLUs) in clinical practice, from the perspective of the UK's National Health Service (NHS). METHOD: This was a modelling study based on a retrospective cohort analysis of the case records of patients with a newly diagnosed VLU randomly extracted from the The Health Improvement Network (THIN) database who were treated with TLCCB, TLCS or CIBR. No significant differences were detected between the groups. Nevertheless, analysis of covariance was performed to enable differences in patients' outcomes between the groups to be adjusted for any heterogeneity in baseline covariates. Clinical outcomes and cost-effectiveness of the alternative compression systems were estimated over 12 months after starting treatment. RESULTS: There were 250 patients in each group. Time from wound onset to starting compression was a mean of two months. The healing distribution of the TLCCB-treated patients was significantly different from that of the other two cohorts (p=0.003); the probability of healing at 12 months was 0.62, 0.51 and 0.49 in the TLCCB, TLCS and CIBR groups, respectively. Patients treated with TLCCB experienced better health-related quality of life (HRQoL) over 12 months (0.86 quality-adjusted life years (QALYs) per patient), compared with those treated with TLCS and CIBR (0.83 and 0.82 QALYs per patient, respectively). The 12-month NHS wound management cost was £3693, £4451 and £4399 per patient in the TLCCB, TLCS and CIBR groups, respectively. CONCLUSION: Within the model's limitations, treating newly diagnosed VLUs with TLCCB instead of the other two compression systems appears to afford a more cost-effective use of NHS-funded resources in clinical practice, since it is expected to result in increased healing, better HRQoL and a lower wound management cost for the NHS.

Effect of four-layer dressing on the microbiological profile of venous leg ulcer.

OBJECTIVE: Venous leg ulcer (VLU) is a chronic disease and has periods of exacerbation and remission. Various bandage systems-single-layered, double-layered and multiple-layered with elastic and non-elastic components-have been developed. The requirement for sustained pressure brought about the introduction of the four-layer bandage. We studied the bacteriology of VLUs and the effect of four-layer bandages on their healing. METHOD: Clinical details of all patients, with wound size measurement by gauze piece, wax paper and scale, were recorded. The wounds were initially debrided and photographic records of all patients were maintained. Patients were followed up every week, when the dressings and four-layer bandages were changed. RESULTS: A total of 60 patients were recruited to the study with four patients having bilateral disease and so a total of 64 VLUs were evaluated. Of these, 60 (93.8%) healed completely, one (1.6%) healed partially and three (4.7%) did not heal. After excluding the four VLUs that did not fully heal, 10 (16.7%) had recurrence while 50 (83.3%) had no recurrence in the follow-up period, which lasted for one year. During the first visit (baseline), meticillin-resistant Staphylococcus aureus (MRSA) was isolated in 29 (45.31%) VLUs and Pseudomonas spp. in 20 (31.25%) VLUs. With subsequent dressing, the VLU size decreased and the culture of the VLU was sterile from the third culture onwards in 45 cases. There was a significant correlation (p<0.001) between VLU size and the number of dressings. CONCLUSION: Compression therapy is the mainstay of treatment of VLU, with rapid healing and improvement in bacteriological profile. Compression in the range of 30-40mmHg is the most effective treatment for uncomplicated VLUs with adequate arterial competency.