Management of Moderate-to-Highly Exuding Chronic Leg Ulcers With Superabsorbent Wound Dressings Versus Foams Dressings in Polish Settings: An Early-Stage Cost-Effectiveness Evaluation.

Background: People living with chronic leg ulcers frequently experience moderate to severe wound-related pain with the highest level of pain occurring at dressing change. Wound- related pain is not always able to be alleviated by oral analgesics alone. Persistent poorly- controlled leg ulcer pain physiologically impacts wound healing and prevents timely, effective wound management strategies being implemented which can negatively impact wound healing and health-related quality of life (HRQoL). Topical agents such as morphine gel and ibuprofen foam are used as primary dressings as a strategy for managing chronic leg ulcer pain. Studies investigating ibuprofen foam have shown significant improvement in chronic leg ulcer pain compared to standard care. There is insufficient evidence to suggest morphine gel is effective for chronic leg ulcer pain. Topical local anaesthetics, in particular the eutectic mixture of local anaesthetics (EMLA®), have been used for decades to relieve pain associated with debridement of chronic leg ulcers. However, their effectiveness as a primary dressing for managing chronic wound-related pain is yet to be evaluated. Since there was no known evidence regarding the effectiveness of EMLA® as a primary dressing for painful chronic leg ulcers to relieve wound-related pain and its associated impact on wound healing and HRQoL this feasibility study was conducted. Study aims: The primary aim of this study was to assess the processes, resources, management and scientific aspects of the study to ensure implementation of a larger study is feasible and to generate data that could be used for future sample size calculations. Study feasibility was assessed using the following criteria for determining success: recruitment of at least 80% of eligible patients within 12 months; retention of 80% of participants during the study period and achieving at least 80% adherence to the intervention protocol. Secondary aims were to investigate the effectiveness of the daily topical application of EMLA® as a primary dressing to painful chronic leg ulcers as a pain-relieving strategy and the associated impact on wound healing and HRQoL; and whether improvement in pain levels is associated with reduced need for oral analgesia, particularly opiates. Design: A pilot, parallel group, non-blinded, superior, randomised, controlled trial. There was a 4-week intervention period and a 12-week study period. Setting: Six procedure clinics located in a public community nursing service Central Coast, New South Wales, Australia. Participants: Participants (n = 60) were adult patients with painful chronic leg ulcers of varied aetiology. The preliminary screening criteria included a chronic leg ulcer of more than six weeks duration; pain relieving medications required to manage wound-related pain; and, the participant was able to be treated in a community nursing clinic. Intervention: EMLA® was applied to the chronic leg ulcers daily for four weeks as a primary dressing followed by standard care. Data collection: Feasibility data were collected on human resource requirements, number of home visits, use of consumables and study management including ease of administering data collection instruments. Wound-related pain was measured at baseline and each dressing change; chronic leg ulcer surface areas and HRQoL were measured at baseline, weeks 4 and 12. Outcomes: Feasibility: Although all proposed participants were recruited (n=60) the recruitment rate was lower than expected and it is possible some eligible patients were missed during the screening process. Fifty-four participants remained in the study until completion for a 90% retention rate. Intervention fidelity was influenced by resource availability and participant factors such as increased wound-related pain. Data generated from the primary clinical outcome wound- related pain, was used to calculate the sample size for a larger study. Given two-sided significance of 0.05, a power of 0.8%, effect size 0.45 +/- 0.3 and variability/standard deviation of 2.2 +/- 0.2, 274 to 306 participants will be required for a larger randomised controlled trial. The sizes have been adjusted upwards based on an estimated dropout rate of 10%. However, an effect size of 0.45 is not clinically meaningful so a difference of at least two pain scores on the 11-point pain intensity Numerical Rating Scale used in this study is suggested as a clinically important difference. Recalculation using an effect size of two estimated that 52 participants would be needed to detect a clinically meaningful difference between the treatment and control groups based on pain as the primary outcome. Assuming a dropout of 10%, this figure was adjusted upwards to 58. Wound-related pain: Mean pain scores were similar between the two groups at baseline (p = 0.84). During dressing change, mean pain scores across the 4-week intervention period were significantly lower in the intervention compared to the control group (intervention group: Mean (SD) 3.39 (2.16); control group: Mean (SD) 4.82 (2.27), p = 0.02). Mean pain scores after dressing change were also significantly lower for the intervention group over the 4-week intervention period (intervention group: Mean (SD) 2.71(1.94); control group: Mean (SD) 3.92 (2.03), (p = 0.03). Wound healing and HRQoL: During the intervention period there was no significant difference in wound sizes between groups (intervention group - Median (cm2): 2.4, IQR: 1.3 – 12.7 v control group- Median (cm2): 5.0, IQR: 2.5-9.9; p = 0.05). Mean HRQoL scores for all subscales at baseline, weeks 4 and 12 were similar between groups except for Wellbeing, which was significantly higher in the intervention group at the end of the 4-week intervention period (intervention group - Mean 52.41, SD 24.50 vs. control group- Mean: 38.15, SD 21.25; p = 0.03, d = .62). Conclusion: It is feasible to conduct a larger multisite RCT following modifications to the study protocol. The study findings suggest that daily applications of EMLA® as a primary dressing reduces wound-related pain during and after dressing change, do not inhibit wound healing and may improve a person’s well-being.

To determine the cost-effectiveness/utility of a superabsorbent wound dressing (Zetuvit Plus Silicone) versus the current standard of care (SoC) dressings, from the NHS perspective in England, in patients with moderate-to-high exudating leg ulcers. A model-based economic evaluation was conducted to analyse the cost-effectiveness/utility of a new intervention. We used a microsimulation state-transition model with a time horizon of six months and a cycle length of one week. The model uses a combination of incidence base and risk prediction approach to inform transition probabilities. All clinical efficiency, health-related quality of life (HRQoL), cost and resource use inputs were informed by conducting a systematic review of UK specific literature. Treatment with the superabsorbent dressing leads to a total expected cost per patient for a six month period of £2887, associated with 15.933 expected quality adjusted life weeks and 10.9% healing rate. When treated with SoC, the total expected cost per patient for a six month period is £3109, 15.852 expected quality adjusted life weeks and 8% healing rate. Therefore, the superabsorbent dressing leads to an increase in quality-adjusted life weeks, an increase in healing rate by 2.9% and a cost-saving of £222 per single average patient over six months. Results of several scenario analyses, one-way deterministic sensitivity analysis, and probabilistic sensitivity analysis confirmed the robustness of base-case results. The probabilistic analysis confirmed that, in any combination of variable values, the superabsorbent dressing leads to cost saving results. According to the model prediction, the superabsorbent dressing leads to an increase in health benefits and a decrease in associated costs of treatment.

The aim of the research is to assess the benefit-harm of superabsorbent polymers wound dressings based on polyacrylate polymers (SAPs) compared with standard of care (SoC) dressing mix for patients with moderate-to-highly exuding hard-to-heal leg ulcers. The SoC dressings mix was composed of other superabsorbents in 29% of cases, antimicrobials 26%, foams 20%, alginates 5%, and other dressings 19% weighted according to their frequency. We have used the decision-analytic modeling method, Markov process, as an adequate analytical solution for medical prognosis. We have combined the systematic literature search to identify the most relevant inputs for the analysis, with available patient-level clinical data concerning benefits of superabsorbent to generate a robust prediction of patient-relevant outcomes, including healing rates and health-related quality of life. Besides, we have qualitatively described adverse events associated with those treatments. Our research indicates that SAPs when compared with SoC dressing mix in a patient with moderate-to-highly excluding leg ulcers are leading to an improved healing rate with an absolute risk difference of 2.20% in 6 months and a relative risk of 1.07 in favor of SAP dressings. The attributable fraction among those exposed to SAP dressings of 6.6%, meaning that 6.6% of the healed ulcers could be attributed to having had the SAP dressing treatment instead of the SoC dressing treatment. Besides, SAP dressings lead to improved quality of life measured as incremental quality-adjusted life weeks (QALWs) of 0.13 QALWs.

Numerous mast cells are present in chronic leg ulcers. Tryptase and chymase are the major mediators of mast cells, but their significance is mostly dependent on their activity. In addition, the proteinases may affect ulcer epithelialization. To study levels and activity of tryptase and chymase in wash samples and biopsies from chronic leg ulcers and the possible effect of these proteinases on keratinocyte growth and adherence. Wash samples were taken from 16 patients and a superficial shave biopsy was taken in eight of these patients; a second biopsy series was obtained from the edge of chronic venous leg ulcers (n = 6). Significant levels of soluble tryptase activity and histamine, but low levels of chymase activity, were measured in wash samples from chronic ulcers. No tryptase-inhibiting activity, but clear chymase-inhibiting activity, was detected in the wash samples. In superficial wound bed biopsies, relatively marked levels of chymase activity together with histamine and tryptase activity were detected. In the second biopsy series, about 80% of the mast cells belonged to the MC(TC) type (tryptase- and chymase-immunopositive). However, about 55-61% of the chymase-immunopositive cells displayed chymase activity and 64 +/- 17% of the tryptase-positive cells revealed immunoreactivity of alpha(1)-antichymotrypsin. As the activity of chymase and tryptase was detected in the ulcer base in a ratio of 1:8, a preparation containing both chymase and tryptase was partially purified from human skin yielding a similar activity ratio of 1:11-13. Treatment of fibronectin-coated plastic surfaces with this preparation decreased the adherence of cultured human keratinocytes, this effect being attributable mainly to chymase. In 2-day cultures using growth factor/serum-deficient low- or high-calcium medium, the tryptase-chymase preparation inhibited the slow growth and at higher concentrations it even induced detachment of keratinocytes. This effect was attributed to chymase, and it was partially regulated by heparin and histamine. Even though chymase is partially inactivated in chronic leg ulcers, accumulated mast cells in the close proximity of the epithelium edge and their chymase may impair keratinocyte adherence and migration.

The aim of this study was to validate a Dutch translation of the Cardiff wound impact schedule (CWIS), a disease‐specific instrument to measure the health‐related quality of life (HRQoL) in patients with chronic leg ulcers. To achieve this, the original instrument was translated. A total of 83 patients with chronic lower leg ulcers were included and completed the translated instrument and SF36 at baseline after assessment of their wound severity. Follow‐up was performed 1 week after inclusion. The psychometric properties of the instrument were assessed. Construct validity was positively evaluated by an expert panel. Face validity was positively evaluated in a cognitive debriefing of a pilot group. Discriminant validity was assessed by correlating 1‐year amputation risk according to the Wound, Ischaemia, foot Infection classification system with the instrument scores. Significant correlation could not be proven. Criterion validity was assessed by correlating domain scores of the instrument with domain scores of the gold standard: SF36. Moderate to high correlation was calculated for most domains of the instrument. Test‐retest reliability and internal consistency were evaluated as acceptable. In conclusion, the Dutch translation of the CWIS is a valid and reliable disease‐specific instrument to assess the HRQoL in patients with chronic lower leg ulcers.

The management of chronic leg ulcers, including venous leg ulcers (VLUs), causes a considerable economic and clinical burden to healthcare systems. Factors such as nursing time, hospital care, and wound dressings account for approximately 85% of the total cost. Superabsorbent dressings (eg, superabsorbent polymers [SAPs]) are recommended as a first-line treatment for moderately to highly exuding VLUs. To assess the cost-effectiveness of utilizing SAPs compared with the standard of care (SoC) for managing patients with moderately to highly exuding VLUs within the Slovakia healthcare settings. The decision-analytic modeling method used a Markov process as microsimulation, with a time horizon of 6 months, from the perspective of the third-party payer in Slovakia. All model inputs were based on data identified through systematic literature reviews. According to model predictions, the use of SAPs instead of SoC in patients with moderately to highly exuding leg ulcers in Slovakian settings would lead to an improved healing rate of 2.2%, incremental health-related quality of life of 0.143 quality-adjusted life-weeks, and total direct cost savings of €75 (USD $82) per patient over a 6-month period. The evaluation's results align with clinical recommendations that endorse superabsorbent wound dressings as the preferred first-line treatment for moderately to highly exuding VLUs. The findings support the use of these dressings as a cost-saving solution for the National Insurance in Slovakia, when compared with SoC.

Wound products that reliably support healing of chronic leg ulcers remain a huge unmet need in clinical practice. Due to the lack of standardized comparable protocols and different systems for platelet-rich plasma (PRP) preparation, there is limited data on healing rates in chronic venous ulcers. In our case series with a total of seven chronic leg ulcers in four patients, we investigated the healing rates based on standardized digital photographs of chronic venous ulcers after application of topical PRP using a digital imaging software. In 5 out of 7 ulcers, the PRP-treated wound half showed faster healing as compared the control half of the wound. In this case series, PRP-treated sides of chronic venous leg ulcers showed a tendency for accelerated healing as compared to nontreated collateral wound side. Our data support the evaluation of topical PRP treatment in the management of chronic venous leg ulcers.

Slough in chronic venous leg ulcers may be associated with delayed healing. The purpose of this study was to assess larval debridement in chronic venous leg ulcers and to assess subsequent effect on healing. All patients with chronic leg ulcers presenting to the leg ulcer service were evaluated for the study. Exclusion criteria were: ankle brachial pressure indices <0.85 or >1.25, no venous reflux on duplex and <20% of ulcer surface covered with slough. Participants were randomly allocated to either 4-layer compression bandaging alone or 4-layer compression bandaging + larvae. Surface areas of ulcer and slough were assessed on day 4; 4-layer compression bandaging was then continued and ulcer size was measured every 2 weeks for up to 12 weeks. A total of 601 patients with chronic leg ulcers were screened between November 2008 and July 2012. Of these, 20 were randomised to 4-layer compression bandaging and 20 to 4-layer compression bandaging + larvae. Median (range) ulcer size was 10.8 (3-21.3) cm(2) and 8.1 (4.3-13.5) cm(2) in the 4-layer compression bandaging and 4-layer compression bandaging + larvae groups, respectively (Mann-Whitney U test, P = 0.184). On day 4, median reduction in slough area was 3.7 cm(2) in the 4-layer compression bandaging group (P < 0.05) and 4.2 cm(2) (P < 0.001) in the 4-layer compression bandaging + larvae group. Median percentage area reduction of slough was 50% in the 4-layer compression bandaging group and 84% in the 4-layer compression bandaging + larvae group (Mann-Whitney U test, P < 0.05). The 12-week healing rate was 73% and 68% in the 4-layer compression bandaging and 4-layer compression bandaging + larvae groups, respectively (Kaplan-Meier analysis, P = 0.664). Larval debridement therapy improves wound debridement in chronic venous leg ulcers treated with multilayer compression bandages. However, no subsequent improvement in ulcer healing was demonstrated.

The aim of the study was to determine the demand on health service utilisation and to estimate the therapeutical costs caused by patients with chronic leg ulcer (CLU) in German primary care. A population-based case-control study was conducted using electronic medical records of 116 059 patients extracted from the CONTENT primary care database of Heidelberg, Germany, between April 2007 and March 2010. The drug and non drug prescription rates among patients with CLU were analysed by means of a unified German identification key and compared with those of patients with chronic venous insufficiency (CVI) without CLU. In the 3-year-contact group, CLU patients had significantly more patient-doctor encounters (55·9 versus 40·3; p < 0·0001), more referrals to home-care services (6·12 versus 3·08; p < 0·0001), and more admissions to hospitals (0·9 versus 0·4; p < 0·0001) than CVI patients, but no difference in referrals to specialists. The annual treatment costs for drugs and non drugs in CLU patients were substantially higher than in CVI patients (1645·75 € versus 1188·17 €; p < 0·0001). Wound dressings were identified as the most cost-enlarging factor. Summarising, CLU patients in primary care settings place a higher demand on health service utilisation and need nearly one-third higher therapeutical costs compared to venous patients without ulceration.

Chronic venous leg ulcer (CVLU) is a common and refractory complication of chronic venous diseases, and is clinically characterized by chronic leg ulcers and pain. Matrix metalloproteinases (MMPs) are a kind of highly conservative and zinc-dependent endopeptidases, and can be divided into 6 types according to their substrates and structures. Among the 6 types, collagenases, gelatinases and stromelysins play a key role in the occurrence and development of CVLU. Moreover, the up-regulation of MMP-1,-2,-3,-8 and ratio of MMP-2 to tissue inhibitor of metalloproteinase-2 (TIMP-2) is associated with delayed ulcer healing, whereas the up-regulation of MMP-7,-10,-13 and TIMP-1,-2 facilitates ulcer healing. However, roles of MMP-9 and -12 in venous ulcers are still unclear and need further study. According to functional characteristics of some MMPs, intervention of their composition and functions may provide new therapeutic targets for the treatment of CVLU. Key words: Varicose ulcer; Lower extremity; Matrix metalloproteinases; Extracellular matrix; Wound healing

Chronic venous leg ulcers have a major medical and economic impact on the elderly worldwide. Healing of the large ulcers (>10 cm2) occurs only in two-thirds of the patients and reulceration of healed ulcers recurs in one-third within 1 year. Because both healing and relapse rate influence greatly a patient's quality of life and the overall cost of treatment, every effort should be made to improve these two parameters. To determine the safety and efficacy of topical low-dose recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) for the treatment of venous ulcers, and to document any improvement in healing rates. Thirty-eight patients (29 women, 9 men; median age, 74 years) with chronic venous insufficiency were treated with topical rhu GM-CSF (5 microg/mL 0.9% sodium chloride solution), followed by application of a compression dressing. All subjects were treated as outpatients. Complete healing was observed in 47 of the 52 ulcers (90.4%). The average healing time was 19 weeks. No systemic or local side-effects from the therapy were observed. Nine chronic ulcers, previously refractory to conventional treatment (pretreatment for more than 46 weeks), showed the same response rate (9/8, or 88.9%) and healing time (mean, 19 weeks). After 40 months, no reulceration of the healed ulcers was observed, but two patients developed new ulcers on the same leg. Healing remained stable, with excellent cosmetic results. In this first study, topically applied low-dose rhu GM-CSF was a safe treatment for chronic venous leg ulcers. Healing rates were significantly increased and relapse rates were minimal.

In cold plasma medicine, anti-inflammatory, anti-itch, antimicrobic, ultravio - let, and other therapeutic modalities are combined within one treatment. Two types of cold plasma can be discerned: direct (dielectric barrier discharge (DBD)) and indirect plasma. DBD generates a low-temperature plasma under atmospheric pressure. The PlasmaDerm VU-2010 device is a noninvasive active medical intervention that does not come into direct contact with skin. For our medical application, a nonequilibrium, weakly ionized, physical DBD plasma is generated by the application of high voltages across small gaps; the electrode is covered by a dielectric. The skin itself acts as the second electrode. Chronic leg ulcers are a major problem among the elderly. The prevalence corresponds to 2-4% of the population. Eighty percent of chronic leg ulcers are caused by varicosis. In general, 3 phases of wound healing (cleaning of the wound ground, granulation, and epithelialization) can be discerned as disturbed in chronic venous leg ulcers. Wound debridement, modern wound dressings, and compression hosiery comprise methods of standard care. Despite these measures, leg ulcers often persist. Addi- tional plasma treatment may have the potential to facilitate wound healing by disinfection, stimulation of tissue regeneration and microcirculation, and acidification of the wound envi- ronment. We are currently conducting an ongoing clinical trial with the PlasmaDerm VU-2010 device to assess the safety, applicability, and efficacy of plasma treatment for chronic venous leg ulcers. So far, no adverse effects of plasma treatment have been reported, pointing toward a positive outcome of our study.

Pinch grafting for treatment of chronic leg ulcers has been evaluated mainly in hospitalized and immobilized patients. This study describes the results of 199 pinch graft operations of 126 chronic leg and foot ulcers in 85 patients in primary care between 1987 and 2001. The aetiology of the ulcers was venous insufficiency in 43% and multi-factorial in 25% (77% with venous insufficiency as the main determinant). The mean ulcer size was 13.5 cm2 and the mean ulcer duration was 15.9 months. The overall healing rate within 3 months was 33%, ranging from 19% for multi-factorial or combined venous and arterial ulcers to 48% for venous ulcers. Within 12 months the overall healing rate was 60%, with 67% healed venous ulcers. The results from our study suggest that pinch grafting is suitable for treating chronic leg ulcers, especially venous ulcers, in primary care.

Aim This study evaluates the incremental cost‑effectiveness and budget impact of polyacrylate Superabsorbent (SAP) dressings compared with foam dressings for the management of moderate‑to‑highly exuding leg ulcers in the Spanish healthcare setting. Methods We developed a weekly-cycle microsimulation state-transition model over 24 weeks from the Spanish National Health System perspective. Clinical effectiveness inputs for SAP dressings were derived from IPD from two observational clinical studies (n = 84, 2-week follow-up). Foam-dressing effectiveness was informed by a systematic review and meta-analysis of three eligible studies reporting 14-day wound-area reduction. The modelled cohort represented patients with moderate-to-highly exuding leg ulcers managed with compression therapy as standard of care; baseline severity was parameterised from the IPD (mean ulcer duration 15.1 months; baseline wound size 5,765 mm2). Results This early-stage model predicts an absolute incremental improvement in healing rate of 2.41 percentage points, an absolute incremental gain of 0.135 quality‑adjusted life weeks (QALWs) over a 24‑week period, and an absolute per‑patient direct cost reduction of €729 when SAP dressings are compared with foam dressings. When these incremental results are extrapolated to a hypothetical scenario of 100% adoption, the Spanish National Health System could achieve annual cost savings of €55.557 million. These estimates should be interpreted cautiously given the early‑stage, non‑comparative nature of the underlying evidence. Limitations Treatment‑effect estimates were derived from non‑randomized studies, which may introduce unmeasured confounding. As a result, the magnitude of the incremental effects is uncertain. To evaluate robustness, we conducted deterministic and probabilistic sensitivity analyses, both of which showed that the direction of the base‑case findings remained consistent across all plausible parameter ranges. Conclusions Preliminary model predictions suggest that polyacrylate wound dressings may provide additional health benefits and potentially reduce costs compared with foam dressings within the Spanish Health Care System.

Factors associated with health-related quality of life of south indian population with chronic venous leg ulcers - A hospital based pilot study