Effectiveness of interventions to enhance healing of chronic foot ulcers in diabetes: A systematic review.

BACKGROUND: It is critical that interventions used to enhance the healing of chronic foot ulcers in diabetes are backed by high-quality evidence and cost-effectiveness. In previous years, the systematic review accompanying guidelines published by the International Working Group of the Diabetic Foot performed 4-yearly updates of previous searches, including trials of prospective, cross-sectional and case-control design. AIMS: Due to a need to re-evaluate older studies against newer standards of reporting and assessment of risk of bias, we performed a whole new search from conception, but limiting studies to randomised control trials only. MATERIALS AND METHODS: For this systematic review, we searched PubMed, Scopus and Web of Science databases for published studies on randomised control trials of interventions to enhance healing of diabetes-related foot ulcers. We only included trials comparing interventions to standard of care. Two independent reviewers selected articles for inclusion and assessed relevant outcomes as well as methodological quality. RESULTS: The literature search identified 22,250 articles, of which 262 were selected for full text review across 10 categories of interventions. Overall, the certainty of evidence for a majority of wound healing interventions was low or very low, with moderate evidence existing for two interventions (sucrose-octasulfate and leucocyte, platelet and fibrin patch) and low quality evidence for a further four (hyperbaric oxygen, topical oxygen, placental derived products and negative pressure wound therapy). The majority of interventions had insufficient evidence. CONCLUSION: Overall, the evidence to support any other intervention to enhance wound healing is lacking and further high-quality randomised control trials are encouraged.

Guidelines on interventions to enhance healing of foot ulcers in people with diabetes (IWGDF 2023 update).

AIMS: Principles of wound management, including debridement, wound bed preparation, and newer technologies involving alternation of wound physiology to facilitate healing, are of utmost importance when attempting to heal a chronic diabetes-related foot ulcer. However, the rising incidence and costs of diabetes-related foot ulcer management necessitate that interventions to enhance wound healing of chronic diabetes-related foot ulcers are supported by high-quality evidence of efficacy and cost effectiveness when used in conjunction with established aspects of gold-standard multidisciplinary care. This is the 2023 International Working Group on the Diabetic Foot (IWGDF) evidence-based guideline on wound healing interventions to promote healing of foot ulcers in persons with diabetes. It serves as an update of the 2019 IWGDF guideline. MATERIALS AND METHODS: We followed the GRADE approach by devising clinical questions and important outcomes in the Patient-Intervention-Control-Outcome (PICO) format, undertaking a systematic review, developing summary of judgements tables, and writing recommendations and rationale for each question. Each recommendation is based on the evidence found in the systematic review and, using the GRADE summary of judgement items, including desirable and undesirable effects, certainty of evidence, patient values, resources required, cost effectiveness, equity, feasibility, and acceptability, we formulated recommendations that were agreed by the authors and reviewed by independent experts and stakeholders. RESULTS: From the results of the systematic review and evidence-to-decision making process, we were able to make 29 separate recommendations. We made a number of conditional supportive recommendations for the use of interventions to improve healing of foot ulcers in people with diabetes. These include the use of sucrose octasulfate dressings, the use of negative pressure wound therapies for post-operative wounds, the use of placental-derived products, the use of the autologous leucocyte/platelet/fibrin patch, the use of topical oxygen therapy, and the use of hyperbaric oxygen. Although in all cases it was stressed that these should be used where best standard of care was not able to heal the wound alone and where resources were available for the interventions. CONCLUSIONS: These wound healing recommendations should support improved outcomes for people with diabetes and ulcers of the foot, and we hope that widescale implementation will follow. However, although the certainty of much of the evidence on which to base the recommendations is improving, it remains poor overall. We encourage not more, but better quality trials including those with a health economic analysis, into this area.

[Risk factors for outcome and mortality in hospitalized geriatric patients with SARS-CoV-2 infection : Data from a hospital of maximum care during in the period of the second corona wave 2020/2021 in Germany]. / Risikofaktoren für Outcome und Mortalität bei hospitalisierten geriatrischen Patienten mit SARS-CoV-2-Infektion : Daten aus einem Maximalversorger im Zeitraum der zweiten Coronawelle 2020/2021 in Deutschland.

BACKGROUND: From autumn 2020 until spring 2021 Germany experienced the second wave of SARS-CoV­2 infections. As in the previous wave, the older population in nursing homes was hard hit by this infection because of the lack of available vaccines. Due to the multimorbidity in this susceptible group the mortality was high. METHODS: Retrospectively collected patient data of geriatric patients treated from 1 October 2020 to 31 March 2021 due to proven SARS-CoV­2 infection were evaluated concerning the duration of symptoms, hospital stay, and laboratory results. The results are presented descriptively and significance tests were performed with t­test and log-rank test to reveal some risk factors for a worse outcome. RESULTS: A total of 168 patients aged from 65 to 97 years were included, with a mean mortality rate of 28% and was highest in the age group over 90 years old. Most patients died within the first 10 days of hospitalization. Intensive care treatment prolonged the hospital stay by 6 days, but the average survival time became equal at the end. Risk factors for worse outcome and the need of intensive care treatment were neutrophilia, lymphopenia, high levels of ferritin and high D­dimer levels on the day of admission. Age, short duration of symptoms and pre-existing dementia, administration of neuroleptic drugs and antidepressants increased the risk of death.

Bacterial Diversity, Antibiotic Resistance, and the Risk of Lower Limb Amputation in Younger and Older Individuals With Diabetic Foot Infection.

INTRODUCTION: A diabetic foot infection (DFI) contributes to high mortality and morbidity in diabetics due to its often rapid progressive and intricately treatable infection. DFIs are usually a polymicrobial infection and characterizing the entire bacterial load is still challenging. Prompt and effective treatment of DFI is nevertheless mandatory to safe limbs and lives. It is therefore crucial to know the local pathogen spectrum and its antibiotic susceptibility. METHODS AND MATERIAL: For a 12-month period, we investigated 353 individuals with infected diabetic foot ulcer, their bacterial diversity, and antimicrobial susceptibility at fist-time visit in a Diabetic Foot Care Center in southern Germany. RESULTS: Cultures yielded 888 species, most of them gram-positive cocci (primary Staphylococcus aureus). The gram-negative sector was mainly formed by Pseudomonas aeruginosa and Enterobacteriacae. Because the prevalence of multiresistant species was surprisingly low (0.9% of isolated strains), we suggest penicillins with ß-lactamase inhibitor in case of gram-positive-dominated infection or piperacillin/tazobactam or rather carbapenems with equal efficacy when gram-negative species are involved.

Screening and diagnosis of diabetic polyneuropathy in clinical practice: A survey among German physicians (PROTECT Study Survey).

AIMS: We sought to obtain detailed information on the procedures and appraisal of screening for and diagnosing diabetic sensorimotor polyneuropathy (DSPN) in clinical practice. METHODS: This cross-sectional survey included 574 physicians from 13 federal states across Germany who responded to a tripartite questionnaire. RESULTS: The vast majority of the respondents reported to screen for DSPN at least once a year (87 %), while 65 % reported to examine the feet of DSPN patients at least twice a year. However, only 28 % and 20 % of the respondents used questionnaires and scores to assess the severity of neuropathic symptoms and signs, respectively. The rates of participants reporting that they do not use a standardized testing procedure were 58 % for pressure sensation, 62 % for pain sensation, and 54 % for thermal sensation. The rates of respondents reporting that they do not deploy a standardized assessment were 41 % for vibration sensation, 73 % for pressure sensation, 77 % for pain sensation, and 66 % for thermal sensation. Half of the physicians oriented themselves towards clinical guidelines when diagnosing DSPN. CONCLUSIONS: Despite relatively high screening rates, the willingness to implement both standardized testing procedures and assessment and to follow guidelines is low among physicians when screening for and clinically diagnosing DSPN.

Clinical evaluation of UrgoStart Plus dressings in real-life conditions: results of a prospective multicentre study on 961 patients.

AIMS: This study aimed to evaluate the performances of lipid colloid technology with nano-oligosaccharide factor (TLC-NOSF) dressings with polyabsorbent fibres in an unselected population of patients under real-life conditions. METHODS: A large, prospective, multicentre, observational study with three polyabsorbent TLC-NOSF dressings (UrgoStart Plus Pad, UrgoStart Plus and UrgoStart Plus Border, Laboratoires Urgo, France) was conducted in Germany between January 2019 and June 2020. Main outcomes included wound healing rate, clinical assessment of wound healing progression, local tolerance and acceptance of dressings, and changes in health-related quality of life (HRQoL) of the patients, assessed with the validated Wound-QoL questionnaire. RESULTS: A total of 961 patients with wounds of various aetiologies (leg ulcers (LU), diabetic foot ulcers (DFU), pressure ulcers (PU) and other types of wounds) were treated with the evaluated dressings in 105 centres for a mean duration of 62 days (standard deviation 37 days). By the last visit, a wound closure or an improvement in wound healing was reported in 92.0% of the treated wounds. The highest wound closure rates were achieved when the dressings were used as first-line treatment: 71.3% in DFUs, 52.9% in LUs, 53.6% in PUs and 61.8% in the other wounds. Improvement of the wound healing process was also associated with an 87.5% relative reduction of sloughy tissue, a decrease of the level of exudate in 68.9% of the wounds, and an improvement in the periwound skin condition in 66.4% of the patients at the final visit. The dressings were 'very well' or 'well' tolerated and 'very well' or 'well' accepted by the large majority of patients. The HRQoL questionnaires were completed both at initial and final visits by 337 patients, representative of the total cohort. Despite the relatively short duration of the wounds, the HRQoL of the patients was already impaired at baseline, with 81.6% of the patients being severely affected in at least one aspect of their HRQoL. By the final visit, significant improvements in each dimension of the patients' HRQoL were reported (p<0.001), along with a reduction of the proportion of patients in need of intervention and in the number of actions needed per patient in relation to their HRQoL. CONCLUSIONS: These results are consistent with previous clinical evidence on TLC-NOSF dressings. They confirm the good healing properties and safety profile of these dressings, and that a significant improvement in patient HRQoL is achieved in non-selected patients treated in real-life practice. These data support the use of such dressings as a first-line intervention and until wound healing in the management of chronic wounds, in association with appropriate standard of care.

Predictive Effect of Inflammatory Response and Foot Ulcer Localization on Outcome in Younger and Older Individuals with Infected Diabetic Foot Syndrome.

The diabetic foot syndrome (DFS) is the most important cause for non-traumatic major amputation in adult individuals and actually one of the most frightening events in diabetics' life. Despite the often protracted treatment of infected DFS at the end patients are often confronted with amputation. We investigated 352 individuals with infected DFS in two age separated-groups. Older individuals presented with significant worse renal function and lower HbA1c on day of admittance. Most detected ulcers involved the plantar sides of the metatarsal heads (MTH) and the toes. We saw an age-dependent translocation of foot ulcers from plantar and hindfoot to the forefoot and toes. In average every third wound provoked amputation, in the majority (94%) minor amputations, only 1.9% major amputations occurred. Lesions of the 5th toe or its MTH and interdigital or interphalangeal joint ulcers led to amputation in more than 60%. Worse renal function and WBC above 11 tsd/µl were linked with higher amputation risk. But in particular current scoring systems like SINBAD or Wagner-Armstrong scale and thus finally clinician's assessment of the wound situation gave a substantial hint for subsequent amputation - regardless of age.

Bacterial diversity and inflammatory response at first-time visit in younger and older individuals with diabetic foot infection (DFI).

AIM: Infection of a diabetic foot ulcer (DFU) is common. More than the half of DFUs become infected and 15-20% of them necessitate amputation in course of treatment. Diabetic foot infection (DFI) is therefore the major cause for non-traumatic lower limb amputation in Germany. Prompt and effective treatment of DFI is mandatory to safe limbs and lives. We investigated if there are relevant differences in evoked inflammatory response between different species and age-separated groups. We further investigated if there is an impact of ulcer localization on bacterial diversity. METHODS: For a 12-month period, we investigated 353 individuals with infected DFU, their laboratory results and bacterial diversity at first-time visit in a Diabetic Foot Care Center in Southern Germany. RESULTS: The ulcer microbiota was dominated by gram-positive species, primary Staphylococcus aureus. The gram-negative sector was mainly formed by Pseudomonas aeruginosa and Enterobacteriaceae (Proteus spp., Enterobacter spp., Escherichia coli and Klebsiella spp.). With increase in age, P. aeruginosa and S. aureus became more frequent, while Streptococci decreased. Ischemic and/or deep wounds were more likely to bear gram-negative species. Inflammatory response did not differ between gram-positive and gram-negative species, while Streptococci and Proteus spp. induced the highest serum inflammation reaction in their category. Streptococci, Enterobacter spp. and E. coli were more frequent in summer, while Enterococci spp., coagulase-negative Staphylococci and P. aeruginosa were more prevalent in winter half-year. DFIs of the forefoot and plantar side are mostly caused by gram-positive species, while Enterobacteriaceae were most frequent in plantar ulcerations. CONCLUSION: Gram-positive species dominate bacterial spectrum in DFI. With increase in age, S. aureus, Streptococci and Pseudomonas aeruginosa became more frequent. The inflammatory response did not differ significantly between different species, but gram-negative species were slightly but not significant more frequent in ischemic wounds. Climatic distinction like summer or winter half-year as well as foot ulcer localization seems to influence bacterial diversity in DFUs.

Preulcerous Risk Situation in Diabetic Foot Syndrome: Proposal for a Simple Ulcer Prevention Score.

BACKGROUND: Preulcerous risk situations in patients with diabetes are often undiagnosed and care administered too late. Even with regular medical check-ups and status documentation, foot examinations have not been given enough attention. Diagnosing an individual patients' risk of developing diabetic foot ulcers may increase vigilance for diabetic foot syndrome (DFS), and the appropriate prevention measures matching the risk involved may prevent the emergence of diabetic ulcers. The classical DFS risk factors are well established and have been extensively covered in the literature; however, there is a lack of efficient screening tools that could be used for a rapid assessment of diabetic foot ulcer risk. METHODS: A methodical literature search was conducted to assess relevant publications for the preparation of a simple risk score for amputation related to diabetic foot ulcer. We then analyzed the risk factors for predictive value as odds ratios in foot ulcers and/or amputation. We used the available data to deduce a mean value to reflect the authors' consensus. RESULTS: In view of the current literature on the matter, we have developed a semi-quantitative scoring system using just a few items to allow rapid and visual risk assessment for diabetic foot ulcers alongside recommendations for prevention and a sensible follow-up strategy to match the risk. CONCLUSION: This relatively simple score enables rapid risk classification for patients that can ease the way for both physicians and patients in gaining an insight into individual risk situations. The score provides more effective preventative measures for high-risk patients against future complications.

Therapeutic index for local infections score (TILI): a new diagnostic tool.

OBJECTIVE: Local wound infections are a major challenge for patients and health professionals. Various diagnostic and therapeutic options are available. However, a generally accepted standard is still lacking in Europe. The aim was to develop an easy-to-use clinical score for the early detection of local wound infections, as a basis for decision-making on antiseptic therapy or decolonisation. METHOD: An interdisciplinary and interprofessional panel of experts from seven European countries was brought together to discuss the various aspects of diagnosing local wound infections. RESULTS: The result was the adoption of the Therapeutic Index for Local Infections (TILI) score, developed in Germany by Initiative Chronische Wunden e.V., specifically for health professionals not specialised in wound care. Available in six European languages, the TILI score could also be adapted for different European countries, depending on their specific national healthcare requirements. The six clinical criteria for local wound infection are erythema to surrounding skin; heat; oedema, induration or swelling; spontaneous pain or pressure pain; stalled wound healing; and increase and/or change in colour or smell of exudate. Meeting all criteria indicates that antiseptic wound therapy could be started. Regardless of these unspecific clinical signs, there are also health conditions for the clinical situation which are a direct indication for antimicrobial wound therapy. These include the presence of wound pathogens, such as meticillin-resistant Staphylococcus aureus, septic surgical wound or the presence of free pus. CONCLUSION: The development of the new internationally adapted TILI score, which could also be used by any caregiver in daily practice to diagnose local infections in acute and hard-to-heal wounds, is the result of expert consensus. However, the score system has to be validated through a clinical evaluation. This is to be performed in expert centres throughout Europe.

[Macroangiopathy in diabetes mellitus]. / Makroangiopathie bei Diabetes mellitus.

Peripheral artery occlusive disease is a prevalent but underdiagnosed manifestation in patients with diabetes and also in patients with diabetic foot ulceration. There is insufficient awareness of its clinical manifestations, including intermittent claudication and critical limb ischemia and of its risk of adverse limb outcomes. This review aims to highlight essential elements of the prevalence of peripheral artery disease in patients with diabetes and the the pathway of clinical diagnosis. We report the actual standards and evidence based, interdisciplinary management including conservative, interventional and surgical treatment options and also the needs of follow-up care.

Impact of wound duration on diabetic foot ulcer healing: evaluation of a new sucrose octasulfate wound dressing.

OBJECTIVE: A common and frequent complication of diabetes is diabetic foot ulcers (DFU), which can have high treatment costs and severe adverse events. This study aims to evaluate the effects of wound duration on wound healing and the impact on costs, including treatment with a new sucrose octasulfate dressing compared with a control dressing. METHOD: Based on the Explorer study (a two-armed randomised double-blind clinical trial), a cost-effectiveness analysis compared four different patient groups distinguished by their wound duration and additionally two DFU treatment options: a sucrose octasulfate dressing and a neutral dressing (as control). Clinical outcomes and total direct costs of wound dressings were evaluated over 20 weeks from the perspective of the Social Health Insurance in Germany. Simulation of long-term outcomes and costs were demonstrated by a five cycle Markov model. RESULTS: The results show total wound healing rates between 71% and 14.8%, and direct treatment costs for DFU in the range of €2482-3278 (sucrose octasulfate dressing) and €2768-3194 (control dressing). Patients with a wound duration of ≤2 months revealed the highest wound healing rates for both the sucrose octasulfate dressing and control dressing (71% and 41%, respectively) and had the lowest direct treatment costs of €2482 and €2768, respectively. The 100-week Markov model amplified the results. Patients with ≤2 months' wound duration achieved wound healing rates of 98% and 88%, respectively and costs of €3450 and €6054, respectively (CE=€3520, €6864). Sensitivity analysis revealed that the dressing changes per week were the most significant uncertainty factor. CONCLUSION: Based on the findings of this study, early treatment of DFU with a sucrose octasulfate dressing is recommended from a health economic view due to lower treatment costs, greater cost-effectiveness and higher wound healing rates.

[Sucrose octasulfate-evidence in the treatment of chronic wounds]. / Sucrose Octasulfat ­ Evidenz in der Behandlung chronischer Wunden.

Patients with chronic wounds should receive wound treatment in addition to causative therapy. In this context, the lack of adequate evidence for wound healing products has been repeatedly discussed. Using the example of TLC-sucrose octasulfate (TLC: technology lipido-colloid), the present review shows that there is significant data with good evidence and comparability in this area. One therapeutic approach to promote wound healing is the inhibition of matrix-metalloproteinases, for example by sucrose octasulfate. For wound products containing TLC-sucrose octasulfate, several sequential clinical studies have been conducted in recent years. The WHAT study was an open randomized controlled trial (RCT) with 117 patients with venous leg ulcers (VLU). The CHALLENGE study was a double-blind RCT with 187 patients with VLU. The SPID study was a pilot study with 33 patients with diabetic foot ulcers (DFU). The two prospective, multicenter clinical pilot studies NEREIDES and CASSIOPEE examined a total of 88 patients with VLU in different phases of healing. In the REALITY study, a pooled data analysis was performed on eight observational studies with 10,220 patients with chronic wounds of different genesis. In the double-blind, two-armed EXPLORER RCT, 240 patients with neuro-ischemic DFU were followed from first presentation until complete healing. In all studies, a significant promotion of wound healing could be shown by the use of wound healing products with TLC-sucrose octasulfate.

Polyneuropathy is inadequately treated despite increasing symptom intensity in individuals with and without diabetes (PROTECT follow-up study).

AIMS/INTRODUCTION: Despite its major clinical impact, distal symmetric polyneuropathy remains frequently undiagnosed and undertreated in clinical practice. We previously reported in the PROTECT Study that 70% of type 2 diabetes patients with distal symmetric polyneuropathy were unaware of having the latter condition. MATERIALS AND METHODS: In the present follow up after 2.5 ± 0.7 years, 122 and 85 participants with and without type 2 diabetes, respectively, completed questionnaires to obtain information about the further course of disease and its management. RESULTS: At follow up, 49 and 48% of the respondents with type 2 diabetes and without diabetes, respectively, reported that the intensity of paresthesia or numbness in the feet increased, whereas for burning and pain in the feet the corresponding percentages were 56 and 61%. However, 33 and 40% of the respondents with type 2 diabetes and without diabetes, respectively, reporting neuropathic symptoms at follow up did not receive any pharmacotherapy. Pharmacotherapy of neuropathic symptoms at follow up among participants with type 2 diabetes and without diabetes included mainly World Health Organization Step 1 analgesics (17% each; excluding acetylsalicylic acid), pregabalin/gabapentin (20 and 12%), vitamin B complex (13 and 22%), benfotiamine (13 and 2%), opioids (7 and 12%), antidepressants (4 and 5%) and α-lipoic acid (4 and 2%). CONCLUSIONS: These findings point to insufficient care, inadequate treatment adherence or limited efficacy of treatments in patients with polyneuropathy, suggesting that effective measures should be implemented to correct these healthcare deficits.

Antimicrobial Photodynamic Therapy in Infected Diabetic Foot Ulcers: A Multicenter Preliminary Experience.

BACKGROUND: The increasing resistance of bacteria to antibiotics and the frequency of comorbid conditions of patients make the treatment of diabetic foot infections problematic. In this context, photodynamic therapy could be a useful tool to treat infected wounds. The aim of this study was to evaluate the effect of repeated applications of a phthalocyanine derivative (RLP068) on the bacterial load and on the healing process. METHODS: The present analysis was performed on patients with clinically infected ulcers who had been treated with RLP068. A sample for microbiological culture was collected at the first visit before and immediately after the application of RLP068 on the ulcer surface, and the area was illuminated for 8 minutes with a red light. The whole procedure was repeated three times per week at two centers (Florence and Arezzo, Italy) (sample A), and two times per week at the third center (Stuttgart, Germany) (sample B) for 2 weeks. RESULTS: Sample A and sample B were composed of 55 and nine patients, respectively. In sample A, bacterial load decreased significantly after a single treatment, and the benefit persisted for 2 weeks. Similar effects of the first treatment were observed in sample B. In both samples, the ulcer area showed a significant reduction during follow-up, even in patients with ulcers infected with gram-negative germs or with exposed bone. CONCLUSIONS: RLP068 seems to be a promising topical wound management procedure for the treatment of infected diabetic foot ulcers.

Efficacy of MMP-inhibiting wound dressings in the treatment of chronic wounds: a systematic review.

OBJECTIVE: Matrix metalloproteinases (MMPs) substantially contribute to the development of chronicity in wounds. Thus, MMP-inhibiting dressings may support healing. A systematic review was performed to determine the existing evidence base for the treatment of hard-to-heal wounds with these dressings. METHODS: A systematic literature search in databases and clinical trial registers was conducted to identify randomised controlled trials (RCTs) investigating the efficacy of MMP-inhibiting dressings. Studies were analysed regarding their quality and clinical evidence. RESULTS: Of 721 hits, 16 relevant studies were assessed. There were 13 studies performed with collagen and three with technology lipido-colloid nano oligosaccharide factor (TLC-NOSF) dressings. Indications included diabetic foot ulcers, venous leg ulcers, pressure ulcers or wounds of mixed origin. Patient-relevant endpoints comprised wound size reduction, complete wound closure, healing time and rate. Considerable differences in the quality and subsequent clinical evidence exist between the studies identified. Substantial evidence for significant improvement in healing was identified only for some dressings. CONCLUSION: Evidence for the superiority of some MMP-inhibiting wound dressings exists regarding wound closure, wound size reduction, healing time and healing rate. More research is required to substantiate the existing evidence for different types of hard-to-heal wounds and to generate evidence for some of the different types of MMP-inhibiting wound dressings.

Cost-effectiveness of TLC-sucrose octasulfate versus control dressings in the treatment of diabetic foot ulcers.

OBJECTIVE: Diabetes is one of the most widespread diseases in Germany. Common complications are diabetic foot ulcers (DFU), which are associated with a cost-intensive treatment and serious adverse events, such as infections, amputations. This cost-effectiveness analysis compares two treatment options for patients with DFU: a TLC-NOSF dressing versus a neutral dressing, assessed through a European double-blind randomised controlled trial (RCT), Explorer. METHODS: The evaluation of the clinical outcomes was associated to direct costs (costs for dressings, nursing time, hospitalisation etc.) of both dressings, from the perspective of the statutory health insurance in Germany. Due to the long mean healing time of a DFU, the observation period was extended from 20 to 100 weeks in a Markov model. RESULTS: After 20 weeks, and with complete closure as a primary endpoint, the model revealed direct treatment costs for DFU of €2,864.21 when treated with a TLC-NOSF dressing compared with €2,958.69 with the neutral control dressing (cost-effectiveness: €6,017.25 versus €9,928.49). In the Markov model (100 weeks) the costs for the TLC-NOSF dressing were €5,882.87 compared with €8,449.39 with the neutral dressing (cost-effectiveness: €6,277.58 versus €10,375.56). The robustness of results was underlined by several sensitivity analyses for varying assumptions. The frequency of weekly dressing changes had the most significant influence in terms of parameter uncertainty. CONCLUSION: Overall, the treatment of DFU with a TLC-NOSF dressing is supported from a health economic perspective, because both the treatment costs and the cost-effectiveness were superior compared with the neutral wound dressing.