The impact of a new intervention for venous leg ulcers: A within-patient controlled trial.

A major obstacle to the development of new treatments for venous leg ulcers is the difficulty in generating evidence for their effectiveness. Randomised controlled trials using complete healing as the endpoint are seldom powered to be successful, owing to the heterogeneity of cohorts. A novel approach to the evaluation of treatments is presented, using a self-controlled trial model and two metrics of short-term healing rate as alternate endpoints: rate of wound margin advance, and percentage area reduction over 4 weeks. Two different treatment regimens are compared: multi-layer compression alone, versus multi-layer compression combined with activation of the venous leg pump by neuromuscular stimulation. With 60 patients, adding neuromuscular stimulation to multilayer compression resulted in a significant two-fold increase in the rate of wound healing over a 4-week period, both in terms of wound margin advance and in terms of percentage area reduction. The use of these short-term intermediate endpoint metrics together with a self-controlled study design offers potential for distinguishing between the relative efficacies of interventions more rapidly, with greater sensitivity, and with fewer subjects than a conventional RCT cohort model.

A prospective study on the wound healing and quality of life outcomes of patients with venous leg ulcers in Singapore-Interim analysis at 6 month follow up.

Venous leg ulceration results in significant morbidity. However, the majority of studies conducted are on Western populations. This study aims to evaluate the wound healing and quality of life for patients with venous leg ulcers (VLUs) in a Southeast Asian population. This is a multi-centre prospective cohort study from Nov 2019 to Nov 2021. All patients were started on 2- or 4-layer compression bandage and were reviewed weekly or fortnightly. Our outcomes were wound healing, factors predictive of wound healing and the EuroQol 5-dimensional 5-level (EQ-5D-5L) health states. Within our cohort, there were 255 patients with VLU. Mean age was 65.2 ± 11.6 years. Incidence of diabetes mellitus was 42.0%. Median duration of ulcer at baseline was 0.30 years (interquartile range 0.136-0.834). Overall, the median time to wound healing was 4.5 months (95% confidence interval [CI]: 3.77-5.43). The incidence of complete wound healing at 3- and 6-month was 47.0% and 60.9%, respectively. The duration of the wound at baseline was independently associated with worse wound healing (Hazard ratio 0.94, 95% CI: 0.89-0.99, P = .014). Patients with healed VLU had a significantly higher incidence of perfect EQ-5D-5L health states at 6 months (57.8% vs 13.8%, P < .001). We intend to present longer term results in subsequent publications.

A cross-sector systematic review and synthesis of knowledge on telemedicine interventions in chronic wound management-Implications from a system perspective.

Based on initially identified needs for further telemedicine (TM) and chronic wound management research, the objective of this article is twofold: to conduct a systematic review of existing knowledge on TM interventions in chronic wound management-including barriers and opportunities-across the specialist and primary care sectors, and to incorporate the review findings into a system framework that can be further developed and validated through empirical data. We conclude that there is a pressing need for broader and more comprehensive empirical explorations into quality improvement and integration of TM in chronic wound management, including using system frameworks that can capture cross-sector system perspectives and associated implications. Of practical consideration, we suggest that the design and execution of TM improvement interventions and associated research projects should be conducted in close cooperation with managers and practitioners knowledgeable about barriers and opportunities that can influence the implementation of important interventions within chronic wound management.

Measuring progress to healing: A challenge and an opportunity.

Complete healing is problematic as an endpoint for evaluating interventions for wound healing. The great heterogeneity of wounds makes it difficult to match groups, and this is only possible with multivariate stratification and/or very large numbers of subjects. The substantial time taken for wounds to heal necessitates a very lengthy study. Consequently, high quality randomised controlled trials demonstrating an effect of an intervention to a satisfactory level of statistical significance and with a satisfactory level of generalisability are extremely rare. This study determines that the healing of venous leg ulcers receiving multi-component compression bandaging follows a linear trajectory over a 4-week period, as measured by gross area healed, percentage area healed, and advance of the wound margin. The linear trajectories of these surrogates make it possible to identify an acceleration in healing resulting from an intervention, and allows self-controlled or crossover designs with attendant advantages of statistical power and speed. Of the metrics investigated, wound margin advance was the most linear, and was also independent of initial ulcer size.

Major limb amputation and mortality in patients with neuro-ischaemic lower extremity wounds managed in a tertiary hospital: Focus on the differences among patients with diabetes, peripheral arterial disease and both.

A majority of lower extremities neuro-ischaemic wounds (NIU) are related to: (a) only diabetes (DM); (b) only peripheral artery disease (PAD); (c) co-existing diabetes and peripheral artery disease (DM-PAD). This study aims to characterise the major clinical outcomes of forementioned three groups of lower extremity wound patients in Singapore. Patients hospitalised for lower extremity NIU between January 2014 and October 2017 in a tertiary hospital in Singapore were analysed. Patients' major limb amputation and mortality were assessed using Cox regression models. Cumulative survival and amputation-free survival among the three classified groups were calculated using Kaplan-Meier analysis. Compared with patients with only DM, those in the PAD group and the DM-PAD group had higher risk of major limb amputation (adjusted hazard ratio: 2.47, 95% CI: 1.65-3.70; adjusted hazard ratio: 2.01, 95% CI: 1.53-2.65 respectively) and mortality (adjusted hazard ratio: 2.36, 95% CI: 1.57-3.55; adjusted hazard ratio: 2.46, 95% CI: 1.86-3.26 respectively). The 3-year survival and amputation-free survival were lowest in the DM-PAD group (52.1% and 41.5% respectively), followed by the PAD group (53.3% and 44.6% respectively) and the DM group (74.2% and 68.5% respectively). Lower extremity NIU patients with PAD or DM-PAD were found to have poorer clinical prognosis than those with DM only.

Microcirculatory Flux and Pulsatility in Arterial Leg Ulcers is Increased by Intermittent Neuromuscular Electrostimulation of the Common Peroneal Nerve.

BACKGROUND: Neuromuscular electrical stimulator (NMES) devices increase blood flow to the lower limb by a process of intermittent muscular contraction initiated by a transdermal stimulus to the common peroneal nerve. However, its effects on localized microvascular blood supply to lower limb wounds are unknown. This study is a single-center open label study measuring the effect of neuromuscular stimulation of the common peroneal nerve on the microvascular blood flow within the wound bed of arterial leg ulcers. METHODS: Eights patients with ischemic lower limb wounds had an NMES (geko™) applied to the common peroneal nerve. Baseline and intervention analysis of blood flow to the wound bed and edge was performed using Laser Speckle Contrast Imaging. Mean flow (flux) and pulse amplitude (pulsatility) were measured. RESULTS: Stimulation of the common peroneal nerve with the NMES resulted in a significantly increased flux and pulsatility in both the wound bed and the wound edge in all 8 patients. CONCLUSIONS: Neuromuscular electrical stimulation immediately increases microcirculatory blood flow to the wound bed and edge in patients with ischemic lower limb wounds. These data may provide mechanistic insight into the clinical efficacy of NMES in healing wounds. www.clinicaltrials.gov NCT03186560.

Modified compression therapy in mixed arterial-venous leg ulcers: An integrative review.

Leg ulcers remain an increased burden to healthcare cost and morbidity in modern society. While most leg ulcers are venous in origin, recognition and prompt identification of concomitant arterial occlusive disease is critical to determine underlying aetiology and subsequent management. This integrative review presents the current evidence to establish the role of modified compression therapy (MCT) in treatment of mixed arterial venous leg ulcers (MAVLU). A literature search was conducted using the electronic databases CINAHL, MEDLINE, PUBMED, and Embase. Ten studies met the eligibility criteria and were subsequently analysed. Our review concludes that MCT, with compression pressures between 20 and 30 mmHg, can promote healing in MAVLU with moderate arterial insufficiency (0.5 ≤ ABPI ≤0.8). If ABPI is <0.5, MCT can be considered once restoration of acceptable ABPI is achieved. Intolerance, lack of response or further deterioration of disease within 3 months should prompt further arterial imaging and intervention. MCT is generally well tolerated with no adverse outcomes reported. A holistic yet individualised approach is vital in order to account for all factors influencing this patient-led decision-making process, ultimately ensuring effective treatment, which improves patient's quality of life and reduces socioeconomic burden of the disease.

Does localized iron loss in venous disease lead to systemic iron deficiency? A descriptive pilot study.

Haemosiderin deposition in the legs of patients with venous leg ulcers is well established, and several theories suggest this stored iron has a role in disease pathophysiology. In this novel pilot study of patients with chronic venous leg ulcers, we aimed to establish the relationship between wound fluid iron levels, serum iron parameters and healing. Fifteen patients with venous ulcers were included in the study. Blood samples were taken for full blood count and iron studies, while simultaneously wound fluid was obtained from the wound surface using filter paper. Wound areas were measured at initial and 4 week (+/- 2 day) follow-up visits. We found a positive correlation between wound fluid and serum iron (correlation co-efficient 0.27) and those with the lowest wound fluid iron level were also anemic. No association was found between initial wound area and wound fluid iron level but the largest wound areas were found in patients with anemia. Only 38% of patients demonstrated a reduction in wound area during the 4 week study, and 80% of those were not anemic or iron deficient. Conversely in those patients whose wounds did not reduce in size 88% were anemic or iron deficient. These findings demonstrate a previously unrecognized phenomenon of systemic iron store depletion secondary to leaching out of the body in wound exudate. In addition, these results suggest a high prevalence of anemia in patients with chronic venous ulcers, though whether this is cause or effect requires further research. Our findings also suggest that patients with venous ulcers have a high prevalence of iron deficiency and anemia, which appears to be often undiagnosed, and that diagnostic criteria for iron deficiency in patients with chronic wounds need to be revised to reflect the effect of chronic inflammation on iron metabolism.

Hyperspectral imaging in wound care: A systematic review.

Multispectral and hyperspectral imaging (HSI) are emerging imaging techniques with the potential to transform the way patients with wounds are cared for, but it is not clear whether current systems are capable of delivering real-time tissue characterisation and treatment guidance. We conducted a systematic review of HSI systems that have been assessed in patients, published over the past 32 years. We analysed 140 studies, including 10 different HSI systems. Current in vivo HSI systems generate a tissue oxygenation map. Tissue oxygenation measurements may help to predict those patients at risk of wound formation or delayed healing. No safety concerns were reported in any studies. A small number of studies have demonstrated the capabilities of in vivo label-free HSI, but further work is needed to fully integrate it into the current clinical workflow for different wound aetiologies. As an emerging imaging modality for medical applications, HSI offers great potential for non-invasive disease diagnosis and guidance when treating patients with both acute and chronic wounds.

Pressure injuries among admissions to a hospital in the tropics.

We report incidence rates for pressure injuries seen in an acute hospital in Singapore that were classified as Stage 3 or Stage 4. The characteristics of patients and the factors that explain variation in the primary outcome of duration of hospital stay are summarized. Existing data were available from Singapore General Hospital for all admissions from January 2016 to December 2019. Univariable analysis was done and a multivariable Poisson regression model estimated. Incidence rates declined from 4.05 to 3.4 per 1000 admissions in the 48 months between 2016 and 2019. The vast majority were community acquired with 75% in admission from the patients' home. Factors that explain variation in length of stay were, ethnicity; site of injury; community versus healthcare associated; inter-hospital transfer; fracture as reason for admission; and the number of days between admission and assessment of wound by specialist nurse. Stage 3 and 4 injuries arise in a home environment most often and are subsequently managed in acute hospital at high cost. These are novel epidemiological data from a hospital in the tropics where the potential to improve outcomes, implement screening and prevention, and thus increase the performance of health services is strong.

A pilot multi-centre prospective randomised controlled trial of RECELL for the treatment of venous leg ulcers.

Venous leg ulcers (VLUs) have a significant impact on approximately 3% of the adult population worldwide, with a mean NHS wound care cost of £7600 per VLU over 12 months. The standard care for VLUs is compression therapy, with a significant number of ulcers failing to heal with this treatment, especially with wound size being a risk factor for non-healing. This multicentre, prospective, randomised trial evaluated the safety and effectiveness of autologous skin cell suspension (ASCS) combined with compression therapy compared with standard compression alone (Control) for the treatment of VLUs. Incidence of complete wound closure at 14 weeks, donor site closure, pain, Health-Related Quality of Life (HRQoL), satisfaction, and safety were assessed in 52 patients. At Week 14, VLUs treated with ASCS + compression had a statistically greater decrease in ulcer area compared with the Control (8.94 cm2 versus 1.23 cm2 , P = .0143). This finding was largely driven by ulcers >10 to 80 cm2 in size, as these ulcers had a higher mean percentage of reepithelialization at 14 weeks (ASCS + compression: 69.97% and Control: 11.07%, P = .0480). Additionally, subjects treated with ASCS + compression experienced a decrease in pain and an increase in HRQoL compared with the Control. This study indicates that application of ASCS + compression accelerates healing in large venous ulcers.

Cost of managing patients with venous leg ulcers.

The aim of this study was to estimate costs associated with the management of patients with venous leg ulcers (VLUs) from the perspective of the UK National Health Service (NHS). The analysis was undertaken through the Secure Anonymised Information Linkage Databank which brings together and anonymously links a wide range of person-based data from around 75% of general practitioner (GP) practices within Wales (population coverage ~2.5 million). The data covered an 11-year period from 2007 to 2017. All patients linked to the relevant codes were tracked through primary care settings, recording the number of GP practice visits (number of days with an event recorded), and wound treatment utilisation (eg, dressings, bandages, etc.) Resources were valued in monetary terms (£ sterling) and the costs were determined from national published sources of unit costs. This is the first attempt to estimate the costs of managing of VLUs using routine data sources. The direct costs to the Welsh NHS are considerable and represent 1.2% of the annual budget. Nurse visits are the main cost driver with annual estimates of £67.8 million. At a UK level, these costs amount to £1.98 billion. Dressings and compression bandages are also major cost drivers with annual Welsh estimates of £828 790. The direct cost of managing patients with VLUs is £7706 per patient per annum, which translates to an annual cost of over £2 billion, when extrapolated to the UK population. The primary cost driver is the number of district nurse visits. Initiatives to reduce healing times through improving accuracy of initial diagnosis, and improved evidence-based treatment pathways would result in major financial savings.

Clinical and economic burden of wound care in the tropics: a 5-year institutional population health review.

The aim of this study is to evaluate the clinical and economic burden of wound care in the Tropics via a 5-year institutional population health review. Within our data analysis, wounds are broadly classified into neuro-ischaemic ulcers (NIUs), venous leg ulcers (VLUs), pressure injuries (PIs), and surgical site infections (SSIs). Between 2013 and 2017, there were a total of 56 583 wound-related inpatient admissions for 41 461 patients, with a 95.1% increase in wound episodes per 1000 inpatient admissions over this period (142 and 277 wound episodes per 1000 inpatient admissions in 2013 and 2017, respectively). In 2017, the average length of stay for each wound episode was 17.7 days, which was 2.4 times that of an average acute admission at our institution. The average gross charge per wound episode was USD $12 967. Among the 12 218 patients with 16 674 wound episodes in 2017, 71.5% were more than 65 years of age with an average Charlson Comorbidity Index (CCI) of 7.2. Half (51.9%) were moderately or severely frail, while 41.3% had two or more wound-related admission episodes. In 2017, within our healthcare cluster, the gross healthcare costs for all inpatient wound episodes stand at USD $216 million within hospital care and USD $596 000 within primary care. Most NIU patients (97.2%) had diabetes and they had the most comorbidities (average CCI 8.4) and were the frailest group of patients (44.9% severely frail). The majority of the VLU disease burden was at the specialist outpatient setting, with the average 1-year VLU recurrence rate at 52.5% and median time between healing and recurrence at 9.5 months. PI patients were the oldest (86.5% more than 65 years-old), constituted the largest cohort of patients with 3874 patients at an incidence of 64.6 per 1000 admissions in 2017, and have a 1-year all-cause mortality rate of 14.3%. For SSI patients, there was a 125% increase of 14.2 SSI wound episodes per 1000 inpatient admissions in 2013 to 32.0 in 2017, and a 413% increase in wound-related 30-day re-admissions, from 40 in 2013 (4.1% of all surgeries) to 205 (8.3% of all surgeries) in 2017. The estimated gross healthcare cost per patient ranges from USD $15789-17 761 across the wound categories. Similar to global data, there is a significant and rising trend in the clinical and economic burden of wound care in Tropics.

Pressure ulcers in patients receiving palliative care: A systematic review.

BACKGROUND: Pressure ulcers are associated with significant morbidity and mortality as well as high cost to the health service. Although often linked with inadequate care, in some patients, they may be unavoidable. AIM: This systematic review aims to quantify the prevalence and incidence of pressure ulcers in patients receiving palliative care and identify the risk factors for pressure ulcer development in these patients as well as the temporal relationship between pressure ulcer development and death. DESIGN: The systematic review is registered in the PROSPERO database (CRD42017078211) and conducted in accordance with the 'PRISMA' pro forma. Articles were reviewed by two independent authors. DATA SOURCES: MEDLINE (1946-22 September 2017), EMBASE (1996-22 September 2017), CINAHL (1937-22 September 2017) and Cochrane Library databases were searched. In all, 1037 articles were identified and 12 selected for analysis based on pre-defined inclusion and exclusion criteria. RESULTS: Overall pressure ulcer prevalence and incidence were found to be 12.4% and 11.7%, respectively. The most frequently identified risk factors were decreased mobility, increased age, high Waterlow score and long duration of stay. CONCLUSION: The prevalence of pressure ulcers is higher in patients receiving palliative care than the general population. While this should not be an excuse for poor care, it does not necessarily mean that inadequate care has been provided. Skin failure, as with other organ failures, may be an inevitable part of the dying process for some patients.

An overview of the relationship between anaemia, iron, and venous leg ulcers.

The factors preventing healing in venous leg ulcers are still not fully understood. Iron-mediated tissue damage has been hypothesised, yet anecdotally anaemia is also thought to have a negative effect on wound healing. This article summarises the current evidence for these theories and their likely effects in the context of venous ulceration. A comprehensive search of the literature was conducted. Studies suggest that a number of forms of iron including haemosiderin and ferritin are implicated in progression of venous disease, ulcer formation, and impaired healing, which is thought to be primarily free radical mediated. There is a paucity of evidence for the role of iron deficiency and anaemia on ulcer healing; however, there is likely to be a highly complex interplay between the damaging effects of iron on local tissues and the negative effects of anaemia-mediated tissue hypoxia. Studies looking at options to increase local oxygen delivery such as topical haemoglobin suggest that this may have an impact on some aspects of healing, but findings are generally inconclusive. There is growing evidence that locally elevated iron levels may have a detrimental effect on ulcer healing and formation; however, more robust research is needed.

A prospective pilot study of thigh-administered intermittent pneumatic compression in the management of hard-to-heal lower limb venous and mixed aetiology ulcers.

This was a prospective observational pilot study of a unique intermittent pneumatic compression (IPC) device designed to be applied in the thigh region of the affected limb in patients with lower limb ulceration of both venous and mixed (venous and arterial) aetiologies. This compression system consists of a circumferential three-chamber thigh garment and an electronic pneumatic compression pump operating over a repeated 4-minute cycle. Patients were recruited from outpatient wound clinics. Those recruited were treated with standard therapy in addition to IPC, which was applied for 2 hours per day, and followed up for a total of 8 weeks. The primary objective of the study was to examine the effects of IPC on wound healing over an 8-week period. The other objectives were to assess patients' experiences of pain and the acceptability of IPC device. Twenty-one patients were recruited, and wounds progressed towards healing in 95.24% (20/21) of the patients. Pain scores decreased in 83.33% (15/18) of the patients. Most patients felt that the thigh-applied IPC device was comfortable and easy to apply and remove. The thigh-administered IPC device can be recommended for use in routine clinical practice, especially when other treatment options are limited.