A randomised controlled trial of compression therapies for the treatment of venous leg ulcers (VenUS 6): study protocol for a pragmatic, multicentre, parallel-group, three-arm randomised controlled trial.

BACKGROUND: Venous leg ulcer(s) are common, recurring, open wounds on the lower leg, resulting from diseased or damaged leg veins impairing blood flow. Wound healing is the primary treatment aim for venous leg ulceration, alongside the management of pain, wound exudate and infection. Full (high) compression therapy delivering 40 mmHg of pressure at the ankle is the recommended first-line treatment for venous leg ulcers. There are several different forms of compression therapy available including wraps, two-layer hosiery, and two-layer or four-layer bandages. There is good evidence for the clinical and cost-effectiveness of four-layer bandage and two-layer hosiery but more limited evidence for other treatments (two-layer bandage and compression wraps). Robust evidence is required to compare clinical and cost-effectiveness of these and to investigate which is the best compression treatment for reducing time to healing of venous leg ulcers whilst offering value for money. VenUS 6 will therefore investigate the clinical and cost-effectiveness of evidence-based compression, two-layer bandage and compression wraps for time to healing of venous leg ulcers. METHODS: VenUS 6 is a pragmatic, multi-centre, three-arm, parallel-group, randomised controlled trial. Adult patients with a venous leg ulcer will be randomised to receive (1) compression wraps, (2) two-layer bandage or (3) evidence-based compression (two-layer hosiery or four-layer bandage). Participants will be followed up for between 4 and 12 months. The primary outcome will be time to healing (full epithelial cover in the absence of a scab) in days since randomisation. Secondary outcomes will include key clinical events (e.g. healing of the reference leg, ulcer recurrence, ulcer/skin deterioration, amputation, admission/discharge, surgery to close/remove incompetent superficial veins, infection or death), treatment changes, adherence and ease of use, ulcer related pain, health-related quality of life and resource use. DISCUSSION: VenUS 6 will provide robust evidence on the clinical and cost-effectiveness of the different forms of compression therapies for venous leg ulceration. VenUS 6 opened to recruitment in January 2021 and is currently recruiting across 30 participating centres. TRIAL REGISTRATION: ISRCTN67321719 . Prospectively registered on 14 September 2020.

Effectiveness of psychosocial interventions for the prevention and treatment of foot ulcers in people with diabetes: a systematic review.

AIM: To identify and synthesize the evidence for the effectiveness of psychosocial interventions to promote the healing, and/or reduce the occurrence of, foot ulceration in people with diabetes. METHODS: In March 2019 we searched CENTRAL, Medline, Embase and PsycInfo for randomized controlled trials of interventions with psychosocial components for people with diabetes. The primary outcomes of this review were foot ulceration and healing. We assessed studies using the Cochrane risk-of-bias tool, the TIDieR checklist and GRADE. We conducted narrative synthesis and random-effects meta-analysis. RESULTS: We included 31 randomized controlled trials (4511 participants), of which most (24 randomized controlled trials, 4093 participants) were prevention studies. Most interventions were educational with a modest psychosocial component. Ulceration and healing were not reported in most studies; secondary outcomes varied. Evidence was of low or very low quality because of high risks of bias and imprecision, and few studies reported adherence or fidelity. In groups where participants had prior ulceration, educational interventions had no clear effect on new ulceration (low-quality evidence). Two treatment studies, assessing continuous pharmacist support and an intervention to promote understanding of well-being, reported healing but their evidence was also of very low quality. CONCLUSION: Most psychosocial intervention randomized controlled trials assessing foot ulcer outcomes in people with diabetes were prevention studies, and most interventions were primarily educational. Ulcer healing and development were not well reported. There is a need for better understanding of psychological and behavioural influences on ulcer incidence, healing and recurrence in people with diabetes. Randomized controlled trials of theoretically informed interventions, which assess clinical outcomes, are urgently required. (PROSPERO registration: CRD42016052960).

Psychosocial and behavioural prognostic factors for diabetic foot ulcer development and healing: a systematic review.

AIM: To investigate whether ulceration, amputation and healing of foot ulcers in people living with diabetes are associated with psychosocial and behavioural factors. METHODS: We searched MEDLINE, Embase, PsychINFO, CINAHL and The Cochrane Library to March 2019 for longitudinal studies with multivariable analyses investigating independent associations. Two reviewers extracted data and assessed risk of bias. RESULTS: We identified 15 eligible studies involving over 12 000 participants. Clinical and methodological heterogeneity precluded meta-analysis, so we summarize narratively. Risk of bias was moderate or high. For ulceration, we found significantly different results for people with and without an ulcer history. For those with no ulcer history, moderate quality evidence suggests depression increases ulcer risk [three studies; e.g. hazard ratio (HR) 1.68 (1.20, 2.35) per Hospital Anxiety and Depression Scale (HADS) standard unit]. Better foot self-care behaviour reduces ulcer risk [HR 0.61 (0.40, 0.93) per Summary of Diabetes Self-Care Activities scale standard unit; one study]. For people with diabetes and previous ulcers, low- or very low-quality evidence suggests little discernible association between ulcer recurrence and depression [e.g. HR 0.88 (0.61, 1.27) per HADS standard unit], foot self-care, footwear adherence or exercise. Low-quality evidence suggests incomplete clinic attendance is strongly associated with amputation [odds ratio (OR) 3.84 (1.54, 9.52); one study]. Evidence for the effects of other psychosocial or behavioural factors on ulcer healing and amputation is very low quality and inconclusive. CONCLUSIONS: Psychosocial and behavioural factors may influence the development of first ulcers. More high quality research is needed on ulcer recurrence and healing. (Open Science Framework Registration: https://osf.io/ej689).

Nonblanchable erythema for predicting pressure ulcer development: a systematic review with an individual participant data meta-analysis.

BACKGROUND: Empirical evidence is uncertain regarding the value of nonblanchable erythema in predicting the incidence of stage 2 (or more severe) pressure ulcers. OBJECTIVES: To investigate whether nonblanchable erythema is an independent prognostic factor for pressure ulcer incidence using individual patient data. METHODS: We performed an electronic database search in February 2017 to identify longitudinal studies that considered nonblanchable erythema for predicting pressure ulcer risk in any population. We collected individual participant data for the included studies, and assessed the risk of bias of these studies using the Quality In Prognosis Studies tool. We analysed individual participant data in Stata using mixed-effects logistic regression to investigate the association of interest. The certainty of evidence from individual participant data analysis was assessed using the Grades of Recommendation Assessment, Development and Evaluation. The study was registered with PROSPERO (CRD42017081151). RESULTS: From the 13 included studies (total 68 077 participants) we had access to individual participant data from four (n = 3223), and 11·9% of participants (383 of 3223) developed new pressure ulcers of stage 2 or above within 28 days. Mixed-effects logistic regression showed that participants with nonblanchable erythema had higher odds of developing new pressure ulcers of stage 2 or above within 28 days of follow-up than those without nonblanchable erythema (multivariable association: n = 2684; odds ratio 2·72, 95% confidence interval 2·02-3·69; τ2 = 0; moderate-certainty evidence). CONCLUSIONS: This first prognostic factor review with individual-level data analysis in patients with pressure ulcers suggests that people with nonblanchable erythema are more likely to develop new pressure ulcers of stage 2 or above within 28 days than people without nonblanchable erythema. It is important to identify nonblanchable erythema in practice and to intervene appropriately to prevent pressure ulceration. What's already known about this topic? Pressure ulcer reduction is a high priority for healthcare systems. Regularly inspecting skin to identify skin abnormalities is one key practice for preventing ulceration. Nonblanchable erythema - discoloration of the skin that does not turn white when pressed - is one clinically important skin abnormality. Empirical evidence synthesized using conventional meta-analysis is uncertain regarding the value of nonblanchable erythema for predicting open pressure ulcer incidence; this is partly because the conventional technique has weakness in terms of pooling prognostic effects of different multivariable analyses across studies. What does this study add? This prognostic factor review used individual-level data analysis to overcome the limitations of the conventional meta-analysis technique. For the first time there is confirmatory and moderate-certainty evidence on the association of nonblanchable erythema with pressure ulcer incidence. People with nonblanchable erythema are more likely to develop new pressure ulcers of stage 2 or more severe within 28 days than people without nonblanchable erythema, regardless of their age, baseline pressure ulcer risk or received support surfaces.

Cost-effectiveness analysis of a randomized clinical trial of early versus deferred endovenous ablation of superficial venous reflux in patients with venous ulceration.

BACKGROUND: Treatment of superficial venous reflux in addition to compression therapy accelerates venous leg ulcer healing and reduces ulcer recurrence. The aim of this study was to evaluate the costs and cost-effectiveness of early versus delayed endovenous treatment of patients with venous leg ulcers. METHODS: This was a within-trial cost-utility analysis with a 1-year time horizon using data from the EVRA (Early Venous Reflux Ablation) trial. The study compared early versus deferred endovenous ablation for superficial venous truncal reflux in patients with a venous leg ulcer. The outcome measure was the cost per quality-adjusted life-year (QALY) over 1 year. Sensitivity analyses were conducted with alternative methods of handling missing data, alternative preference weights for health-related quality of life, and per protocol. RESULTS: After early intervention, the mean(s.e.m.) cost was higher (difference in cost per patient £163(318) (€184(358))) and early intervention was associated with more QALYs at 1 year (mean(s.e.m.) difference 0·041(0·017)). The incremental cost-effectiveness ratio (ICER) was £3976 (€4482) per QALY. There was an 89 per cent probability that early venous intervention is cost-effective at a threshold of £20 000 (€22 546)/QALY. Sensitivity analyses produced similar results, confirming that early treatment of superficial reflux is highly likely to be cost-effective. CONCLUSION: Early treatment of superficial reflux is highly likely to be cost-effective in patients with venous leg ulcers over 1 year. Registration number: ISRCTN02335796 (http://www.isrctn.com).

Patients with surgical wounds healing by secondary intention: A prospective, cohort study.

BACKGROUND: Surgical wounds healing by secondary intention can be difficult and costly to manage and are profoundly under researched. This prospective inception, cohort study aimed to derive a better understanding of surgical wounds healing by secondary intention and to facilitate the design of future research investigating effective treatments. OBJECTIVES: To investigate the clinical characteristics of patients with surgical wounds healing by secondary intention and the surgeries that preceded their wounds; to clearly delineate the clinical outcomes of these patients, specifically focusing on time to wound healing and its determinants; to explore the types of treatments for surgical wounds healing by secondary intention; and to assess the impact surgical wounds healing by secondary intention have on patients' quality of life. DESIGN: Prospective, inception cohort study. SETTING: Acute and community settings in eight sites across two large centres in the United Kingdom (Hull and Leeds, UK). METHODS: Patients with a surgical wounds healing by secondary intention (an open wound, <3 weeks' duration, resulting from surgery), were recruited and followed up for at least 12 months. Key outcome events included: time to healing; treatment type; infection; hospital re-admission and further procedures; health-related quality of life and pain. RESULTS: In total, 393 patients were recruited. Common co-morbidities were cardiovascular disease (38%), diabetes (26%) and peripheral vascular disease (14.5%). Baseline median SWHSI area was 6 cm2 (range 0.01-1200). Abdominal (n = 132), foot (n = 59), leg (n = 58) and peri-anal (n = 34) wounds were common. The majority of wounds (236, 60.1%) were intentionally left open following surgery; the remainder were mostly dehisced wounds. Healing was observed in 320 (81.4%) wounds with a median time to healing of 86 days (95% CI: 75-130). Factors associated with delayed healing included wound infection at any point and baseline wound area above the median. Health-related quality of life scores were low at baseline but improved with time and healing. CONCLUSIONS: This is the first inception cohort study in patients with surgical wounds healing by secondary intention. Patient characteristics have been clearly defined, with prolonged healing times and adverse events being common impacting on patient's health-related quality of life. Areas for, and factors crucial to the design of, future research have been identified.

Pilot feasibility randomized clinical trial of negative-pressure wound therapy versus usual care in patients with surgical wounds healing by secondary intention.

BACKGROUND: Surgical wounds healing by secondary intention (SWHSI) are increasingly being treated with negative-pressure wound therapy (NPWT) despite a lack of high-quality research evidence regarding its clinical and cost-effectiveness. This pilot feasibility RCT aimed to assess the methods for and feasibility of conducting a future definitive RCT of NPWT for the treatment of SWHSI. METHODS: Eligible consenting adult patients receiving care at the study sites (2 acute and 1 community) and with a SWHSI appropriate for NPWT or wound dressing treatment were randomized 1 : 1 centrally to receive NPWT or usual care (no NPWT). Participants were followed up every 1-2 weeks for 3 months. Feasibility (recruitment rate, time to intervention delivery) and clinical (time to wound healing) outcomes were assessed. RESULTS: A total of 248 participants were screened for eligibility; 40 (16·1 per cent) were randomized, 19 to NPWT and 21 to usual care. Twenty-four of the 40 wounds were located on the foot. Participants received NPWT for a median of 18 (range 0-72) days. Two participants in the NPWT group never received the intervention and 14 received NPWT within 48 h of randomization. Five participants in the usual care group received NPWT during the study. Ten of the 40 wounds were deemed to have healed during the study. CONCLUSION: A full-scale RCT to investigate the clinical and cost-effectiveness of NPWT for SWHSI is feasible. This study identified crucial information on recruitment rates and data collection methods to consider during the design of a definitive RCT. Registration number: ISRCTN12761776 (http://www.iscrtn.com).

Association between psychological health and wound complications after surgery.

BACKGROUND: Surgical wound complications remain a major cause of morbidity, leading to higher costs and reduced quality of life. Although psychological health is widely considered to affect wound healing, the evidence on wound outcomes after surgery is mixed. Studies generally focus on small samples of patients undergoing a specific procedure and have limited statistical power. METHODS: This study investigated the relationship between three different measures of anxiety and/or depression and seven adverse surgical outcomes using observational data collected before and after surgery between 2009 and 2011. A wide range of confounding factors was adjusted for, including patient demographics, physical co-morbidities, health-related behaviours, month of operation, procedure complexity and treating hospital. RESULTS: The estimation sample included 176 827 patients undergoing 59 410 hip replacements, 64 145 knee replacements, 38 328 hernia repairs and 14 944 varicose vein operations. Patients with moderate anxiety or depression had an increased probability of wound complications after a hip replacement (odds ratio (OR) 1·17, 95 per cent c.i. 1·11 to 1·24). They were more likely to be readmitted for a wound complication (OR 1·20, 1·02 to 1·41) and had an increased duration of hospital stay by 0·19 (95 per cent c.i. 0·15 to 0·24) days. Estimated associations were consistent across all four types of operation and for each measure of anxiety and/or depression. CONCLUSION: Preoperative psychological health is a significant risk factor for adverse wound outcomes after surgery for four of the procedures most commonly performed in England.

A survey of patients with surgical wounds healing by secondary intention; an assessment of prevalence, aetiology, duration and management.

BACKGROUND: Surgical wounds healing by secondary intention (SWHSI) are often difficult and costly to treat. There is a dearth of clinical and research information regarding SWHSI. The aim of this survey was to estimate the prevalence of SWHSI and to characterise the aetiology, duration and management of these wounds. METHODS: Anonymised data were collected from patients with SWHSI receiving treatment in primary, secondary and community settings. Over a two weeks period, data were collected on the patients, their SWHSI, clinical and treatment details. RESULTS: Data were collected from 187 patients with a median age of 58.0 (95% CI = 55 to 61) years. The prevalence of SWHSI was 0.41 (95% CI = 0.35 to 0.47) per 1000 population. More patients with SWHSI were being treated in community (109/187, 58.3%) than in secondary (56/187, 29.9%) care settings. Most patients (164/187, 87.7%) had one SWHSI and the median duration of wounds was 28.0 (95% CI = 21 to 35) days. The most common surgical specialities associated with SWHSI were colorectal (80/187, 42.8%), plastics (24/187, 12.8%) and vascular (22/187, 11.8%) surgery. Nearly half of SWHSI were planned to heal by secondary intention (90/187, 48.1%) and 77/187 (41.2%) were wounds that had dehisced. Dressings were the most common single treatment for SWHSI, received by 169/181 (93.4%) patients. Eleven (6.1%) patients were receiving negative pressure wound therapy. CONCLUSIONS: This survey provides a previously unknown insight into the occurrence, duration, treatment and types of surgery that lead to SWHSI. This information will be of value to patients, health care providers and researchers.

Systematic review and mixed treatment comparison: dressings to heal diabetic foot ulcers.

AIMS/HYPOTHESIS: Foot ulcers in people with diabetes are a common and serious global health issue. Dressings form a key part of ulcer treatment. Existing systematic reviews are limited by the lack of head-to-head comparisons of alternative dressings in a field where there are several different dressing options. We aimed to determine the relative effects of alternative wound dressings on the healing of diabetic foot ulcers. METHODS: This study was a systematic review involving Bayesian mixed treatment comparison. We included randomised controlled trials evaluating the effects on diabetic foot ulcer healing of one or more wound dressings. There were no restrictions based on language or publication status. RESULTS: Fifteen eligible studies, evaluating nine dressing types, were included. Ten direct treatment comparisons were made. Whilst there was increased healing associated with hydrogel and foam dressings compared with basic wound contact materials, these findings were based on data from small studies at unclear or high risk of bias. The mixed treatment comparison suggested that hydrocolloid-matrix dressings were associated with higher odds of ulcer healing than all other dressing types; there was a high degree of uncertainty around these estimates, which were deemed to be of very low quality. CONCLUSIONS/INTERPRETATION: These findings summarise all available trial evidence regarding the use of dressings to heal diabetic foot ulcers. More expensive dressings may offer no advantages in terms of healing than cheaper basic dressings. In addition, evidence pointing to a difference in favour of 'advanced' dressing types over basic wound contact materials is of low or very low quality.

Development and preliminary evaluation of a psychosocial intervention for modifying psychosocial risk factors associated with foot re-ulceration in diabetes.

Diabetic foot ulcers are a common, chronic and costly complication of Diabetes, with the greatest risk for ulceration being previous ulceration. Previous approaches to reducing re-ulceration risk have not, however, considered the psychosocial factors which may influence this risk. We reviewed the existing evidence in this area and developed a therapeutic model which informed the content, structure and format of a psychosocial intervention designed to modify the psychosocial risk factors associated with re-ulceration. The intervention was subjected to a qualitative evaluation in a feasibility study which involved a randomised controlled trial in which 10 individuals were randomised to receive the intervention and 5 individuals to usual care. Individuals in both arms participated in in-depth qualitative interviews after the first 10 weeks of the intervention and again after the final maintenance session. The intervention was perceived as acceptable and patients' reported evidence of sustained change in several of the psychosocial risks identified in the therapeutic model. These observations were supported in the descriptive findings obtained from questionnaires measuring mood, cognitions, behaviour and social support. The intervention appears to offer an acceptable and effective way of modifying the psychosocial risk factors associated with re-ulceration.

Economic evaluation of a randomized controlled trial of ultrasound therapy for hard-to-heal venous leg ulcers.

BACKGROUND: A pragmatic, multicentre randomized controlled trial (VenUS III) was conducted to determine whether low-dose ultrasound therapy increased the healing rate of hard-to-heal leg ulcers. This study was a cost-effectiveness analysis of the trial data. METHODS: Cost-effectiveness and cost-utility analyses were conducted alongside the VenUS III trial, in which patients were randomly allocated to either ultrasound treatment administered weekly for 12 weeks along with standard care, or standard care alone. The time horizon was 12 months and based on the UK National Health Service (NHS) perspective. RESULTS: The base-case analysis showed that ultrasound therapy added to standard care was likely to be more costly and provide no extra benefit over standard care alone. Individuals who received ultrasound treatment plus standard care took a mean of 14.7 (95 per cent confidence interval - 32.7 to 56.8) days longer to heal, had 0.009 (-0.042 to 0.024) fewer quality-adjusted life years and had higher treatment costs by £ 197.88 (-35.19 to 420.32). Based on these point estimates, ultrasound therapy plus standard care for leg ulcers was dominated by standard care alone. The analysis of uncertainty showed that this treatment strategy is unlikely to be cost-effective. CONCLUSION: Ultrasound treatment was not cost-effective for hard-to-heal leg ulcers and should not be recommended for adoption in the NHS.

VenUS III: a randomised controlled trial of therapeutic ultrasound in the management of venous leg ulcers.

OBJECTIVES: To compare the clinical effectiveness and cost-effectiveness of low-dose ultrasound delivered in conjunction with standard care against standard care alone in the treatment of hard-to-heal venous ulcers. DESIGN: A multicentre, pragmatic, two-armed randomised controlled trial with an economic evaluation. SETTING: Community nurse services; community leg ulcer clinics; hospital outpatient leg ulcer clinics, among both urban and rural settings in England, Scotland, Northern Ireland and Ireland. PARTICIPANTS: Patients with a venous leg ulcer of > 6 months' duration or > 5 cm2 and an ankle-brachial pressure index of ≥ 0.8. In total, 337 patients were recruited to the study. INTERVENTIONS: Participants in the intervention group received low-dose ultrasound (0.5 W/cm2) delivered at 1 MHz, pulsed pattern of 1 : 4, applied to periulcer skin (via a water-based contact gel) weekly for up to 12 weeks alongside standard care. Standard care consisted of low-adherent dressings and compression therapy, renewed as recommended by the patient's nurse and modified if required to reflect changes in ulcer and skin condition. The output of the ultrasound machines was checked every 3 months to confirm intervention fidelity. MAIN OUTCOME MEASURES: The primary end point was time to healing of the largest eligible ulcer (reference ulcer). Secondary outcomes were time to healing of all ulcers, proportion of patients healed, percentage and absolute change in ulcer size, proportion of time patients were ulcer free, cost of treatments, health-related quality of life (HRQoL), adverse events, withdrawal and loss to follow-up. RESULTS: There was a small, and statistically not significant, difference in the median time to complete ulcer healing of all ulcers in favour of standard care [median 328 days, 95% confidence interval (CI) 235 days, inestimable] compared with ultrasound (median 365 days, 95% CI 224 days, inestimable). There was no difference between groups in the proportion of patients with ulcers healed at 12 months (72/168 in ultrasound vs 78/169 standard care), nor in the change in ulcer size at 4 weeks. There was no evidence of a difference in recurrence of healed ulcers. There was no difference in HRQoL [measured using the Short Form questionnaire-12 items (SF-12)] between the two groups. There were more adverse events with ultrasound than with standard care. Ultrasound therapy as an adjuvant to standard care was found not to be a cost-effective treatment when compared with standard care. The mean cost of ultrasound was £197.88 (bias-corrected 95% CI -£35.19 to £420.32) higher than standard care per participant per year. There was a significant relationship between ulcer healing and area and duration at baseline. In addition, those centres with high recruitment rates had the highest healing rates. CONCLUSIONS: Low-dose ultrasound, delivered weekly during dressing changes, added to the package of current best practice (dressings, compression therapy) did not increase ulcer healing rates, affect quality of life (QoL) or reduce recurrence. It was associated with higher costs and more adverse events. There is no evidence that adding low-dose ultrasound to standard care for 'hard-to-heal' ulcers aids healing, improves QoL or reduces recurrence. It increases costs and adverse events. The relationship between ulcer healing rates and patient recruitment is worthy of further study. TRIAL REGISTRATION: Current Controlled Trials ISRCTN21175670. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 15, No. 13. See the HTA programme website for further project information.

Coping style and depression influence the healing of diabetic foot ulcers: observational and mechanistic evidence.

AIMS/HYPOTHESIS: Experimental evidence suggests that the healing of diabetic foot ulcers is affected by psychosocial factors such as distress. We examined this proposal in a prospective study, in which we considered the role of psychological distress and coping style in the healing of diabetic foot ulcers over a 24 week period. We also explored the role of salivary cortisol and matrix metalloproteinases (MMPs) as potential mechanisms. METHODS: For this prospective observational study we recruited 93 (68 men; mean age 60 years) patients with neuropathic or neuroischaemic diabetic foot ulcers from specialist podiatry clinics in secondary care. Clinical and demographic determinants of healing, psychological distress, coping, salivary cortisol and both MMP2 and MMP9 were assessed at baseline. Ulcers were assessed at baseline and at 6, 12 and 24 weeks post-baseline. The primary outcome was ulcer status at 24 weeks, i.e. healed vs not healed. RESULTS: After controlling for clinical and demographic determinants of healing, ulcer healing at 24 weeks was predicted by confrontation coping, but not by depression or anxiety. Patients with unhealed ulcers exhibited greater confrontation coping (model including depression: OR 0.809, 95% CI 0.704-0.929, p = 0.003; model including anxiety: OR 0.810, 95% CI 0.704-0.930, p = 0.003). However, change in ulcer size over the observation period was associated with depression only (p = 0.04, d = 0.31). Healed ulcers by 24 weeks were also associated with lower evening cortisol, higher precursor MMP2 and a greater cortisol awakening response. CONCLUSIONS/INTERPRETATION: Confrontation coping and depression predict ulcer healing. Our preliminary enquiry into biological mechanisms suggests that cortisol and precursor MMP2 may underlie these relationships.

Value of a modified clinical signs and symptoms of infection checklist for leg ulcer management.

BACKGROUND: The aim of this study was to analyse the validity of a modified Clinical Signs and Symptoms Checklist used to measure infection in a sample of patients with a leg ulcer. METHODS: Data from patients recruited to a randomized controlled trial evaluating larval therapy (VenUS II) were analysed using factor analysis to identify the underlying checklist structure. Linear regression analysis identified whether checklist items, patient characteristics and subjective judgement of infection could predict bacterial load. RESULTS: There were several redundant checklist items when implemented in this sample and items forming the scale had low internal consistency (alpha = 0.27). No clear structure to the checklist was detected, with only one underlying theme revealed which had low internal consistency (alpha = 0.45). Predictions of bacterial count were possible using the emerged theme, some checklist items and ankle circumference, but not using clinicians' subjective judgement alone (P = 0.315). CONCLUSION: The modified Clinical Signs and Symptoms Checklist does not currently represent a valid tool to measure infection in leg ulcers. Some checklist items may predict bacterial load and may be better than subjective judgement alone.

VenUS II: a randomised controlled trial of larval therapy in the management of leg ulcers.

OBJECTIVES: To compare the clinical effectiveness and cost-effectiveness of larval therapy with a standard debridement technique (hydrogel). DESIGN: A pragmatic, three-arm, randomised controlled trial with an economic evaluation. SETTING: Community nursing services, community leg ulcer clinics and hospital outpatient leg ulcer clinics. A range of urban and rural settings. PARTICIPANTS: Patients with venous or mixed venous/arterial ulcers (minimum ankle brachial pressure index of 0.6) where a minimum of 25% of ulcer area was covered by slough and/or necrotic material. INTERVENTIONS: Loose larval therapy and bagged larval therapy compared with hydrogel. MAIN OUTCOME MEASURES: The primary end point was complete healing of the largest eligible ulcer. The primary outcome was time to complete healing of the reference ulcer. Secondary outcomes were: time to debridement, cost of treatments, health-related quality of life (including ulcer-related pain), bacterial load, presence of methicillin-resistant Staphylococcus aureus and staff and patient attitudes to and beliefs about larval therapy. RESULTS: Between July 2004 and May 2007 the trial recruited 267 people aged 20-94 years at trial entry. There were more female (n = 158) than male (n = 109) participants and most ulcers were classified by the nurse as having an area greater than 5 cm(2). The time to healing for the three treatment arms was compared using the log rank test. The difference in time to healing in the three treatments was not statistically significant at the 5% level. Adjustment was then made for stratification and prespecified prognostic factors (centre, baseline ulcer area, ulcer duration and type of ulcer) using a Cox proportional hazards model. No difference was found in healing rates between the loose and bagged larvae groups. Results for larvae (loose and bagged pooled) compared with hydrogel showed no evidence of a difference in time to healing. When the same analytical steps were used to investigate time to debridement, larvae-treated ulcers debrided significantly more rapidly than hydrogel-treated ulcers; however, the difference in time to debridement between loose and bagged larvae was not significant. The adjusted analysis reported the hazard of debriding at any time for those in loose and bagged larvae groups as approximately twice that of the hydrogel group. No differences in health-related quality of life or bacteriology were observed between trial arms. Larval therapy was associated with significantly more ulcer-related pain than hydrogel. Our base-case economic evaluation showed large decision uncertainty associated with the cost-effectiveness of larval therapy compared with hydrogel, suggesting that larval therapy and hydrogel therapy have similar costs and effects in the treatment of sloughy and/or necrotic leg ulcers. CONCLUSIONS: Larval therapy significantly reduced the time to debridement of sloughy and/or necrotic, chronic venous and mixed venous/arterial leg ulcers, compared with hydrogel; however, larval therapy did not significantly increase the rate of healing of the ulcers. It was impossible to distinguish between larval therapy and hydrogel in terms of cost-effectiveness. Future research should investigate the association of debridement and healing and the value of debridement as a clinical outcome for patients and clinicians. To inform decision-makers' selection of debriding agents where debridement is the treatment goal, decision analytic modelling of all alternative debridement treatments is required. TRIAL REGISTRATION: Current Controlled Trials ISRCTN55114812.

Therapeutic ultrasound for pressure ulcers.

BACKGROUND: Pressure ulcers have been recorded as occurring in 5 to 32% of patients admitted to a UK District General Hospital (the precise rate depends on case-mix) and 4 to 7% in the community. They represent a major burden of sickness and reduced quality of life for patients and their carers, and are costly to health service providers. Pressure ulcers are treated by using wound dressings, relieving pressure on the wound, by treating concurrent conditions which may delay healing, and by the use of physical therapies such as electrical stimulation, laser therapy and ultrasound. OBJECTIVES: To assess the effect of therapeutic ultrasound on the healing of pressure ulcers. SEARCH STRATEGY: We searched the Cochrane Wounds Group Specialised Register and the Cochrane Central Register of Controlled Trials in May 2006. In addition we hand searched journals, conference proceedings, bibliographies and reference lists of articles. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing therapeutic ultrasound with sham ultrasound or standard treatment. DATA COLLECTION AND ANALYSIS: Two authors independently checked the result of the search to identify relevant RCTs. Details of eligible studies were extracted and summarised using a data extraction sheet. Attempts were made to obtain missing information by contacting authors. Data extraction was checked by a second author. Meta-analysis was used to combine the results of trials where the interventions and outcome measures were sufficiently similar. MAIN RESULTS: Three trials involving 146 people were included. Two RCTs compared ultrasound therapy with sham ultrasound and the third compared a combination of ultrasound and ultraviolet light with laser and with standard treatment. Neither of the two RCTs comparing ultrasound with sham found a significant difference in healing rates. The trials were pooled, in the absence of significant heterogeneity. There was no evidence of benefit associated with the use of ultrasound in the treatment of pressure ulcers. In the three-arm comparison there was no statistically significant difference in ulcers healed. AUTHORS' CONCLUSIONS: There is no evidence of benefit of ultrasound therapy in the treatment of pressure ulcers. However, the possibility of beneficial or harmful effect cannot be ruled out due to the small number of trials, some with methodological limitations and small numbers of participants. Further research is needed.

Pressure relieving support surfaces: a randomised evaluation.

OBJECTIVES: To determine differences between alternating pressure overlays and alternating pressure replacement mattresses with respect to the development of new pressure ulcers, healing of existing pressure ulcers, patient acceptability and cost-effectiveness of the different pressure-relieving surfaces. Also to investigate the specific additional impact of pressure ulcers on patients' well-being. DESIGN: A multicentre, randomised, controlled, open, fixed sample, parallel-group trial with equal randomisation was undertaken. The trial used remote, concealed allocation and intention-to-treat (ITT) analysis. The main trial design was supplemented with a qualitative study involving a purposive sample of 20-30 patients who developed pressure ulcers, to assess the impact of the pressure ulcers on their well-being. In addition, a focus group interview was carried out with clinical research nurses, who participated in the PRESSURE (Pressure RElieving Support SUrfaces: a Randomised Evaluation) Trial, to explore the experiences of their role and observations of pressure area care. SETTING: The study took place in 11 hospital-based research centres within six NHS trusts in England. PARTICIPANTS: Acute and elective patients aged 55 years or older and admitted to vascular, orthopaedic, medical or care of the elderly wards in the previous 24 hours were investigated. INTERVENTIONS: Patients were randomised to either an alternating pressure overlay or an alternating pressure mattress replacement, with mattress specifications clearly defined to enable the inclusion of centres using products from different manufacturers, and to exclude hybrid mattress systems (which either combine foam or constant low pressure with alternating pressure in one mattress, or can be used as either an overlay or a replacement mattress). MAIN OUTCOME MEASURES: Development of a new pressure ulcer (grade < or =2, i.e. partial-thickness wound involving epidermis/dermis only) on any skin site. Also healing of existing pressures ulcers, patient acceptability and cost-effectiveness. RESULTS: In total, 6155 patients were assessed for eligibility to the trial and 1972 were randomised: 990 to the alternating pressure overlay (989 after one postrandomisation exclusion) and 982 to the alternating pressure mattress replacement. ITT analysis found no statistically significant difference in the proportions of patients developing a new pressure ulcer of grade 2 or above [10.7% overlay patients, 10.3% mattress replacement patients, a difference of 0.4%, 95% confidence interval (CI) -2.3 to 3.1%, p = 0.75]. When logistic regression analysis was used to adjust for minimisation factors and prespecified baseline covariates, there was no difference between the mattresses with respect to the odds of ulceration (odds ratio 0.94, 95% CI 0.68 to 1.29). There was no evidence of a difference between the mattress groups with respect to time to healing (p = 0.86). The Kaplan-Meier estimate of the median time to healing was 20 days for each intervention. More patients allocated overlays requested mattress changes due to dissatisfaction (23.3%) than mattress replacement patients (18.9%, p = 0.02) and more than one-third of patients reporting difficulties associated with movement in bed and getting into or out of bed. There is a higher probability (64%) that alternating mattress replacements are cost-saving; they were associated with lower overall costs (74.50 pounds sterling per patient on average, mainly due to reduced length of stay) and greater benefits (a delay in time to ulceration of 10.64 days on average). Patients' accounts highlighted that the development of a pressure ulcer could be pivotal in the trajectory from illness to recovery, by preventing full recovery or causing varied impacts on their quality of life. CONCLUSIONS: There is no difference between alternating pressure mattress replacements and overlays in terms of the proportion of patients developing new pressure ulcers; however, alternating pressure mattress replacements are more likely to be cost-saving. The results suggest that when renewing alternating pressure surfaces or ordering equipment within a rental contract, mattress replacements should be specified; however, overlays are acceptable if no replacement mattress is available. Similarly, patient preferences can be supported, without any great increase in risk, if individual patients request an overlay rather than a replacement mattress. Further research could include a randomised controlled trial comparing alternating pressure mattress replacements and high-specification foam mattresses in patients at moderate to high risk; an accurate costing study to understand better how much pressure ulcers cost health and social services in the UK; and trials in higher risk groups of patients. Also future trials should measure time to ulceration as the primary end-point, since this is more informative economically and possibly also from a patient and clinical perspective.

Electromagnetic therapy for treating pressure ulcers.

BACKGROUND: Pressure ulcers are defined as areas "of localized damage to the skin and underlying tissue caused by pressure, shear, friction and/or the combination of these". In the UK, pressure ulcers occur in 5 to 32% of District General Hospitals people and in 4 to 7% of people in community settings. Electromagnetic therapy, in which electrodes produce an electromagnetic field across the wound, may improve healing of chronic wounds such as pressure ulcers. OBJECTIVES: To assess the effects of electromagnetic therapy on the healing of pressure ulcers. SEARCH STRATEGY: For this first update, we searched the Cochrane Wounds Group Specialised Register (last searched October 2005); CENTRAL (The Cochrane Library 2005, Issue 4); MEDLINE (1966 to October 2005); EMBASE (1980 to October 2005); and CINAHL (1982 to October 2005). SELECTION CRITERIA: Randomised controlled trials comparing electromagnetic therapy with sham electromagnetic therapy, or other (standard) treatment. DATA COLLECTION AND ANALYSIS: For this first update, two authors independently scrutinized the results of the search to identify relevant RCTs and obtained full reports of potentially eligible studies. For the original review, details of eligible studies were extracted and summarised using a data extraction sheet. Attempts were made to obtain missing data by contacting authors. Data extraction was checked by a second author. Meta-analysis was applied to combine the results of trials when the interventions and outcome measures were sufficiently similar. MAIN RESULTS: This update identified no new trials. Two RCTs were identified for inclusion in the original review (total of 60 participants). One was a three-armed study comparing electromagnetic therapy with electromagnetic therapy in combination with standard therapy, and with standard therapy alone, on 17 female and 13 male with grade II and III pressure ulcers. The other study compared electromagnetic therapy with sham therapy in 30 male participants with a spinal cord injury and a grade II or grade III pressure ulcer.Neither study found a statistically significant difference between the healing rates of pressure ulcers in people treated with electromagnetic therapy compared with those in the control group. AUTHORS' CONCLUSIONS: The results provide no evidence of benefit in using electromagnetic therapy to treat pressure ulcers. However, the possibility of a beneficial or harmful effect cannot be ruled out, due to the fact that there were only two included trials both with methodological limitations and small numbers of participants. Further research is recommended.