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.

Consensus demonstrates four indicators needed to standardize burn wound infection reporting across trials in a single-country study (ICon-B study).

INTRODUCTION: Evidence-based interventions are needed to treat burn wound infection (BWI). Evidence syntheses have been limited by heterogeneity of indicators used to report BWI across trials. Consistent reporting of BWI would be facilitated by an agreed minimum set of indicators. The Infection Consensus in Burns study aimed to achieve expert consensus about a core indicator set (CIS) for BWI. METHODS: The CIS was established through development of a long list of BWI indicators identified from a systematic review and expert input. In a Delphi survey, UK expert participants rated the indicators according to use in everyday practice, importance for diagnosis and frequency of observation in patients with BWI. Indicators were included in the CIS if ≥75% of participants agreed it was important for diagnosis and used in everyday practice, and ≥50% of participants rated it as frequently observed in patients with BWI. RESULTS: One hundred and ninety-five indicators were identified from the systematic review and reduced to 29 survey items through merging of items with the same meaning. Seventy-five UK experts participated in the Delphi survey. Following a single survey round and a consensus meeting with an expert panel, four items were included in the CIS: pyrexia, spreading erythema, change in white cell count, and presence of pathogenic microbes. DISCUSSION AND CONCLUSIONS: To facilitate evidence synthesis, a single-country systematic, expert-informed approach was taken to develop a CIS to be reported consistently across trials reporting BWI as an outcome. Future work requires verification of the CIS with international experts.

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.

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).

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 meta-analysis of wound dressings in the prevention of surgical-site infections in surgical wounds healing by primary intention.

BACKGROUND: Postoperative surgical-site infections are a major source of morbidity and cost. This study aimed to identify and present all randomized controlled trial evidence evaluating the effects of dressings on surgical-site infection rates in surgical wounds healing by primary intention; the secondary outcomes included comparisons of pain, scar and acceptability between dressings. METHODS: Randomized controlled trials comparing alternative wound dressings, or wound dressings with leaving wounds exposed for postoperative management of surgical wounds were included in the review regardless of their language. Databases searched included the Cochrane Wounds Group Specialised Register and Central Register of Controlled Trials, Ovid MEDLINE, Ovid Embase and EBSCO CINAHL from inception to May 2011. Two authors performed study selection, risk of bias assessment and data extraction, including an assessment of surgical contamination according to the surgical procedure. Where levels of clinical and statistical heterogeneity permitted, data were pooled for meta-analysis. RESULTS: Sixteen controlled trials with 2594 participants examining a range of wound contamination levels were included. They were all unclear or at high risk of bias. There was no evidence that any dressing significantly reduced surgical-site infection rates compared with any other dressing or leaving the wound exposed. Furthermore, no significant differences in pain, scarring or acceptability were seen between the dressings. CONCLUSION: No difference in surgical-site infection rates was demonstrated between surgical wounds covered with different dressings and those left uncovered. No difference was seen in pain, scar or acceptability between dressings.

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.

Cost-effectiveness analysis of general anaesthesia versus local anaesthesia for carotid surgery (GALA Trial).

BACKGROUND: Health outcomes and costs are both important when deciding whether general (GA) or local (LA) anaesthesia should be used during carotid endarterectomy. The aim of this study was to assess the cost-effectiveness of carotid endarterectomy under LA or GA in patients with symptomatic or asymptomatic carotid stenosis for whom surgery was advised. METHODS: Using patient-level data from a large, multinational, randomized controlled trial (GALA Trial) time free from stroke, myocardial infarction or death, and costs incurred were evaluated. The cost-effectiveness outcome was incremental cost per day free from an event, within a time horizon of 30 days. RESULTS: A patient undergoing carotid endarterectomy under LA incurred fewer costs (mean difference pound178) and had a slightly longer event-free survival (difference 0.16 days, but the 95 per cent confidence limits around this estimate were wide) compared with a patient who had GA. Existing uncertainty did not have a significant impact on the decision to adopt LA, over a wide range of willingness-to-pay values. CONCLUSION: If cost-effectiveness was considered in the decision to adopt GA or LA for carotid endarterectomy, given the evidence provided by this study, LA is likely to be the favoured treatment for patients for whom either anaesthetic approach is clinically appropriate.

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.

Enhanced recovery in colorectal resections: a systematic review and meta-analysis.

OBJECTIVE: The study aimed to produce a comprehensive up-to-date meta-analysis exploring the safety and efficacy of enhanced recovery (ER) programmes after colorectal resection. METHOD: Key-word and MESH-heading searches of MEDLINE, EMBASE and the Cochrane Databases from 1966 to February 2007 were used to identify all available randomized and clinical controlled studies. Two independent reviewers assessed studies for inclusion and exclusion based on methodological quality criteria prior to undertaking data extraction. Summary estimates of treatment effects using a fixed effect model were produced with RevMan 1.0.2, using weighted means for length-of-stay data and relative risks of morbidity, mortality and readmission rates. RESULTS: Analysis of four papers including 376 patients demonstrated primary and total length-of-stays (primary + readmission length-of-stay) to be significantly reduced (P < 0.001) with ER programmes [weighted mean differences of -3.64 days (95% confidence interval, 95% CI -4.98 to -2.29) and -3.75 days (95% CI-5.11 to -2.40)]. Analysis of controlled clinical trial data showed morbidity rates to be reduced and readmission rates increased. These trends were not seen amongst the randomized controlled trial data. There were no differences in mortality rates. CONCLUSION: Enhanced recovery programmes after colorectal resections reduce length-of-stay and may reduce 30 days morbidity and increase 30 days readmission without increasing mortality.

Randomized trial of two physiotherapy interventions for primary care back and neck pain patients: cost effectiveness analysis.

OBJECTIVES: To assess the cost-effectiveness of a brief physiotherapy pain management approach using cognitive-behavioural principles (Solution-Finding Approach) when compared with a commonly used traditional method of physical therapy (McKenzie Approach). METHODS: Economic evaluation conducted alongside a randomized trial. The study related incremental differences in costs and benefits associated with the Solution Finding and McKenzie approaches over 12 months. Costs were measured in UK pounds sterling. Benefit was measured as health-related quality of life using the EQ-5D, which was used to estimate patient-specific quality adjusted life years (QALYs). RESULTS: The McKenzie treatment required, on average, one extra physiotherapist visit (4.15 vs 3.10). Over a 12-month period, Solution Finding was associated with a lower per patient cost of pound-24.4 (95% CI pound-49.6 to 0.789 pounds). The mean difference in QALYs between the two groups was -0.020 (95% CI -0.057 to 0.017); favouring those receiving McKenzie. Relating incremental mean costs and QALYs gave an incremental cost effectiveness ratio of 1220 pounds (-24.4/-0.020) suggesting the McKenzie treatment is cost effective. CONCLUSIONS: Results suggest that the additional cost associated with the McKenzie treatment when compared with the Solution Finding Approach may be worth paying, given the additional benefit the approach seems more likely to provide. Further research is needed to assess the extent to which the difference in physiotherapy visits between the two strategies is generalizable to other treatment settings.

Non-cardiac chest pain: a retrospective cohort study of patients who attended a Rapid Access Chest Pain Clinic.

BACKGROUND: Rapid Access Chest Pain Clinics have recently been introduced to assist in the management of primary care patients experiencing suspected cardiac chest pain. OBJECTIVE: To study the longer term outcome for patients referred to a Rapid Access Chest Pain Clinic and then given a non-cardiac diagnosis. METHODS: The study collected retrospective data from a cohort of all patients attending the Rapid Access Chest Pain Clinic based in the cardiorespiratory Department at the York District Hospital, England. Questionnaires were sent to all patients who attended the Rapid Access Chest Pain Clinic during the previous 14 months and were diagnosed with non-cardiac chest pain. Participants reported on their chest pain, subsequent episodes of primary and secondary care and their beliefs about causation of pain. RESULTS: Of the patients referred to the Rapid Access Chest Pain Clinic, 235 (52%) did not have cardiac chest pain. Of these patients, 161 (69%) returned the questionnaire, nearly half of whom reported ongoing chest pain. The mean time since Clinic attendance was approximately 8 months and the median duration of ongoing chest pain was 5.4 months. Women were twice as likely as men to continue to be experiencing pain but did not report more frequent or severe pain on average. More than 50% of the non-cardiac group were not convinced by their negative cardiac diagnosis. CONCLUSION: There is an ongoing challenge to support patients with non-cardiac chest pain, including the provision of reassurance that their pain is very unlikely to be caused by their heart.

Cost-effectiveness analysis of open colposuspension versus laparoscopic colposuspension in the treatment of urodynamic stress incontinence.

OBJECTIVES: To compare the cost effectiveness of laparoscopic versus open colposuspension for the treatment of female urinary stress incontinence. DESIGN: Cost utility analysis alongside a randomised controlled trial. SETTING: Six gynaecological surgical centres within the UK. POPULATION/SAMPLE: Women with proven stress urinary incontinence requiring surgery. METHODS: Open abdominal retropubic colposuspension or laparoscopic colposuspension carried out by experienced surgeons. MAIN OUTCOME MEASURES: Cost, measured in pounds sterling and generic health-related quality of life, measured using the EQ-5D. The latter was used to estimate patient-specific quality-adjusted life years (QALYs). RESULTS: Healthcare resource use over 6-month follow up translated into costs of pound 1805 for the laparoscopic arm and pound 1433 for the open arm (differential mean cost pound 372; 95% credibility interval [CrI]: 274-471). At 6 months, QALYs were slightly higher in the laparoscopic arm relative to the open arm (0.005; 95% CrI: -0.012 to 0.023). Therefore, the cost of each extra QALY in the laparoscopic group (the incremental cost-effectiveness ratio [ICER]) was pound 74,400 at 6 months. At 24 months, the laparoscopic arm again had a higher mean QALY score compared to the open surgery group. Thus, assuming that beyond 6 months the laparoscopic colposuspension would not lead to any significant additional costs compared with open colposuspension, the ICER was reduced to pound 9300 at 24 months. Extensive sensitivity analyses were carried out to test assumptions made in the base case scenario. CONCLUSIONS: Laparoscopic colposuspension is not cost effective when compared with open colposuspension during the first 6 months following surgery, but it may be cost effective over 24 months.

Can vitamin D supplementation prevent winter-time blues? A randomised trial among older women.

BACKGROUND: Seasonal Affective Disorder (SAD) is a sub-type of depression that only occurs during the winter months. A reduction in vitamin D may be linked to SAD. Since vitamin D deficiency has been reported to be common in older people, vitamin D supplementation may be expected to reduce seasonal mood disturbance in this group. OBJECTIVE: To assess the effect of vitamin D supplementation on the mental health of older women. SETTING: Primary care in three areas of the UK (Herts, Newcastle, York). SUBJECTS: Women aged 70 years or more recruited to the trial in the months May-October. INTERVENTION: Eligible women were randomised to receive calcium and vitamin D supplementation or no supplementation. OUTCOME MEASURE: At baseline and the six monthly assessment the mental component score (MCS), calculated from the SF-12 questionnaire was used to assess participants' subjective psychological well-being. RESULTS: A total of 2117 women recruited to the trial had their baseline measures taken between the months of May-October (1205 woman in the control group and 912 women in the intervention group). Of these women, 1621 had a MCS score at baseline and six months. Comparison of the six month mean MCS scores, adjusting for baseline MCS score and age, showed there was no significant difference between the two scores (p = 0.262). CONCLUSIONS: Supplementing elderly women with 800 IU of vitamin D daily did not lead to an improvement in mental health scores.

The use of unequal randomisation ratios in clinical trials: a review.

OBJECTIVE: To examine reasons given for the use of unequal randomisation in randomised controlled trials (RCTs). MAIN MEASURES: Setting of the trial; intervention being tested; randomisation ratio; sample size calculation; reason given for randomisation. METHODS: Review of trials using unequal randomisation. DATABASES AND SOURCES: Cochrane library, Medline, Pub Med and Science Citation Index. RESULTS: A total of 65 trials were identified; 56 were two-armed trials and nine trials had more than two arms. Of the two-arm trials, 50 trials recruited patients in favour of the experimental group. Various reasons for the use of unequal randomisation were given. Six studies stated that they used unequal randomisation to reduce the cost of the trial, with one screening trial limited by the availability of the intervention. Other reasons for using unequal allocation were: avoiding loss of power from drop-out or cross-over, ethics and the gaining of additional information on the treatment. Thirty seven trials papers (57%) did not state why they had used unequal randomisation and only 14 trials (22%) appeared to have taken the unequal randomisation into account in their sample size calculation. CONCLUSION: Although unequal randomisation offers a number of advantages to trials the method is rarely used and is especially under-utilised to reduce trial costs. Unequal randomisation should be considered more in trial design especially where there are large differences between treatment costs.

Fingerprinting of polysaccharides attacked by hydroxyl radicals in vitro and in the cell walls of ripening pear fruit.

Hydroxyl radicals (*OH) may cause non-enzymic scission of polysaccharides in vivo, e.g. in plant cell walls and mammalian connective tissues. To provide a method for detecting the action of endogenous *OH in vivo, we investigated the products formed when polysaccharides were treated with *OH (generated in situ by ascorbate-H(2)O(2)-Cu(2+) mixtures) followed by NaB(3)H(4). Treatment with *OH increased the number of NaB(3)H(4)-reacting groups present in citrus pectin, homogalacturonan and tamarind xyloglucan. This increase is attributed partly to the formation of glycosulose and glycosulosuronic acid residues, which are then reduced back to the original (but radioactive) sugar residues and their epimers by NaB(3)H(4). The glycosulose and glycosulosuronic acid residues were stable for >16 h at 20 degrees C in ethanol or buffer (pH 4.7), but were destroyed in alkali. Driselase-digestion of the radiolabelled polysaccharides yielded characteristic patterns of (3)H-products, which included galactose and galacturonate from pectin, and isoprimeverose, galactose, glucose and arabinose from xyloglucan. Pectin yielded at least eight (3)H-labelled anionic products, separable by electrophoresis at pH 3.5. The patterns of radioactive products form useful 'fingerprints' by which *OH-attacked polysaccharides may be recognized. Applied to the cell walls of ripening pear (Pyrus communis) fruit, the method gave evidence for progressive *OH radical attack on polysaccharides during the softening process.