Jo C Dumville

Randomised controlled trial of calcium and supplementation with cholecalciferol (vitamin D3) for prevention of fractures in primary care

Abstract Objective To assess whether supplementation with calcium and cholecaliferol (vitamin D3) reduces the risk of fracture in women with one or more risk factors for fracture of the hip. Design Pragmatic open randomised controlled trial. Setting Practice nurse led clinics in primary care. Participants 3314 women aged 70 and over with one or more risk factors for hip fracture: any previous fracture, low body weight (< 58 kg), smoker, family history of hip fracture, or fair or poor self reported health. Intervention Daily oral supplementation using 1000 mg calcium with 800 IU cholecaliferol and information leaflet on dietary calcium intake and prevention of falls, or leaflet only (control group). Main outcome measures Primary outcome measure was all clinical fractures and secondary outcome measures were adherence to treatment, falls, and quality of life (measured with the SF-12). Results 69% of the women who completed the follow-up questionnaire at 24 months were still taking supplements (55% with inclusion of randomised participants known to be alive). After a median follow-up of 25 months (range 18 to 42 months), clinical fracture rates were lower than expected in both groups but did not significantly differ for all clinical fractures (odds ratio for fracture in supplemented group 1.01, 95% confidence interval 0.71 to 1.43). The odds ratio for hip fracture was 0.75 (0.31 to 1.78). The odds of a woman having a fall at six and 12 months was 0.99 and 0.98, respectively. Quality of life did not significantly differ between the groups. Conclusion We found no evidence that calcium and vitamin D supplementation reduces the risk of clinical fractures in women with one or more risk factors for hip fracture. Registration ISRCTN26118436, controlled trials registry.

Larval therapy for leg ulcers (VenUS II): randomised controlled trial

Objective To compare the clinical effectiveness of larval therapy with a standard debridement technique (hydrogel) for sloughy or necrotic leg ulcers. Design Pragmatic, three armed randomised controlled trial. Setting Community nurse led services, hospital wards, and hospital outpatient leg ulcer clinics in urban and rural settings, United Kingdom. Participants 267 patients with at least one venous or mixed venous and arterial ulcer with at least 25% coverage of slough or necrotic tissue, and an ankle brachial pressure index of 0.6 or more. Interventions Loose larvae, bagged larvae, and hydrogel. Main outcome measures The primary outcome was time to healing of the largest eligible ulcer. Secondary outcomes were time to debridement, health related quality of life (SF-12), bacterial load, presence of meticillin resistant Staphylococcus aureus, adverse events, and ulcer related pain (visual analogue scale, from 0 mm for no pain to 150 mm for worst pain imaginable). Results Time to healing was not significantly different between the loose or bagged larvae group and the hydrogel group (hazard ratio for healing using larvae v hydrogel 1.13, 95% confidence interval 0.76 to 1.68; P=0.54). Larval therapy significantly reduced the time to debridement (2.31, 1.65 to 3.2; P<0.001). Health related quality of life and change in bacterial load over time were not significantly different between the groups. 6.7% of participants had MRSA at baseline. No difference was found between larval therapy and hydrogel in their ability to eradicate MRSA by the end of the debridement phase (75% (9/12) v 50% (3/6); P=0.34), although this comparison was underpowered. Mean ulcer related pain scores were higher in either larvae group compared with hydrogel (mean difference in pain score: loose larvae v hydrogel 46.74 (95% confidence interval 32.44 to 61.04), P<0.001; bagged larvae v hydrogel 38.58 (23.46 to 53.70), P<0.001). Conclusions Larval therapy did not improve the rate of healing of sloughy or necrotic leg ulcers or reduce bacterial load compared with hydrogel but did significantly reduce the time to debridement and increase ulcer pain. Trial registration Current Controlled Trials ISRCTN55114812 and National Research Register N0484123692.

Reporting attrition in randomised controlled trials

Loss to follow-up can greatly affect the strength of a trials findings. But most reports do not give readers enough information for them to be able to understand the potential effects

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.

Clinical and cost-effectiveness of compression hosiery versus compression bandages in treatment of venous leg ulcers (Venous leg Ulcer Study IV, VenUS IV): a randomised controlled trial

BACKGROUND Drawbacks exist with the standard treatment (four-layer compression bandages) for venous leg ulcers. We have therefore compared the clinical effectiveness and cost-effectiveness of two-layer compression hosiery with the four-layer bandage for the treatment of such ulcers. METHODS We undertook this pragmatic, open, randomised controlled trial with two parallel groups in 34 centres in England and Northern Ireland. The centres were community nurse teams or services, family doctor practices, leg ulcer clinics, tissue viability clinics or services, and wound clinics. Participants were aged 18 years or older with a venous leg ulcer and an ankle brachial pressure index of at least 0·8, and were tolerant of high compression. We randomly allocated participants (1:1) to receive two-layer compression hosiery or a four-layer bandage, using a remote randomisation service and prevalidated computer randomisation program. Participants were stratified by ulcer duration and ulcer area with permuted blocks (block sizes four and six). The primary endpoint was time to ulcer healing, with a maximum follow-up of 12 months. Although participants and health-care providers were not masked to treatment allocation, the primary endpoint was measured by masked assessment of photographs. Primary analysis was intention to treat with Cox regression, with adjustment for ulcer area, ulcer duration, physical mobility, and centre. This trial is registered with the ISRCTN register, number ISRCTN49373072. FINDINGS We randomly allocated 457 participants to the two treatment groups: 230 to two-layer hosiery and 227 to the four-layer bandage, of whom 453 (230 hosiery and 223 bandage) contributed data for analysis. Median time to ulcer healing was 99 days (95% CI 84-126) in the hosiery group and 98 days (85-112) in the bandage group, and the proportion of ulcers healing was much the same in the two groups (70·9% hosiery and 70·4% bandage). More hosiery participants changed their allocated treatment (38·3% hosiery vs 27·0% bandage; p=0·02). 300 participants had 895 adverse events, of which 85 (9·5%) were classed as serious but unrelated to trial treatment. INTERPRETATION Two-layer compression hosiery is a viable alternative to the four-layer bandage-it is equally as effective at healing venous leg ulcers. However, a higher rate of treatment changes in participants in the hosiery group than in the bandage group suggests that hosiery might not be suitable for all patients. FUNDING NIHR Health Technology Assessment programme (07/60/26).

Prehabilitation prior to CABG surgery improves physical functioning and depression.

Background Many patients demonstrate psychological distress and reduced physical activity before coronary artery bypass graft surgery (CABG). Here we evaluated the addition of a brief, cognitive-behavioural intervention (the HeartOp Programme) to routine nurse counselling for people waiting for CABG surgery. Methods Randomised controlled trial comparing nurse counselling with the HeartOp programme to routine nurse counselling in 204 patients awaiting first time elective CABG. Primary outcome measures were: anxiety and length of hospital stay; secondary outcome measures were: depression, physical functioning, cardiac misconceptions and cost utility. Measures were collected prior to randomisation and after 8 weeks of their intervention prior to surgery, excepting length of hospital stay which was collected after discharge following surgery. Results 100 patients were randomised to intervention, 104 to control. At follow-up there were no differences in anxiety or length of hospital stay. There were significant differences in depression (difference = 7.79, p = 0.008, 95% CI = 2.04–13.54), physical functioning (difference = 0.82, p = 0.001, 95%CI = 0.34–1.3) and cardiac misconceptions (difference = 2.56, p < 0.001, 95%CI = 1.64–3.48) in favour of the HeartOp Programme. The only difference to be maintained following surgery was in cardiac misconceptions. The HeartOp Programme was found to have an Incremental Cost Effectiveness Ratio (ICER) of £288.83 per Quality-Adjusted Life Year. Conclusions Nurse counselling with the HeartOp Programme reduces depression and cardiac misconceptions and improves physical functioning before bypass surgery significantly more than nurse counselling alone and meets the accepted criteria for cost efficacy.

Silver treatments for leg ulcers : a systematic review

To determine the quantity and quality of current research on the effectiveness of silver‐based dressings and topical agents for the treatment of leg ulcers, this paper presents a systematic review of randomized controlled trials (RCTs) looking at the effects of silver‐based dressings and topical agents on leg ulcer healing. Electronic databases were searched up to May 2006 for relevant randomized controlled trials. Journals and conference proceedings were also searched. The methodological quality of selected trials was assessed and statistical pooling of the results from similar studies undertaken. Rate of healing, proportion of ulcers completely healed and change in ulcer size were observed. Nine studies were considered eligible for inclusion. These studies varied in terms of the types of leg ulcers treated, interventions used, and outcomes assessed. Studies provided inconsistent evidence regarding the effects of silver‐based dressings and topical agents on leg ulcer healing. Studies generally provided poor evidence due to a lack of statistical power, poor study designs, and incomplete reporting. In conclusion, the current evidence base on the use of these silver‐based products on leg ulcers is limited, both in terms of the quantity available and the quality of the evidence. This review highlights the need for further, more rigorous research to be carried out before the use of these silver‐based interventions in routine leg ulcer management is supported.

Cost effectiveness analysis of larval therapy for leg ulcers

Objective To assess the cost effectiveness of larval therapy compared with hydrogel in the management of leg ulcers. Design Cost effectiveness and cost utility analyses carried out alongside a pragmatic multicentre, randomised, open trial with equal randomisation. Population Intention to treat population comprising 267 patients with a venous or mixed venous and arterial ulcers with at least 25% coverage of slough or necrotic tissue. Interventions Patients were randomly allocated to debridement with bagged larvae, loose larvae, or hydrogel. Main outcome measure The time horizon was 12 months and costs were estimated from the UK National Health Service perspective. Cost effectiveness outcomes are expressed in terms of incremental costs per ulcer-free day (cost effectiveness analysis) and incremental costs per quality adjusted life years (cost utility analysis). Results The larvae arms were pooled for the main analysis. Treatment with larval therapy cost, on average, £96.70 (€109.61;

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

140.57) more per participant per year (95% confidence interval −£491.9 to £685.8) than treatment with hydrogel. Participants treated with larval therapy healed, on average, 2.42 days before those in the hydrogel arm (95% confidence interval −0.95 to 31.91 days) and had a slightly better health related quality of life, as the annual difference in QALYs was 0.011 (95% confidence interval −0.067 to 0.071). However, none of these differences was statistically significant. The incremental cost effectiveness ratio for the base case analysis was estimated at £8826 per QALY gained and £40 per ulcer-free day. Considerable uncertainty surrounds the outcome estimates. Conclusions Debridement of sloughy or necrotic leg ulcers with larval therapy is likely to produce similar health benefits and have similar costs to treatment with hydrogel. Trial registration Current Controlled Trials ISRCTN55114812 and National Research Register N0484123692.

Assessing the impact of attrition in randomized controlled trials

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.