Cynthia P Iglesias

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.

Randomised, controlled trial of alternating pressure mattresses compared with alternating pressure overlays for the prevention of pressure ulcers: PRESSURE (pressure relieving support surfaces) trial

Abstract Objective To compare whether differences exist between alternating pressure overlays and alternating pressure mattresses in the development of new pressure ulcers, healing of existing pressure ulcers, and patient acceptability. Design Pragmatic, open, multicentre, randomised controlled trial. Setting 11 hospitals in six NHS trusts. Participants 1972 people admitted to hospital as acute or elective patients. Interventions Participants were randomised to an alternating pressure mattress (n = 982) or an alternating pressure overlay (n = 990). Main outcome measures The proportion of participants developing a new pressure ulcer of grade 2 or worse; time to development of new pressure ulcers; proportions of participants developing a new ulcer within 30 days; healing of existing pressure ulcers; and patient acceptability. Results Intention to treat analysis found no difference in the proportions of participants developing a new pressure ulcer of grade 2 or worse (10.7% overlay patients, 10.3% mattress patients; difference 0.4%, 95% confidence interval - 2.3% to 3.1%, P = 0.75). More overlay patients requested change owing to dissatisfaction (23.3%) than mattress patients (18.9%, P = 0.02). Conclusion No difference was found between alternating pressure mattresses and alternating pressure overlays in the proportion of people who develop a pressure ulcer. Trial registration ISRCTN 78646179

Systematic review of antimicrobial treatments for diabetic foot ulcers

Background  Foot ulcers in diabetes are associated with increased mortality, illness and reduced quality of life. Ulcer infection impairs healing and antimicrobial interventions may cure infection, aid healing and reduce amputation rates.

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).

The health-related quality of life and cost implications of falls in elderly women

SummaryFractures and falls are serious cause of morbidity and cost to society. Our results suggest that the main burden to morbidity, measured as impact on health-related quality of life, is due to fear of falling rather than falls or their sequelae, such as fractures.IntroductionFractures and falls are serious cause of morbidity and cost to society. We investigated the impact on health-related quality of life (HRQoL) associated with falls, fractures and fear of falling and falls and fractures cost.MethodsThree datasets providing longitudinal data on fear of falling, HRQoL and a common set of baseline risk factors for fracture (smoking status, weight and age) were analysed. Multilevel random effects models were used to estimate the long-term impact on HRQoL associated with falls, fractures and fear of falling. Healthcare resource use primary data were collected to estimate falls and fractures cost.ResultsOlder, low weight and smoking women reported lower HRQoL. The impact on HRQoL of a fracture was at least twice as large as that associated with falls. The largest negative effect on HRQoL was associated with self-reported fear of falling. The cost of falls was £1088. Similarly, the cost of falls leading to a fracture was £15,133, £2,753, £1,863, £1,331 and £3,498 for hip, wrist, arm, vertebral and other fractures, respectively.DiscussionThe main burden to morbidity is due to fear of falling. Interventions aimed at reducing fear of falling may produce larger gains in HRQoL.

Pressure relieving support surfaces (PRESSURE) trial: cost effectiveness analysis

Abstract Objective To assess the cost effectiveness of alternating pressure mattresses compared with alternating pressure overlays for the prevention of pressure ulcers in patients admitted to hospital. Design Cost effectiveness analysis carried out alongside the pressure relieving support surfaces (PRESSURE) trial; a multicentre UK based pragmatic randomised controlled trial. Setting 11 hospitals in six UK NHS trusts. Participants Intention to treat population comprising 1971 participants. Main outcome measures Kaplan Meier estimates of restricted mean time to development of pressure ulcers and total costs for treatment in hospital. Results Alternating pressure mattresses were associated with lower overall costs (£283.6 per patient on average, 95% confidence interval - £377.59 to £976.79) mainly due to reduced length of stay in hospital, and greater benefits (a delay in time to ulceration of 10.64 days on average, - 24.40 to 3.09). The differences in health benefits and total costs for hospital stay between alternating pressure mattresses and alternating pressure overlays were not statistically significant; however, a cost effectiveness acceptability curve indicated that on average alternating pressure mattresses compared with alternating pressure overlays were associated with an 80% probability of being cost saving. Conclusion Alternating pressure mattresses for the prevention of pressure ulcers are more likely to be cost effective and are more acceptable to patients than alternating pressure overlays.

Randomized clinical trial of four-layer and short-stretch compression bandages for venous leg ulcers (VenUS I)

A randomized clinical trial was undertaken to determine the relative effectiveness of four‐layer and short‐stretch bandaging for venous ulceration.

The Cost Effectiveness of Bisphosphonates for the Prevention and Treatment of Osteoporosis: A Structured Review of the Literature

Osteoporotic fragility fractures constitute a significant public health concern. The lifetime risk of any osteoporotic fracture is very high (40–50% in women and 13–22% in men). Fractures are associated with significant mortality and morbidity and represent a substantial economic burden to society. Bisphosphonates (alendronate, etidronate, risedronate and ibandronate) are indicated for the treatment and prevention of osteoporosis but are costly compared with other treatments, such as vitamin D and calcium.Our search identified 23 studies evaluating the cost effectiveness of bisphosphonate therapy for the treatment and prevention of fragility fractures; these studies were from five geographical areas and employed a variety of comparators and assumptions. We identified 11 studies investigating bisphosphonates in women with low bone mineral density (BMD) [T-score >2.5 standard deviations {SDs} below normal {mean} peak values for young adults] and previous fractures, five studies investigating bisphosphonates in women with low BMD and no previous fracture, one study of bisphosphonates in women with osteopenia, five studies involving screening and two studies of bisphosphonates in special populations (women initiating corticosteroid treatment and men).In women with low BMD and previous fractures, bisphosphonate therapy was most cost effective in populations aged ≥70 years and was unlikely to be cost effective in populations aged ≤50 years. There was uncertainty concerning the cost effectiveness of bisphosphonates in such populations aged 60–69 years. In women with low BMD without previous fractures, treatment with alendronate or risedronate appeared to be cost effective across countries (UK, US, Denmark), but there was some uncertainty about the cost effectiveness of etidronate in patients in the highest age groups.Identifying risk factors for fractures through means such as spine radiographs to detect vertebral deformities improves the cost effectiveness of treatment. In women with osteopenia, alendronate therapy may be cost effective in women with a T-score of -2.4SD in the US. Screening for low BMD and treatment with alendronate or etidronate appears to be cost effective in postmenopausal women in general and in women with rheumatoid arthritis initiating corticosteroid therapy. Alendronate therapy without screening was also shown to be potentially cost effective in certain at-risk male populations, as well as in women initiating corticosteroid therapy after the age of 40 years.Decision makers in the US, UK and Sweden should consider funding the use of bisphosphonates for the prevention and treatment of osteoporosis in women aged >70 years, particularly if they have other risk factors for fracture. Further studies are required to make more definitive conclusions in other countries and patient populations. Screening strategies for low BMD followed by bisphosphonate treatment should also be considered in the general female population aged >65 years in the UK and US and in patients with rheumatoid arthritis initiating corticosteroid therapy.

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;