Economic evaluation alongside a phase II, multi-centre, randomised controlled trial of very early rehabilitation after stroke (AVERT)

BACKGROUND/PURPOSE: The effectiveness and costs of very early rehabilitation after stroke are unknown. This study assessed the cost effectiveness of very early mobilisation in addition to standard care (VEM) compared with standard care alone (SC). METHODS: Cost-effectiveness analysis alongside a phase II, multi-centre, randomised controlled trial (RCT) with blinded outcome assessments. Less than 24 h after stroke, patients were recruited from two stroke units and randomised to receive VEM or SC. The intervention continued until discharge or 14 days, whichever was sooner. The efficacy measure was a dichotomised modified Rankin Scale (mRS) at 3 months with mRS < or =2 representing good outcome. Costs were determined from medical records and patient interviews at 3, 6 and 12 months. National average (where available) or local costs were applied for the reference year 2004. Differences in mean total costs at 3 and 12 months were tested using t test assuming unequal variances. An incremental cost-effectiveness ratio was calculated and probabilistic uncertainty analysis was undertaken. RESULTS: The sample consisted of 38 VEM and 33 SC patients. A trend for good outcome with VEM compared to SC was found (adjusted OR 4.10, 95% CI 0.99-16.88, p = 0.051). Patients receiving VEM incurred significantly less costs at 3 months (AUD 13,559) compared with SC (AUD 21,860; p = 0.02). This difference in mean per patient total cost persisted at the 12-month assessment (VEM: AUD 17,564; SC: AUD 29,750; p = 0.03). VEM was found to be a 'dominant' (more effective, less cost) intervention when compared to SC at 3 months. CONCLUSION: These findings provide preliminary evidence that VEM is likely to be cost-effective. A large RCT is currently underway to confirm the cost effectiveness of VEM.

Effects of a multi-component exercise program and calcium–vitamin-D3-fortified milk on bone mineral density in older men : a randomised controlled trial

Summary We examined the independent and combined effects of a multi-component exercise program and calcium–vitamin-D3-fortified milk on bone mineral density (BMD) in older men. Exercise resulted in a 1.8% net gain in femoral neck BMD, but additional calcium–vitamin D3 did not enhance the response in this group of older well-nourished men.

Introduction This 12-month randomised controlled trial assessed whether calcium–vitamin-D3-fortified milk could enhance the effects of a multi-component exercise program on BMD in older men.

Methods Men (n  = 180) aged 50–79 years were randomised into: (1) exercise + fortified milk; (2) exercise; (3) fortified milk; or (4) controls. Exercise consisted of high intensity progressive resistance training with weight-bearing impact exercise. Men assigned to fortified milk consumed 400 mL/day of low fat milk providing an additional 1,000 mg/day calcium and 800 IU/day vitamin D3. Femoral neck (FN), total hip, lumbar spine and trochanter BMD and body composition (DXA), muscle strength 25-hydroxyvitamin D and parathyroid hormone (PTH) were assessed.

Results There were no exercise-by-fortified milk interactions at any skeletal site. Exercise resulted in a 1.8% net gain in FN BMD relative to no-exercise (p < 0.001); lean mass (0.6 kg, p < 0.05) and muscle strength (20–52%, p < 0.001) also increased in response to exercise. For lumbar spine BMD, there was a net 1.4–1.5% increase in all treatment groups relative to controls (all p < 0.01). There were no main effects of fortified milk at any skeletal site.

Conclusion A multi-component community-based exercise program was effective for increasing FN BMD in older men, but additional calcium–vitamin D3 did not enhance the osteogenic response.

Use of a decision aid for prenatal testing of fetal abnormalities to improve women's informed decision making: a cluster randomised controlled trial [ISRCTN22532458]

Objective To evaluate the effectiveness of a decision aid for prenatal testing of fetal abnormalities compared with a pamphlet in supporting women's decision making.
Design A cluster randomised controlled trial.
Setting Primary health care.
Population Women in early pregnancy consulting a GP.
Methods GPs were randomised to provide women with either a decision aid or a pamphlet. The decision aid was a 24-page booklet designed using the Ottowa Decision Framework. The pamphlet was an existing resource available in the trial setting.
Main outcome measures Validated scales were used to measure the primary outcomes, informed choice and decisional conflict, and the secondary outcomes, anxiety, depression, attitudes to the pregnancy/fetus and acceptability of the resource. Outcomes were measured at 14 weeks of gestation from questionnaires that women completed and returned by post.
Findings Women in the intervention group were more likely to make an informed decision 76% (126/165) than those in the control group 65% (107/165) (adjusted OR 2.08; 95% CI 1.14–3.81). A greater proportion of women in the intervention group 88% (147/167) had a 'good' level of knowledge than those in the control group 72% (123/171) (adjusted OR 3.43; 95% CI 1.79–6.58). Mean (SD) decisional conflict scores were low in both groups, decision aid 1.71 (0.49), pamphlet 1.65 (0.55) (adjusted mean difference 0.10; 95% CI −0.02 to 0.22). There was no strong evidence of differences between the trial arms in the measures of psychological or acceptability outcomes.
Conclusion A tailored prenatal testing decision aid plays an important role in improving women's knowledge of first and second trimester screening tests and assisting them to make decisions about screening and diagnostic tests that are consistent with their values.

Evaluation of nasopharyngeal oxygen, nasal prongs and facemask oxygen therapy devices in adult patients: a randomised crossover trial

Nasopharyngeal oxygen (NPO) therapy may overcome some of the difficulties associated with nasal prongs and facemask oxygen delivery devices. In response to a lack of published studies of NPO therapy in adults, we conducted a prospective randomised crossover trial to compare the effectiveness of NPO, nasal prongs (NP) and facemasks (FM) when used in an adult population (n=37) from the intensive care unit and general hospital wards. We measured oxygen saturation (Sp[O.sub.2]) using pulse oximetry, oxygen flow (litres per minute), respiration rate (per minute) and comfort using a horizontal visual analogue scale. All three devices were effective in maintaining a Sp[O.sub.2] of [greater than or equal to]95% (NP 97.0[+ or -]1.9, NPO 97.7[+ or -]1.7, FM 98.8[+ or -]1.3%). NPO therapy consumed less oxygen than NP and FM therapy (NP 2.6[+ or -]1.0, NPO 2.2[+ or -]0.9, FM 6.1[+ or -]0.4 l/min, P <0.001). There was no significant difference in patients' respiratory rates (NP 19.9[+ or -]3.2, NPO 19.9[+ or -]3.0, FM 19.8[+ or -]3.1 per minute, P=0.491). In terms of comfort, patients rated NP higher than NPO and FM using a horizontal visual analogue scale (100 mm=most comfortable) (NP 65.5[+ or -]14.3, NPO 62.8[+ or -]19.4, FM 49.4[+ or -]21.4 mm, P <0.001). We conclude that for adult patients, nasal prongs and nasopharyngeal oxygen therapy consume less oxygen and provide greater comfort than facemasks while still maintaining Sp[O.sub.2] [greater than or equal to]95%.

Effects of laterally wedged insoles on symptoms and disease progression in medial knee osteoarthritis: a protocol for a randomised, double-blind, placebo controlled trial

Background: Whilst laterally wedged insoles, worn inside the shoes, are advocated as a simple, inexpensive, non-toxic self-administered intervention for knee osteoarthritis (OA), there is currently limited evidence to support their use. The aim of this randomised, double-blind controlled trial is to determine whether laterally wedges insoles lead to greater improvements in knee pain, physical function and health-related quality of life, and slower structural disease progression as well as being more cost-effective, than control flat insoles in people with medial knee OA.

Methods/Design: Two hundred participants with painful radiographic medial knee OA and varus malalignment will be recruited from the community and randomly allocated to lateral wedge or control insole groups using concealed allocation. Participants will be blinded as to which insole is considered therapeutic. Blinded follow up assessment will be conducted at 12 months after randomisation. The outcome measures are valid and reliable measures recommended for OA clinical trials. Questionnaires will assess changes in pain, physical function and health-related quality-of-life. Magnetic resonance imaging will measure changes in tibial cartilage volume. To evaluate cost-effectiveness, participants will record the use of all health-related treatments in a log-book returned to the assessor on a monthly basis. To test the effect of the intervention using an intention-to-treat analysis, linear regression modelling will be applied adjusting for baseline outcome values and other demographic characteristics.

Discussion: Results from this trial will contribute to the evidence regarding the effectiveness of laterally wedged insoles for the management of medial knee OA.

Trial registration: ACTR12605000503628; NCT00415259.

Efficacy and safety of vertebroplasty for treatment of painful osteoporotic vertebral fractures: a randomised controlled trial [ACTRN012605000079640]

Background: Vertebroplasty is a promising but as yet unproven treatment for painful osteoporotic vertebral fractures. It involves radiographic-guided injection of various types of bone cement directly into the vertebral fracture site. Uncontrolled studies and two controlled quasi-experimental before-after studies comparing volunteers who were offered treatment to those who refused it, have suggested an early benefit including rapid pain relief and improved function. Conversely, several uncontrolled studies and one of the controlled before-after studies have also suggested that vertebroplasty may increase the risk of subsequent vertebral fractures, particularly in vertebrae adjacent to treated levels or if cement leakage into the adjacent disc has occurred. As yet, there are no completed randomised controlled trials of vertebroplasty for osteoporotic vertebral fractures. The aims of this participant and outcome assessor-blinded randomised placebo-controlled trial are to i) determine the short-term efficacy and safety (3 months) of vertebroplasty for alleviating pain and improving function for painful osteoporotic vertebral fractures; and ii) determine its medium to longer-term efficacy and safety, particularly the risk of further fracture over 2 years.

Design: A double-blind randomised controlled trial of 200 participants with one or two recent painful osteoporotic vertebral fractures. Participants will be stratified by duration of symptoms (< and ≥ 6 weeks), gender and treating radiologist and randomly allocated to either the treatment or placebo. Outcomes will be assessed at baseline, 1 week, 1, 3, 6, 12 and 24 months. Outcome measures include overall, night and rest pain on 10 cm visual analogue scales, quality of life measured by the Assessment of Quality of Life, Osteoporosis Quality of Life and EQ-5D questionnaires; participant perceived recovery on a 7-point ordinal scale ranging from 'a great deal worse' to 'a great deal better'; disability measured by the Roland-Morris Disability Questionnaire; timed 'Up and Go' test; and adverse effects. The presence of new fractures will be assessed by radiographs of the thoracic and lumbar spine performed at 12 and 24 months.

Discussion: The results of this trial will be of major international importance and findings will be immediately translatable into clinical practice.

Trial registration: Australian Clinical Trial Register # [ACTRN012605000079640]

Outcomes and costs of primary care surveillance and intervention for overweight or obese children : the LEAP 2 randomised controlled trial

Objective To determine whether ascertainment of childhood obesity by surveillance followed by structured secondary prevention in primary care improved outcomes in overweight or mildly obese children.

Design Randomised controlled trial nested within a baseline cross sectional survey of body mass index (BMI). Randomisation and outcomes measurement, but not participants, were blinded to group assignment.

Setting 45 family practices (66 general practitioners) in Melbourne, Australia.

Participants 3958 children visiting their general practitioner in May 2005-July 2006 were surveyed for BMI. Of these, 258 children aged 5 years 0 months up to their 10th birthday who were overweight or obese by International Obesity Taskforce criteria were randomised to intervention (n=139) or control (n=119) groups. Children who were very obese (UK BMI z score 3.0) were excluded.

Intervention Four standard consultations over 12 weeks targeting change in nutrition, physical activity, and sedentary behaviour, supported by purpose designed family materials.

Main outcomes measures Primary measure was BMI at 6 and 12 months after randomisation. Secondary measures were mean activity count/min by 7-day accelerometry, nutrition score from 4-day abbreviated food frequency diary, and child health related quality of life. Differences were adjusted for socioeconomic status, age, sex, and baseline BMI.

Results Of 781 eligible children, 258 (33%) entered the trial; attrition was 3.1% at 6 months and 6.2% at 12 months. Adjusted mean differences (intervention – control) at 6 and 12 months were, for BMI, –0.12 (95% CI –0.40 to 0.15, P=0.4) and –0.11 (–0.45 to 0.22, P=0.5); for physical activity in counts/min, 24 (–4 to 52, P=0.09) and 11 (–26 to 49, P=0.6); and, for nutrition score, 0.2 (–0.03 to 0.4, P=0.1) and 0.1 (–0.1 to 0.4, P=0.2). There was no evidence of harm to the child. Costs to the healthcare system were significantly higher in the intervention arm.

Conclusions Primary care screening followed by brief counselling did not improve BMI, physical activity, or nutrition in overweight or mildly obese 5-10 year olds, and it would be very costly if universally implemented. These findings are at odds with national policies in countries including the US, UK, and Australia.

Adolescents' use of purpose built shade in secondary schools : cluster randomised controlled trial

Objective To examine whether students use or avoid newly shaded areas created by shade sails installed at schools.

Design Cluster randomised controlled trial with secondary schools as the unit of randomisation.

Setting 51 secondary schools with limited available shade, in Australia, assessed over two spring and summer terms.

Participants Students outside at lunch times.

Intervention Purpose built shade sails were installed in winter 2005 at full sun study sites to increase available shade for students in the school grounds.

Main outcome measure Mean number of students using the primary study sites during weekly observations at lunch time.

Results Over the study period the mean change in students using the primary study site from pre-test to post-test was 2.63 (95% confidence interval 0.87 to 4.39) students in intervention schools and –0.03 (–1.16 to 1.09) students in control schools. The difference in mean change between groups was 2.67 (0.65 to 4.68) students (P=0.011).

Conclusions Students used rather than avoided newly shaded areas provided by purpose built shade sails at secondary schools in this trial, suggesting a practical means of reducing adolescents’ exposure to ultraviolet radiation.

Trial registration Exempt.

Beating the blues after cancer : randomised control trial of a tele-based psychological intervention for high distress patients and carers

Background : The diagnosis and treatment of cancer is a major life stress such that approximately 35% of patients experience persistent clinically significant distress and carers often experience even higher distress than patients. This paper presents the design of a two arm randomised controlled trial with patients and carers who have elevated psychological distress comparing minimal contact self management vs. an individualised tele-based cognitive behavioural intervention.

Methods/design : 140 patients and 140 carers per condition (560 participants in total) will been recruited after being identified as high distress through caller screening at two community-based cancer helplines and randomised to 1) a single 30-minute telephone support and education session with a nurse counsellor with self management materials 2) a tele-based psychologist delivered five session individualised cognitive behavioural intervention. Session components will include stress reduction, problem-solving, cognitive challenging and enhancing relationship support and will be delivered weekly. Participants will be assessed at baseline and 3, 6 and 12 months after recruitment. Outcome measures include: anxiety and depression, cancer specific distress, unmet psychological supportive care needs, positive adjustment, overall Quality of life.

Discussion : The study will provide recommendations about the efficacy and potential economic value of minimal contact self management vs. tele-based psychologist delivered cognitive behavioural intervention to facilitate better psychosocial adjustment and mental health for people with cancer and their carers.

Efficacy and safety of vertebroplasty for treatment of painful osteoporotic vertebral fractures : a randomised double-blind placebo-controlled trial

Background: Vertebroplasty has become a common treatment for painful osteoporotic vertebral fractures despite limited evidence to support its use. The primary aim of this study was to determine its short-term efficacy and safety in this patient population.

Methods: In a multicentre randomized placebo-controlled trial, participants with one or two painful osteoporotic vertebral fractures < 12 months duration confirmed active by MRI were randomly assigned, stratified by center, gender and duration of symptoms (< or ≥ 6 weeks), to receive vertebroplasty or sham treatment. Primary outcome was overall pain (0–10 scale) at 3 months. Participants, investigators (other than the interventional radiologist) and outcome assessors were blinded to treatment assignment.

Results: 78 participants were enrolled and 73 (36/38 active, 37/40 placebo, 94%) completed 3-month follow up. Vertebroplasty did not show any statistically significant advantage in any measured outcome with 95% confidence intervals indicating no plausible practically important benefits of vertebroplasty over placebo. At 1 week, 1 and 3 months, there were significant improvements in overall pain in both treatment groups (mean improvement (SD): 1.5 (2.5), 2.1 (2.8), 2.3 (2.6), and 1.7 (3.3), 2.5 (2.9), 1.9 (3.4) in the active and placebo groups respectively). Similar improvements in both groups were observed for night and rest pain, function, quality of life and perceived improvement. Eight incident clinical vertebral fractures (3 active, 5 placebo) occurred during 3-month follow up.

Conclusion: We found no evidence of a beneficial effect of vertebroplasty over sham treatment for painful osteoporotic vertebral fractures, 1 week, 1 and 3 months following treatment. [Australian Clinical Trial Register number, ACTRN012605000079640]

The role of focus groups in a randomised controlled trial : the ADEPT study

In a recent study we developed a decision aid for prenatal testing of fetal abnormalities. The effectiveness of the decision aid compared with a pamphlet in increasing women's informed choice and decreasing conflict was evaluated using a cluster randomised controlled trial, A DEcision aid for Prenatal Testing for fetal abnormalities (ADEPT) [ISRCTN22532458]. Challenged with the need to ensure that the decision aid best suited the needs of women and health professionals involved General Practitioners (GPs), we explored the potential of both quantitative and qualitative methodologies to inform the development phase. In this article we discuss our rationale for, and provide some insights regarding our experience of, using qualitative methods during the development phase of the decision aid.