No effect of n - 3 long-chain polyunsaturated fatty acid (EPA and DHA) supplementation on depressed mood and cognitive function : a randomised controlled trial

Low dietary intakes of the n-3 long-chain PUFA (LCPUFA) EPA and DHA are thought to be associated with increased risk for a variety of adverse  outcomes, including some psychiatric disorders. Evidence from  observational and intervention studies for a role of n-3 LCPUFA in depression is mixed, with some support for a benefit of EPA and/or DHA in major depressive illness. The present study was a double-blind randomised controlled trial that evaluated the effects of EPA+DHA supplementation (1.5 g/d) on mood and cognitive function in mild to moderately depressed  individuals. Of 218 participants who entered the trial, 190 completed the planned 12 weeks intervention. Compliance, confirmed by plasma fatty acid concentrations, was good, but there was no evidence of a difference between supplemented and placebo groups in the primary outcome - namely, the depression subscale of the Depression Anxiety and Stress Scales at 12 weeks. Mean depression score was 8.4 for the EPA+DHA group and 9.6 for the placebo group, with an adjusted difference of - 1.0 (95 % CI - 2.8, 0.8; P = 0.27). Other measures of mood, mental health and cognitive function, including Beck Depression Inventory score and attentional bias toward threat words, were similarly little affected by the intervention. In conclusion, substantially increasing EPA+DHA intake for 3 months was found not to have beneficial or harmful effects on mood in mild to moderate depression. Adding the present result to a meta-analysis of previous relevant randomised controlled trial results confirmed an overall negligible benefit of n-3 LCPUFA supplementation for depressed mood.

COSMOS: COmparing standard maternity care with one-to-one midwifery support: a randomised controlled trial

Background: In Australia and internationally, there is concern about the growing proportion of women giving birth by caesarean section. There is evidence of increased risk of placenta accreta and percreta in subsequent pregnancies as well as decreased fertility; and significant resource implications. Randomised controlled trials (RCTs) of continuity of midwifery care have reported reduced caesareans and other interventions in labour, as well as increased maternal satisfaction, with no statistically significant differences in perinatal morbidity or mortality. RCTs conducted in the UK and in Australia have largely measured the effect of teams of care providers (commonly 6–12 midwives) with very few testing caseload (one-to-one) midwifery care. This study aims to determine whether caseload (one-to-one) midwifery care for women at low risk of medical complications decreases the proportion of women delivering by caesarean section compared with women receiving 'standard' care. This paper presents the trial protocol in detail.

Methods/design: A two-arm RCT design will be used. Women who are identified at low medical risk will be recruited from the antenatal booking clinics of a tertiary women's hospital in Melbourne, Australia. Baseline data will be collected, then women randomised to caseload midwifery or standard low risk care. Women allocated to the caseload intervention will receive antenatal, intrapartum and postpartum care from a designated primary midwife with one or two antenatal visits conducted by a 'back-up' midwife. The midwives will collaborate with obstetricians and other health professionals as necessary. If the woman has an extended labour, or if the primary midwife is unavailable, care will be provided by the back-up midwife. For women allocated to standard care, options include midwifery-led care with varying levels of continuity, junior obstetric care and community based general medical practitioner care. Data will be collected at recruitment (self administered survey) and at 2 and 6 months postpartum by postal survey. Medical/obstetric outcomes will be abstracted from the medical record. The sample size of 2008 was calculated to identify a decrease in caesarean birth from 19 to 14% and detect a range of other significant clinical differences. Comprehensive process and economic evaluations will be conducted.

Trial registration: Australian New Zealand Clinical Trials Registry ACTRN012607000073404.

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.

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%.

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]

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.