Single vs. two steroid injections for carpal tunnel syndrome: a randomised clinical trial

We investigated the efficacy of a single vs. double steroid injections in the treatment of carpal tunnel syndrome (CTS) in a randomised double-blind controlled trial. Patients with idiopathic CTS were randomised into (i) one group receiving a baseline methylprednisolone acetate injection plus a saline injection 8 weeks later and (ii) a second group receiving methylprednisolone acetate injection at baseline and at 8 weeks. The primary outcome was the Global Symptom Score (GSS). Forty patients were recruited. By 40 weeks, the mean GSS improved from 25.6 to 14.1 in the single-injection group whereas from 26.7 to 12.6 in the reinjection group, but there was no significant difference in GSS between the two groups (p = 0.26). There were also no significant differences in terms of electrophysiological and functional outcomes. The results suggest that an additional steroid injection confers no added benefit to a single injection in terms of symptom relief.

Application of the gradient boosted method in randomised clinical trials: participant variables that contribute to depression treatment efficacy of duloxetine, SSRIs or placebo

Randomised, placebo-controlled trials of treatments for depression typically collect outcomes data but traditionally only analyse data to demonstrate efficacy and safety. Additional post-hoc statistical techniques may reveal important insights about treatment variables useful when considering inter-individual differences amongst depressed patients. This paper aims to examine the Gradient Boosted Model (GBM), a statistical technique that uses regression tree analyses and can be applied to clinical trial data to identify and measure variables that may influence treatment outcomes.

Assessing randomised clinical trials of cognitive and exposure therapies for gambling disorders : a systematic review

Aims: Problem or pathological gambling is associated with significant disruption to the individual, family and community with a range of adverse outcomes, including legal, financial and mental health impairment. It occurs more frequently in younger populations, and comorbid conditions are common. Cognitive–behaviour therapy (CBT) is the most empirically established class of treatments for problematic gambling. This article reports on a systematic review and evaluation of randomised clinical trials (RCTs) concerning two core techniques of CBT: cognitive and behavioural (exposure-based) therapies. Methods: PsycINFO, MEDLINE and the Cochrane library were searched from database inception to December 2012. The CONsolidated Standards Of Reporting Trials (CONSORT) for non-pharmacological treatments was used to evaluate each study. Results: The initial search identified 104 references. After two screening phases, seven RCTs evaluating either cognitive (n = 3), exposure (n = 3) or both (n = 1) interventions remained. The studies were published between 1983 and 2003 and conducted across Australia, Canada, and Spain. On average, approximately 31% of CONSORT items were rated as ‘absent’ for each study and more than 52% rated as ‘present with some limitations’. For all studies, 70.83% of items rated as ‘absent’ were in the methods section. Conclusions: The findings from this review of randomised clinical trials involving cognitive and exposure-based treatments for gambling disorders show that the current evidence base is limited. Trials with low risk of bias are needed to be reported before recommendations are given on their effectiveness and clinicians can appraise their potential utility with confidence.

Does interpersonal psychotherapy improve clinical care for adolescents with depression attending a rural child and adolescent mental health service? Study protocol for a cluster randomised feasibility trial

Background: Depression amongst adolescents is a costly societal problem. Little research documents the effectiveness of public mental health services in mapping this problem. Further, it is not clear whether usual care in such services can be improved via clinician training in a relevant evidence based intervention. One such intervention, found to be effective and easily learned amongst novice clinicians, is Interpersonal Psychotherapy (IPT). The study described in the current paper has two main objectives. First, it aims to investigate the impact on clinical care of implementing Interpersonal Psychotherapy for Adolescents for the treatment of adolescent depression within a rural mental health service compared with Treatment as Usual (TAU). The second objective is to record the process and challenges (i.e. feasibility, acceptability, sustainability) associated with implementing and evaluating an evidence-based intervention within a community service. This paper outlines the study rationale and design for this community based research trial.

Methods/design: The study involves a cluster randomisation trial to be conducted within a Child and Adolescent Mental Health Service in rural Australia. All clinicians in the service will be invited to participate.  Participating clinicians will be randomised via block design at each of four sites to (a) training and delivery of IPT, or (b) TAU. The primary measure of impact on care will be a clinically significant change in depressive  symptomatology, with secondary outcomes involving treatment satisfaction and changes in other symptomatology. Participating adolescents with significant depressive symptomatology, aged 12 to 18 years, will complete assessment measures at Weeks 0, 12 and 24 of treatment. They will also complete a depression inventory once a month during that period. This study aims to recruit 60 adolescent participants and their parent/guardian/s. A power analysis is not indicated as an intra-class correlation coefficient will be calculated and used to inform sample size calculations for subsequent large-scale trials. Qualitative data regarding process implementation will be collected quarterly from focus groups with participating clinicians over 18 months, plus phone interviews with participating adolescents and parent/guardians at 12 weeks and 24 weeks of treatment. The focus group qualitative data will be analysed using a Fourth Generation Evaluation methodology that includes a constant comparative cyclic analysis method.

Discussion: This study protocol will be informative for researchers and clinicians interested in considering, designing and/or conducting cluster randomised trials within community practice such as mental health services.

Falls and mobility in Parkinson’s disease : protocol for a randomised controlled clinical trial

Background Although physical therapy and falls prevention education are argued to reduce falls and disability in people with idiopathic Parkinson's disease, this has not yet been confirmed with a large scale randomised controlled clinical trial. The study will investigate the effects on falls, mobility and quality of life of (i) movement strategy training combined with falls prevention education, (ii) progressive resistance strength training combined with falls prevention education, (iii) a generic life-skills social program (control group).
Methods/Design People with idiopathic Parkinson's disease who live at home will be recruited and randomly allocated to one of three groups. Each person shall receive therapy in an out-patient setting in groups of 3-4. Each group shall be scheduled to meet once per week for 2 hours for 8 consecutive weeks. All participants will also have a structured 2 hour home practice program for each week during the 8 week intervention phase. Assessments will occur before therapy, after the 8 week therapy program, and at 3 and 12 months after the intervention. A falls calendar will be kept by each participant for 12 months after outpatient therapy. Consistent with the recommendations of the Prevention of Falls Network Europe group, three falls variables will be used as the primary outcome measures: the number of fallers, the number of multiple fallers and the falls rate. In addition to quantifying falls, we shall measure mobility, activity limitations and quality of life as secondary outcomes.
Discussion This study has the potential to determine whether outpatient movement strategy training combined with falls prevention education or progressive resistance strength training combined with falls prevention education are effective for reducing falls and improving mobility and life quality in people with Parkinson's disease who live at home.

Improving communication when seeking informed consent: a randomised controlled study of a computer-based method for providing information to prospective clinical trial participants

OBJECTIVE: To assess the efficacy, with respect to participant understanding of information, of a computer-based approach to communication about complex, technical issues that commonly arise when seeking informed consent for clinical research trials. DESIGN, SETTING AND PARTICIPANTS: An open, randomised controlled study of 60 patients with diabetes mellitus, aged 27-70 years, recruited between August 2006 and October 2007 from the Department of Diabetes and Endocrinology at the Alfred Hospital and Baker IDI Heart and Diabetes Institute, Melbourne. INTERVENTION: Participants were asked to read information about a mock study via a computer-based presentation (n = 30) or a conventional paper-based information statement (n = 30). The computer-based presentation contained visual aids, including diagrams, video, hyperlinks and quiz pages. MAIN OUTCOME MEASURES: Understanding of information as assessed by quantitative and qualitative means. RESULTS: Assessment scores used to measure level of understanding were significantly higher in the group that completed the computer-based task than the group that completed the paper-based task (82% v 73%; P = 0.005). More participants in the group that completed the computer-based task expressed interest in taking part in the mock study (23 v 17 participants; P = 0.01). Most participants from both groups preferred the idea of a computer-based presentation to the paper-based statement (21 in the computer-based task group, 18 in the paper-based task group). CONCLUSIONS: A computer-based method of providing information may help overcome existing deficiencies in communication about clinical research, and may reduce costs and improve efficiency in recruiting participants for clinical trials.

The functional and clinical outcomes of exercise training following a very low energy diet for severely obese women: study protocol for a randomised controlled trial

BACKGROUND: Clinical practice guidelines globally recommend lifestyle modification including diet and exercise training as first-line treatment for obesity. The clinical benefits of exercise training in adults with obesity is well-documented; however, there is no strong evidence for the effectiveness of exercise training for weight loss in class II and class III obesity. The purpose of the randomised controlled trial described in this protocol article is to examine the effect of exercise training, in addition to a very low energy diet (VLED), in clinically severe obese women for changes in body composition, physical function, quality of life, and markers of cardiometabolic risk.

METHODS/DESIGN: Sixty women, aged 18-50 years with a body mass index (BMI) greater than 34.9 kg.m(2) and at least one obesity-related co-morbidity, will be recruited for this 12-month study. Participants will be randomised to either exercise plus energy restriction (n = 30), or energy restriction alone (n = 30). All participants will follow an energy-restricted individualised diet incorporating a VLED component. The exercise intervention group will also receive exercise by supervised aerobic and resistance training and a home-based exercise programme totalling 300 minutes per week. Primary outcome measures include body composition and aerobic fitness. Secondary outcome measures include: physical function, cardiometabolic risk factors, quality of life, physical activity, and mental health. All outcome measures will be conducted at baseline, 3, 6 and 12 months.

DISCUSSION: Previous research demonstrates various health benefits of including exercise training as part of a healthy lifestyle at all BMI ranges. Although clinical practice guidelines recommend exercise training as part of first-line treatment for overweight and obesity, there are few studies that demonstrate the effectiveness of exercise in class II and class III obesity. The study aims to determine whether the addition of exercise training to a VLED provides more favourable improvements in body composition, physical function, quality of life, and markers of cardiometabolic risk for women with clinically severe obesity, compared to VLED alone.

Treatment with supplementary arginine, vitamin C and zinc in patients with pressure ulcers: A randomised controlled trial

Background & Aims
Nutrients putatively implicated in pressure ulcer healing were evaluated in a clinical setting.

Methods
Sixteen inpatients with a stage 2, 3 or 4 pressure ulcer randomised to receive daily a standard hospital diet; a standard diet plus two high-protein/energy supplements; or a standard diet plus two high-protein/energy supplements containing additional arginine (9 g), vitamin C (500 mg) and zinc (30 mg). Nutritional status measurements (dietary, anthropometric and biochemical) and pressure ulcer size and severity (by PUSH tool; Pressure Ulcer Scale for Healing; 0=completely healed, 17=greatest severity) were measured weekly for 3 weeks.

Results
Patients’ age and BMI ranges were 37–92 years and 16.4–28.1 kg/m2, respectively. Baseline PUSH scores were similar between groups (8.7±0.5). Only patients receiving additional arginine, vitamin C and zinc demonstrated a clinically significant improvement in pressure ulcer healing (9.4±1.2 vs. 2.6±0.6; baseline and week 3, respectively; P<0.01). All patient groups presented with low serum albumin and zinc and elevated C-reactive protein. There were no significant changes in biochemical markers, oral dietary intake or weight in any group.

Conclusions
In this small set of patients, supplementary arginine, vitamin C and zinc significantly improved the rate of pressure ulcer healing. The results need to be confirmed in a larger study.

Patient engagement and coaching for health: the PEACH study- a cluster randomised controlled trial using the telephone to coach people with type 2 diabetes to engage with their GPs to improve diabetes care: a study protocol.

Background
The PEACH study is based on an innovative 'telephone coaching' program that has been used effectively in a post cardiac event trial. This intervention will be tested in a General Practice setting in a pragmatic trial using existing Practice Nurses (PN) as coaches for people with type 2 diabetes (T2D). Actual clinical care often fails to achieve standards, that are based on evidence that self-management interventions (educational and psychological) and intensive pharmacotherapy improve diabetes control. Telephone coaching in our study focuses on both. This paper describes our study protocol, which aims to test whether goal focused telephone coaching in T2D can improve diabetes control and reduce the treatment gap between guideline based standards and actual clinical practice.
Methods/design
In a cluster randomised controlled trial, general practices employing Practice Nurses (PNs) are randomly allocated to an intervention or control group. We aim to recruit 546 patients with poorly controlled T2D (HbA1c >7.5%) from 42 General Practices that employ PNs in Melbourne, Australia. PNs from General Practices allocated to the intervention group will be trained in diabetes telephone coaching focusing on biochemical targets addressing both patient self-management and engaging patients to work with their General Practitioners (GPs) to intensify pharmacological treatment according to the study clinical protocol. Patients of intervention group practices will receive 8 telephone coaching sessions and one face-to-face coaching session from existing PNs over 18 months plus usual care and outcomes will be compared to the control group, who will only receive only usual care from their GPs. The primary outcome is HbA1c levels and secondary outcomes include cardiovascular disease risk factors, behavioral risk factors and process of care measures.
Discussion
Understanding how to achieve comprehensive treatment of T2D in a General Practice setting is the focus of the PEACH study. This study explores the potential role for PNs to help reduce the treatment and outcomes gap in people with T2D by using telephone coaching. The intervention, if found to be effective, has potential to be sustained and embedded within real world General Practice.

Safety and efficacy of routine postoperative ibuprofen for pain and disability related to ectopic bone formation after hip replacement surgery (HIPAID): a randomised control trial

Objectives To determine the benefits and risks of a non-steroidal anti-inflammatory drug (NSAID) as prophylaxis for ectopic bone formation in patients undergoing total hip replacement (or revision) surgery.
Design Double blind randomised placebo controlled clinical trial, stratified by treatment site and surgery (primary or revision).
Setting 20 orthopaedic surgery centres in Australia and New Zealand.
Participants 902 patients undergoing elective primary or revision total hip replacement surgery.
Intervention 14 days' treatment with ibuprofen (1200 mg daily) or matching placebo started within 24 hours of surgery.
Main outcome measures Changes in self reported hip pain and physical function 6 to 12 months after surgery (Western Ontario and McMaster University Arthritis index).
Results There were no significant differences between the groups for improvements in hip pain (mean difference -0.1, 95% confidence interval -0.4 to 0.2, P = 0.6) or physical function (-0.1, -0.4 to 0.2, P = 0.5), despite a decreased risk of ectopic bone formation (relative risk 0.69, 0.56 to 0.83) associated with ibuprofen. There was a significantly increased risk of major bleeding complications in the ibuprofen group during the admission period (2.09, 1.00 to 4.39).
Conclusions These data do not support the use of routine prophylaxis with NSAIDs in patients undergoing total hip replacement surgery.
Trial registration NCT00145730.

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.

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]

Evaluation of a community pharmacy-based intervention for improving patient adherence to antihypertensives: a randomised controlled trial

Background
The majority of patients using antihypertensive medications fail to achieve their recommended target blood pressure. Poor daily adherence with medication regimens and a lack of persistence with medication use are two of the major reasons for failure to reach target blood pressure. There is no single intervention to improve adherence with antihypertensives that is consistently effective. Community pharmacists are in an ideal position to promote adherence to chronic medications. This study aims to test a specific intervention package that could be integrated into the community pharmacy workflow to enable pharmacists to improve patient adherence and/or persistence with antihypertensive medications - Hypertension Adherence Program in Pharmacy (HAPPY).

Methods/Design
The HAPPY trial is a multi-centre prospective randomised controlled trial. Fifty-six pharmacies have been recruited from three Australian states. To identify potential patients, a software application (MedeMine CVD) extracted data from a community pharmacy dispensing software system (FRED Dispense®). The pharmacies have been randomised to either 'Pharmacist Care Group' (PCG) or 'Usual Care Group' (UCG). To check for 'Hawthorne effect' in the UCG, a third group of patients 'Hidden Control Group' (HCG) will be identified in the UCG pharmacies, which will be made known to the pharmacists at the end of six months. Each study group requires 182 patients. Data will be collected at baseline, three and six months in the PCG and at baseline and six months in the UCG. Changes in patient adherence and persistence at the end of six months will be measured using the self-reported Morisky score, the Tool for Adherence Behaviour Screening and medication refill data.

Discussion
To our knowledge, this is the first research testing a comprehensive package of evidence-based interventions that could be integrated into the community pharmacy workflow to enable pharmacists to improve patient adherence and/or persistence with antihypertensive medications. The unique features of the HAPPY trial include the use of MedeMine CVD to identify patients who could potentially benefit from the service, control for the 'Hawthorne effect' in the UCG and the offer of the intervention package at the end of six months to patients in the UCG, a strategy that is expected to improve retention.

Trial Registration
Australian New Zealand Clinical Trial Registry ACTRN12609000705280