Maintenance N-acetyl cysteine treatment for bipolar disorder : a double-blind randomised placebo controlled trial

Background N-acetyl cysteine (NAC) is a glutathione precursor that has been shown to have antidepressant efficacy in a placebo-controlled trial. The current study aimed to investigate the maintenance effects of NAC following eight weeks of open-label treatment for bipolar disorder.

Method The efficacy of a double blind randomized placebo controlled trial of 2 g/day NAC as adjunct maintenance treatment for bipolar disorder was examined. Participants (n = 149) had a Montgomery Asberg Depression Rating Score of [greater than or equal to]12 at trial entry and, after eight weeks of open-label NAC treatment, were randomized to adjunctive NAC or placebo, in addition to treatment as usual. Participants (primarily outpatients) were recruited through public and private services and through newspaper advertisements. Time to intervention for a mood episode was the primary endpoint of the study, and changes in mood symptoms, functionality and quality of life measures were secondary outcomes.

Results There was a substantial decrease in symptoms during the eight-week open-label NAC treatment phase. During the subsequent double-blind phase, there was minimal further change in outcome measures with scores remaining low. Consequently, from this low plateau, between-group differences did not emerge on recurrence, clinical functioning or quality of life measures.

Conclusions There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial; however, these findings may be confounded by limitations. Trial Registration The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000074493).

Effect of a telephone-delivered coronary heart disease secondary prevention program (ProActive Heart) on quality of life and health behaviours: primary outcomes of a randomised controlled trial

Background Participation in coronary heart disease secondary prevention programs is low. Innovative programs to meet this treatment gap are required.

Purpose To aim of this study is to describe the effectiveness of a telephone-delivered secondary prevention program for myocardial infarction patients.

Methods Four hundred and thirty adult myocardial infarction patients in Brisbane, Australia were randomised to a 6-month secondary prevention program or usual care. Primary outcomes were health-related quality of life (Short Form-36) and physical activity (Active Australia Survey).

Results Significant intervention effects were observed for health-related quality of life on the mental component summary score (p = 0.02), and the social functioning (p = 0.04) and role-emotional (p = 0.03) subscales, compared with usual care. Intervention participants were also more likely to meet recommended levels of physical activity (p = 0.02), body mass index (p = 0.05), vegetable intake (p = 0.04) and alcohol consumption (p = 0.05).

Conclusions Telephone-delivered secondary prevention programs can significantly improve health outcomes and could meet the treatment gap for myocardial infarction patients.

Annual high-dose oral vitamin D and falls and fractures in older women : a randomized controlled trial

Context Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures; however, adherence to daily supplementation is typically poor.

Objective To determine whether a single annual dose of 500 000 IU of cholecalciferol administered orally to older women in autumn or winter would improve adherence and reduce the risk of falls and fracture.

Design, Setting, and Participants A double-blind, placebo-controlled trial of 2256 community-dwelling women, aged 70 years or older, considered to be at high risk of fracture were recruited from June 2003 to June 2005 and were randomly assigned to receive cholecalciferol or placebo each autumn to winter for 3 to 5 years. The study concluded in 2008.

Intervention 500 000 IU of cholecalciferol or placebo.

Main Outcome Measures Falls and fractures were ascertained using monthly calendars; details were confirmed by telephone interview. Fractures were radiologically confirmed. In a substudy, 137 randomly selected participants underwent serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels.

Results Women in the cholecalciferol (vitamin D) group had 171 fractures vs 135 in the placebo group; 837 women in the vitamin D group fell 2892 times (rate, 83.4 per 100 person-years) while 769 women in the placebo group fell 2512 times (rate, 72.7 per 100 person-years; incidence rate ratio [RR], 1.15; 95% confidence interval [CI], 1.02-1.30; P = .03). The incidence RR for fracture in the vitamin D group was 1.26 (95% CI, 1.00-1.59; P = .047) vs the placebo group (rates per 100 person-years, 4.9 vitamin D vs 3.9 placebo). A temporal pattern was observed in a post hoc analysis of falls. The incidence RR of falling in the vitamin D group vs the placebo group was 1.31 in the first 3 months after dosing and 1.13 during the following 9 months (test for homogeneity; P = .02). In the substudy, the median baseline serum 25-hydroxycholecalciferol was 49 nmol/L. Less than 3% of the substudy participants had 25-hydroxycholecalciferol levels lower than 25 nmol/L. In the vitamin D group, 25-hydroxycholecalciferol levels increased at 1 month after dosing to approximately 120 nmol/L, were approximately 90 nmol/L at 3 months, and remained higher than the placebo group 12 months after dosing.

Conclusion Among older community-dwelling women, annual oral administration of high-dose cholecalciferol resulted in an increased risk of falls and fractures.

Cluster randomized controlled trial of a peer support program for people with diabetes: study protocol for the Australasian peers for progress study

Background
Well managed diabetes requires active self-management in order to ensure optimal glycaemic control and appropriate use of available clinical services and other supports. Peer supporters can assist people with their daily diabetes self-management activities, provide emotional and social support, assist and encourage clinical care and be available when needed.
Methods
A national database of Australians diagnosed with type 2 diabetes is being used to invite people in pre-determined locations to participate in community-based peer support groups. Peer supporters are self-identified from these communities. All consenting participants receive diabetes self-management education and education manual prior to randomization by community to a peer support intervention or usual care. This multi-faceted intervention comprises four interconnected components for delivering support to the participants. (1) Trained supporters lead 12 monthly group meetings. Participants are assisted to set goals to improve diabetes self-management, discuss with and encourage each other to strengthen linkages with local clinical services (including allied health services) as well as provide social and emotional support. (2) Support through regular supporter-participant or participant-participant contact, between monthly sessions, is also promoted in order to maintain motivation and encourage self-improvement and confidence in diabetes self-management. (3) Participants receive a workbook containing diabetes information, resources and community support services, key diabetes management behaviors and monthly goal setting activity sheets. (4) Finally, a password protected website contains further resources for the participants. Supporters are mentored and assisted throughout the intervention by other supporters and the research team through attendance at a weekly teleconference. Data, including a self-administered lifestyle survey, anthropometric and biomedical measures are collected on all participants at baseline, 6 and 12 months. The primary outcome is change in cardiovascular disease risk using the UKPDS risk equation. Secondary outcomes include biomedical, quality of life, psychosocial functioning, and other lifestyle measures. An economic evaluation will determine whether the program is cost effective.
Discussion
This manuscript presents the protocol for a cluster randomized controlled trial of group-based peer support for people with type 2 diabetes in a community setting. Results from this trial will contribute evidence about the effectiveness of peer support in achieving effective self-management of diabetes.

Factors limiting participation in arthritis self-management programmes : an exploration of barriers and patient preferences within a randomized controlled trial

Objective. To improve understanding of barriers to participation in community-based arthritis self-management programmes and patient preferences for self-management education.

Methods. Individuals with hip or knee OA referred to orthopaedic surgeons or rheumatologists at six public and private hospitals in Victoria, Australia, were recruited for a randomized controlled trial (RCT) of the Stanford Arthritis Self-Management Programme (ASMP). As part of the study design, potential participants were asked during the screening and recruitment process about reasons for being unable to attend the course, reasons for not participating in the study and individual preferences for course scheduling.

Results. Of 1125 individuals assessed, 216 (19%) were unable to attend six ASMP sessions. This was commonly due to physical limitations, including illness, restricted mobility and pain (22%), difficulty getting to or from courses (22%), work commitments (22%), the time commitment required (17%) and family roles (12%). Among those who did not want to participate in the study (n = 258), the overwhelming reason was disinterest (74%). Specific preferences for course scheduling were frequent, confirming the practical challenges faced in organizing courses for the RCT.

Conclusion. Incorporating patients from public and private settings, this study has elicited new insights into barriers to ASMP participation. Many people with hip or knee OA have limited capacity and motivation to attend community-based group programmes. Future self-management programmes and research should include more accessible options for those who cannot attend group-based programmes.

Treatment acceptability and psychosocial outcomes of a randomised controlled trial of a cognitive behavioural lifestyle intervention for overweight and obese adolescents

This study explores the impact of a cognitive behavioural lifestyle program, the CHOOSE HEALTH Program, on psychosocial wellbeing in overweight and obese adolescents. The sample comprised 29 male and 34 female adolescents aged 11.5 to 18.9 years (M = 14.3, SD = 1.9) and classified as overweight (n = 15) or obese (n=48). Participantswere randomly allocated to treatment or wait-list control conditions; participants allocated the wait-list condition were offered treatment after 6 months. Adolescents and parents completed self-report measures of psychopathology, psychosocial and family functioning. Treatment did not have detrimental effects on the psychosocial factors assessed. It resulted in significant improvements in weight control behaviour, impulse regulation, social support from family and parent–adolescent problem communication (p<.05). Similar results were obtained with completer and intention-to-treat analyses. Treatment acceptability was high, with all respondents indicating that they made progress. Combined, results indicate that treatment did not have detrimental effects on psychopathology, psychosocial functioning, or family functioning. Treatment resulted in significant improvements in impulse regulation, social support from family and parent–adolescent communication. Thus, parents and professionals can be assured that a comprehensive, multifaceted, parent-supported, cognitive behavioural intervention for overweight and obese adolescents does not cause psychological harm.

Reducing parental anxiety using a family based intervention for youth mental health : a randomized controlled trial

This paper presents findings on parent anxiety and attachment relationship style from the Deakin Family Options (DFO) pilot study, a randomized controlled pilot study comparing a family-based treatment (BEST Plus), versus a youth only treatment (CBT) versus a group who received both of these treatments (COMBINED). Eligible participants were families with a young person (aged 12 - 25 years) with a high prevalence mental health problem. Youth from participating families scored in the clinical or subclinical range for depression, anxiety and/or substance misuse symptoms on standardized measures during the initial assessment. The collected sample was drawn from regional and urban centers in Victoria, Australia and allocated to treatment condition using a simple randomization procedure (parallel design). It was hypothesized that families receiving the BEST Plus would experience greater reductions in youth and parent mental health symptoms, and improved parent-child relationships, compared with those in the CBT condition. This paper describes and discusses changes in parent anxiety and parent attachment, according to whether the parent participated in a treatment (BEST Plus) or did not (NONBEST Plus). Participants were blind to the study hypotheses. In total 71 parent participants returned pre data and were allocated to a treatment group. In this paper, data from parent participants who completed pre and post measures (n = 48) and pre, post, and 6-month follow-up measures (n = 28) on anxiety and attachment were analyzed by group (BEST Plus versus NONBEST Plus). The results of this study suggest that parent anxiety decreased significantly more following parent involvement in a group treatment, than for parents that did not receive treatment. Unexpectedly, avoidant attachment increased in the no treatment group, but remained relatively stable following the BEST Plus group. There were no significant findings in relation to compulsive traits and anxious attachment. These findings are discussed in light of the study limitations.

Impact of medical Qigong on quality of life, fatigue, mood and inflammation in cancer patients : a randomized controlled trial

Background: Substantial numbers of cancer patients use complementary medicine therapies, even without a supportive evidence base. This study aimed to evaluate in a randomized controlled trial, the use of Medical Qigong (MQ) compared with usual care to improve the quality of life (QOL) of cancer patients. Patients and methods: One hundred and sixty-two patients with a range of cancers were recruited. QOL and fatigue were measured by Functional Assessment of Cancer Therapy—General and Functional Assessment of Cancer Therapy—Fatigue, respectively, and mood status by Profile of Mood State. The inflammatory marker serum C-reactive protein (CRP) was monitored serially. Results: Regression analysis indicated that the MQ group significantly improved overall QOL (t144 = −5.761, P < 0.001), fatigue (t153 = −5.621, P < 0.001), mood disturbance (t122 =2.346, P = 0.021) and inflammation (CRP) (t99 = 2.042, P < 0.044) compared with usual care after controlling for baseline variables. Conclusions: This study indicates that MQ can improve cancer patients’ overall QOL and mood status and reduce specific side-effects of treatment. It may also produce physical benefits in the long term through reduced inflammation.

Transdermal estrogen patches for aggressive behavior in male patients with dementia : a randomized, controlled trial

Objectives: To investigate the efficacy and tolerability of transdermal estrogen patches for the adjunctive treatment of aggressive behavior in male patients with advanced dementia. Methods: The study was designed as an 8-week, randomized, controlled trial in acute aged psychiatry inpatient units and specialized nursing homes in Melbourne, Australia, between 1998 and 1999. The participants were 27 men with established dementia, identified as displaying aggressive behavior not responding to treatment for at least 2 weeks prior to referral. The instruments used to measure aggressive behavior were the Rating Scale for Aggressive Behavior in the Elderly (RAGE), the Cornell Scale for Depression in Dementia (CSDD) and the Mini-mental State Examination (MMSE). Physical examination was performed and biochemistry and serum hormone concentrations were measured at baseline and at 8 weeks. Concomitant psychotropic medication use was recorded and analyzed. Results: There was no significant difference in aggressive behavior at 8 weeks, but significant “rebound” in aggressive behavior (change in scores between week 8 and week 10, p<0.009) and benzodiazepine use in the estrogen group (p<0.03), following removal of the patches. Only behavioral items of the CSDD improved in the experimental group (p=0.031). The use of patches was associated with a significant rise in serum estrogen (p<0.001) but not with a significant decrease in serum testosterone (p=0.077). There were no adverse effects associated with their use. Conclusions: The use of transdermal estrogen yielding up to 100μg per day was not associated with discernable improvement in aggressive behavior in men with advanced dementia. Small subject numbers, multiple variables and a lack of statistical power impair interpretation of these results. However, the tolerability and apparent rebound effect on removal of patches indicate the need for larger studies in this area.

Primary prevention of gestational diabetes for women who are overweight and obese : a randomised controlled trial

Background: Gestational Diabetes Mellitus (GDM) has well recognised adverse health implications for the  mother and her newborn that are both short and long term. Obesity is a significant risk factor for developing GDM and the prevalence of obesity is increasing globally. It is a matter of public health importance that clinicians have evidence based strategies to inform practice and currently there is insufficient evidence regarding the impact of dietary and lifestyle interventions on improving maternal and newborn outcomes. The primary aim of this study is to measure the impact of a telephone based intervention that promotes positive lifestyle modifications on the incidence of GDM. Secondary aims include: the impact on gestational weight gain; large for gestational age babies; differences in blood glucose levels taken at the Oral Glucose Tolerance Test (OGTT) and selected factors relating to self-efficacy and psychological wellbeing. 

The Melbourne Diabetes Prevention Study (MDPS) : study protocol for a randomized controlled trial

Background
Worldwide, type 2 diabetes (T2DM) prevalence has more than doubled over two decades. In Australia, diabetes is the second highest contributor to the burden of disease. Lifestyle modification programs comprising diet changes, weight loss and moderate physical activity, have been proven to reduce the incidence of T2DM in high risk individuals.

As part of the Council of Australia Governments, the State of Victoria committed to develop and support the diabetes prevention program ‘Life! Taking action on diabetes’ (Life!) which has direct lineage from effective clinical and implementation trials from Finland and Australia. The Melbourne Diabetes Prevention Study (MDPS) has been set up to evaluate the effectiveness and cost-effectiveness of a specific version of the Life! program.

Methods/design
We intend to recruit 796 participants for this open randomized clinical trial; 398 will be allocated to the intervention arm and 398 to the usual care arm. Several methods of recruitment will be used in order to maximize the number of participants. Individuals aged 50 to 75 years will be screened with a risk tool (AUSDRISK) to detect those at high risk of developing T2DM. Those with existing diabetes will be excluded. Intervention participants will undergo anthropometric and laboratory tests, and comprehensive surveys at baseline, following the fourth group session (approximately three months after the commencement of the intervention) and 12 months after commencement of the intervention, while control participants will undergo testing at baseline and 12 months only.

The intervention consists of an initial individual session followed by a series of five structured-group sessions. The first four group sessions will be carried out at two week intervals and the fifth session will occur eight months after the first group session. The intervention is based on the Health Action Process Approach (HAPA) model and sessions will empower and enable the participants to follow the five goals of the Life! program.

Discussion
This study will determine whether the effect of this intervention is larger than the effect of usual care in reducing central obesity and cardiovascular risk factors and thus the risk of developing diabetes and cardiovascular disease. Also it will evaluate how these two options compare economically.

ShopSmart 4 Health - protocol of a skills-based randomised controlled trial promoting fruit and vegetable consumption among socioeconomically disadvantaged women

Background
There is a need for evidence on the most effective and cost-effective approaches for promoting healthy eating among groups that do not meet dietary recommendations for good health, such as those with low incomes or experiencing socioeconomic disadvantage. This paper describes the ShopSmart 4 Health study, a randomised controlled trial conducted by Deakin University, Coles Supermarkets and the Heart Foundation, to investigate the effectiveness and cost-effectiveness of a skill-building intervention for promoting increased purchasing and consumption of fruits and vegetables amongst women of low socioeconomic position (SEP).

Methods/design
ShopSmart 4 Health employed a randomised controlled trial design. Women aged 18–60 years, holding a Coles store loyalty card, who shopped at Coles stores within socioeconomically disadvantaged neighbourhoods and met low-income eligibility criteria were invited to participate. Consenting women completed a baseline survey assessing food shopping and eating habits and food-related behaviours and attitudes. On receipt of their completed survey, women were randomised to either a skill-building intervention or a wait-list control condition. Intervention effects will be evaluated via self-completion surveys and using supermarket transaction sales data, collected at pre- and post-intervention and 6-month follow-up. An economic evaluation from a societal perspective using a cost-consequences approach will compare the costs and outcomes between intervention and control groups. Process evaluation will be undertaken to identify perceived value and effects of intervention components.

Discussion
This study will provide data to address the currently limited evidence base regarding the effectiveness and cost-effectiveness of skill-building intervention strategies aimed at increasing fruit and vegetable consumption among socioeconomically disadvantaged women, a target group at high risk of poor diets.