Study protocol for a randomised controlled trial of internet-based cognitive-behavioural therapy for obsessive-compulsive disorder.

Obsessive-Compulsive Disorder (OCD) is a common chronic psychiatric disorder that constitutes a leading cause of disability. Although Cognitive-Behaviour Therapy (CBT) has been shown to be an effective treatment for OCD, this specialised treatment is unavailable to many due to access issues and the social stigma associated with seeing a mental health specialist. Internet-based psychological treatments have shown to provide effective, accessible and affordable treatment for a range of anxiety disorders, and two Randomised Controlled Trials (RCTs) have demonstrated the efficacy and acceptability of internet-based CBT (iCBT) for OCD, as compared to waitlist or supportive therapy. Although these initial findings are promising, they do not isolate the specific effect of iCBT. This paper details the study protocol for the first randomised control trial evaluating the efficacy of therapist-assisted iCBT for OCD, as compared to a matched control intervention; internet-based therapist-assisted progressive relaxation training (iPRT). It will aim to examine whether therapist-assisted iCBT is an acceptable and efficacious treatment, and to examine how effectiveness is influenced by patient characteristics.

Stage managing bipolar disorder

Clinical staging is widespread in medicine - it informs prognosis, clinical course, and treatment, and assists individualized care. Staging places an individual on a probabilistic continuum of increasing potential disease severity, ranging from clinically at-risk or latency stage through first threshold episode of illness or recurrence, and, finally, to late or end-stage disease. The aim of the present paper was to examine and update the evidence regarding staging in bipolar disorder, and how this might inform targeted and individualized intervention approaches.

The impact of insight in a first-episode mania with psychosis population on outcome at 18 months

To explore whether poor initial insight during a first episode of mania with psychotic features was predictive of poor psychosocial and clinical outcomes at 18 months.

Relationship between membrane fatty acids and cognitive symptoms and information processing in individuals at ultra-high risk for psychosis

Cognitive symptoms and impairment are central to schizophrenia and often an early sign of this condition. The present study investigated biological correlates of cognitive symptoms and performance in individuals at ultra-high risk (UHR) for psychosis. The study sample comprised 80 neuroleptic-naïve UHR individuals aged 13-25 years. Associations among erythrocyte membrane fatty acid levels, measured by gas chromatography, and cognitive functioning were investigated in UHR patients. Subjects were divided into terciles based on their scores on the cognitive factor of the Positive and Negative Syndrome Scale. The Zahlen-Verbindungs Test (ZVT) (the number-combination test) was also used as a measure of information-processing speed. Exploratory analysis was conducted to investigate the relationship between membrane fatty acid levels with the size of the intracranial area (ICA), a neurodevelopmental measure relevant to schizophrenia, in half of subjects (n=40) using magnetic resonance imaging. The adjusted analysis revealed that omega-9 eicosenoic and erucic acid levels were significantly higher, but omega-3 docosahexaenoic acid levels were significantly lower, in the cognitively impaired than in the cognitively intact group. We found a significant negative association of eicosenoic, erucic, and gamma-linoleic acids with ZVT scores. A negative association between ICA and membrane levels of eicosenoic acid was also found. This is the first study to demonstrate the relationship between membrane fatty acids and cognitive function in neuroleptic-naïve subjects at UHR for psychosis. The study findings indicate that abnormalities in membrane fatty acids may be associated with the neurodevelopmental disruption associated with the cognitive impairments of individuals at UHR for psychosis.

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.

Data Integration Protocol In Ten-steps (DIPIT) : a new standard for medical researchers

The exponential increase in data, computing power and the availability of readily accessible analytical software has allowed organisations around the world to leverage the benefits of integrating multiple heterogeneous data files for enterprise-level planning and decision making. Benefits from effective data integration to the health and medical research community include more trustworthy research, higher service quality, improved personnel efficiency, reduction of redundant tasks, facilitation of auditing and more timely, relevant and specific information. The costs of poor quality processes elevate the risk of erroneous outcomes, an erosion of confidence in the data and the organisations using these data. To date there are no documented set of standards for best practice integration of heterogeneous data files for research purposes. Therefore, the aim of this paper is to describe a set of clear protocol for data file integration (Data Integration Protocol In Ten-steps; DIPIT) translational to any field of research.

Quality of life in bipolar and schizoaffective disorder - a naturalistic approach

The aim of this study was to evaluate the health-related quality of life (HRQoL) in bipolar type I (BD I) and schizoaffective (SQA) patients during a 2-year period in a naturalistic study.

A head-to-head comparison of aripiprazole and risperidone for safety and treating autistic disorders, a randomized double blind clinical trial

Aripiprazole and risperidone are the only FDA approved medications for treating irritability in autistic disorder, however there are no head-to-head data comparing these agents. This is the first prospective randomized clinical trial comparing the safety and efficacy of these two medications in patients with autism spectrum disorders. Fifty nine children and adolescents with autism spectrum disorders were randomized to receive either aripiprazole or risperidone for 2 months. The primary outcome measure was change in Aberrant Behavior Checklist (ABC) scores. Adverse events were assessed. Aripiprazole as well as risperidone lowered ABC scores during 2 months. The rates of adverse effects were not significantly different between the two groups. The safety and efficacy of aripiprazole (mean dose 5.5 mg/day) and risperidone (mean dose 1.12 mg/day) were comparable. The choice between these two medications should be on the basis of clinical equipoise considering the patient's preference and clinical profile.

The predictive validity of bipolar at-risk (prodromal) criteria in help-seeking adolescents and young adults: a prospective study.

There are no established tools to identify individuals at risk for developing bipolar disorder. We developed a set of ultra-high-risk criteria for bipolar disorder [bipolar at-risk (BAR)]. The primary aim of the present study was to determine the predictive validity of the BAR criteria.

Atypical antipsychotic agents; peas in a pod or chalk and cheese?

With escalating health expenditure and a shrinking purse, there is increased focus on the cost efficacy of still patented versus generic medications in general, and for atypical antipsychotics in particular. In a recent BMC Medicine article, Godman and colleagues presented data indicating poor uptake of the off patent atypical antipsychotic risperidone, arguing for authorities to mandate its greater use. This is under the assumption of clinical equivalence of atypical antipsychotics. This commentary argues that there are clinically meaningful differences between atypical antipsychotics and important inter-individual heterogeneity in clinical response and tolerability. Access to a broad range of atypical antipsychotics enables clinicians to tailor care, taking consideration of differential efficacy and adverse effects profile in order to meet the needs of individual patients with improved real world effectiveness of treatment. Restriction of agent choice risks detracting from optimal clinical care, with possible poorer outcomes and greater costs of care. A balance between encouraging use of cheapest in class agent and allowing access to various atypical agents for tailored care is likely to produce optimal health outcomes.Please see related article: http://www.biomedcentral.com/1741-7015/12/98.

Staging systems in bipolar disorder: an International Society for Bipolar Disorders Task Force report

We discuss the rationale behind staging systems described specifically for bipolar disorders. Current applications, future directions and research gaps in clinical staging models for bipolar disorders are outlined.

Response of BRAF-mutant melanoma to BRAF inhibition is mediated by a network of transcriptional regulators of glycolysis.

Deregulated glucose metabolism fulfills the energetic and biosynthetic requirements for tumor growth driven by oncogenes. Because inhibition of oncogenic BRAF causes profound reductions in glucose uptake and a strong clinical benefit in BRAF-mutant melanoma, we examined the role of energy metabolism in responses to BRAF inhibition. We observed pronounced and consistent decreases in glycolytic activity in BRAF-mutant melanoma cells. Moreover, we identified a network of BRAF-regulated transcription factors that control glycolysis in melanoma cells. Remarkably, this network of transcription factors, including hypoxia-inducible factor-1α, MYC, and MONDOA (MLXIP), drives glycolysis downstream of BRAF(V600), is critical for responses to BRAF inhibition, and is modulated by BRAF inhibition in clinical melanoma specimens. Furthermore, we show that concurrent inhibition of BRAF and glycolysis induces cell death in BRAF inhibitor (BRAFi)-resistant melanoma cells. Thus, we provide a proof-of-principle for treatment of melanoma with combinations of BRAFis and glycolysis inhibitors.

Exploring associations between parental and peer variables, personal variables and physical activity among adolescents: a mediation analysis

This study aimed to investigate how parental and peer variables are associated with moderate- to-vigorous intensity physical activity (MVPA) on week- and weekend days among Australian adolescents (13-15 y), and whether perceived internal barriers (e.g. lack of time), external barriers (e.g. lack of others to be physically active with) and self-efficacy mediated these associations.