Feasibility and acceptability of web-based enhanced relapse prevention for bipolar disorder (ERPonline):trial protocol

BACKGROUND: Relapse prevention interventions for Bipolar Disorder are effective but implementation in routine clinical services is poor. Web-based approaches offer a way to offer easily accessible access to evidence based interventions at low cost, and have been shown to be effective for other mood disorders. METHODS/DESIGN: This protocol describes the development and feasibility testing of the ERPonline web-based intervention using a single blind randomised controlled trial. Data will include the extent to which the site was used, detailed feedback from users about their experiences of the site, reported benefits and costs to mental health and wellbeing of users, and costs and savings to health services. We will gain an estimate of the likely effect size of ERPonline on a range of important outcomes including mood, functioning, quality of life and recovery. We will explore potential mechanisms of change, giving us a greater understanding of the underlying processes of change, and consequently how the site could be made more effective. We will be able to determine rates of recruitment and retention, and identify what factors could improve these rates. DISCUSSION: The findings will be used to improve the site in accordance with user needs, and inform the design of a large scale evaluation of the clinical and cost effectiveness of ERPonline. They will further contribute to the growing evidence base for web-based interventions designed to support people with mental health problems

Developing employability in higher education music

The development of employability in higher music education concerns students, musicians, educators, administrators and funding bodies, and yet employability is both impossible to measure and poorly defined. This paper sets the context for a set of short papers that explore employability from the perspective of music. Because many of the issues they raise have relevance across the creative industries, this paper discusses research that positions them within this broader context. The paper highlights the need for both the functional (how-to) aspects of employability and those that are cognitive: development of students' cognitive dispositions and their capacity to engage as professionals. As such, the paper argues that employability requires collaborative action on three fronts: enhancement of the ways in which employment outcomes are defined and measured; initiatives that engage students in career- and life-relevant activities; and advocacy work that re-aligns stakeholder perceptions of graduate work and employability itself

Assessing feasibility and acceptability of web-based enhanced relapse prevention for bipolar disorder (ERPonline): a randomized controlled trial

Background: Interventions that teach people with Bipolar Disorder (BD) to recognise and respond to early warning signs of relapse are NICE recommended but implementation in clinical practice is poor. Objective: This study tests the feasibility and acceptability of a randomised controlled trial to evaluate an online enhanced relapse prevention intervention (ERPonline), and reports preliminary evidence of effectiveness. Methods: Single blind, parallel primarily online randomised controlled trial (n=96) over 48 weeks comparing ERPonline plus usual treatment to waitlist (WL) control plus usual treatment for people with BD recruited through National Health Services, voluntary organisations, and media. Randomisation was independent, minimised on number of previous episodes (<8,8-20,21+). Primary outcomes were feasibility and acceptability assessed by rates of study recruitment and retention, levels of intervention use, adverse events and participant feedback. Process and clinical outcomes were assessed by telephone and online and compared using linear models with intention-to-treat analysis. Results: Two hundred and eighty people registered interest online, from which ninety-six met inclusion criteria, consented and were randomised (49 to WL, 47 to ERPonline) over seventeen months, with 80% retention in telephone and online follow up, except week 48 online (76%). Acceptability was high for both ERPonline and trial methods. ERPonline cost approximately £19,340 to create, and £2176 per year to host and maintain the site. Qualitative data highlighted the importance of the relationship users have with online interventions and how this is created as an extension of the relationship with the humans perceived as offering and supporting its use. Differences between the group means suggested that access to ERPonline was associated with: a more positive model of bipolar disorder at 24 (10.70 (0.90-20.5 95%CIs)) and 48 weeks (13.1 (2.44-23.93 95%CIs)); increased monitoring of early warning signs of depression at 48 weeks (-1.39 (-2.61, -.163 95%CIs)) and of (hypo)mania at 24 (-1.72 (-2.98, -0.47 95%CIs)) and 48 weeks (-1.61 (-2.92, -0.30 95%CIs)), compared to WL. There was no evidence of impact of ERPonline on clinical outcomes or medication adherence, but relapse rates across both arms were very low (15%) and the sample remained high functioning throughout. One person died by suicide prior to randomisation. Five people in ERPonline and six in WL control reported ideas of suicide or self-harm during the study. None were deemed study related by an independent Trial Steering Committee. Conclusions: ERPonline offers a cheap accessible option for people seeking ongoing support following successful treatment. However, given high functioning and low relapse rates in this study, testing clinical effectiveness for this population would require very large sample sizes. Building in human support to use ERPonline should be considere

Supporting people with intellectual disabilities in psychological therapies for depression:A qualitative analysis of supporters' experiences

BACKGROUND: Clinicians recommend including carers or others in a supporting role in the therapy as an important adaptation of psychological therapies for people with intellectual disabilities. This nested qualitative study from a larger trial explored supporters' experiences of supporting people with intellectual disabilities receiving behavioural activation or guided self-help therapies for depression. METHOD: Twenty-one purposively sampled supporters were interviewed. The semi-structured interviews were subject to framework analysis, covering expectations of therapy, views of therapy sessions, relationships with therapist and participant, and perceived changes. RESULTS: Supporters were positive about both therapies and reported both therapy-specific and nonspecific therapeutic factors that had significant positive impacts on people's lives. Most supporters reported their involvement contributed to the interventions' effectiveness, and helped establish closer relationships to the people they were supporting. CONCLUSIONS: The presence of supporters within psychological therapies for people with intellectual disabilities can be an effective adaptation to therapies for this population

The feasibility and acceptability of a novel anxiety in bipolar disorder intervention compared to treatment as usual:a randomized controlled trial

1 Background Comorbid anxiety is common in bipolar disorder (BD) and associated with worse clinical outcomes including increased suicidality. Despite effective psychological treatments for anxiety, research into treating anxiety in BD is underdeveloped. This paper describes a novel psychological intervention to address anxiety in context of bipolar disorder (AIBD). 2 Methods Adults with BD and clinically significant anxiety symptoms were randomized to AIBD plus treatment as usual (TAU) or TAU alone. AIBD offered 10 sessions of psychological therapy using a formulation‐based approach. Feasibility and acceptability were evaluated through recruitment, retention, therapy attendance, alliance, fidelity, and qualitative feedback. Clinical outcomes were assessed at baseline, 16, 48, and 80 weeks: interim assessments of relapse at 32 and 64 weeks. 3 Results Seventy‐two participants were recruited with 88% retention to 16 weeks and 74% to 80 weeks (similar between arms). Therapy participants attended urn:x-wiley:10914269:media:da22781:da22781-math-00017.7 (SD 2.8) sessions. Therapeutic alliance and therapy fidelity were acceptable. Qualitative interviews indicated that participants valued integrated support for anxiety with BD and coping strategies. Some suggested a longer intervention period. Clinical outcomes were not significantly different between arms up to 80 weeks follow‐up. 4 Conclusions AIBD is feasible and acceptable but lack of impact on clinical outcomes indicates that adaptations are required. These are discussed in relation to qualitative feedback and recent literature published since the trial completed

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

A Naturally Occurring Plant Cysteine Protease Possesses Remarkable Toxicity against Insect Pests and Synergizes Bacillus thuringiensis Toxin

When caterpillars feed on maize (Zea maize L.) lines with native resistance to several Lepidopteran pests, a defensive cysteine protease, Mir1-CP, rapidly accumulates at the wound site. Mir1-CP has been shown to inhibit caterpillar growth in vivo by attacking and permeabilizing the insect's peritrophic matrix (PM), a structure that surrounds the food bolus, assists in digestion and protects the midgut from microbes and toxins. PM permeabilization weakens the caterpillar defenses by facilitating the movement of other insecticidal proteins in the diet to the midgut microvilli and thereby enhancing their toxicity. To directly determine the toxicity of Mir1-CP, the purified recombinant enzyme was directly tested against four economically significant Lepidopteran pests in bioassays. Mir1-CP LC50 values were 1.8, 3.6, 0.6, and 8.0 ppm for corn earworm, tobacco budworm, fall armyworm and southwestern corn borer, respectively. These values were the same order of magnitude as those determined for the Bacillus thuringiensis toxin Bt-CryIIA. In addition to being directly toxic to the larvae, 60 ppb Mir1-CP synergized sublethal concentrations of Bt-CryIIA in all four species. Permeabilization of the PM by Mir1-CP probably provides ready access to Bt-binding sites on the midgut microvilli and increases its activity. Consequently, Mir1-CP could be used for controlling caterpillar pests in maize using non-transgenic approaches and potentially could be used in other crops either singly or in combination with Bt-toxins

Proceedings of Patient Reported Outcome Measure’s (PROMs) Conference Oxford 2017: Advances in Patient Reported Outcomes Research

A33-Effects of Out-of-Pocket (OOP) Payments and Financial Distress on Quality of Life (QoL) of People with Parkinson’s (PwP) and their Carer

RANTES/CCL5 and Risk for Coronary Events: Results from the MONICA/KORA Augsburg Case-Cohort, Athero-Express and CARDIoGRAM Studies

BACKGROUND: The chemokine RANTES (regulated on activation, normal T-cell expressed and secreted)/CCL5 is involved in the pathogenesis of cardiovascular disease in mice, whereas less is known in humans. We hypothesised that its relevance for atherosclerosis should be reflected by associations between CCL5 gene variants, RANTES serum concentrations and protein levels in atherosclerotic plaques and risk for coronary events. METHODS AND FINDINGS: We conducted a case-cohort study within the population-based MONICA/KORA Augsburg studies. Baseline RANTES serum levels were measured in 363 individuals with incident coronary events and 1,908 non-cases (mean follow-up: 10.2±4.8 years). Cox proportional hazard models adjusting for age, sex, body mass index, metabolic factors and lifestyle factors revealed no significant association between RANTES and incident coronary events (HR [95% CI] for increasing RANTES tertiles 1.0, 1.03 [0.75-1.42] and 1.11 [0.81-1.54]). None of six CCL5 single nucleotide polymorphisms and no common haplotype showed significant associations with coronary events. Also in the CARDIoGRAM study (&gt;22,000 cases, &gt;60,000 controls), none of these CCL5 SNPs was significantly associated with coronary artery disease. In the prospective Athero-Express biobank study, RANTES plaque levels were measured in 606 atherosclerotic lesions from patients who underwent carotid endarterectomy. RANTES content in atherosclerotic plaques was positively associated with macrophage infiltration and inversely associated with plaque calcification. However, there was no significant association between RANTES content in plaques and risk for coronary events (mean follow-up 2.8±0.8 years). CONCLUSIONS: High RANTES plaque levels were associated with an unstable plaque phenotype. However, the absence of associations between (i) RANTES serum levels, (ii) CCL5 genotypes and (iii) RANTES content in carotid plaques and either coronary artery disease or incident coronary events in our cohorts suggests that RANTES may not be a novel coronary risk biomarker. However, the potential relevance of RANTES levels in platelet-poor plasma needs to be investigated in further studies