Clinical effectiveness, cost-effectiveness and acceptability of low-intensity interventions in the management of obsessive–compulsive disorder: the Obsessive–Compulsive Treatment Efficacy randomised controlled Trial (OCTET)

Background: The Obsessive–Compulsive Treatment Efficacy randomised controlled Trial emerged from a research recommendation in National Institute for Health and Care Excellence obsessive–compulsive disorder (OCD) guidelines, which specified the need to evaluate cognitive–behavioural therapy (CBT) treatment intensity formats. Objectives: To determine the clinical effectiveness and cost-effectiveness of two low-intensity CBT interventions [supported computerised cognitive–behavioural therapy (cCBT) and guided self-help]: (1) compared with waiting list for high-intensity CBT in adults with OCD at 3 months; and (2) plus high-intensity CBT compared with waiting list plus high-intensity CBT in adults with OCD at 12 months. To determine patient and professional acceptability of low-intensity CBT interventions. Design: A three-arm, multicentre, randomised controlled trial. Setting: Improving Access to Psychological Therapies services and primary/secondary care mental health services in 15 NHS trusts. Participants: Patients aged ≥ 18 years meeting Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria for OCD, on a waiting list for high-intensity CBT and scoring ≥ 16 on the Yale–Brown Obsessive Compulsive Scale (indicative of at least moderate severity OCD) and able to read English. Interventions: Participants were randomised to (1) supported cCBT, (2) guided self-help or (3) a waiting list for high-intensity CBT. Main outcome measures: The primary outcome was OCD symptoms using the Yale–Brown Obsessive Compulsive Scale – Observer Rated. Results: Patients were recruited from 14 NHS trusts between February 2011 and May 2014. Follow-up data collection was complete by May 2015. There were 475 patients randomised: supported cCBT (n = 158); guided self-help (n = 158) and waiting list for high-intensity CBT (n = 159). Two patients were excluded post randomisation (one supported cCBT and one waiting list for high-intensity CBT); therefore, data were analysed for 473 patients. In the short term, prior to accessing high-intensity CBT, guided self-help demonstrated statistically significant benefits over waiting list, but these benefits did not meet the prespecified criterion for clinical significance [adjusted mean difference –1.91, 95% confidence interval (CI) –3.27 to –0.55; p = 0.006]. Supported cCBT did not demonstrate any significant benefit (adjusted mean difference –0.71, 95% CI –2.12 to 0.70). In the longer term, access to guided self-help and supported cCBT, prior to high-intensity CBT, did not lead to differences in outcomes compared with access to high-intensity CBT alone. Access to guided self-help and supported cCBT led to significant reductions in the uptake of high-intensity CBT; this did not seem to compromise patient outcomes at 12 months. Taking a decision-making approach, which focuses on which decision has a higher probability of being cost-effective, rather than the statistical significance of the results, there was little evidence that supported cCBT and guided self-help are cost-effective at the 3-month follow-up compared with a waiting list. However, by the 12-month follow-up, data suggested a greater probability of guided self-help being cost-effective than a waiting list from the health- and social-care perspective (60%) and the societal perspective (80%), and of supported cCBT being cost-effective compared with a waiting list from both perspectives (70%). Qualitative interviews found that guided self-help was more acceptable to patients than supported cCBT. Professionals acknowledged the advantages of low intensity interventions at a population level. No adverse events occurred during the trial that were deemed to be suspected or unexpected serious events. Limitations: A significant issue in the interpretation of the results concerns the high level of access to high-intensity CBT during the waiting list period. Conclusions: Although low-intensity interventions are not associated with clinically significant improvements in OCD symptoms, economic analysis over 12 months suggests that low-intensity interventions are cost-effective and may have an important role in OCD care pathways. Further research to enhance the clinical effectiveness of these interventions may be warranted, alongside research on how best to incorporate them into care pathways

Environmental performance of miscanthus-lime lightweight concrete using life cycle assessment:Application in external wall assemblies

This is the final version. Available from Elsevier via the DOI in this record. In the UK context, miscanthus is a potential alternative perennial crop for the development of bio-based building materials. This paper presents the environmental benefits of using miscanthus shives in lightweight blocks and their potential application in wall assemblies. A systemic life cycle assessment (LCA) is carried out for miscanthus-lime blocks, and the effects of binder type and binder content are discussed. The environmental performance-based analysis reveals that miscanthus blocks can capture 135 kg CO eq/m for an assumed 100-years life period. The impact analysis using the University of Leiden, institute of environmental science (CML) baseline (v4.4) method shows that 75% of the greenhouse gas emissions are attributable to the production of mineral binders. A reduction of binder to aggregate ratio from 2.0 to 1.5 reduces greenhouse gas emissions by 32.9%. The use of 10 wt% mineral additions can potentially stabilise blocks while having little effect on their overall environmental impacts. The environmental profiles of wall systems incorporating miscanthus-lime blocks have been evaluated in this this study. Combining miscanthus blocks with fired clay bricks enables a potential low carbon retrofitting technique for the current stock of residential buildings in the UK. Timber-framed system filled with miscanthus blocks enables a carbon storage of ~97.3 kg CO eq/m , which presents a potential carbon offsetting strategy in new-build dwellings. Consideration should be given to the potential negative impacts related to agricultural activities for the production of miscanthus shives. The largest negative environmental impact was ozone layer depletion, where a relative difference of 12.8% was recorded between miscanthus timber-framed wall and a typical solid wall insulated with mineral wool. It appears that miscanthus-lime composites can substantially improve the environmental profile of wall assemblies and sustainability be applied in existing uninsulated masonry walls or incorporated in timber- framed new-build houses.Engineering and Physical Sciences Research Council (EPSRC)Natural Environment Research Council (NERC)NERC GW4+ Doctoral Training Partnership studentshi

Comparative effectiveness of approved first-line anti-angiogenic and molecularly targeted therapeutic agents in the treatment of good and intermediate risk metastatic clear cell renal cell carcinoma

BACKGROUND: Based on improved clinical outcomes in randomized controlled clinical trials (RCTs) the FDA and EMA have approved bevacizumab with interferon, sunitinib, and pazopanib in the first-line treatment of low to intermediate risk metastatic clear cell renal cell carcinoma (mRCC). However, there is little comparative data to help in choosing the most effective drug among these agents. METHODS: We performed an indirect comparative effectiveness analysis of the pivotal RCTs of bevacizumab with interferon, sunitinib, or pazopanib compared to one another or interferon alone in first-line treatment of metastatic or advanced RCC. Endpoints of interest were overall survival (OS), progression free survival (PFS), and response rate (RR). Adverse events were also examined. RESULTS: The meta-estimate of the hazard ratio (95% confidence interval) for OS for bevacizumab with interferon vs. interferon alone was 0.86 (0.76-0.97), for sunitinib vs. interferon alone was 0.82 (0.67-1.00), for pazopanib vs. interferon alone was 0.74 (0.57-0.97), for sunitinib vs. bevacizumab with interferon was 0.95 (0.75-1.20), for pazopanib vs. bevacizumab with interferon was 0.86 (0.64-1.16), and for pazopanib vs. sunitinib was 0.91 (0.76-1.08). Similarly, bevacizumab with interferon, sunitinib, or pazopanib had better PFS and RR than interferon alone. Sunitinib and pazopanib had better RR than bevacizumab with interferon and there was suggestive evidence pazopanib may outperform sunitinib in terms of RR. CONCLUSIONS: Bevacizumab with interferon, sunitinib, and pazopanib are adequate first-line options in treatment of mRCC. Interferon alone should not be considered an optimal first-line treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2407-14-592) contains supplementary material, which is available to authorized users

Handbook of toxicology.

Includes bibliographical references.v. 1. Acute toxicities of solids, liquids and gases to laboratory animals, edited by W.S. Spector.--v. 2. Antibiotics, edited by W.S. Spector.--v. 3. Insecticides, by W.O. Negherbon.--v. 4. Tranquilizers, edited by R.M. Grebe.--v. 5. Fungicides, edited by D.S. Dittmer.Mode of access: Internet