Preventing Bias in Cluster Randomised Trials

Bruno Giraudeau and Philippe Ravaud discuss the difficulties in preventing selection bias and applying intention-to-treat analysis in cluster randomized trials, and propose some solutions

Wave interaction with defects in pressurised composite structures

There exists a great variety of structural failure modes which must be frequently inspected to ensure continuous structural integrity of composite structures. This work presents a Finite Element (FE) based method for calculating wave interaction with damage within structures of arbitrary layering and geometric complexity. The principal novelty is the investigation of pre-stress effect on wave propagation and scattering in layered structures. A Wave Finite Element (WFE) method, which combines FE analysis with periodic structure theory (PST), is used to predict the wave propagation properties along periodic waveguides of the structural system. This is then coupled to the full FE model of a coupling joint within which structural damage is modelled, in order to quantify wave interaction coeffcients through the joint. Pre-stress impact is quantified by comparison of results under pressurised and non-pressurised scenarios. The results show that including these pressurisation effects in calculations is essential. This is of specific relevance to aircraft structures being intensely pressurised while on air. Numerical case studies are exhibited for different forms of damage type. The exhibited results are validated against available analytical and experimental results

Nanoparticles that communicate in vivo to amplify tumour targeting

Author Manuscript: 2012 May 29Nanomedicines have enormous potential to improve the precision of cancer therapy, yet our ability to efficiently home these materials to regions of disease in vivo remains very limited. Inspired by the ability of communication to improve targeting in biological systems, such as inflammatory-cell recruitment to sites of disease, we construct systems where synthetic biological and nanotechnological components communicate to amplify disease targeting in vivo. These systems are composed of ‘signalling’ modules (nanoparticles or engineered proteins) that target tumours and then locally activate the coagulation cascade to broadcast tumour location to clot-targeted ‘receiving’ nanoparticles in circulation that carry a diagnostic or therapeutic cargo, thereby amplifying their delivery. We show that communicating nanoparticle systems can be composed of multiple types of signalling and receiving modules, can transmit information through multiple molecular pathways in coagulation, can operate autonomously and can target over 40 times higher doses of chemotherapeutics to tumours than non-communicating controls.National Cancer Institute (U.S.) (SBMRI Cancer Center Support Grant 5 P30 CA30199-28)National Cancer Institute (U.S.) (MIT CCNE Grant U54 CA119349)National Cancer Institute (U.S.) (Bioengineering Research Partnership Grant 5-R01-CA124427)National Cancer Institute (U.S.) (UCSD CCNE Grant U54 CA 119335)National Science Foundation (U.S.) (Whitaker Graduate Fellowship

Collaborative Depression Trial (CADET): multi-centre randomised controlled trial of collaborative care for depression - study protocol

<p>Abstract</p> <p>Background</p> <p>Comprising of both organisational and patient level components, collaborative care is a potentially powerful intervention for improving depression treatment in UK primary Care. However, as previous models have been developed and evaluated in the United States, it is necessary to establish the effect of collaborative care in the UK in order to determine whether this innovative treatment model can replicate benefits for patients outside the US. This Phase III trial was preceded by a Phase II patient level RCT, following the MRC Complex Intervention Framework.</p> <p>Methods/Design</p> <p>A multi-centre controlled trial with cluster-randomised allocation of GP practices. GP practices will be randomised to usual care control or to "collaborative care" - a combination of case manager coordinated support and brief psychological treatment, enhanced specialist and GP communication. The primary outcome will be symptoms of depression as assessed by the PHQ-9.</p> <p>Discussion</p> <p>If collaborative care is demonstrated to be effective we will have evidence to enable the NHS to substantially improve the organisation of depressed patients in primary care, and to assist primary care providers to deliver a model of enhanced depression care which is both effective and acceptable to patients.</p> <p>Trial Registration Number</p> <p>ISRCTN32829227</p

Frequency of anxiety after stroke: a systematic review and meta-analysis of observational studies.

BACKGROUND AND PURPOSE: Negative psychological outcomes occur frequently after stroke; however, there is uncertainty regarding the occurrence of anxiety disorders and anxiety symptoms after stroke. A systematic review of observational studies was conducted that assessed the frequency of anxiety in stroke patients using a diagnostic or screening tool. SUMMARY OF REVIEW: Databases were searched up to March 2011. A random effects model was used to summarize the pooled estimate. Statistical heterogeneity was assessed using the I(2) statistic. Forty-four published studies comprising 5760 stroke patients were included. The overall pooled estimate of anxiety disorders assessed by clinical interview was 18% (95%confidence interval 8-29%, I(2)  = 97%) and was 25% (95% confidence interval 21-28%, I(2)  = 90%) for anxiety assessed by rating scale. The Hospital Anxiety and Depression Scale-Anxiety subscale 'probable' and 'possible' cutoff scores were the most widely used assessment criteria. The combined rate of anxiety by time after stroke was: 20% (95% confidence interval 13-27%, I(2)  = 96%) within one-month of stroke; 23% (95% confidence interval 19-27%, I(2)  = 84%) one to five-months after stroke; and 24% (95% confidence interval 19-29%, I(2)  = 89%) six-months or more after stroke. CONCLUSION: Anxiety after stroke occurs frequently although methodological limitations in the primary studies may limit generalizability. Given the association between prevalence rates and the Hospital Anxiety and Depression Scale-Anxiety cutoff used in studies, reported rates could in fact underrepresent the extent of the problem. Additionally, risk factors for anxiety, its impact on patient outcomes, and effects in tangent with depression remain unclear