Magnetic resonance imaging protocols for paediatric neuroradiology

Increasingly, radiologists are encouraged to have protocols for all imaging studies and to include imaging guidelines in care pathways set up by the referring clinicians. This is particularly advantageous in MRI where magnet time is limited and a radiologist’s review of each patient’s images often results in additional sequences and longer scanning times without the advantage of improvement in diagnostic ability. The difficulties of imaging small children and the challenges presented to the radiologist as the brain develops are discussed. We present our protocols for imaging the brain and spine of children based on 20 years experience of paediatric neurological MRI. The protocols are adapted to suit children under the age of 2 years, small body parts and paediatric clinical scenarios

The utilization of antidepressants and benzodiazepines among people with major depression in Canada

Objective: Although clinical guidelines recommend monotherapy with antidepressants (ADs) for major depression, polypharmacy with benzodiazepines (BDZs) remains an issue. Risks associated with such treatments include tolerance and dependence, among others. We assessed the prevalence and determinants of AD and BDZ utilization among Canadians who experienced a major depressive episode (MDE) in the previous 12 months, and determined the association of seeing a psychiatrist on the utilization of ADs and BDZs. Method: Data were drawn from the 2002 Canadian Community Health Survey: Health and Well-Being, a nationally representative sample of Canadians aged 15 years and older. Descriptive statistics quantified utilization, while logistic regression identified factors associated with utilization, such as sociodemographic characteristics or type of physician seen. Sampling weights and bootstrap variance estimations were used for all analysis. Results: The overall prevalence of AD and BDZ utilization was 49.3% of respondents who experienced an MDE in the past 12 months and reported AD use. Key determinants of utilization were younger age and unemployment in the past week (OR 2.6; P < 0.001). Being seen by a psychiatrist increased utilization (OR 2.5; P < 0.001), possibly because psychiatrists were seeing patients with severe depression. Conclusion: A large proportion of people with past-year MDEs utilized ADs and BDZs. It is unclear how much of this is appropriate given that evidence-based clinical guidelines recommend monotherapy with ADs in the treatment of major depression

Direct and Inverse Variational Problems on Time Scales: A Survey

We deal with direct and inverse problems of the calculus of variations on arbitrary time scales. Firstly, using the Euler-Lagrange equation and the strengthened Legendre condition, we give a general form for a variational functional to attain a local minimum at a given point of the vector space. Furthermore, we provide a necessary condition for a dynamic integro-differential equation to be an Euler-Lagrange equation (Helmholtz's problem of the calculus of variations on time scales). New and interesting results for the discrete and quantum settings are obtained as particular cases. Finally, we consider very general problems of the calculus of variations given by the composition of a certain scalar function with delta and nabla integrals of a vector valued field.Comment: This is a preprint of a paper whose final and definite form will be published in the Springer Volume 'Modeling, Dynamics, Optimization and Bioeconomics II', Edited by A. A. Pinto and D. Zilberman (Eds.), Springer Proceedings in Mathematics & Statistics. Submitted 03/Sept/2014; Accepted, after a revision, 19/Jan/201

Randomised trial of combination cytokine and adult autologous bone marrow progenitor cell administration in patients with non-ischaemic dilated cardiomyopathy - the regenerate-dcm randomized phase II

The REGENERATE-DCM trial is the first phase II randomized, placebo-controlled trial aiming to assess if granulocyte colony-stimulating factor (G-CSF) administration with or without adjunctive intracoronary (IC) delivery of autologous bone marrow-derived cells (BMCs) improves global left ventricular (LV) function in patients with dilated cardiomyopathy (DCM) and significant cardiac dysfunction. Methods and results Sixty patients with DCM and left ventricular ejection fraction (LVEF) at referral of ≤45%, New York Heart Association (NYHA) classification ≥2 and no secondary cause for the cardiomyopathy were randomized equally into four groups: peripheral placebo (saline), peripheral G-CSF, peripheral G-CSF and IC serum, and peripheral G-CSF and IC BMC. All patients, except the peripheral placebo group, received 5 days of G-CSF. In the IC groups, this was followed by bone marrow harvest and IC infusion of cells or serum on Day 6. The primary endpoint was LVEF change from baseline to 3 months, determined by advanced cardiac imaging. At 3 months, peripheral G-CSF combined with IC BMC therapy was associated with a 5.37% point increase in LVEF (38.30%+12.97 from 32.93%+16.46 P ¼ 0.0138), which was maintained to 1 year. This was associated with a decrease in NYHA classification, reduced NT-pro BNP, and improved exercise capacity and quality of life. No significant change in LVEF was seen in the remaining treatment groups. Conclusion This is the first randomized, placebo-controlled trial with a novel combination of G-CSF and IC cell therapy that demonstrates an improvement in cardiac function, symptoms, and biochemical parameters in patients with DCM.The trial was supported by unrestricted grants from the Heart Cells Foundation and Barts and the London Charity. Chugai Pharmaceutical donated supplies of G-CSF and pharmaceutical costs. Funding to pay the Open Access publication charges for this article was provided by the Barts Cardiovascular Biomedical Research Unit (CVBRU)

Multiple breath washout in bronchiectasis clinical trials: is it feasible?

BACKDGROUND: Evaluation of multiple breath washout (MBW) set-up including staff training, certification and central “over-reading” for data quality control is essential to determine the feasibility of MBW in future bronchiectasis studies. AIMS: To assess the outcomes of a MBW training, certification and central over-reading programme. METHODS: MBW training and certification was conducted in European sites collecting lung clearance index (LCI) data in the BronchUK Clinimetrics and/or i-BEST-1 studies. The blended training programme included the use of an eLearning tool and a 1-day face-to-face session. Sites submitted MBW data to trained central over-readers who determined validity and quality. RESULTS: Thirteen training days were delivered to 56 participants from 22 sites. Of 22 sites, 18 (82%) were MBW naïve. Participant knowledge and confidence increased significantly (p<0.001). By the end of the study recruitment, 15 of 22 sites (68%) had completed certification with a mean (range) time since training of 6.2 (3–14) months. In the BronchUK Clinimetrics study, 468 of 589 (79%) tests met the quality criteria following central over-reading, compared with 137 of 236 (58%) tests in the i-BEST-1 study. CONCLUSIONS: LCI is feasible in a bronchiectasis multicentre clinical trial setting; however, consideration of site experience in terms of training as well as assessment of skill drift and the need for re-training may be important to reduce time to certification and optimise data quality. Longer times to certification, a higher percentage of naïve sites and patients with worse lung function may have contributed to the lower success rate in the i-BEST-1 study

All clinically-relevant blood components transmit prion disease following a single blood transfusion: a sheep model of vCJD

Variant CJD (vCJD) is an incurable, infectious human disease, likely arising from the consumption of BSE-contaminated meat products. Whilst the epidemic appears to be waning, there is much concern that vCJD infection may be perpetuated in humans by the transfusion of contaminated blood products. Since 2004, several cases of transfusion-associated vCJD transmission have been reported and linked to blood collected from pre-clinically affected donors. Using an animal model in which the disease manifested resembles that of humans affected with vCJD, we examined which blood components used in human medicine are likely to pose the greatest risk of transmitting vCJD via transfusion. We collected two full units of blood from BSE-infected donor animals during the pre-clinical phase of infection. Using methods employed by transfusion services we prepared red cell concentrates, plasma and platelets units (including leucoreduced equivalents). Following transfusion, we showed that all components contain sufficient levels of infectivity to cause disease following only a single transfusion and also that leucoreduction did not prevent disease transmission. These data suggest that all blood components are vectors for prion disease transmission, and highlight the importance of multiple control measures to minimise the risk of human to human transmission of vCJD by blood transfusion

Continuous Evolution of Statistical Estimators for Optimal Decision-Making

In many everyday situations, humans must make precise decisions in the presence of uncertain sensory information. For example, when asked to combine information from multiple sources we often assign greater weight to the more reliable information. It has been proposed that statistical-optimality often observed in human perception and decision-making requires that humans have access to the uncertainty of both their senses and their decisions. However, the mechanisms underlying the processes of uncertainty estimation remain largely unexplored. In this paper we introduce a novel visual tracking experiment that requires subjects to continuously report their evolving perception of the mean and uncertainty of noisy visual cues over time. We show that subjects accumulate sensory information over the course of a trial to form a continuous estimate of the mean, hindered only by natural kinematic constraints (sensorimotor latency etc.). Furthermore, subjects have access to a measure of their continuous objective uncertainty, rapidly acquired from sensory information available within a trial, but limited by natural kinematic constraints and a conservative margin for error. Our results provide the first direct evidence of the continuous mean and uncertainty estimation mechanisms in humans that may underlie optimal decision making